SABCS 2014

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – Electroacupuncture proved significantly more effective than gabapentin for treatment of hot flashes in breast cancer survivors in a randomized, placebo-controlled clinical trial.

Acupuncture was far better tolerated as well. The rate of treatment-related adverse events was higher in patients randomized to gabapentin than to women assigned to electroacupuncture, sham acupuncture, or placebo, Dr. Jun J. Mao reported at the San Antonio Breast Cancer Symposium.

The study included 120 women who had completed their primary treatment for breast cancer and were experiencing troublesome hot flashes at least twice daily. Participants were randomized to 8 weeks of treatment with electroacupuncture, sham acupuncture, gabapentin at 300 mg t.i.d., or placebo. The primary endpoint was change from baseline to week 8 in patients’ hot flash composite score as gleaned from their daily hot flash diary. The secondary endpoint was durability of response based upon the hot flash composite score at week 24, fully 4 months after patients went off treatment, explained Dr. Mao, a family physician and licensed acupuncturist at the University of Pennsylvania, Philadelphia.

From a baseline mean hot flash score of 14.3, scores dropped by a mean of 7.4 points by week 8 in the electroacupuncture recipients. This represented a significantly greater treatment effect, compared with the reductions of 5.9 points with sham acupuncture, 5.2 points with gabapentin, and 3.4 points with placebo.

Only acupuncture showed a durable treatment benefit at 24 weeks. Indeed, the magnitude of the reduction in hot flash scores 4 months after the final acupuncture session was, intriguingly, even greater than at 8 weeks, both for electroacupuncture and sham acupuncture. The mean reduction in hot flash score at 24 weeks was 8.5 points in the electroacupuncture group, as compared with 7.4 points at week 8. Sham acupuncture showed a mean 6.1-point decrease in the hot flash score at week 24, gabapentin a 4.6-point reduction, and placebo a 2.8-point drop.

No serious adverse events were noted during the study. However, 48% of gabapentin-treated patients reported treatment-related adverse events, compared with 29% on placebo, 19% who got electroacupuncture, and 3% with sham acupuncture, Dr. Mao continued.

The adherence rate to acupuncture was 90%, versus 75% with gabapentin.

Electroacupuncture entailed using a TENS unit to pass a 2-Hz current through acupuncture needles placed at traditional points. There were two sessions per week for the first 2 weeks, then once-weekly sessions for the remaining 6 weeks.

“The needle insertion is generally brief, 5-10 minutes. Then the patient rests for about 20 minutes,” according to the family physician.

Sham acupuncture utilized nonpenetrating Streitberger needles at nontraditional acupuncture points.

Discussant Dr. Michelle E. Melisko noted that this is one of the largest randomized trials of acupuncture for hot flashes ever done, and it included women of widely varied ages and a substantial African American population. It’s also the first study she’s aware of to compare acupuncture to a nonhormonal medication.

She observed that hot flashes tend to be particularly frequent, severe, and often more debilitating in breast cancer survivors than in the general population. Gabapentin (Neurontin) and venlafaxine (Effexor) are probably the two most widely prescribed centrally acting drugs for treatment of hot flashes in breast cancer survivors.

“Gabapentin is often an appealing choice. In my practice it’s a drug often used to kill two birds with one stone. It can make people sleepy, so if patients are having hot flashes and night sweats it’s nice to give them an agent they can take at bedtime that might have the dual effects of reducing hot flashes as well as improving their sleep,” said Dr. Melisko, an oncologist at the University of California, San Francisco.

She noted that a systematic review of gabapentin for hot flashes in 901 patients in seven clinical trials, including four studies in breast cancer survivors, concluded the drug resulted in 20%-30% reductions in hot flash frequency and severity, but with a dropout rate twice that for placebo (Clin. Therapeutics 2009;31:221-35).But lots of breast cancer survivors say they don’t want to take an additional side effect–laden medication to treat a different set of treatment-induced side effects, Dr. Melisko continued. They’re interested in trying complementary and alternative medicine. And while a Cochrane review has concluded that acupuncture resulted in a significant reduction in hot flash severity but not frequency (Cochrane Database Syst. Rev. 2013 July 30;7:CD007410), Dr. Melisko noted that many of the trials included in that analysis may have been too brief to give acupuncture a fair shake.

