TBD Meeting (3274-23)

SAN ANTONIO — There’s a long-standing concern among oncologists that many women with ductal carcinoma in situ (DCIS), a potential precursor to invasive breast cancer, receive more treatment than they need. The potential for overtreatment largely revolves around the extent of surgery and the use of radiation.

Using the Oncotype DX Breast DCIS Score test, a laboratory test that estimates DCIS recurrence risk, may help identify patients with low-risk DCIS who can safely avoid adjuvant radiation after surgery, according to new research (abstract GS03-01) presented at the San Antonio Breast Cancer Symposium. 

Researchers found that the Oncotype DX score helped identify patients who are at low and high risk for DCIS recurrence. Low-risk patients who skipped adjuvant radiotherapy after breast-conserving surgery demonstrated similar 5-year recurrence rates compared with high-risk patients who received adjuvant radiotherapy.

This is the first prospective study to evaluate radiation decisions among patients with DCIS. 

Lead author Seema A. Khan, MD, who presented the research, called the findings “reassuring.”

However, “we need larger and better trials” as well as longer follow-up to confirm this less-is-more approach, said Dr. Khan, a breast cancer surgeon and researcher at Northwestern University, Chicago. 

Virginia Kaklamani, MD, who moderated the presentation, noted that it is good to finally have prospective data on this topic. And although they are not definitive, “I personally think these results should be used” for counseling, said Dr. Kaklamani, leader of the breast cancer program at UT Health San Antonio. 

To reduce the risk for DCIS recurrence or progression to invasive breast cancer, most patients with DCIS undergo breast-conserving surgery followed by adjuvant radiotherapy, Dr. Khan explained. Instead of breast-conserving surgery, about one in four patients opt for mastectomy.

Earlier results from this trial revealed that MRI helped identify patients who can safely receive breast-conserving surgery instead of mastectomy.

The current results assessed whether the Oncotype DX score can guide radiation treatment decisions. 

The study included 171 patients with DCIS who had wide local excisions after MRI confirmed that they could forgo more extensive surgery. 

Surgical specimens were then sent for testing to determine the DCIS score using the 12-gene Oncotype DX test.

Women who scored < 39 points on the 100-point Oncotype DX scale were considered to be at low risk for recurrence and were advised to skip radiation. Women who scored > 39 were advised to undergo radiation. Overall, 93% of the patients followed the radiation recommendations: 75 of 82 patients (91.4%) deemed as low risk skipped adjuvant radiotherapy and 84 of 89 patients (94.4%) deemed as high risk had radiotherapy. 

At a median follow-up of 5 years, 5.1% (4 of 82) of low-risk patients experienced a recurrence vs. 4.5% (4 of 89) of higher-risk patients. 

Recurrence rates among patients who followed the radiation recommendations mirrored these overall findings: 5.5% of 75 patients with low-risk DCIS who skipped radiotherapy experienced disease recurrence vs. 4.8% of 84 patients with high-risk DCIS who received radiotherapy.

Age did not appear to affect the outcomes. Among the 33 women younger than 50 years, two experienced a recurrence (4%), both invasive. One occurred in the low-risk group and the other in the higher-risk group. Among the 138 older women, six had recurrences, three in each group, and one recurrence in each was invasive.

In short, “women who skipped radiation based on this score did not experience an excess risk of” ipsilateral recurrence over 5 years, said Dr. Khan. 

Overall, the study offers “strong evidence” that the DCIS score might help “prevent excessive treatment for some patients,” she concluded, adding that 10-year outcomes will be reported. 

The work was funded by the National Cancer Institute. Dr. Khan has no conflicts of interest. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.
 

A version in the article appeared on Medscape.com.

SAN ANTONIO — There’s a long-standing concern among oncologists that many women with ductal carcinoma in situ (DCIS), a potential precursor to invasive breast cancer, receive more treatment than they need. The potential for overtreatment largely revolves around the extent of surgery and the use of radiation.

Using the Oncotype DX Breast DCIS Score test, a laboratory test that estimates DCIS recurrence risk, may help identify patients with low-risk DCIS who can safely avoid adjuvant radiation after surgery, according to new research (abstract GS03-01) presented at the San Antonio Breast Cancer Symposium. 

Researchers found that the Oncotype DX score helped identify patients who are at low and high risk for DCIS recurrence. Low-risk patients who skipped adjuvant radiotherapy after breast-conserving surgery demonstrated similar 5-year recurrence rates compared with high-risk patients who received adjuvant radiotherapy.

This is the first prospective study to evaluate radiation decisions among patients with DCIS. 

Lead author Seema A. Khan, MD, who presented the research, called the findings “reassuring.”

However, “we need larger and better trials” as well as longer follow-up to confirm this less-is-more approach, said Dr. Khan, a breast cancer surgeon and researcher at Northwestern University, Chicago. 

Virginia Kaklamani, MD, who moderated the presentation, noted that it is good to finally have prospective data on this topic. And although they are not definitive, “I personally think these results should be used” for counseling, said Dr. Kaklamani, leader of the breast cancer program at UT Health San Antonio. 

To reduce the risk for DCIS recurrence or progression to invasive breast cancer, most patients with DCIS undergo breast-conserving surgery followed by adjuvant radiotherapy, Dr. Khan explained. Instead of breast-conserving surgery, about one in four patients opt for mastectomy.

Earlier results from this trial revealed that MRI helped identify patients who can safely receive breast-conserving surgery instead of mastectomy.

The current results assessed whether the Oncotype DX score can guide radiation treatment decisions. 

The study included 171 patients with DCIS who had wide local excisions after MRI confirmed that they could forgo more extensive surgery. 

Surgical specimens were then sent for testing to determine the DCIS score using the 12-gene Oncotype DX test.

Women who scored < 39 points on the 100-point Oncotype DX scale were considered to be at low risk for recurrence and were advised to skip radiation. Women who scored > 39 were advised to undergo radiation. Overall, 93% of the patients followed the radiation recommendations: 75 of 82 patients (91.4%) deemed as low risk skipped adjuvant radiotherapy and 84 of 89 patients (94.4%) deemed as high risk had radiotherapy. 

At a median follow-up of 5 years, 5.1% (4 of 82) of low-risk patients experienced a recurrence vs. 4.5% (4 of 89) of higher-risk patients. 

