Metastatic Breast Cancer

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The San Antonio Breast Cancer Symposium (SABCS) 2021 will “be a great meeting,” according to Carlos Arteaga, MD, director of Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas.

Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.

The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.

Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
 

On the horizon for advanced breast cancer

A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.

This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.

The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.

The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.

Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.

“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.

Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.

In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.

The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.

In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.

In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.

The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
 

Refining who gets the ‘kitchen sink’

Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.

The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.

Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.

But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”

The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.

Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
 

Metformin trial: ‘This is it’

Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.

The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.

The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.

“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
 

TKI for breast cancer with brain mets

The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).

Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.

In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.

This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.

As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.

The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.

TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”

Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.

A version of this article first appeared on Medscape.com.

The San Antonio Breast Cancer Symposium (SABCS) 2021 will “be a great meeting,” according to Carlos Arteaga, MD, director of Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas.

Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.

The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.

Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
 

On the horizon for advanced breast cancer

A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.

This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.

The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.

The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.

Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.

“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.

Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.

In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.

The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.

In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.

In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.

The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
 

Refining who gets the ‘kitchen sink’

Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.

The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.

Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.

But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”

The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.

Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
 

Metformin trial: ‘This is it’

Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.

The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.

The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.

“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
 

TKI for breast cancer with brain mets

The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).

Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.

In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.

This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.

As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.

The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.

TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”

Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.

A version of this article first appeared on Medscape.com.

The San Antonio Breast Cancer Symposium (SABCS) 2021 will “be a great meeting,” according to Carlos Arteaga, MD, director of Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas.

Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.

The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.

Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
 

On the horizon for advanced breast cancer

A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.

This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.

The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.

The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.

Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.

“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.

Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.

In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.

The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.

In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.

In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.

The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
 

Refining who gets the ‘kitchen sink’

Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.

The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.

Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.

But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”

The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.

Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
 

Metformin trial: ‘This is it’

Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.

The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.

The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.

“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
 

TKI for breast cancer with brain mets

The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).

Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.

In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.

This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.

As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.

The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.

TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”

Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.

A version of this article first appeared on Medscape.com.

For the first time, new data show that risk for breast cancer recurrence extends past 30 years.

The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.

Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.

The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.

Recurrence risk was greatest early in the study period.

Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.

“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.

“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.

The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).

This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.

The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.

Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.  
 

Further details from the study

Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.

Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).

The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.

The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.

Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.

The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, new data show that risk for breast cancer recurrence extends past 30 years.

The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.

Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.

The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.

Recurrence risk was greatest early in the study period.

Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.

“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.

“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.

The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).

This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.

The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.

Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.  
 

Further details from the study

Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.

Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).

The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.

The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.

Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.

The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, new data show that risk for breast cancer recurrence extends past 30 years.

The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.

Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.

The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.

Recurrence risk was greatest early in the study period.

Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.

“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.

“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.

The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).

This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.

The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.

Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.  
 

Further details from the study

Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.

Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).

The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.

The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.

Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.

The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new survey of U.S. patients with breast cancer found that 42% were using cannabis, primarily to relieve side effects associated with treatment, such as pain, anxiety, nausea, and insomnia.

Most (75%) of the patients who reported using cannabis said it was extremely helpful or very helpful in alleviating symptoms.

The authors warn of potential safety concerns with cannabis, especially with the use of unregulated products.

In addition, the survey found that physicians were not highly regarded as a source of information about cannabis use. Only 39% of patients said that they discussed cannabis with their physicians; 28% reported feeling uncomfortable when broaching the topic. Only 4% indicated that physicians were the most helpful source of information about cannabis.

The survey involved 612 patients with breast cancer. The results were published online Oct. 12 in Cancer.

“Our study highlights an important opportunity for providers to initiate informed conversations about medical cannabis with their patients, as the evidence shows that many are using medical cannabis without our knowledge or guidance,” said lead author Marisa Weiss, MD, of Breastcancer.org and the Lankenau Medical Center, near Philadelphia. “Not knowing whether or not our cancer patients are using cannabis is a major blind spot in our ability to provide optimal care,” she said.

Cannabis in one form or another has been legalized in many states across America, and even in states where it hasn’t been legalized, people are using it.

“Even though many states have relaxed their laws on cannabis, it remains a Schedule I drug on the federal level and is essentially still considered illegal,” commented Donald I. Abrams, MD, professor of medicine at the University of California, San Francisco, and an integrative oncologist at the UCSF Osher Center for Integrative Medicine. “This is why many physicians are uncomfortable discussing it with patients,” he said.

“Cannabis use isn’t taught in medical school, and until that changes, I don’t know how physicians are going to be advisers for this,” said Dr. Abrams, who was approached by this news organization for comment.

This “is a really nice study in that it looks at a large group of breast cancer patients from the community ... It’s not from a single institution [such as this previous study] and so a more representative mix,” Dr. Abrams said.

However, he also commented that the article had a “scent of ‘reefer madness’” about it, given its emphasis on potential harms and safety concerns.

“It’s interesting how alcohol is considered mainstream but cannabis has been demonized,” he said. “Especially for women with breast cancer, it’s so clear that alcohol is related to the development of postmenopausal breast cancer. As a recreational intervention, cannabis in my mind appears to be much safer for women for relaxation.”

“The one thing I worry about are patients who take highly concentrated CBD [cannabidiol] oil, as it can block the metabolism of prescription drugs and allow them to build up in the blood,” Dr. Abrams said. “I advise people against using these products.”
 

Cannabis to relieve symptoms

Previous studies have noted widespread use of cannabis among patients with cancer. For example, a large study from Israel that included nearly 3,000 participants found that cannabis use improved a variety of cancer-related symptoms, including nausea and vomiting, sleep disorders, pain, anxiety, and depression. Among those with cancer who survived to 6 months and who finished the study protocol, 60% achieved “treatment success.” Of note, at 6 months, 36% of patients had stopped taking opioids, and for 9.9%, the dose of opioids had decreased.

In the current study, dubbed the Coala-T-Cannabis study, the investigators approached U.S. members of the Breastcancer.org and Healthline.com communities who self-reported that they had been diagnosed with breast cancer within the past 5 years; 612 surveys were completed.

