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Intraoperative pathology spurs overtreatment in mastectomy
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASBRS 2023
Novel fluorescence guidance improves lumpectomy outcomes
, new phase 3 findings show.
Pegulicianine (Lumisight), an investigational and activatable fluorescent imaging agent used with a novel direct visualization system, helped identify residual tumor or circumvent second surgeries in about 10% of patients in the trial.
Use of the agent and direct visualization system – both from Lumicell and currently under review by the Food and Drug Administration – could provide more complete resection for patients with early breast cancer and avert the need for reexcisions, the investigators write.
The findings were published online in NEJM Evidence and were subsequently presented at the annual meeting of the American Society of Breast Surgeons.
Local recurrence following lumpectomy increases the risk of dying from breast cancer, and the risk of local recurrence is directly linked to inadequate tumor removal during lumpectomy. In about 20%-40% of lumpectomies, positive margins are identified after surgery.
To improve patient outcomes, investigators assessed whether a novel fluorescence-guided surgery system helped surgeons perform more complete resections during lumpectomy.
In the Novel Surgical Imaging for Tumor Excision (INSITE) trial, 392 patients were randomly assigned to undergo pegulicianine fluorescence-guided surgery (n = 357) or standard lumpectomy (n = 35).
To prevent surgeons from performing a smaller than standard lumpectomy in anticipation of using the pegulicianine fluorescence-guided system, patients were randomly assigned to the pegulicianine fluorescence-guided surgery group or the control group. The groups were revealed only after the surgeon completed the standard lumpectomy.
“Randomization was not designed to provide a control group for analysis of device performance,” The authors explain. “In this study design, each patient undergoing pegulicianine fluorescence-guided surgery served as her own control,” they write. The investigators compared final margin pathology after standard lumpectomy and after guided surgery. Those in the control group were included in the safety analysis.
Study participants were women aged 18 years or older who were undergoing lumpectomy for stage I–III breast cancer and/or ductal carcinoma in situ. All patients received pegulicianine 1.0 mg/kg via a 3-minute intravenous infusion 2-6 hours before surgery.
The agent produces a signal at sites of residual tumor, and a handheld probe illuminates the cavity during surgery. A tumor detection algorithm then analyzes and displays the images to the surgeon in real time – an overall process that adds about 7 minutes to the operative procedure, the authors say.
Investigators identified invasive cancers in 316 patients and in situ cancers in 76 patients. Among the 357 patients in the treatment group, 27 (7.6%) were found to have residual tumor after standard lumpectomy. For 22 patients, cavity orientations were deemed negative on standard margin evaluations, the authors report.
With use of pegulicianine fluorescence-guided surgery, positive margins were converted to negative margins for 9 of 62 patients (14.5%), potentially averting a second surgery in those patients.
Overall, the authors say that pegulicianine fluorescence-guided surgery removed residual tumor (27 of 357) or avoided second surgeries (9 of 357) in 10% of patients in the trial.
The current trial findings confirm results regarding the safety and efficacy of pegulicianine fluorescence-guided surgery and the direct visualization system that were reported in a prior multicenter feasibility study, the authors say.
Pegulicianine fluorescence-guided surgery met prespecified thresholds for removal of residual tumor and specificity, at 85.2%, but did not meet the prespecified threshold for sensitivity, which was only 49.3%.
The rate of serious adverse events with pegulicianine was 0.5% (two patients), similar to that of other contrast agents. Administration of the agent was stopped because of adverse events for six patients, the investigators write.
Serious adverse events included grade 3 hypersensitivity in one patient and an anaphylactic reaction in another. The other four adverse events included an allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation. All adverse events resolved, and patients proceeded to standard lumpectomy.
Overall, the trial findings “suggest that a more complete breast cancer resection may be achieved” with pegulicianine fluorescence-guided surgery and the direct visualization system, lead investigator Barbara Smith, MD, PhD, director of the breast program at Massachusetts General Hospital and professor of surgery at Harvard Medical School, both in Boston, said in a press release. “Given the low complication rate, minimal added operative time and, most importantly, the discovery of additional cancer left behind after a lumpectomy, the Lumicell [system] has the potential to be a critical adjunct to enhance standard practice for breast cancer patients.”
The system also has the potential to reduce “the patient burden of additional surgery” and decrease “costs associated with a return to the operating room,” the authors conclude.