Recurrence rates among patients who followed the radiation recommendations mirrored these overall findings: 5.5% of 75 patients with low-risk DCIS who skipped radiotherapy experienced disease recurrence vs. 4.8% of 84 patients with high-risk DCIS who received radiotherapy.

Age did not appear to affect the outcomes. Among the 33 women younger than 50 years, two experienced a recurrence (4%), both invasive. One occurred in the low-risk group and the other in the higher-risk group. Among the 138 older women, six had recurrences, three in each group, and one recurrence in each was invasive.

In short, “women who skipped radiation based on this score did not experience an excess risk of” ipsilateral recurrence over 5 years, said Dr. Khan. 

Overall, the study offers “strong evidence” that the DCIS score might help “prevent excessive treatment for some patients,” she concluded, adding that 10-year outcomes will be reported. 

The work was funded by the National Cancer Institute. Dr. Khan has no conflicts of interest. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.
 

A version in the article appeared on Medscape.com.

SAN ANTONIO — There’s a long-standing concern among oncologists that many women with ductal carcinoma in situ (DCIS), a potential precursor to invasive breast cancer, receive more treatment than they need. The potential for overtreatment largely revolves around the extent of surgery and the use of radiation.

Using the Oncotype DX Breast DCIS Score test, a laboratory test that estimates DCIS recurrence risk, may help identify patients with low-risk DCIS who can safely avoid adjuvant radiation after surgery, according to new research (abstract GS03-01) presented at the San Antonio Breast Cancer Symposium. 

Researchers found that the Oncotype DX score helped identify patients who are at low and high risk for DCIS recurrence. Low-risk patients who skipped adjuvant radiotherapy after breast-conserving surgery demonstrated similar 5-year recurrence rates compared with high-risk patients who received adjuvant radiotherapy.

This is the first prospective study to evaluate radiation decisions among patients with DCIS. 

Lead author Seema A. Khan, MD, who presented the research, called the findings “reassuring.”

However, “we need larger and better trials” as well as longer follow-up to confirm this less-is-more approach, said Dr. Khan, a breast cancer surgeon and researcher at Northwestern University, Chicago. 

Virginia Kaklamani, MD, who moderated the presentation, noted that it is good to finally have prospective data on this topic. And although they are not definitive, “I personally think these results should be used” for counseling, said Dr. Kaklamani, leader of the breast cancer program at UT Health San Antonio. 

To reduce the risk for DCIS recurrence or progression to invasive breast cancer, most patients with DCIS undergo breast-conserving surgery followed by adjuvant radiotherapy, Dr. Khan explained. Instead of breast-conserving surgery, about one in four patients opt for mastectomy.

Earlier results from this trial revealed that MRI helped identify patients who can safely receive breast-conserving surgery instead of mastectomy.

The current results assessed whether the Oncotype DX score can guide radiation treatment decisions. 

The study included 171 patients with DCIS who had wide local excisions after MRI confirmed that they could forgo more extensive surgery. 

Surgical specimens were then sent for testing to determine the DCIS score using the 12-gene Oncotype DX test.

Women who scored < 39 points on the 100-point Oncotype DX scale were considered to be at low risk for recurrence and were advised to skip radiation. Women who scored > 39 were advised to undergo radiation. Overall, 93% of the patients followed the radiation recommendations: 75 of 82 patients (91.4%) deemed as low risk skipped adjuvant radiotherapy and 84 of 89 patients (94.4%) deemed as high risk had radiotherapy. 

At a median follow-up of 5 years, 5.1% (4 of 82) of low-risk patients experienced a recurrence vs. 4.5% (4 of 89) of higher-risk patients. 

Recurrence rates among patients who followed the radiation recommendations mirrored these overall findings: 5.5% of 75 patients with low-risk DCIS who skipped radiotherapy experienced disease recurrence vs. 4.8% of 84 patients with high-risk DCIS who received radiotherapy.

Age did not appear to affect the outcomes. Among the 33 women younger than 50 years, two experienced a recurrence (4%), both invasive. One occurred in the low-risk group and the other in the higher-risk group. Among the 138 older women, six had recurrences, three in each group, and one recurrence in each was invasive.

In short, “women who skipped radiation based on this score did not experience an excess risk of” ipsilateral recurrence over 5 years, said Dr. Khan. 

Overall, the study offers “strong evidence” that the DCIS score might help “prevent excessive treatment for some patients,” she concluded, adding that 10-year outcomes will be reported. 

The work was funded by the National Cancer Institute. Dr. Khan has no conflicts of interest. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.
 

A version in the article appeared on Medscape.com.

San Antonio – Taxane exposure during pregnancy appears to be safe for mothers and offspring, according to a new retrospective cohort analysis. The findings shed light on a relatively unstudied topic. “Our cohort with 103 patients represents the most extensive study to date, and our main goal was to have homogeneous reporting of adverse events,” Ana Ferrigno Guajardo, MD, said in an interview. She presented the results at the San Antonio Breast Cancer Symposium.

“Breast cancer during pregnancy is a very challenging clinical situation as the expected antineoplastic effects of treatment must be carefully balanced against potential detrimental consequences on the developing fetus,” said Dr. Guajardo. She is a resident physician at Yale University School of Medicine.

Anthracycline-based chemotherapy agents are generally used during pregnancy because there is more safety data available for them, but some studies have shown that taxanes may have better efficacy in some clinical situations. “Cohort studies that have been done in the past [show] that taxane use is mostly deferred to the postpartum period, and we are not really sure of the impact that can have on survival in patients postponing treatment,” said Dr. Guajardo.

There are potential safety concerns with taxanes because neonates lack the cytochrome enzymes to metabolize the drugs, which creates a theoretical risk of adverse effects due to prolonged activity. On the other hand, pregnant women metabolize taxanes faster, and there are placental barriers that can inhibit high molecular weight molecules like taxanes from reaching the fetus, according to Dr. Guajardo.

In addition to pregnancy outcomes, the researchers followed 28 infants, and found that 87% were found to be completely healthy, “so we were relatively reassured. But of course we think that there’s a need for prospective studies that validate our findings regarding the safety taxanes,” said Dr. Guajardo.

Although there is no direct comparison group, the findings correlate well with studies of the general population and other chemotherapy agents. “We have large cohorts with mostly anthracycline-based chemotherapy agents during pregnancy that we can compare our results to, and overall, we were reassured that the prevalence of complications that we found in our cohort was very similar or even lower to those reported in the literature with patients treated with anthracycline-based therapy,” said Dr. Guajardo.