Dr. Mao agreed.

“By 4 weeks in our trial you see only about one-half of the eventual effect of electroacupuncture. So if you design a short trial you may not get to the full therapeutic dose,” he said. “With acupuncture, it’s a slow start but eventual substantial effect. I tell patients you need to give acupuncture a therapeutic trial of at least six treatments. If at that point you don’t have any benefit, it may not work for you, but if you don’t try that amount it’s suboptimal.”

In acupuncture trials across the board, whether in the setting of cancer, chronic pain, or various other conditions, roughly one-third of patients are nonresponders, according to Dr. Mao.

His study was funded by the NIH’s National Center for Complementary and Alternative Medicine. He reported having no financial conflicts.

[email protected]

SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.

Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.

Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – An analysis from 2 decades of follow-up in women who took tamoxifen or placebo for breast cancer prevention showed the benefit in prevention persists, but no benefit in survival has yet to emerge.

Dr. Erica Mayer of the Dana-Farber Cancer Institute, Boston, discusses IBIS-1 results in an interview and details what those results will mean in the clinic, at the San Antonio Breast Cancer Symposium.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.

However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.

“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.

He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.

“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”

The study was simultaneously published on Dec. 13 in Lancet Oncology

IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.

IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).

In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.

The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.

At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).

“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”

The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.

“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”

Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.

However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.

“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”

Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.

Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.

There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”

The tamoxifen-associated risk of any other cancers was nonsignificant.

The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.

However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.

“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.

He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.

“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”

The study was simultaneously published on Dec. 13 in Lancet Oncology

IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.

IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).

In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.

The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.

At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).

“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”

The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.

“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”

Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.

However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.

“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”

Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.

Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.

There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”

The tamoxifen-associated risk of any other cancers was nonsignificant.

The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Five years of tamoxifen provided 20 years of breast cancer prevention to some at-risk women who took it prophylactically.

However, their 20-year all-cause mortality was no different from those taking placebo (182 vs. 166 deaths), nor was their mortality from breast cancer (31 vs. 26, respectively), Jack Cuzick, Ph.D., said at the San Antonio Breast Cancer Symposium.

“While we saw clear, lasting benefits of tamoxifen in reducing breast cancer incidence, uncertainty with respect to mortality remains,” said Dr. Cuzick, the John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University, London.

He suggested that, in light of the small number of deaths, the study was not sufficiently powered to detect any significant survival difference. But women in the IBIS-1 trial will continue to be observed, and future analyses could clarify the issue, he added.

“Although 20 years seems like a long follow-up time, it is actually too early to make any clear statement about mortality,” he said. “However, we are concerned about an excess emergence of ER-negative tumors, which we saw after 10 years.”

The study was simultaneously published on Dec. 13 in Lancet Oncology

IBIS-1 randomized 7,154 healthy pre- and postmenopausal women to 5 years of either 20 mg daily tamoxifen or placebo. These women were aged 35-70 years at baseline and presented with an increased breast cancer risk attributable to a family history.

IBIS-1 was first reported in 2002, when 4-year follow-up found a 32% reduction in breast cancer risk associated with tamoxifen. But it also found a significant increase in deaths among that group (25 vs.11 in placebo), many of which were attributable to more endometrial cancer (11 vs. 5).

In 2007, the investigators published the trial’s 8-10 year findings. At that time, tamoxifen was associated with a 27% decreased risk of any breast cancer, and a 34% decreased risk of developing an ER-positive cancer. It found a consistent prophylactic benefit for tamoxifen; most of the risk reduction, however, occurred in the 5-year active treatment phase.

The significant increase in death had continued (25 vs. 11), although that report indicated that no specific cause, including endometrial cancer, drove that finding.

At the meeting, Dr. Cuzick discussed the latest findings of IBIS-1, which has now followed the cohort for up to 20 years (median, 16 years).

“We have seen a continued separation of the cancer incidence curves, with a 20-year incidence of 7.8% vs. 12.3%,” Dr. Cuzick said. “We saw that the 30% overall reduction was maintained; the number needed to treat to prevent one breast cancer was 22, which is very favorable when compared to prevention strategies for other diseases.”