Half of all respondents said they had looked for information on medical cannabis, but most were unsatisfied with the information that they had received. Only 6% were extremely satisfied; 25% were very satisfied with the information.

Most patients (39%) did not discuss cannabis use with their physicians. Of those who did, 28% reported feeling uncomfortable discussing the topic. Only 4% of survey respondents indicated that physicians were the most helpful source of cannabis information.

Regarding which source of information was most helpful, 22% said websites, 18% said family members or friends, 12% said staffers and pharmacists in dispensaries, and 7% said other patients with breast cancer.

Forty-two percent of the survey respondents said they used cannabis for medical purposes and for relief of symptoms, which included pain (78%), insomnia (70%), anxiety (57%), stress (51%), and nausea/vomiting (46%).

In addition, 49% believed that medical cannabis could be used to treat the cancer itself.

A fair number were also using cannabis for recreational purposes. Of those who used cannabis, only 23% reported that they used it for medical purposes only.

Participants used cannabis in a variety of forms. The most popular form of consumption was as edibles (70%), followed by liquids/tinctures (65%), smoking (51%), topicals (46%), and vape pens (45%). Participants reported using an average of 3.7 different products.
 

Safety concerns?

The authors caution about the use of cannabis while receiving anticancer therapies because such use “raises important efficacy and safety concerns.”

“Many chemotherapy agents as well as cannabinoids are metabolized in the liver’s p450 cytochrome system,” Dr. Weiss and colleagues note, and the mechanism by which cannabinoids interact with particular CYP450 isoenzymes “has the potential to alter the metabolism of other medications and lead to adverse side effects.”

They also question the safety of some of the cannabis products that are being used. Participants reported receiving cannabis from a variety of sources, which included state-regulated dispensaries, “dealers,” and family/friends.

Three-quarters of respondents believed that cannabis was better than “chemicals” and that the benefits outweighed the risks. But many of the products used are unregulated, the authors point out.

“Providers should communicate clearly about the health and safety concerns associated with certain cannabis products and methods of delivery,” they conclude. “Without these measures, patients may make these decisions without qualified medical guidance, obtain poor-quality cannabis products, and consume them through potentially hazardous delivery methods during various types of cancer therapies.”

The study was supported by research grants from Ananda Health/Ecofibre and the Dr. Philip Reeves Legacy Fund. Several coauthors reported relationships with industry, as noted in the article. Dr. Abrams owns stock in Cannformatics and Lumen; he has received honorarium from Clever Leaves and Maui Grown Therapies and speaker honorarium from GW Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A new survey of U.S. patients with breast cancer found that 42% were using cannabis, primarily to relieve side effects associated with treatment, such as pain, anxiety, nausea, and insomnia.

Most (75%) of the patients who reported using cannabis said it was extremely helpful or very helpful in alleviating symptoms.

The authors warn of potential safety concerns with cannabis, especially with the use of unregulated products.

In addition, the survey found that physicians were not highly regarded as a source of information about cannabis use. Only 39% of patients said that they discussed cannabis with their physicians; 28% reported feeling uncomfortable when broaching the topic. Only 4% indicated that physicians were the most helpful source of information about cannabis.

The survey involved 612 patients with breast cancer. The results were published online Oct. 12 in Cancer.

“Our study highlights an important opportunity for providers to initiate informed conversations about medical cannabis with their patients, as the evidence shows that many are using medical cannabis without our knowledge or guidance,” said lead author Marisa Weiss, MD, of Breastcancer.org and the Lankenau Medical Center, near Philadelphia. “Not knowing whether or not our cancer patients are using cannabis is a major blind spot in our ability to provide optimal care,” she said.

Cannabis in one form or another has been legalized in many states across America, and even in states where it hasn’t been legalized, people are using it.

“Even though many states have relaxed their laws on cannabis, it remains a Schedule I drug on the federal level and is essentially still considered illegal,” commented Donald I. Abrams, MD, professor of medicine at the University of California, San Francisco, and an integrative oncologist at the UCSF Osher Center for Integrative Medicine. “This is why many physicians are uncomfortable discussing it with patients,” he said.

“Cannabis use isn’t taught in medical school, and until that changes, I don’t know how physicians are going to be advisers for this,” said Dr. Abrams, who was approached by this news organization for comment.

This “is a really nice study in that it looks at a large group of breast cancer patients from the community ... It’s not from a single institution [such as this previous study] and so a more representative mix,” Dr. Abrams said.

However, he also commented that the article had a “scent of ‘reefer madness’” about it, given its emphasis on potential harms and safety concerns.

“It’s interesting how alcohol is considered mainstream but cannabis has been demonized,” he said. “Especially for women with breast cancer, it’s so clear that alcohol is related to the development of postmenopausal breast cancer. As a recreational intervention, cannabis in my mind appears to be much safer for women for relaxation.”

“The one thing I worry about are patients who take highly concentrated CBD [cannabidiol] oil, as it can block the metabolism of prescription drugs and allow them to build up in the blood,” Dr. Abrams said. “I advise people against using these products.”
 

Cannabis to relieve symptoms

Previous studies have noted widespread use of cannabis among patients with cancer. For example, a large study from Israel that included nearly 3,000 participants found that cannabis use improved a variety of cancer-related symptoms, including nausea and vomiting, sleep disorders, pain, anxiety, and depression. Among those with cancer who survived to 6 months and who finished the study protocol, 60% achieved “treatment success.” Of note, at 6 months, 36% of patients had stopped taking opioids, and for 9.9%, the dose of opioids had decreased.

In the current study, dubbed the Coala-T-Cannabis study, the investigators approached U.S. members of the Breastcancer.org and Healthline.com communities who self-reported that they had been diagnosed with breast cancer within the past 5 years; 612 surveys were completed.

Half of all respondents said they had looked for information on medical cannabis, but most were unsatisfied with the information that they had received. Only 6% were extremely satisfied; 25% were very satisfied with the information.

Most patients (39%) did not discuss cannabis use with their physicians. Of those who did, 28% reported feeling uncomfortable discussing the topic. Only 4% of survey respondents indicated that physicians were the most helpful source of cannabis information.