Compared with the general population, the team found higher rates of preterm births, neonatal ICU admissions, and premature membrane rupture, and infants that are small for gestational age. However, with the exception of the latter, all of these risks have been seen in pregnant women treated with other types of chemotherapy. “Perhaps it would be interesting to see if the incidence of small for gestational age neonates might be a bit higher in this population when compared to anthracycline-based therapy agents, but that does require a study that has a comparator group,” said Dr. Guajardo.

The researchers recruited 103 women with an average age of 34 years from 10 centers in 6 countries: United States, France, Spain, Mexico, Italy, and Costa Rica. The great majority were also treated with anthracyclines during gestation, and nearly all (97%) were treated with paclitaxel. The live birth rate was 98%, and 43.4% were preterm, 24% were small for gestational age, 16% were admitted to the neonate ICU, and 12.5% had hyperbilirubinemia.

Obstetric complications included intrauterine growth restriction (9%), preterm premature rupture of membranes (5%), gestational diabetes mellitus (5%), hypertensive disorders (4%), and pregnancy loss (2%).

After the presentation, Virginia Borges, MD, professor of medical oncology at University of Colorado Anschutz Medical Center, served as a discussant.

“Highlights of this study [include] that it is an international cohort from over six countries with over 100 cases of women included specifically focusing on the use of paclitaxel. They demonstrated safe outcomes for the pregnancies and the mothers,” Dr. Borges said during her presentation.

She went on to highlight several key points that physicians should consider when treating pregnancy-related breast cancer. “We want to achieve prepartum treatment wherever feasible to tackle that cancer before delivery of the child to prevent a pregnancy-related breast cancer from potentially turning into a postpartum breast cancer,” she said.

“If the tumor is ER+/HER2-, we now see we can safely give anthracyclines and taxanes from 12 to about 35 weeks of gestation. We don’t want to get too close to the delivery with chemotherapy. If a patient is HER2+, I prefer to give the anthracycline portion while the person is pregnant and then after delivery incorporate the taxane with the HER2 targeted therapies as there’s some older data showing concurrent therapy looks a bit better than sequential. In triple negative breast cancer, again I prefer to give the anthracycline and delay the taxane and carboplatin to overlap with immunotherapy so we are getting the necessary synergy there as well,” Dr. Borges added.

Dr. Guajardo has no relevant financial disclosures. Dr. Borges has consulted for SeaGen, Gilead, and AstraZeneca, and has received research funding from AstraZeneca, Gilead, Olema, and SeaGen.

San Antonio – Taxane exposure during pregnancy appears to be safe for mothers and offspring, according to a new retrospective cohort analysis. The findings shed light on a relatively unstudied topic. “Our cohort with 103 patients represents the most extensive study to date, and our main goal was to have homogeneous reporting of adverse events,” Ana Ferrigno Guajardo, MD, said in an interview. She presented the results at the San Antonio Breast Cancer Symposium.

“Breast cancer during pregnancy is a very challenging clinical situation as the expected antineoplastic effects of treatment must be carefully balanced against potential detrimental consequences on the developing fetus,” said Dr. Guajardo. She is a resident physician at Yale University School of Medicine.

Anthracycline-based chemotherapy agents are generally used during pregnancy because there is more safety data available for them, but some studies have shown that taxanes may have better efficacy in some clinical situations. “Cohort studies that have been done in the past [show] that taxane use is mostly deferred to the postpartum period, and we are not really sure of the impact that can have on survival in patients postponing treatment,” said Dr. Guajardo.

There are potential safety concerns with taxanes because neonates lack the cytochrome enzymes to metabolize the drugs, which creates a theoretical risk of adverse effects due to prolonged activity. On the other hand, pregnant women metabolize taxanes faster, and there are placental barriers that can inhibit high molecular weight molecules like taxanes from reaching the fetus, according to Dr. Guajardo.

In addition to pregnancy outcomes, the researchers followed 28 infants, and found that 87% were found to be completely healthy, “so we were relatively reassured. But of course we think that there’s a need for prospective studies that validate our findings regarding the safety taxanes,” said Dr. Guajardo.

Although there is no direct comparison group, the findings correlate well with studies of the general population and other chemotherapy agents. “We have large cohorts with mostly anthracycline-based chemotherapy agents during pregnancy that we can compare our results to, and overall, we were reassured that the prevalence of complications that we found in our cohort was very similar or even lower to those reported in the literature with patients treated with anthracycline-based therapy,” said Dr. Guajardo.

Compared with the general population, the team found higher rates of preterm births, neonatal ICU admissions, and premature membrane rupture, and infants that are small for gestational age. However, with the exception of the latter, all of these risks have been seen in pregnant women treated with other types of chemotherapy. “Perhaps it would be interesting to see if the incidence of small for gestational age neonates might be a bit higher in this population when compared to anthracycline-based therapy agents, but that does require a study that has a comparator group,” said Dr. Guajardo.

The researchers recruited 103 women with an average age of 34 years from 10 centers in 6 countries: United States, France, Spain, Mexico, Italy, and Costa Rica. The great majority were also treated with anthracyclines during gestation, and nearly all (97%) were treated with paclitaxel. The live birth rate was 98%, and 43.4% were preterm, 24% were small for gestational age, 16% were admitted to the neonate ICU, and 12.5% had hyperbilirubinemia.

Obstetric complications included intrauterine growth restriction (9%), preterm premature rupture of membranes (5%), gestational diabetes mellitus (5%), hypertensive disorders (4%), and pregnancy loss (2%).

After the presentation, Virginia Borges, MD, professor of medical oncology at University of Colorado Anschutz Medical Center, served as a discussant.

“Highlights of this study [include] that it is an international cohort from over six countries with over 100 cases of women included specifically focusing on the use of paclitaxel. They demonstrated safe outcomes for the pregnancies and the mothers,” Dr. Borges said during her presentation.

She went on to highlight several key points that physicians should consider when treating pregnancy-related breast cancer. “We want to achieve prepartum treatment wherever feasible to tackle that cancer before delivery of the child to prevent a pregnancy-related breast cancer from potentially turning into a postpartum breast cancer,” she said.