The INSITE trial was funded by Lumicell and the National Institutes of Health. Dr. Smith reported unpaid research collaboration with Lumicell.
A version of this article first appeared on Medscape.com.
, new phase 3 findings show.
Pegulicianine (Lumisight), an investigational and activatable fluorescent imaging agent used with a novel direct visualization system, helped identify residual tumor or circumvent second surgeries in about 10% of patients in the trial.
Use of the agent and direct visualization system – both from Lumicell and currently under review by the Food and Drug Administration – could provide more complete resection for patients with early breast cancer and avert the need for reexcisions, the investigators write.
The findings were published online in NEJM Evidence and were subsequently presented at the annual meeting of the American Society of Breast Surgeons.
Local recurrence following lumpectomy increases the risk of dying from breast cancer, and the risk of local recurrence is directly linked to inadequate tumor removal during lumpectomy. In about 20%-40% of lumpectomies, positive margins are identified after surgery.
To improve patient outcomes, investigators assessed whether a novel fluorescence-guided surgery system helped surgeons perform more complete resections during lumpectomy.
In the Novel Surgical Imaging for Tumor Excision (INSITE) trial, 392 patients were randomly assigned to undergo pegulicianine fluorescence-guided surgery (n = 357) or standard lumpectomy (n = 35).
To prevent surgeons from performing a smaller than standard lumpectomy in anticipation of using the pegulicianine fluorescence-guided system, patients were randomly assigned to the pegulicianine fluorescence-guided surgery group or the control group. The groups were revealed only after the surgeon completed the standard lumpectomy.
“Randomization was not designed to provide a control group for analysis of device performance,” The authors explain. “In this study design, each patient undergoing pegulicianine fluorescence-guided surgery served as her own control,” they write. The investigators compared final margin pathology after standard lumpectomy and after guided surgery. Those in the control group were included in the safety analysis.
Study participants were women aged 18 years or older who were undergoing lumpectomy for stage I–III breast cancer and/or ductal carcinoma in situ. All patients received pegulicianine 1.0 mg/kg via a 3-minute intravenous infusion 2-6 hours before surgery.
The agent produces a signal at sites of residual tumor, and a handheld probe illuminates the cavity during surgery. A tumor detection algorithm then analyzes and displays the images to the surgeon in real time – an overall process that adds about 7 minutes to the operative procedure, the authors say.
Investigators identified invasive cancers in 316 patients and in situ cancers in 76 patients. Among the 357 patients in the treatment group, 27 (7.6%) were found to have residual tumor after standard lumpectomy. For 22 patients, cavity orientations were deemed negative on standard margin evaluations, the authors report.
With use of pegulicianine fluorescence-guided surgery, positive margins were converted to negative margins for 9 of 62 patients (14.5%), potentially averting a second surgery in those patients.
Overall, the authors say that pegulicianine fluorescence-guided surgery removed residual tumor (27 of 357) or avoided second surgeries (9 of 357) in 10% of patients in the trial.
The current trial findings confirm results regarding the safety and efficacy of pegulicianine fluorescence-guided surgery and the direct visualization system that were reported in a prior multicenter feasibility study, the authors say.
Pegulicianine fluorescence-guided surgery met prespecified thresholds for removal of residual tumor and specificity, at 85.2%, but did not meet the prespecified threshold for sensitivity, which was only 49.3%.
The rate of serious adverse events with pegulicianine was 0.5% (two patients), similar to that of other contrast agents. Administration of the agent was stopped because of adverse events for six patients, the investigators write.
Serious adverse events included grade 3 hypersensitivity in one patient and an anaphylactic reaction in another. The other four adverse events included an allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation. All adverse events resolved, and patients proceeded to standard lumpectomy.
Overall, the trial findings “suggest that a more complete breast cancer resection may be achieved” with pegulicianine fluorescence-guided surgery and the direct visualization system, lead investigator Barbara Smith, MD, PhD, director of the breast program at Massachusetts General Hospital and professor of surgery at Harvard Medical School, both in Boston, said in a press release. “Given the low complication rate, minimal added operative time and, most importantly, the discovery of additional cancer left behind after a lumpectomy, the Lumicell [system] has the potential to be a critical adjunct to enhance standard practice for breast cancer patients.”
The system also has the potential to reduce “the patient burden of additional surgery” and decrease “costs associated with a return to the operating room,” the authors conclude.