Regarding which source of information was most helpful, 22% said websites, 18% said family members or friends, 12% said staffers and pharmacists in dispensaries, and 7% said other patients with breast cancer.

Forty-two percent of the survey respondents said they used cannabis for medical purposes and for relief of symptoms, which included pain (78%), insomnia (70%), anxiety (57%), stress (51%), and nausea/vomiting (46%).

In addition, 49% believed that medical cannabis could be used to treat the cancer itself.

A fair number were also using cannabis for recreational purposes. Of those who used cannabis, only 23% reported that they used it for medical purposes only.

Participants used cannabis in a variety of forms. The most popular form of consumption was as edibles (70%), followed by liquids/tinctures (65%), smoking (51%), topicals (46%), and vape pens (45%). Participants reported using an average of 3.7 different products.
 

Safety concerns?

The authors caution about the use of cannabis while receiving anticancer therapies because such use “raises important efficacy and safety concerns.”

“Many chemotherapy agents as well as cannabinoids are metabolized in the liver’s p450 cytochrome system,” Dr. Weiss and colleagues note, and the mechanism by which cannabinoids interact with particular CYP450 isoenzymes “has the potential to alter the metabolism of other medications and lead to adverse side effects.”

They also question the safety of some of the cannabis products that are being used. Participants reported receiving cannabis from a variety of sources, which included state-regulated dispensaries, “dealers,” and family/friends.

Three-quarters of respondents believed that cannabis was better than “chemicals” and that the benefits outweighed the risks. But many of the products used are unregulated, the authors point out.

“Providers should communicate clearly about the health and safety concerns associated with certain cannabis products and methods of delivery,” they conclude. “Without these measures, patients may make these decisions without qualified medical guidance, obtain poor-quality cannabis products, and consume them through potentially hazardous delivery methods during various types of cancer therapies.”

The study was supported by research grants from Ananda Health/Ecofibre and the Dr. Philip Reeves Legacy Fund. Several coauthors reported relationships with industry, as noted in the article. Dr. Abrams owns stock in Cannformatics and Lumen; he has received honorarium from Clever Leaves and Maui Grown Therapies and speaker honorarium from GW Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A new survey of U.S. patients with breast cancer found that 42% were using cannabis, primarily to relieve side effects associated with treatment, such as pain, anxiety, nausea, and insomnia.

Most (75%) of the patients who reported using cannabis said it was extremely helpful or very helpful in alleviating symptoms.

The authors warn of potential safety concerns with cannabis, especially with the use of unregulated products.

In addition, the survey found that physicians were not highly regarded as a source of information about cannabis use. Only 39% of patients said that they discussed cannabis with their physicians; 28% reported feeling uncomfortable when broaching the topic. Only 4% indicated that physicians were the most helpful source of information about cannabis.

The survey involved 612 patients with breast cancer. The results were published online Oct. 12 in Cancer.

“Our study highlights an important opportunity for providers to initiate informed conversations about medical cannabis with their patients, as the evidence shows that many are using medical cannabis without our knowledge or guidance,” said lead author Marisa Weiss, MD, of Breastcancer.org and the Lankenau Medical Center, near Philadelphia. “Not knowing whether or not our cancer patients are using cannabis is a major blind spot in our ability to provide optimal care,” she said.

Cannabis in one form or another has been legalized in many states across America, and even in states where it hasn’t been legalized, people are using it.

“Even though many states have relaxed their laws on cannabis, it remains a Schedule I drug on the federal level and is essentially still considered illegal,” commented Donald I. Abrams, MD, professor of medicine at the University of California, San Francisco, and an integrative oncologist at the UCSF Osher Center for Integrative Medicine. “This is why many physicians are uncomfortable discussing it with patients,” he said.

“Cannabis use isn’t taught in medical school, and until that changes, I don’t know how physicians are going to be advisers for this,” said Dr. Abrams, who was approached by this news organization for comment.

This “is a really nice study in that it looks at a large group of breast cancer patients from the community ... It’s not from a single institution [such as this previous study] and so a more representative mix,” Dr. Abrams said.

However, he also commented that the article had a “scent of ‘reefer madness’” about it, given its emphasis on potential harms and safety concerns.

“It’s interesting how alcohol is considered mainstream but cannabis has been demonized,” he said. “Especially for women with breast cancer, it’s so clear that alcohol is related to the development of postmenopausal breast cancer. As a recreational intervention, cannabis in my mind appears to be much safer for women for relaxation.”

“The one thing I worry about are patients who take highly concentrated CBD [cannabidiol] oil, as it can block the metabolism of prescription drugs and allow them to build up in the blood,” Dr. Abrams said. “I advise people against using these products.”
 

Cannabis to relieve symptoms

Previous studies have noted widespread use of cannabis among patients with cancer. For example, a large study from Israel that included nearly 3,000 participants found that cannabis use improved a variety of cancer-related symptoms, including nausea and vomiting, sleep disorders, pain, anxiety, and depression. Among those with cancer who survived to 6 months and who finished the study protocol, 60% achieved “treatment success.” Of note, at 6 months, 36% of patients had stopped taking opioids, and for 9.9%, the dose of opioids had decreased.

In the current study, dubbed the Coala-T-Cannabis study, the investigators approached U.S. members of the Breastcancer.org and Healthline.com communities who self-reported that they had been diagnosed with breast cancer within the past 5 years; 612 surveys were completed.

Half of all respondents said they had looked for information on medical cannabis, but most were unsatisfied with the information that they had received. Only 6% were extremely satisfied; 25% were very satisfied with the information.

Most patients (39%) did not discuss cannabis use with their physicians. Of those who did, 28% reported feeling uncomfortable discussing the topic. Only 4% of survey respondents indicated that physicians were the most helpful source of cannabis information.

Regarding which source of information was most helpful, 22% said websites, 18% said family members or friends, 12% said staffers and pharmacists in dispensaries, and 7% said other patients with breast cancer.