“If the tumor is ER+/HER2-, we now see we can safely give anthracyclines and taxanes from 12 to about 35 weeks of gestation. We don’t want to get too close to the delivery with chemotherapy. If a patient is HER2+, I prefer to give the anthracycline portion while the person is pregnant and then after delivery incorporate the taxane with the HER2 targeted therapies as there’s some older data showing concurrent therapy looks a bit better than sequential. In triple negative breast cancer, again I prefer to give the anthracycline and delay the taxane and carboplatin to overlap with immunotherapy so we are getting the necessary synergy there as well,” Dr. Borges added.

Dr. Guajardo has no relevant financial disclosures. Dr. Borges has consulted for SeaGen, Gilead, and AstraZeneca, and has received research funding from AstraZeneca, Gilead, Olema, and SeaGen.

San Antonio – Taxane exposure during pregnancy appears to be safe for mothers and offspring, according to a new retrospective cohort analysis. The findings shed light on a relatively unstudied topic. “Our cohort with 103 patients represents the most extensive study to date, and our main goal was to have homogeneous reporting of adverse events,” Ana Ferrigno Guajardo, MD, said in an interview. She presented the results at the San Antonio Breast Cancer Symposium.

“Breast cancer during pregnancy is a very challenging clinical situation as the expected antineoplastic effects of treatment must be carefully balanced against potential detrimental consequences on the developing fetus,” said Dr. Guajardo. She is a resident physician at Yale University School of Medicine.

Anthracycline-based chemotherapy agents are generally used during pregnancy because there is more safety data available for them, but some studies have shown that taxanes may have better efficacy in some clinical situations. “Cohort studies that have been done in the past [show] that taxane use is mostly deferred to the postpartum period, and we are not really sure of the impact that can have on survival in patients postponing treatment,” said Dr. Guajardo.

There are potential safety concerns with taxanes because neonates lack the cytochrome enzymes to metabolize the drugs, which creates a theoretical risk of adverse effects due to prolonged activity. On the other hand, pregnant women metabolize taxanes faster, and there are placental barriers that can inhibit high molecular weight molecules like taxanes from reaching the fetus, according to Dr. Guajardo.

In addition to pregnancy outcomes, the researchers followed 28 infants, and found that 87% were found to be completely healthy, “so we were relatively reassured. But of course we think that there’s a need for prospective studies that validate our findings regarding the safety taxanes,” said Dr. Guajardo.

Although there is no direct comparison group, the findings correlate well with studies of the general population and other chemotherapy agents. “We have large cohorts with mostly anthracycline-based chemotherapy agents during pregnancy that we can compare our results to, and overall, we were reassured that the prevalence of complications that we found in our cohort was very similar or even lower to those reported in the literature with patients treated with anthracycline-based therapy,” said Dr. Guajardo.

Compared with the general population, the team found higher rates of preterm births, neonatal ICU admissions, and premature membrane rupture, and infants that are small for gestational age. However, with the exception of the latter, all of these risks have been seen in pregnant women treated with other types of chemotherapy. “Perhaps it would be interesting to see if the incidence of small for gestational age neonates might be a bit higher in this population when compared to anthracycline-based therapy agents, but that does require a study that has a comparator group,” said Dr. Guajardo.

The researchers recruited 103 women with an average age of 34 years from 10 centers in 6 countries: United States, France, Spain, Mexico, Italy, and Costa Rica. The great majority were also treated with anthracyclines during gestation, and nearly all (97%) were treated with paclitaxel. The live birth rate was 98%, and 43.4% were preterm, 24% were small for gestational age, 16% were admitted to the neonate ICU, and 12.5% had hyperbilirubinemia.

Obstetric complications included intrauterine growth restriction (9%), preterm premature rupture of membranes (5%), gestational diabetes mellitus (5%), hypertensive disorders (4%), and pregnancy loss (2%).

After the presentation, Virginia Borges, MD, professor of medical oncology at University of Colorado Anschutz Medical Center, served as a discussant.

“Highlights of this study [include] that it is an international cohort from over six countries with over 100 cases of women included specifically focusing on the use of paclitaxel. They demonstrated safe outcomes for the pregnancies and the mothers,” Dr. Borges said during her presentation.

She went on to highlight several key points that physicians should consider when treating pregnancy-related breast cancer. “We want to achieve prepartum treatment wherever feasible to tackle that cancer before delivery of the child to prevent a pregnancy-related breast cancer from potentially turning into a postpartum breast cancer,” she said.

“If the tumor is ER+/HER2-, we now see we can safely give anthracyclines and taxanes from 12 to about 35 weeks of gestation. We don’t want to get too close to the delivery with chemotherapy. If a patient is HER2+, I prefer to give the anthracycline portion while the person is pregnant and then after delivery incorporate the taxane with the HER2 targeted therapies as there’s some older data showing concurrent therapy looks a bit better than sequential. In triple negative breast cancer, again I prefer to give the anthracycline and delay the taxane and carboplatin to overlap with immunotherapy so we are getting the necessary synergy there as well,” Dr. Borges added.

Dr. Guajardo has no relevant financial disclosures. Dr. Borges has consulted for SeaGen, Gilead, and AstraZeneca, and has received research funding from AstraZeneca, Gilead, Olema, and SeaGen.

SAN ANTONIO – Women aged 50 and over who have undergone curative treatment for breast cancer and remain cancer free after 3 years may safely de-escalate mammogram surveillance from the recommended annual schedule, according to results from a new randomized trial.

In the UK study, researchers found similar recurrence rates and overall survival between patients who continued to undergo annual screening versus women who underwent screening every 2 years after breast-conserving surgery or every 3 years after a mastectomy.

Current US guidelines recommend annual screening with no stopping point, while UK guidelines recommend annual screening for 5 years, followed by every 3 years after that.

The study was commissioned by the UK government after a previously commissioned systematic review showed lack of evidence for the existing frequency and duration of mammograms in this patient population, and a survey showed wide-ranging clinical practices. In response, the UK government funded the new study to evaluate whether it would be safe to reduce screening, according to Janet Dunn, PhD, who presented the study at the San Antonio Breast Cancer Symposium.

“Ladies are going back for years and years and years [for mammograms], and it’s inappropriate, it’s not necessary,” Dr. Dunn, professor of clinical trials and head of cancer trials at University of Warwick in the UK, said in an interview.

The lower frequency schedule requires that the patient be cancer free at 3 years following curative treatment. “We know for anybody going through breast cancer there are a couple of peaks of recurrence. One peak is 2 to 3 years [after curative treatment] for high-risk patients. The other peak is when they start hormone therapy, so at 5 to 6 years you get the peak. But this particular set of patients are at low to moderate risk, so they’re not the high-risk patients going into treatment trials,” said Dr. Dunn.