The incidence of ER-positive tumors was reduced, compared with placebo, he added (4.9% vs. 8.3%), with a number needed to treat of 29. However, Dr. Cuzick said, there was a slight increase in the incidence of ER-negative tumors after 10 years.

“This is likely because these are tumors that would have appeared earlier as ER-positive tumors, but under tamoxifen, they were held back for some time and eventually broke out as ER-negative tumors.”

Hormone therapy was allowed in IBIS-1, and about 50% of women were taking hormones during at least part of the study. They did not experience the same level of benefit form tamoxifen as those who were not taking hormone therapy (12% vs. 38%). “This is very clear evidence that the benefits are substantially greater in those who are not using concurrent [hormone therapy] when on tamoxifen,” he said.

However, tamoxifen was associated with side effects and risks, including an increased risk of developing other cancers. Most concerning was the 45% increase in the risk of endometrial cancer, which accounted for five deaths in the treatment group; there were no deaths from endometrial cancer in the placebo group.

“We had hoped that endometrial cancer might not translate into such a large morality increase as there were no deaths due to this in the 8-year follow-up. We do need to be aware of this.”

Recurrent breast cancer was the single largest cause of death, but the between-group difference was not significant (26 vs. 31). Cardiovascular deaths were similar between the groups, and all that did occur, did so during the treatment period.

Nonmelanoma skin cancers were 39% more likely in the tamoxifen group, although they caused no deaths. “This was a very large increase and a surprise; we really don’t understand it,” Dr. Cuzick said.

There were 12 fewer colorectal cancers in the tamoxifen group. “That there was a slight reduction here is of some interest, as we did not see at all with placebo.”

The tamoxifen-associated risk of any other cancers was nonsignificant.

The IBIS-I trial was supported by Cancer Research UK. Dr. Cuzick has received funding for other trials from AstraZeneca and is a consultant for AstraZeneca. The company also provided both the study drug and placebo.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Our reporter Michele Sullivan asked selected attendees at the San Antonio Breast Cancer Symposium to identify the most interesting or practice-changing study presented at the meeting. The answer was the same across the board - the Suppression of Ovarian Function Trial (SOFT), which showed that selective ovarian suppression reduces disease recurrence in women with early breast cancer.

In our video interview clinicians respond to the implications of the data in their practice.

SAN ANTONIO – Our reporter Michele Sullivan asked selected attendees at the San Antonio Breast Cancer Symposium to identify the most interesting or practice-changing study presented at the meeting. The answer was the same across the board - the Suppression of Ovarian Function Trial (SOFT), which showed that selective ovarian suppression reduces disease recurrence in women with early breast cancer.

In our video interview clinicians respond to the implications of the data in their practice.

SAN ANTONIO – Our reporter Michele Sullivan asked selected attendees at the San Antonio Breast Cancer Symposium to identify the most interesting or practice-changing study presented at the meeting. The answer was the same across the board - the Suppression of Ovarian Function Trial (SOFT), which showed that selective ovarian suppression reduces disease recurrence in women with early breast cancer.

In our video interview clinicians respond to the implications of the data in their practice.

SAN ANTONIO – Adding ovarian suppression to 5 years of either tamoxifen or exemestane following chemotherapy, in women with hormone receptor-positive early breast cancer, provided a markedly greater reduction in breast cancer recurrence compared with standard therapy with tamoxifen alone, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

However, not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, discusses in an interview how these key findings of SOFT (the Suppression of Ovarian Function Trial) should change practice in the clinic next week.

[email protected]

SAN ANTONIO – Adding ovarian suppression to 5 years of either tamoxifen or exemestane following chemotherapy, in women with hormone receptor-positive early breast cancer, provided a markedly greater reduction in breast cancer recurrence compared with standard therapy with tamoxifen alone, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

However, not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, discusses in an interview how these key findings of SOFT (the Suppression of Ovarian Function Trial) should change practice in the clinic next week.

[email protected]

SAN ANTONIO – Adding ovarian suppression to 5 years of either tamoxifen or exemestane following chemotherapy, in women with hormone receptor-positive early breast cancer, provided a markedly greater reduction in breast cancer recurrence compared with standard therapy with tamoxifen alone, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

However, not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, discusses in an interview how these key findings of SOFT (the Suppression of Ovarian Function Trial) should change practice in the clinic next week.