Forty-two percent of the survey respondents said they used cannabis for medical purposes and for relief of symptoms, which included pain (78%), insomnia (70%), anxiety (57%), stress (51%), and nausea/vomiting (46%).

In addition, 49% believed that medical cannabis could be used to treat the cancer itself.

A fair number were also using cannabis for recreational purposes. Of those who used cannabis, only 23% reported that they used it for medical purposes only.

Participants used cannabis in a variety of forms. The most popular form of consumption was as edibles (70%), followed by liquids/tinctures (65%), smoking (51%), topicals (46%), and vape pens (45%). Participants reported using an average of 3.7 different products.
 

Safety concerns?

The authors caution about the use of cannabis while receiving anticancer therapies because such use “raises important efficacy and safety concerns.”

“Many chemotherapy agents as well as cannabinoids are metabolized in the liver’s p450 cytochrome system,” Dr. Weiss and colleagues note, and the mechanism by which cannabinoids interact with particular CYP450 isoenzymes “has the potential to alter the metabolism of other medications and lead to adverse side effects.”

They also question the safety of some of the cannabis products that are being used. Participants reported receiving cannabis from a variety of sources, which included state-regulated dispensaries, “dealers,” and family/friends.

Three-quarters of respondents believed that cannabis was better than “chemicals” and that the benefits outweighed the risks. But many of the products used are unregulated, the authors point out.

“Providers should communicate clearly about the health and safety concerns associated with certain cannabis products and methods of delivery,” they conclude. “Without these measures, patients may make these decisions without qualified medical guidance, obtain poor-quality cannabis products, and consume them through potentially hazardous delivery methods during various types of cancer therapies.”

The study was supported by research grants from Ananda Health/Ecofibre and the Dr. Philip Reeves Legacy Fund. Several coauthors reported relationships with industry, as noted in the article. Dr. Abrams owns stock in Cannformatics and Lumen; he has received honorarium from Clever Leaves and Maui Grown Therapies and speaker honorarium from GW Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

System-level changes to the way cancer care is delivered can help eliminate survival disparities between Black and White patients.

When barriers to completing radiation therapy were identified and addressed in a cohort of patients with early-stage lung and breast cancer, 5-year survival rates improved for all patients and closed the racial disparity gap, researchers reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The findings come from the ACCURE clinical trial. This is the first prospective study designed to erase gaps in cancer treatment completion and survival among Black and White patient populations, explained lead author Matthew A. Manning, MD, a radiation oncologist and chief of oncology at Cone Health in Greensboro, N.C.

“Thousands of studies have looked at racial disparities in health care, but until recently, very few studies have implemented interventions to eliminate those disparities,” he said.

“This study shows that the implementation of ‘systems-change’ can eliminate racial disparities in cancer survival while improving survival for all,” he added.

“These results add to a growing body of evidence that health care disparities in cancer outcomes are eliminated or minimized by providing supportive, timely, and guideline-directed care,” said Lannis Hall, MD, MPH, director of radiation oncology, Siteman Cancer Center, and associate professor of radiation oncology at Washington University School of Medicine, St. Louis, who was approached for comment

“This research supports that access to care and timely treatment completion is critical to eliminating health care disparities,” she told this news organization. The system-based intervention in this trial was designed to reduce treatment delays and provide a supportive matrix for patients confronting real-world difficulties like transportation issues, childcare complications, and work absence, she explained.
 

Eliminating racial disparities

Previous findings from the ACCURE trial showed that it eliminated Black-White disparities in treatment completion rates, which was the study’s primary endpoint (Cancer Med. 2019;8:1095-1102). “It also improved treatment for all patients,” said Dr. Manning. “The current study is a follow-up on the survival of eligible patients treated during the ACCURE enrollment as compared to historical data.”

ACCURE was a multi-institutional trial designed to test a community-created intervention to reduce racial disparities. The intervention involved multiple changes to the way patients were supported while receiving cancer treatment and had four components: 

• an electronic health record with automatic alerts to flag missed appointments or unmet milestones in expected care 
• a nurse navigator trained in race-specific barriers to help patients overcome obstacles to care when alerts are flagged
• a physician champion to engage health care teams with race-related feedback on treatment completion
• regular health equity education training sessions for staff

The cohort was comprised of 1,413 patients with lung and breast cancer (stage 0-II) who were diagnosed from 2013-2015, and survival was compared to historical cases – 2,016 patients who had been treated from 2007-2011.

The results showed a significant improvement in survival for both Black and White patients with breast and lung cancer over time, and the racial gap in survival was reduced. 

The 5-year survival rate for breast cancer increased from 91% for White patients and 89% in Black patients in historical cases, to 94% for both during the study period.  

For patients with lung cancer, the 5-year survival rate improved from 43% in White patients and 37% in Black patients to 56% and 54%, respectively.

A subgroup analysis showed that patients with lung cancer who underwent surgery had 5-year survival rates of 78.5% for White and 70.1% for Black patients, whereas for those who underwent stereotactic body radiation therapy (SBRT) the rates were 41.9% and 50% respectively.

“We’ve shown it’s possible to eliminate disparities in cancer treatment completion and that this change has the potential to close cancer survival gaps downstream,” said Dr. Manning. “But we think the application can be much broader.” 

The ACCURE study was sponsored by the National Institutes of Health. Dr. Manning and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Identifying the molecular features of metastatic breast cancer (MBC) offers a real-time window into a patient’s treatment options as well as the potential to follow the disease as it evolves over time.
 

Tissue biopsy remains the gold standard for characterizing tumor biology and guiding therapeutic decisions, but liquid biopsies — blood analyses that allow oncologists to detect circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the blood — are increasingly demonstrating their value. Last year, the U.S. Food and Drug Administration (FDA) approved two liquid biopsy tests, Guardant360 CDx and FoundationOne Liquid CDx, that can identify more than 300 cancer-related genes in the blood. In 2019, the FDA also approved the first companion diagnostic test, therascreen, to pinpoint PIK3CA gene mutations in patients’ ctDNA and determine whether patients should receive the PI3K inhibitor alpelisib along with fulvestrant.

Here’s an overview of how liquid biopsy is being used in monitoring MBC progression and treatment — and what some oncologists think of it.