The INSITE trial was funded by Lumicell and the National Institutes of Health. Dr. Smith reported unpaid research collaboration with Lumicell.
A version of this article first appeared on Medscape.com.
, new phase 3 findings show.
Pegulicianine (Lumisight), an investigational and activatable fluorescent imaging agent used with a novel direct visualization system, helped identify residual tumor or circumvent second surgeries in about 10% of patients in the trial.
Use of the agent and direct visualization system – both from Lumicell and currently under review by the Food and Drug Administration – could provide more complete resection for patients with early breast cancer and avert the need for reexcisions, the investigators write.
The findings were published online in NEJM Evidence and were subsequently presented at the annual meeting of the American Society of Breast Surgeons.
Local recurrence following lumpectomy increases the risk of dying from breast cancer, and the risk of local recurrence is directly linked to inadequate tumor removal during lumpectomy. In about 20%-40% of lumpectomies, positive margins are identified after surgery.
To improve patient outcomes, investigators assessed whether a novel fluorescence-guided surgery system helped surgeons perform more complete resections during lumpectomy.
In the Novel Surgical Imaging for Tumor Excision (INSITE) trial, 392 patients were randomly assigned to undergo pegulicianine fluorescence-guided surgery (n = 357) or standard lumpectomy (n = 35).
To prevent surgeons from performing a smaller than standard lumpectomy in anticipation of using the pegulicianine fluorescence-guided system, patients were randomly assigned to the pegulicianine fluorescence-guided surgery group or the control group. The groups were revealed only after the surgeon completed the standard lumpectomy.
“Randomization was not designed to provide a control group for analysis of device performance,” The authors explain. “In this study design, each patient undergoing pegulicianine fluorescence-guided surgery served as her own control,” they write. The investigators compared final margin pathology after standard lumpectomy and after guided surgery. Those in the control group were included in the safety analysis.
Study participants were women aged 18 years or older who were undergoing lumpectomy for stage I–III breast cancer and/or ductal carcinoma in situ. All patients received pegulicianine 1.0 mg/kg via a 3-minute intravenous infusion 2-6 hours before surgery.
The agent produces a signal at sites of residual tumor, and a handheld probe illuminates the cavity during surgery. A tumor detection algorithm then analyzes and displays the images to the surgeon in real time – an overall process that adds about 7 minutes to the operative procedure, the authors say.
Investigators identified invasive cancers in 316 patients and in situ cancers in 76 patients. Among the 357 patients in the treatment group, 27 (7.6%) were found to have residual tumor after standard lumpectomy. For 22 patients, cavity orientations were deemed negative on standard margin evaluations, the authors report.
With use of pegulicianine fluorescence-guided surgery, positive margins were converted to negative margins for 9 of 62 patients (14.5%), potentially averting a second surgery in those patients.
Overall, the authors say that pegulicianine fluorescence-guided surgery removed residual tumor (27 of 357) or avoided second surgeries (9 of 357) in 10% of patients in the trial.
The current trial findings confirm results regarding the safety and efficacy of pegulicianine fluorescence-guided surgery and the direct visualization system that were reported in a prior multicenter feasibility study, the authors say.
Pegulicianine fluorescence-guided surgery met prespecified thresholds for removal of residual tumor and specificity, at 85.2%, but did not meet the prespecified threshold for sensitivity, which was only 49.3%.
The rate of serious adverse events with pegulicianine was 0.5% (two patients), similar to that of other contrast agents. Administration of the agent was stopped because of adverse events for six patients, the investigators write.
Serious adverse events included grade 3 hypersensitivity in one patient and an anaphylactic reaction in another. The other four adverse events included an allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation. All adverse events resolved, and patients proceeded to standard lumpectomy.
Overall, the trial findings “suggest that a more complete breast cancer resection may be achieved” with pegulicianine fluorescence-guided surgery and the direct visualization system, lead investigator Barbara Smith, MD, PhD, director of the breast program at Massachusetts General Hospital and professor of surgery at Harvard Medical School, both in Boston, said in a press release. “Given the low complication rate, minimal added operative time and, most importantly, the discovery of additional cancer left behind after a lumpectomy, the Lumicell [system] has the potential to be a critical adjunct to enhance standard practice for breast cancer patients.”
The system also has the potential to reduce “the patient burden of additional surgery” and decrease “costs associated with a return to the operating room,” the authors conclude.