When asked if the findings should change practice, Dr. Dunn suggested that they could. “We would say that this is providing clinical evidence and probably changing guidance for the management of these patients: Instead of giving annual mammograms for years and years and years, after three years post curative surgery, and having gone through treatment with a baseline mammogram that’s clear, in the UK we can manage these patients back within the screening program, certainly for the mastectomy patients,” said Dr. Dunn.

She emphasized the potential mental health impact. “Women who are going through mammograms waiting for the results are much more anxious if they’ve had breast cancer before than those who were who were just going through normal screening. So [deescalation] is reducing anxiety. It’s also reducing the cost. It’s just reducing the burden on the whole health care system,” said Dr. Dunn.

During the Q&A session after the talk, Bruce Mann, MBBS, PhD, asked if there were differences in the pathology of the cancers that occurred in the less frequent group than those that arose in the annual group. If more frequent screening leads to earlier diagnosis of a tumor, “you would expect that those who have less [frequent screening] may be diagnosed with more advanced recurrences or new cancers, and that would eventually lead to a difference in outcome,” Dr. Mann said in an interview. He is director of breast cancer services at the Royal Melbourne Hospital in Australia.

He acknowledged the need to reconsider screening frequency, and complimented the researchers. “This is a nice pragmatic study. It’s interesting. It’s provocative. I think it’s a bit too early [to change practice]. I think we do need to see more information,” he said.

The researchers randomized 5235 women aged 50 and older to annual or less frequent mammography. The disease type was invasive in 87% of women, while 13% had ductal carcinoma in situ.

Over a median follow-up of 8.7 years, 7% experienced a recurrence. At 5 years, breast cancer–specific survival was 98.1% and 98.3% in the annual and less frequent groups, respectively (hazard ratio [HR], 0.92; 95% CI, 0.64-1.32). There was also no difference in recurrence-free survival or overall survival.

Analyses showed noninferiority of less frequent mammograms at a 3% margin (P < .0001) and a 1% margin (P = .003).

The researchers found that 83% of women were compliant with the mammogram schedule in the annual group, versus 69% in the less frequent arm. The COVID-19 pandemic was responsible for 35% of missed mammograms overall.

Quality of life measures showed that levels of distress over mammograms was similar across time and between the two groups, with 24% of women reporting medium or high levels of distress.

Dr. Dunn and Dr. Mann have no relevant financial disclosures.

SAN ANTONIO – Women aged 50 and over who have undergone curative treatment for breast cancer and remain cancer free after 3 years may safely de-escalate mammogram surveillance from the recommended annual schedule, according to results from a new randomized trial.

In the UK study, researchers found similar recurrence rates and overall survival between patients who continued to undergo annual screening versus women who underwent screening every 2 years after breast-conserving surgery or every 3 years after a mastectomy.

Current US guidelines recommend annual screening with no stopping point, while UK guidelines recommend annual screening for 5 years, followed by every 3 years after that.

The study was commissioned by the UK government after a previously commissioned systematic review showed lack of evidence for the existing frequency and duration of mammograms in this patient population, and a survey showed wide-ranging clinical practices. In response, the UK government funded the new study to evaluate whether it would be safe to reduce screening, according to Janet Dunn, PhD, who presented the study at the San Antonio Breast Cancer Symposium.

“Ladies are going back for years and years and years [for mammograms], and it’s inappropriate, it’s not necessary,” Dr. Dunn, professor of clinical trials and head of cancer trials at University of Warwick in the UK, said in an interview.

The lower frequency schedule requires that the patient be cancer free at 3 years following curative treatment. “We know for anybody going through breast cancer there are a couple of peaks of recurrence. One peak is 2 to 3 years [after curative treatment] for high-risk patients. The other peak is when they start hormone therapy, so at 5 to 6 years you get the peak. But this particular set of patients are at low to moderate risk, so they’re not the high-risk patients going into treatment trials,” said Dr. Dunn.

When asked if the findings should change practice, Dr. Dunn suggested that they could. “We would say that this is providing clinical evidence and probably changing guidance for the management of these patients: Instead of giving annual mammograms for years and years and years, after three years post curative surgery, and having gone through treatment with a baseline mammogram that’s clear, in the UK we can manage these patients back within the screening program, certainly for the mastectomy patients,” said Dr. Dunn.

She emphasized the potential mental health impact. “Women who are going through mammograms waiting for the results are much more anxious if they’ve had breast cancer before than those who were who were just going through normal screening. So [deescalation] is reducing anxiety. It’s also reducing the cost. It’s just reducing the burden on the whole health care system,” said Dr. Dunn.

During the Q&A session after the talk, Bruce Mann, MBBS, PhD, asked if there were differences in the pathology of the cancers that occurred in the less frequent group than those that arose in the annual group. If more frequent screening leads to earlier diagnosis of a tumor, “you would expect that those who have less [frequent screening] may be diagnosed with more advanced recurrences or new cancers, and that would eventually lead to a difference in outcome,” Dr. Mann said in an interview. He is director of breast cancer services at the Royal Melbourne Hospital in Australia.

He acknowledged the need to reconsider screening frequency, and complimented the researchers. “This is a nice pragmatic study. It’s interesting. It’s provocative. I think it’s a bit too early [to change practice]. I think we do need to see more information,” he said.

The researchers randomized 5235 women aged 50 and older to annual or less frequent mammography. The disease type was invasive in 87% of women, while 13% had ductal carcinoma in situ.

Over a median follow-up of 8.7 years, 7% experienced a recurrence. At 5 years, breast cancer–specific survival was 98.1% and 98.3% in the annual and less frequent groups, respectively (hazard ratio [HR], 0.92; 95% CI, 0.64-1.32). There was also no difference in recurrence-free survival or overall survival.

Analyses showed noninferiority of less frequent mammograms at a 3% margin (P < .0001) and a 1% margin (P = .003).

The researchers found that 83% of women were compliant with the mammogram schedule in the annual group, versus 69% in the less frequent arm. The COVID-19 pandemic was responsible for 35% of missed mammograms overall.

Quality of life measures showed that levels of distress over mammograms was similar across time and between the two groups, with 24% of women reporting medium or high levels of distress.

Dr. Dunn and Dr. Mann have no relevant financial disclosures.