What we do and don’t know

“Identifying a patient’s targetable mutations, most notably PIK3CA mutations, is currently the main use of liquid biopsy,” said Pedram Razavi, MD, PhD, a medical oncologist who leads the liquid biopsy program for breast cancer at Memorial Sloan Kettering (MSK) Cancer Center in New York City. “Patients who come to MSK are offered a tumor and liquid biopsy at the time of metastatic diagnosis as part of the standard of care.”

Liquid and tissue biopsy analyses can provide a more complete picture of a patient’s condition. Whereas tissue biopsy allows oncologists to target a more saturated sample of the cancer ecosystem and a wider array of biomarkers, liquid biopsy offers important advantages as well, including a less invasive way to sequence a sample, monitor patients’ treatment response, or track tumor evolution. Liquid biopsy also provides a bigger picture view of tumor heterogeneity by pooling information from many tumor locations as opposed to one.

But, cautioned Yuan Yuan, MD, PhD, liquid biopsy technology is not always sensitive enough to detect CTCs, ctDNA, or all relevant mutations. “When you collect a small tube of blood, you’re essentially trying to catch a small fish in a big sea and wading through a lot of background noise,” said Dr. Yuan, medical oncologist at City of Hope, a comprehensive cancer center in Los Angeles County. “The results may be hard to interpret or come back inconclusive.”

And although emerging data suggest that liquid biopsy provides important insights about tumor dynamics — including mapping disease progression, predicting survival, and even detecting signs of cancer recurrence before metastasis develops — the tool has limited utility in clinical practice outside of identifying sensitivity to various therapies or drugs.

“Right now, a lot of research is being done to understand how to use CTC and ctDNA in particular as a means of surveillance in breast cancer, but we’re still in the beginning stages of applying that outside of clinical trials,” said Joseph A. Sparano, MD, deputy director of the Tisch Cancer Institute and chief of the division of hematology and medical oncology, Icahn School of Medicine at Mount Sinai, New York City.

Personalizing treatment

The companion diagnostic test therascreen marked the beginning stages of using liquid biopsy to match treatments to genetic abnormalities in MBC. The SOLAR-1 phase 3 trial, which led to the approval of alpelisib and therascreen, found that the PI3K inhibitor plus fulvestrant almost doubled progression-free survival (PFS) (11 months vs 5.7 months in placebo-fulvestrant group) in patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.

More recent studies have shown that liquid biopsy tests can also identify ESR1 mutations and predict responses to inhibitors that target AKT1 and HER2. Investigators presenting at the 2021 American Society of Clinical Oncology meeting reported that next-generation sequencing of ctDNA in patients with HR-positive MBC, HER-positive MBC, or triple-negative breast cancer detected ESR1 mutations in 14% of patients (71 of 501). Moreover, ESR1 mutations were found only in HR-positive patients who had already received endocrine therapy. (The study also examined PIK3CA mutations, which occurred in about one third of patients). A more in-depth look revealed that ESR1 mutations were strongly associated with liver and bone metastases and that mutations along specific codons negatively affected overall survival (OS) and PFS: codons 537 and 538 for OS and codons 380 and 536 for PFS.

According to Debasish Tripathy, MD, professor and chairman of the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, in addition to tumor sequencing, “liquid biopsy has become a great research tool to track patients in real time and predict, for instance, who will respond to a treatment and identify emerging resistance.”

In terms of predicting responses to treatment, the plasmaMATCH trial assessed ctDNA in 1,034 patients with advanced breast cancer for mutations in ESR1, HER2, and AKT1 using digital droplet polymerase chain reaction (PCR) and Guardant360. Results showed that 357 (34.5%) of these patients had potentially targetable aberrations, including 222 patients with ESR1 mutations, 36 patients with HER2 mutations, and 30 patients with AKT1 mutations.

Agreement between digital droplet PCR and Guardant360 testing was 96%-99%, and liquid biopsy showed 93% sensitivity compared with tumor samples. The investigators also used liquid biopsy findings to match patients’ mutations to targeted treatments: fulvestrant for those with ESR1 mutations, neratinib for HER2 (ERBB2) mutations, and the selective AKT inhibitor capivasertib for estrogen receptor–positive tumors with AKT1 mutations.

Overall, the investigators concluded that ctDNA testing offers “accurate tumor genotyping” in line with tissue-based testing and is ready for routine clinical practice to identify common as well as rare genetic alterations, such as HER2 and AKT1 mutations, that affect only about 5% of patients with advanced disease.

Predicting survival and recurrence

A particularly promising area for liquid biopsy is its usefulness in helping to predict survival outcomes and monitor patients for early signs of recurrence before metastasis occurs. But the data to support this are still in their infancy.

A highly cited study, published over 15 years ago in the New England Journal of Medicine, found that patients with MBC who had five or more CTCs per 7.5 mL of whole blood before receiving first-line therapy exhibited significantly shorter median PFS (2.7 vs 7.0 months) and OS (10 vs > 18 months) compared with patients with fewer than five CTCs. Subsequent analyses performed more than a decade later, including a meta-analysis published last year, helped validate these early findings that levels of CTCs detected in the blood independently and strongly predicted PFS and OS in patients with MBC.

In addition, ctDNA can provide important information about patients’ survival odds. In a retrospective study published last year, investigators tracked changes in ctDNA in 291 plasma samples from 84 patients with locally advanced breast cancer who participated in the I-SPY trial. Patients who remained ctDNA-positive after 3 weeks of neoadjuvant chemotherapy were significantly more likely to have residual disease after completing their treatment compared with patients who cleared ctDNA at that early stage (83% for those with nonpathologic complete response vs 52%). Notably, the presence of ctDNA between therapy initiation and completion was associated with a significantly greater risk for metastatic recurrence, whereas clearance of ctDNA after neoadjuvant therapy was linked to improved survival.

“The study is important because it highlights how tracking circulating ctDNA status in neoadjuvant-treated breast cancer can expose a patient’s risk for distant metastasis,” said Dr. Yuan. But, she added, “I think the biggest attraction of liquid biopsy will be the ability to detect molecular disease even before imaging can, and identify who has a high risk for recurrence.”