The INSITE trial was funded by Lumicell and the National Institutes of Health. Dr. Smith reported unpaid research collaboration with Lumicell.
A version of this article first appeared on Medscape.com.
FROM NEJM EVIDENCE
Study shows higher obesity-related cancer mortality in areas with more fast food
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
FROM JAMA ONCOLOGY
Expert discusses which diets are best, based on the evidence
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
AT INTERNAL MEDICINE 2023
Adherence to cancer prevention guidance linked with reduced breast cancer recurrence, death risk
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
Following such recommendations surrounding smoking, physical activity (PA), eating fruits and vegetables and reducing or eliminating sugar-sweetened beverages seemed to be the most beneficial, wrote the authors of the paper published online in JAMA Network Open.
Rikki A. Cannioto, PhD, EdD, with the department of cancer prevention & control, Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., led the prospective cohort study of 1,340 patients.
The American Institute for Cancer Research and American Cancer Society regularly recommend and publish lifestyle modifications for cancer prevention. To conduct this study Dr. Cannioto and colleagues developed an aggregate lifestyle scoring index to investigate whether those recommendations have an effect on high-risk breast cancer survival.
Highest adherence vs. lowest cut death risk by more than half
The researchers found patients with highest vs. lowest lifestyle index scores saw a 37% reduction in cancer recurrence (hazard ratio, 0.63; 95% confidence interval, 0.48-0.82) and a 58% reduction in mortality (HR, 0.42; 95% CI, 0.30-0.59).
“As a person who has based her career on the belief that our modifiable lifestyle behaviors are associated with cancer survival, I was actually surprised about how strong these associations were, especially for breast cancer recurrence,” Dr. Cannioto said in an interview,
The author also expressed surprise about the associations that were seen “in patients diagnosed with triple-negative breast cancer and HER2-positive breast cancer, which are the two subtypes traditionally more aggressive and more difficult to treat.”
Most patients in the study were diagnosed with hormone receptor–positive breast cancer (873 [65.3%]); completed some education beyond high school (954 [71.2%]); were postmenopausal (696 [52.5%]); and self-identified as non-Hispanic White (1,118 [83.7%]).
Patients were drawn from the Diet, Exercise, Lifestyles, and Cancer Prognosis (DELCaP) study, a prospective, observational cohort study ancillary to a multicenter phase 3 trial led by the Southwest Oncology Group (SWOG). The DELCaP study was designed to examine lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment.
Never smoking, physical activity had strongest links
Never smoking and meeting or exceeding PA guidelines had the strongest and most consistent associations with outcomes; each factor was linked with a 44%-45% reduced risk of mortality and a 35% reduced risk of recurrence.
Strongest adherence to the alcohol and body mass index (BMI) recommendations were not significantly associated with improved outcomes.
Partial and full adherence to red and processed meat recommendations were associated with significant reductions in mortality, but not recurrence.
The authors note that, while medications are the foundation for breast cancer treatment, lifestyle interventions could be a safe and inexpensive additional strategy for delaying and preventing recurrence and death.
“Such developments could be especially impactful for patients diagnosed with more aggressive tumors that do not respond well to current therapies,” they write.
Dr. Cannioto says the guidelines around physical activity advise 150 minutes or more of moderate to vigorous intensity a week. But she noted that this research shows that any physical activity can lead to longer survival.
“The greatest benefits from physical activity occur from moving from a sedentary lifestyle to beginning to be active,” she said.
Dr. Cannioto acknowledged the homogeneity of the study population as a limitation and recommended the associations next be tested in a more racially and ethnically diverse population of breast cancer patients.
This work was supported by the National Cancer Institute, the Breast Cancer Research Foundation, and Amgen.
The authors report receiving grants from the Southwest Oncology Group and the National Cancer Institute during the conduct of the study and receiving personal fees, grants, or serving on the boards or independent monitoring committees of many pharmaceutical companies. A full list of disclosures is available with the paper.
FROM JAMA NETWORK OPEN
Cancer pain declines with cannabis use
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
in a study.
Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.
However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.
In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.
The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.
Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.
Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).
Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).
“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.
In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.
Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.
Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.
The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.
The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.
The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.
FROM BMJ SUPPORTIVE & PALLIATIVE CARE
The next big thing in cancer research
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do.
More sex-specific research
Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.
Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.
“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said.