SAN ANTONIO – Women aged 50 and over who have undergone curative treatment for breast cancer and remain cancer free after 3 years may safely de-escalate mammogram surveillance from the recommended annual schedule, according to results from a new randomized trial.

In the UK study, researchers found similar recurrence rates and overall survival between patients who continued to undergo annual screening versus women who underwent screening every 2 years after breast-conserving surgery or every 3 years after a mastectomy.

Current US guidelines recommend annual screening with no stopping point, while UK guidelines recommend annual screening for 5 years, followed by every 3 years after that.

The study was commissioned by the UK government after a previously commissioned systematic review showed lack of evidence for the existing frequency and duration of mammograms in this patient population, and a survey showed wide-ranging clinical practices. In response, the UK government funded the new study to evaluate whether it would be safe to reduce screening, according to Janet Dunn, PhD, who presented the study at the San Antonio Breast Cancer Symposium.

“Ladies are going back for years and years and years [for mammograms], and it’s inappropriate, it’s not necessary,” Dr. Dunn, professor of clinical trials and head of cancer trials at University of Warwick in the UK, said in an interview.

The lower frequency schedule requires that the patient be cancer free at 3 years following curative treatment. “We know for anybody going through breast cancer there are a couple of peaks of recurrence. One peak is 2 to 3 years [after curative treatment] for high-risk patients. The other peak is when they start hormone therapy, so at 5 to 6 years you get the peak. But this particular set of patients are at low to moderate risk, so they’re not the high-risk patients going into treatment trials,” said Dr. Dunn.

When asked if the findings should change practice, Dr. Dunn suggested that they could. “We would say that this is providing clinical evidence and probably changing guidance for the management of these patients: Instead of giving annual mammograms for years and years and years, after three years post curative surgery, and having gone through treatment with a baseline mammogram that’s clear, in the UK we can manage these patients back within the screening program, certainly for the mastectomy patients,” said Dr. Dunn.

She emphasized the potential mental health impact. “Women who are going through mammograms waiting for the results are much more anxious if they’ve had breast cancer before than those who were who were just going through normal screening. So [deescalation] is reducing anxiety. It’s also reducing the cost. It’s just reducing the burden on the whole health care system,” said Dr. Dunn.

During the Q&A session after the talk, Bruce Mann, MBBS, PhD, asked if there were differences in the pathology of the cancers that occurred in the less frequent group than those that arose in the annual group. If more frequent screening leads to earlier diagnosis of a tumor, “you would expect that those who have less [frequent screening] may be diagnosed with more advanced recurrences or new cancers, and that would eventually lead to a difference in outcome,” Dr. Mann said in an interview. He is director of breast cancer services at the Royal Melbourne Hospital in Australia.

He acknowledged the need to reconsider screening frequency, and complimented the researchers. “This is a nice pragmatic study. It’s interesting. It’s provocative. I think it’s a bit too early [to change practice]. I think we do need to see more information,” he said.

The researchers randomized 5235 women aged 50 and older to annual or less frequent mammography. The disease type was invasive in 87% of women, while 13% had ductal carcinoma in situ.

Over a median follow-up of 8.7 years, 7% experienced a recurrence. At 5 years, breast cancer–specific survival was 98.1% and 98.3% in the annual and less frequent groups, respectively (hazard ratio [HR], 0.92; 95% CI, 0.64-1.32). There was also no difference in recurrence-free survival or overall survival.

Analyses showed noninferiority of less frequent mammograms at a 3% margin (P < .0001) and a 1% margin (P = .003).

The researchers found that 83% of women were compliant with the mammogram schedule in the annual group, versus 69% in the less frequent arm. The COVID-19 pandemic was responsible for 35% of missed mammograms overall.

Quality of life measures showed that levels of distress over mammograms was similar across time and between the two groups, with 24% of women reporting medium or high levels of distress.

Dr. Dunn and Dr. Mann have no relevant financial disclosures.

SAN ANTONIO — In endocrine-resistant, HR+/HER2- metastatic breast cancer, the antibody-drug conjugate (ADC) datopotamab deruxtecan (dato-DXd, Daiichi Sankyo/AstraZeneca) has greater efficacy and a better safety profile than investigator-chosen chemotherapy, according to the latest results from the TROPION-Breast01 clinical trial.

If approved, the ADC would join sacituzumab govitecan (Trodelvy, Gilead) as agents that target trophoblast cell-surface antigen-2 (Trop-2), which is universally expressed in breast cancer, according to Aditya Bardia, MD, who presented the new results at the San Antonio Breast Cancer Symposium.

“Dato-DXd not only showed improvement in efficacy [versus chemotherapy], but had a favorable safety profile and a favorable quality of life profile as compared to standard chemotherapy. If this drug gets approved, we need more work in terms of biomarkers of response and resistance to understand how to select these agents and how to sequence these different agents,” Dr. Bardia said in an interview. He is associate professor of medicine at Harvard Medical School and Massachusetts General Hospital Cancer Center.

Dato-DXd has a proprietary linker technology that makes it more stable in plasma and more selective for tumor cells, where overexpressed enzymes cleave it and lead to release of the drug. This reduces off-target toxicity, said Dr. Bardia.

The primary results from TROPION-Breast01, presented at ESMO 2023, showed statistically significant improvement in progression-free survival compared to investigator’s choice of chemotherapy (hazard ratio, [HR], 0.63; P < .0001) and a higher overall response rate (36.4% versus 22.9%).

At SABCS, Dr. Bardia presented additional PFS sub-analyses and safety data.

TROPION-Breast01 included 732 patients who had failed or were ineligible for endocrine therapy, and who had received 1-2 lines of chemotherapy in the metastatic or inoperable setting. They were randomized to dato-DXd or chemotherapy.

The median PFS as determined by blinded independent central review was longer in the dato-DXd group (6.9 versus 4.5 months; P < .0001). Time to first subsequent therapy was also longer (median 8.2 versus 5.0 months; HR, 0.53; 95% CI, 0.45-0.64).

PFS benefit was similar regardless of duration of previous CDK4/6 inhibitor treatment. There was no significant difference in median PFS among patients with brain metastases at baseline (HR, 0.73; 95% CI, 0.39-1.42).