Dr. Razavi agreed that the potential to prevent metastasis by finding minimal residual disease (MRD) is the most exciting area of liquid biopsy research. “If we can find tumor DNA early before tumors have a chance to establish themselves, we could potentially change the trajectory of the disease for patients,” he said.

Several studies suggest that monitoring patients’ ctDNA levels after neoadjuvant treatment and surgery may help predict their risk for relapse and progression to metastatic disease. A 2015 analysis, which followed 20 patients with breast cancer after surgery, found that ctDNA monitoring accurately differentiated those who ultimately developed metastatic disease from those who didn’t (sensitivity, 93%; specificity, 100%) and detected metastatic disease 11 months earlier, on average, than imaging did. Another 2015 study found that the presence of ctDNA in plasma after neoadjuvant chemotherapy and surgery predicted metastatic relapse a median of almost 8 months before clinical detection. Other recent data show the power of ultrasensitive blood tests to detect MRD and potentially find metastatic disease early.

Although an increasing number of studies show that ctDNA and CTCs are prognostic for breast cancer recurrence, a major question remains: For patients with ctDNA or CTCs but no overt disease after imaging, will initiating therapy prevent or delay the development of metastatic disease?

“We still have to do those clinical trials to determine whether detecting MRD and treating patients early actually positively affects their survival and quality of life,” Dr. Razavi said.

Identifying the molecular features of metastatic breast cancer (MBC) offers a real-time window into a patient’s treatment options as well as the potential to follow the disease as it evolves over time.
 

Tissue biopsy remains the gold standard for characterizing tumor biology and guiding therapeutic decisions, but liquid biopsies — blood analyses that allow oncologists to detect circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the blood — are increasingly demonstrating their value. Last year, the U.S. Food and Drug Administration (FDA) approved two liquid biopsy tests, Guardant360 CDx and FoundationOne Liquid CDx, that can identify more than 300 cancer-related genes in the blood. In 2019, the FDA also approved the first companion diagnostic test, therascreen, to pinpoint PIK3CA gene mutations in patients’ ctDNA and determine whether patients should receive the PI3K inhibitor alpelisib along with fulvestrant.

Here’s an overview of how liquid biopsy is being used in monitoring MBC progression and treatment — and what some oncologists think of it.

What we do and don’t know

“Identifying a patient’s targetable mutations, most notably PIK3CA mutations, is currently the main use of liquid biopsy,” said Pedram Razavi, MD, PhD, a medical oncologist who leads the liquid biopsy program for breast cancer at Memorial Sloan Kettering (MSK) Cancer Center in New York City. “Patients who come to MSK are offered a tumor and liquid biopsy at the time of metastatic diagnosis as part of the standard of care.”

Liquid and tissue biopsy analyses can provide a more complete picture of a patient’s condition. Whereas tissue biopsy allows oncologists to target a more saturated sample of the cancer ecosystem and a wider array of biomarkers, liquid biopsy offers important advantages as well, including a less invasive way to sequence a sample, monitor patients’ treatment response, or track tumor evolution. Liquid biopsy also provides a bigger picture view of tumor heterogeneity by pooling information from many tumor locations as opposed to one.

But, cautioned Yuan Yuan, MD, PhD, liquid biopsy technology is not always sensitive enough to detect CTCs, ctDNA, or all relevant mutations. “When you collect a small tube of blood, you’re essentially trying to catch a small fish in a big sea and wading through a lot of background noise,” said Dr. Yuan, medical oncologist at City of Hope, a comprehensive cancer center in Los Angeles County. “The results may be hard to interpret or come back inconclusive.”

And although emerging data suggest that liquid biopsy provides important insights about tumor dynamics — including mapping disease progression, predicting survival, and even detecting signs of cancer recurrence before metastasis develops — the tool has limited utility in clinical practice outside of identifying sensitivity to various therapies or drugs.

“Right now, a lot of research is being done to understand how to use CTC and ctDNA in particular as a means of surveillance in breast cancer, but we’re still in the beginning stages of applying that outside of clinical trials,” said Joseph A. Sparano, MD, deputy director of the Tisch Cancer Institute and chief of the division of hematology and medical oncology, Icahn School of Medicine at Mount Sinai, New York City.

Personalizing treatment

The companion diagnostic test therascreen marked the beginning stages of using liquid biopsy to match treatments to genetic abnormalities in MBC. The SOLAR-1 phase 3 trial, which led to the approval of alpelisib and therascreen, found that the PI3K inhibitor plus fulvestrant almost doubled progression-free survival (PFS) (11 months vs 5.7 months in placebo-fulvestrant group) in patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.

More recent studies have shown that liquid biopsy tests can also identify ESR1 mutations and predict responses to inhibitors that target AKT1 and HER2. Investigators presenting at the 2021 American Society of Clinical Oncology meeting reported that next-generation sequencing of ctDNA in patients with HR-positive MBC, HER-positive MBC, or triple-negative breast cancer detected ESR1 mutations in 14% of patients (71 of 501). Moreover, ESR1 mutations were found only in HR-positive patients who had already received endocrine therapy. (The study also examined PIK3CA mutations, which occurred in about one third of patients). A more in-depth look revealed that ESR1 mutations were strongly associated with liver and bone metastases and that mutations along specific codons negatively affected overall survival (OS) and PFS: codons 537 and 538 for OS and codons 380 and 536 for PFS.

According to Debasish Tripathy, MD, professor and chairman of the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, in addition to tumor sequencing, “liquid biopsy has become a great research tool to track patients in real time and predict, for instance, who will respond to a treatment and identify emerging resistance.”

In terms of predicting responses to treatment, the plasmaMATCH trial assessed ctDNA in 1,034 patients with advanced breast cancer for mutations in ESR1, HER2, and AKT1 using digital droplet polymerase chain reaction (PCR) and Guardant360. Results showed that 357 (34.5%) of these patients had potentially targetable aberrations, including 222 patients with ESR1 mutations, 36 patients with HER2 mutations, and 30 patients with AKT1 mutations.