The global cancer community
C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.
“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”
Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”
Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.
“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
Prioritizing combination therapies
The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.
“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”
A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma.
“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
Cancer drugs and the heart
Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”
But, Dr. Moslehi explained, “we are entering [uncharted] waters.”
Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.
“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
Inside rare cancers
William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.
After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.
Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers.
“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said.
The researchers reported numerous relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM CELL
Antibody Drug Conjugates: a growing field of targeted therapy for breast cancer
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
The landscape of breast cancer care and how we're working on pushing the targeted treatment movement forward is rapidly changing, especially with antibody drug conjugates (ADCs).
I like to think of ADCs as targeted missiles. They're essentially composed of antibodies against specific antigens, or targets of interest, and then they're combined with a linker to a chemotherapy payload. It's a way to deliver the chemotherapy in a more targeted manner than traditional chemotherapy, which is an exciting opportunity to allow us to target those patients who otherwise prefer agents that were more difficult to tolerate before this technology was invented.
This field has grown exponentially in the last 5 to 10 years and has presented multiple new opportunities for research. What is most exciting is that we have new targets for these treatments—new antigens that we can target with novel ADCs.
The NeoSTAR trial evaluated the ADC sacituzumab govitecan (SG), which is used for patients who have earlier stage triple negative breast cancer before surgery. The idea of this is to hopefully spare patients from many of the more toxic effects of traditional chemotherapy, while still providing them precision in terms of the treatment that we're targeting in the body.
I was involved in the ASCENT trial, which is also notable for precise treatment. It demonstrated the superiority of SG in metastatic triple negative breast cancer, and more recently the US Food and Drug Administration label has been expanded to the metastatic hormone-positive space as well. As we're developing these ADCs and broadening their use, we're able to reach larger patient populations. It's really exciting because we know there's such an appetite among our patients to use these agents, given how effective they can be and, in some situations, less toxic than the standard chemotherapy they would have otherwise gotten.
The other big category of trials involves another ADC called trastuzumab deruxtecan (TD). Trastuzumab is conjugated against HER2, a breast cancer specific agent, and is combined with the linker, deruxtecan—a very potent chemotherapy payload. TD was initially used in patients who had HER2-positive breast cancer. In fact, trastuzumab, the first half of the drug, was used as an antibody in and of itself in a lot of earlier stage and metastatic cancer for years. We've known about that for a long time. But more recently, with the series of DESTINY trials, we have seen the major impact that TD in HER2 can have compared to other chemotherapy agents and against other ADCs as well.
What was so exciting about the trials presented in 2022 is that they created a new category of patients called HER2-low. Before, we had always considered patients as HER2-positive or HER2-negative. We now know it's not that binary. We had already known by the way we do the pathology that people can have levels of HER2 expression. HER2-low patients are people who would have been considered HER2-negative before this—but have some HER2 expression. They have what we consider low on a scale of 0 to 3+, typically. Therefore, they're 1+ or 2+, not 0, and not 3+, because that would be considered HER2-positive. It's a little more complicated because when it's triple 2-positive, they could also do a back-up test, if a patient is positive on that, they are considered as HER2-positive.
There is now a new category of HER2-low patients who were also shown to have a tremendous improvement benefit with TD; this new category of patients could be candidates for this treatment, although they would never have been used for HER2 targeting before. These agents can be so effective that it's even causing us to rethink our classifications of disease.
Some of what we're working on right now is specifically looking at how patients are resistant to these agents; that's one of our major focuses as Mass General. We know these treatments are highly effective, but unfortunately, they don't last forever. Very few of these cancer treatments do, because as we know, cancer has this remarkable ability to evolve resistance to agents that we use. The amazing thing about ADCs is they've extended (in some cases) overall survival for patients, which is fantastic. But as I said, we know that they are not lasting forever. Part of what we're involved in with that clinical and research setting is to look at patients who've had success with these agents and ultimately progressed, and then figure out what changed before and after treatment (down to the single cell or genetic level) in order to continue expanding use of these treatments, extending use of the treatments, and making them more effective for more patients.
Commentary: Surgical, Tamoxifen, and Genetic Considerations in Breast Cancer, May 2023
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.
Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia
Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.
Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC
Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI 0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.
Commentary: Endocrine therapy and mammography, May 2023
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017
Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.
Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.2 A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.
The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.3 A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.
Additional References
- De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
- Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
- Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017