Grade 3 or higher treatment-related adverse events were less common in the dato-DXd group (21% versus 45%), as were the incidences of dose interruption (12% versus 25%), treatment-related neutropenia (11% versus 42%), grade 3 or higher treatment-related neutropenia (1% versus 31%), neutropenia-related dose interruption (0% versus 17%), and neutropenia-related dose reduction (0.3% versus 13%). G-CSF usage was lower in the dato-DXd group during treatment (3% versus 22%) and after treatment (0.3% versus 8%).

Stomatitis was more common in the dato-DXd group (50% versus 13%), including grade 3 (6% versus 3%). Dose reduction due to stomatitis was also more common (12% versus 1%), and discontinuation occurred in just 1 patient (0.3%) in the dato-DXd group.

The median time to confirmed deterioration, as measured by the Global Health Status/Quality of Life scale, was longer in the dato-DXd group (9.0 versus 4.8 months; HR, 0.76; 95% CI, 0.58-0.98).

During the Q & A period after the talk, Marc E. Lippman, MD, professor of oncology and director of the breast cancer program at Georgetown University’s Lombardi Comprehensive Cancer Center, questioned the assumption that Trop-2 is universally expressed in breast cancer, and asked if there were any data on outcomes associated with its expression. “That’s a very good question,” said Dr. Bardia. He said that the team is working on the problem, including identifying the best tool to measure Trop-2 expression, but also addressing whether expression changes over time. Finally, the team hopes to determine if treatment response might relate to levels of expression.

Trop-2 expression was studied in the ASCENT trial that examined sacituzumab govitecan in metastatic triple-negative breast cancer, and there was no apparent link. “In general, we don’t see a very strong correlation between Trop-2 expression and outcomes. In the ASCENT trial, even in patients who had low expression of Trop-2, the outcomes with Trop-2 antibody drug conjugates [were] superior to standard chemotherapy,” replied Dr. Bardia.

Ron Bose, MD, PhD, also asked if there would be broader biomarker analyses of responders versus nonresponders to dato-dxd. “I think it’s very important to know, what are the biomarkers that predict efficacy for dato-dxd. The median progression free survival improvement was only about two months, maybe a little bit more, so knowing which patients are going to get the most benefit will be very important,” Dr. Bose said in an interview. Dr. Bose is associate professor of oncology at the Washington University School of Medicine in St. Louis.

Overall, he was impressed by the results. “The median progression free survival benefit is moderate, but the safety I think is really particularly strong, and when I’m thinking about this for my patients, the fact that there is a progression free survival benefit, plus a safety benefit [compared to chemotherapy] makes it very appealing,” he said.

Dr. Bose has consulted for Genentech. Dr. Bardia has been on advisory boards for Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Mersana, and Foundation Medicine. He has received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Natera, and Eli Lilly.

SAN ANTONIO — In endocrine-resistant, HR+/HER2- metastatic breast cancer, the antibody-drug conjugate (ADC) datopotamab deruxtecan (dato-DXd, Daiichi Sankyo/AstraZeneca) has greater efficacy and a better safety profile than investigator-chosen chemotherapy, according to the latest results from the TROPION-Breast01 clinical trial.

If approved, the ADC would join sacituzumab govitecan (Trodelvy, Gilead) as agents that target trophoblast cell-surface antigen-2 (Trop-2), which is universally expressed in breast cancer, according to Aditya Bardia, MD, who presented the new results at the San Antonio Breast Cancer Symposium.

“Dato-DXd not only showed improvement in efficacy [versus chemotherapy], but had a favorable safety profile and a favorable quality of life profile as compared to standard chemotherapy. If this drug gets approved, we need more work in terms of biomarkers of response and resistance to understand how to select these agents and how to sequence these different agents,” Dr. Bardia said in an interview. He is associate professor of medicine at Harvard Medical School and Massachusetts General Hospital Cancer Center.

Dato-DXd has a proprietary linker technology that makes it more stable in plasma and more selective for tumor cells, where overexpressed enzymes cleave it and lead to release of the drug. This reduces off-target toxicity, said Dr. Bardia.

The primary results from TROPION-Breast01, presented at ESMO 2023, showed statistically significant improvement in progression-free survival compared to investigator’s choice of chemotherapy (hazard ratio, [HR], 0.63; P < .0001) and a higher overall response rate (36.4% versus 22.9%).

At SABCS, Dr. Bardia presented additional PFS sub-analyses and safety data.

TROPION-Breast01 included 732 patients who had failed or were ineligible for endocrine therapy, and who had received 1-2 lines of chemotherapy in the metastatic or inoperable setting. They were randomized to dato-DXd or chemotherapy.

The median PFS as determined by blinded independent central review was longer in the dato-DXd group (6.9 versus 4.5 months; P < .0001). Time to first subsequent therapy was also longer (median 8.2 versus 5.0 months; HR, 0.53; 95% CI, 0.45-0.64).

PFS benefit was similar regardless of duration of previous CDK4/6 inhibitor treatment. There was no significant difference in median PFS among patients with brain metastases at baseline (HR, 0.73; 95% CI, 0.39-1.42).

Grade 3 or higher treatment-related adverse events were less common in the dato-DXd group (21% versus 45%), as were the incidences of dose interruption (12% versus 25%), treatment-related neutropenia (11% versus 42%), grade 3 or higher treatment-related neutropenia (1% versus 31%), neutropenia-related dose interruption (0% versus 17%), and neutropenia-related dose reduction (0.3% versus 13%). G-CSF usage was lower in the dato-DXd group during treatment (3% versus 22%) and after treatment (0.3% versus 8%).

Stomatitis was more common in the dato-DXd group (50% versus 13%), including grade 3 (6% versus 3%). Dose reduction due to stomatitis was also more common (12% versus 1%), and discontinuation occurred in just 1 patient (0.3%) in the dato-DXd group.

The median time to confirmed deterioration, as measured by the Global Health Status/Quality of Life scale, was longer in the dato-DXd group (9.0 versus 4.8 months; HR, 0.76; 95% CI, 0.58-0.98).

During the Q & A period after the talk, Marc E. Lippman, MD, professor of oncology and director of the breast cancer program at Georgetown University’s Lombardi Comprehensive Cancer Center, questioned the assumption that Trop-2 is universally expressed in breast cancer, and asked if there were any data on outcomes associated with its expression. “That’s a very good question,” said Dr. Bardia. He said that the team is working on the problem, including identifying the best tool to measure Trop-2 expression, but also addressing whether expression changes over time. Finally, the team hopes to determine if treatment response might relate to levels of expression.