Agreement between digital droplet PCR and Guardant360 testing was 96%-99%, and liquid biopsy showed 93% sensitivity compared with tumor samples. The investigators also used liquid biopsy findings to match patients’ mutations to targeted treatments: fulvestrant for those with ESR1 mutations, neratinib for HER2 (ERBB2) mutations, and the selective AKT inhibitor capivasertib for estrogen receptor–positive tumors with AKT1 mutations.

Overall, the investigators concluded that ctDNA testing offers “accurate tumor genotyping” in line with tissue-based testing and is ready for routine clinical practice to identify common as well as rare genetic alterations, such as HER2 and AKT1 mutations, that affect only about 5% of patients with advanced disease.

Predicting survival and recurrence

A particularly promising area for liquid biopsy is its usefulness in helping to predict survival outcomes and monitor patients for early signs of recurrence before metastasis occurs. But the data to support this are still in their infancy.

A highly cited study, published over 15 years ago in the New England Journal of Medicine, found that patients with MBC who had five or more CTCs per 7.5 mL of whole blood before receiving first-line therapy exhibited significantly shorter median PFS (2.7 vs 7.0 months) and OS (10 vs > 18 months) compared with patients with fewer than five CTCs. Subsequent analyses performed more than a decade later, including a meta-analysis published last year, helped validate these early findings that levels of CTCs detected in the blood independently and strongly predicted PFS and OS in patients with MBC.

In addition, ctDNA can provide important information about patients’ survival odds. In a retrospective study published last year, investigators tracked changes in ctDNA in 291 plasma samples from 84 patients with locally advanced breast cancer who participated in the I-SPY trial. Patients who remained ctDNA-positive after 3 weeks of neoadjuvant chemotherapy were significantly more likely to have residual disease after completing their treatment compared with patients who cleared ctDNA at that early stage (83% for those with nonpathologic complete response vs 52%). Notably, the presence of ctDNA between therapy initiation and completion was associated with a significantly greater risk for metastatic recurrence, whereas clearance of ctDNA after neoadjuvant therapy was linked to improved survival.

“The study is important because it highlights how tracking circulating ctDNA status in neoadjuvant-treated breast cancer can expose a patient’s risk for distant metastasis,” said Dr. Yuan. But, she added, “I think the biggest attraction of liquid biopsy will be the ability to detect molecular disease even before imaging can, and identify who has a high risk for recurrence.”

Dr. Razavi agreed that the potential to prevent metastasis by finding minimal residual disease (MRD) is the most exciting area of liquid biopsy research. “If we can find tumor DNA early before tumors have a chance to establish themselves, we could potentially change the trajectory of the disease for patients,” he said.

Several studies suggest that monitoring patients’ ctDNA levels after neoadjuvant treatment and surgery may help predict their risk for relapse and progression to metastatic disease. A 2015 analysis, which followed 20 patients with breast cancer after surgery, found that ctDNA monitoring accurately differentiated those who ultimately developed metastatic disease from those who didn’t (sensitivity, 93%; specificity, 100%) and detected metastatic disease 11 months earlier, on average, than imaging did. Another 2015 study found that the presence of ctDNA in plasma after neoadjuvant chemotherapy and surgery predicted metastatic relapse a median of almost 8 months before clinical detection. Other recent data show the power of ultrasensitive blood tests to detect MRD and potentially find metastatic disease early.

Although an increasing number of studies show that ctDNA and CTCs are prognostic for breast cancer recurrence, a major question remains: For patients with ctDNA or CTCs but no overt disease after imaging, will initiating therapy prevent or delay the development of metastatic disease?

“We still have to do those clinical trials to determine whether detecting MRD and treating patients early actually positively affects their survival and quality of life,” Dr. Razavi said.

Identifying the molecular features of metastatic breast cancer (MBC) offers a real-time window into a patient’s treatment options as well as the potential to follow the disease as it evolves over time.
 

Tissue biopsy remains the gold standard for characterizing tumor biology and guiding therapeutic decisions, but liquid biopsies — blood analyses that allow oncologists to detect circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the blood — are increasingly demonstrating their value. Last year, the U.S. Food and Drug Administration (FDA) approved two liquid biopsy tests, Guardant360 CDx and FoundationOne Liquid CDx, that can identify more than 300 cancer-related genes in the blood. In 2019, the FDA also approved the first companion diagnostic test, therascreen, to pinpoint PIK3CA gene mutations in patients’ ctDNA and determine whether patients should receive the PI3K inhibitor alpelisib along with fulvestrant.

Here’s an overview of how liquid biopsy is being used in monitoring MBC progression and treatment — and what some oncologists think of it.

What we do and don’t know

“Identifying a patient’s targetable mutations, most notably PIK3CA mutations, is currently the main use of liquid biopsy,” said Pedram Razavi, MD, PhD, a medical oncologist who leads the liquid biopsy program for breast cancer at Memorial Sloan Kettering (MSK) Cancer Center in New York City. “Patients who come to MSK are offered a tumor and liquid biopsy at the time of metastatic diagnosis as part of the standard of care.”

Liquid and tissue biopsy analyses can provide a more complete picture of a patient’s condition. Whereas tissue biopsy allows oncologists to target a more saturated sample of the cancer ecosystem and a wider array of biomarkers, liquid biopsy offers important advantages as well, including a less invasive way to sequence a sample, monitor patients’ treatment response, or track tumor evolution. Liquid biopsy also provides a bigger picture view of tumor heterogeneity by pooling information from many tumor locations as opposed to one.

But, cautioned Yuan Yuan, MD, PhD, liquid biopsy technology is not always sensitive enough to detect CTCs, ctDNA, or all relevant mutations. “When you collect a small tube of blood, you’re essentially trying to catch a small fish in a big sea and wading through a lot of background noise,” said Dr. Yuan, medical oncologist at City of Hope, a comprehensive cancer center in Los Angeles County. “The results may be hard to interpret or come back inconclusive.”

