Breast Cancer

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.

Susan London/MDedge News

The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.

Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.

The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.

“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”

Putting data into practice

Susan London/MDedge News

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).

They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”


Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.

“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”

Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”

Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”

At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”

Study details

The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.

The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.

The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.

The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”

The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).

Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.

SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.

Susan London/MDedge News

The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.

Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.

The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.

“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”

Putting data into practice

Susan London/MDedge News

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).

They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”


Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.

“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”

Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”

Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”

At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”

Study details

The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.

The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.

The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.

The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”

The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).

Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.

SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.

Susan London/MDedge News

The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.

Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.

The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.

“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”

Putting data into practice

Susan London/MDedge News

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).

They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”


Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.

“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”

Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”

Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”

At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”

Study details

The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.

The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.

The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.

The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”

The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).

Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.

SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.

Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.

In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.

However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”

Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.

“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.

Dr. Mayer reported having no relevant disclosures.

[email protected]

SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.

Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.

In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.

However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”

Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.

“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.

Dr. Mayer reported having no relevant disclosures.

[email protected]

SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.

Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.

In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.

However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”

Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.

“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.

Dr. Mayer reported having no relevant disclosures.

[email protected]

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.