Trop-2 expression was studied in the ASCENT trial that examined sacituzumab govitecan in metastatic triple-negative breast cancer, and there was no apparent link. “In general, we don’t see a very strong correlation between Trop-2 expression and outcomes. In the ASCENT trial, even in patients who had low expression of Trop-2, the outcomes with Trop-2 antibody drug conjugates [were] superior to standard chemotherapy,” replied Dr. Bardia.

Ron Bose, MD, PhD, also asked if there would be broader biomarker analyses of responders versus nonresponders to dato-dxd. “I think it’s very important to know, what are the biomarkers that predict efficacy for dato-dxd. The median progression free survival improvement was only about two months, maybe a little bit more, so knowing which patients are going to get the most benefit will be very important,” Dr. Bose said in an interview. Dr. Bose is associate professor of oncology at the Washington University School of Medicine in St. Louis.

Overall, he was impressed by the results. “The median progression free survival benefit is moderate, but the safety I think is really particularly strong, and when I’m thinking about this for my patients, the fact that there is a progression free survival benefit, plus a safety benefit [compared to chemotherapy] makes it very appealing,” he said.

Dr. Bose has consulted for Genentech. Dr. Bardia has been on advisory boards for Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Mersana, and Foundation Medicine. He has received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Natera, and Eli Lilly.

SAN ANTONIO — In endocrine-resistant, HR+/HER2- metastatic breast cancer, the antibody-drug conjugate (ADC) datopotamab deruxtecan (dato-DXd, Daiichi Sankyo/AstraZeneca) has greater efficacy and a better safety profile than investigator-chosen chemotherapy, according to the latest results from the TROPION-Breast01 clinical trial.

If approved, the ADC would join sacituzumab govitecan (Trodelvy, Gilead) as agents that target trophoblast cell-surface antigen-2 (Trop-2), which is universally expressed in breast cancer, according to Aditya Bardia, MD, who presented the new results at the San Antonio Breast Cancer Symposium.

“Dato-DXd not only showed improvement in efficacy [versus chemotherapy], but had a favorable safety profile and a favorable quality of life profile as compared to standard chemotherapy. If this drug gets approved, we need more work in terms of biomarkers of response and resistance to understand how to select these agents and how to sequence these different agents,” Dr. Bardia said in an interview. He is associate professor of medicine at Harvard Medical School and Massachusetts General Hospital Cancer Center.

Dato-DXd has a proprietary linker technology that makes it more stable in plasma and more selective for tumor cells, where overexpressed enzymes cleave it and lead to release of the drug. This reduces off-target toxicity, said Dr. Bardia.

The primary results from TROPION-Breast01, presented at ESMO 2023, showed statistically significant improvement in progression-free survival compared to investigator’s choice of chemotherapy (hazard ratio, [HR], 0.63; P < .0001) and a higher overall response rate (36.4% versus 22.9%).

At SABCS, Dr. Bardia presented additional PFS sub-analyses and safety data.

TROPION-Breast01 included 732 patients who had failed or were ineligible for endocrine therapy, and who had received 1-2 lines of chemotherapy in the metastatic or inoperable setting. They were randomized to dato-DXd or chemotherapy.

The median PFS as determined by blinded independent central review was longer in the dato-DXd group (6.9 versus 4.5 months; P < .0001). Time to first subsequent therapy was also longer (median 8.2 versus 5.0 months; HR, 0.53; 95% CI, 0.45-0.64).

PFS benefit was similar regardless of duration of previous CDK4/6 inhibitor treatment. There was no significant difference in median PFS among patients with brain metastases at baseline (HR, 0.73; 95% CI, 0.39-1.42).

Grade 3 or higher treatment-related adverse events were less common in the dato-DXd group (21% versus 45%), as were the incidences of dose interruption (12% versus 25%), treatment-related neutropenia (11% versus 42%), grade 3 or higher treatment-related neutropenia (1% versus 31%), neutropenia-related dose interruption (0% versus 17%), and neutropenia-related dose reduction (0.3% versus 13%). G-CSF usage was lower in the dato-DXd group during treatment (3% versus 22%) and after treatment (0.3% versus 8%).

Stomatitis was more common in the dato-DXd group (50% versus 13%), including grade 3 (6% versus 3%). Dose reduction due to stomatitis was also more common (12% versus 1%), and discontinuation occurred in just 1 patient (0.3%) in the dato-DXd group.

The median time to confirmed deterioration, as measured by the Global Health Status/Quality of Life scale, was longer in the dato-DXd group (9.0 versus 4.8 months; HR, 0.76; 95% CI, 0.58-0.98).

During the Q & A period after the talk, Marc E. Lippman, MD, professor of oncology and director of the breast cancer program at Georgetown University’s Lombardi Comprehensive Cancer Center, questioned the assumption that Trop-2 is universally expressed in breast cancer, and asked if there were any data on outcomes associated with its expression. “That’s a very good question,” said Dr. Bardia. He said that the team is working on the problem, including identifying the best tool to measure Trop-2 expression, but also addressing whether expression changes over time. Finally, the team hopes to determine if treatment response might relate to levels of expression.

Trop-2 expression was studied in the ASCENT trial that examined sacituzumab govitecan in metastatic triple-negative breast cancer, and there was no apparent link. “In general, we don’t see a very strong correlation between Trop-2 expression and outcomes. In the ASCENT trial, even in patients who had low expression of Trop-2, the outcomes with Trop-2 antibody drug conjugates [were] superior to standard chemotherapy,” replied Dr. Bardia.

Ron Bose, MD, PhD, also asked if there would be broader biomarker analyses of responders versus nonresponders to dato-dxd. “I think it’s very important to know, what are the biomarkers that predict efficacy for dato-dxd. The median progression free survival improvement was only about two months, maybe a little bit more, so knowing which patients are going to get the most benefit will be very important,” Dr. Bose said in an interview. Dr. Bose is associate professor of oncology at the Washington University School of Medicine in St. Louis.

Overall, he was impressed by the results. “The median progression free survival benefit is moderate, but the safety I think is really particularly strong, and when I’m thinking about this for my patients, the fact that there is a progression free survival benefit, plus a safety benefit [compared to chemotherapy] makes it very appealing,” he said.

Dr. Bose has consulted for Genentech. Dr. Bardia has been on advisory boards for Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Mersana, and Foundation Medicine. He has received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Natera, and Eli Lilly.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.