And although emerging data suggest that liquid biopsy provides important insights about tumor dynamics — including mapping disease progression, predicting survival, and even detecting signs of cancer recurrence before metastasis develops — the tool has limited utility in clinical practice outside of identifying sensitivity to various therapies or drugs.

“Right now, a lot of research is being done to understand how to use CTC and ctDNA in particular as a means of surveillance in breast cancer, but we’re still in the beginning stages of applying that outside of clinical trials,” said Joseph A. Sparano, MD, deputy director of the Tisch Cancer Institute and chief of the division of hematology and medical oncology, Icahn School of Medicine at Mount Sinai, New York City.

Personalizing treatment

The companion diagnostic test therascreen marked the beginning stages of using liquid biopsy to match treatments to genetic abnormalities in MBC. The SOLAR-1 phase 3 trial, which led to the approval of alpelisib and therascreen, found that the PI3K inhibitor plus fulvestrant almost doubled progression-free survival (PFS) (11 months vs 5.7 months in placebo-fulvestrant group) in patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.

More recent studies have shown that liquid biopsy tests can also identify ESR1 mutations and predict responses to inhibitors that target AKT1 and HER2. Investigators presenting at the 2021 American Society of Clinical Oncology meeting reported that next-generation sequencing of ctDNA in patients with HR-positive MBC, HER-positive MBC, or triple-negative breast cancer detected ESR1 mutations in 14% of patients (71 of 501). Moreover, ESR1 mutations were found only in HR-positive patients who had already received endocrine therapy. (The study also examined PIK3CA mutations, which occurred in about one third of patients). A more in-depth look revealed that ESR1 mutations were strongly associated with liver and bone metastases and that mutations along specific codons negatively affected overall survival (OS) and PFS: codons 537 and 538 for OS and codons 380 and 536 for PFS.

According to Debasish Tripathy, MD, professor and chairman of the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, in addition to tumor sequencing, “liquid biopsy has become a great research tool to track patients in real time and predict, for instance, who will respond to a treatment and identify emerging resistance.”

In terms of predicting responses to treatment, the plasmaMATCH trial assessed ctDNA in 1,034 patients with advanced breast cancer for mutations in ESR1, HER2, and AKT1 using digital droplet polymerase chain reaction (PCR) and Guardant360. Results showed that 357 (34.5%) of these patients had potentially targetable aberrations, including 222 patients with ESR1 mutations, 36 patients with HER2 mutations, and 30 patients with AKT1 mutations.

Agreement between digital droplet PCR and Guardant360 testing was 96%-99%, and liquid biopsy showed 93% sensitivity compared with tumor samples. The investigators also used liquid biopsy findings to match patients’ mutations to targeted treatments: fulvestrant for those with ESR1 mutations, neratinib for HER2 (ERBB2) mutations, and the selective AKT inhibitor capivasertib for estrogen receptor–positive tumors with AKT1 mutations.

Overall, the investigators concluded that ctDNA testing offers “accurate tumor genotyping” in line with tissue-based testing and is ready for routine clinical practice to identify common as well as rare genetic alterations, such as HER2 and AKT1 mutations, that affect only about 5% of patients with advanced disease.

Predicting survival and recurrence

A particularly promising area for liquid biopsy is its usefulness in helping to predict survival outcomes and monitor patients for early signs of recurrence before metastasis occurs. But the data to support this are still in their infancy.

A highly cited study, published over 15 years ago in the New England Journal of Medicine, found that patients with MBC who had five or more CTCs per 7.5 mL of whole blood before receiving first-line therapy exhibited significantly shorter median PFS (2.7 vs 7.0 months) and OS (10 vs > 18 months) compared with patients with fewer than five CTCs. Subsequent analyses performed more than a decade later, including a meta-analysis published last year, helped validate these early findings that levels of CTCs detected in the blood independently and strongly predicted PFS and OS in patients with MBC.

In addition, ctDNA can provide important information about patients’ survival odds. In a retrospective study published last year, investigators tracked changes in ctDNA in 291 plasma samples from 84 patients with locally advanced breast cancer who participated in the I-SPY trial. Patients who remained ctDNA-positive after 3 weeks of neoadjuvant chemotherapy were significantly more likely to have residual disease after completing their treatment compared with patients who cleared ctDNA at that early stage (83% for those with nonpathologic complete response vs 52%). Notably, the presence of ctDNA between therapy initiation and completion was associated with a significantly greater risk for metastatic recurrence, whereas clearance of ctDNA after neoadjuvant therapy was linked to improved survival.

“The study is important because it highlights how tracking circulating ctDNA status in neoadjuvant-treated breast cancer can expose a patient’s risk for distant metastasis,” said Dr. Yuan. But, she added, “I think the biggest attraction of liquid biopsy will be the ability to detect molecular disease even before imaging can, and identify who has a high risk for recurrence.”

Dr. Razavi agreed that the potential to prevent metastasis by finding minimal residual disease (MRD) is the most exciting area of liquid biopsy research. “If we can find tumor DNA early before tumors have a chance to establish themselves, we could potentially change the trajectory of the disease for patients,” he said.

Several studies suggest that monitoring patients’ ctDNA levels after neoadjuvant treatment and surgery may help predict their risk for relapse and progression to metastatic disease. A 2015 analysis, which followed 20 patients with breast cancer after surgery, found that ctDNA monitoring accurately differentiated those who ultimately developed metastatic disease from those who didn’t (sensitivity, 93%; specificity, 100%) and detected metastatic disease 11 months earlier, on average, than imaging did. Another 2015 study found that the presence of ctDNA in plasma after neoadjuvant chemotherapy and surgery predicted metastatic relapse a median of almost 8 months before clinical detection. Other recent data show the power of ultrasensitive blood tests to detect MRD and potentially find metastatic disease early.

Although an increasing number of studies show that ctDNA and CTCs are prognostic for breast cancer recurrence, a major question remains: For patients with ctDNA or CTCs but no overt disease after imaging, will initiating therapy prevent or delay the development of metastatic disease?

“We still have to do those clinical trials to determine whether detecting MRD and treating patients early actually positively affects their survival and quality of life,” Dr. Razavi said.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.