[email protected]

SAN ANTONIO – Adding ovarian suppression to 5 years of tamoxifen in women with hormone receptor–positive early breast cancer who remain premenopausal following chemotherapy provides a markedly greater reduction in breast cancer recurrence, compared with standard adjuvant therapy with tamoxifen alone – and combining ovarian suppression with an aromatase inhibitor instead of tamoxifen further improves outcomes, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

This was a key finding of SOFT (Suppression of Ovarian Function Trial), a randomized comparison of adjuvant tamoxifen or exemestane plus ovarian suppression versus tamoxifen alone in 3,047 patients in 25 countries, making this the largest randomized trial ever conducted in premenopausal women with hormone receptor–positive breast cancer.

The other key finding in SOFT was that not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy based upon a decision made with their physician had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. In these patients, who were typically closer to the age of natural menopause onset and had cancers with a more favorable pathology than women who underwent chemotherapy, adding ovarian suppression offered no further advantage over tamoxifen alone, added Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, Australia.

Bruce Jancin/Frontline Medical News

She called the SOFT results practice changing, and other experts agreed.

“For me, when I go back to my practice on Monday and I see a woman under age 35 with a hormone-sensitive breast cancer, I will now know what to advise that woman,” Dr. Francis said. “The strength of my recommendation for exemestane plus ovarian function suppression following chemotherapy will be greater in that woman; I’ll feel like maybe I should be recommending it rather than discussing it, because the advantage is so great. And when I see a premenopausal woman who is 48 and who’s got a small, screen-detected, nonaggressive breast cancer, I will feel very comfortable that she can do quite well with tamoxifen alone.”

The SOFT trial was unique in that it mandated that only women with documented recovery of ovarian function within 8 months of completing chemotherapy were eligible for enrollment.

At a median follow-up of 5.6 years, the 5-year disease-free survival rate was 84.7% in patients randomized to tamoxifen alone and not significantly different at 86.6% in those assigned to tamoxifen combined with ovarian function suppression. But the study design included two distinct populations – 53% who received chemotherapy and 47% who didn’t – and their outcomes were distinctly different.

The group who had undergone chemotherapy tended to have a higher baseline recurrence risk. They were younger – average age 40 – and typically had larger, higher-grade tumors and were more likely to be node positive. Their 5-year rate of freedom from breast cancer recurrence was 78% with tamoxifen alone, 82.5% with tamoxifen and ovarian suppression, and 85.7% with exemestane combined with ovarian suppression. That translates to a 22% decrease in the relative risk of recurrence in women on tamoxifen plus ovarian suppression. The absolute 7.7% difference in freedom from recurrent breast cancer at 5 years between women on exemestane plus ovarian suppression, compared with tamoxifen alone equated to a 35% relative risk reduction.

The advantage of ovarian suppression was most dramatic in the 350 study participants under age 35. Their 5-year rate of freedom from recurrent breast cancer was 67.7% with tamoxifen alone, 78.9% with tamoxifen combined with ovarian suppression, and 83.4% with exemestane and ovarian suppression, for a hefty absolute difference of 15.7%, compared with tamoxifen only.

Prior studies suggested that women diagnosed with hormone receptor–positive breast cancer before age 35 are at particularly high risk of disease recurrence. This was borne out in SOFT. One in three women under age 35 assigned to tamoxifen alone had further breast cancer within 5 years, compared with just one in six on exemestane plus ovarian suppression, Dr. Francis reported.

Systematic assessment of quality of life and treatment toxicities featured prominently in the SOFT trial. Add-on ovarian suppression was associated with increased rates of menopausal symptoms, insomnia, hypertension, diabetes, osteoporosis, and depression. The endocrine toxicities became less pronounced after 2 years. Patient reports of sexual dysfunction were more prominent and longer lasting in the exemestane group. Fifteen percent of women stopped ovarian suppression by 2 years, and 22% by 3 years.

Discussant Dr. Hope S. Rugo noted that while only 4.7% of breast cancers are diagnosed in women under age 40, that still adds up to roughly 11,000 new cases per year in the United States alone.

The SOFT results inspired Dr. Rugo to propose a new treatment algorithm for women with premenopausal hormone receptor–positive early-stage breast cancer. Patients who receive chemotherapy for high-risk disease – that is, women who are younger and especially those under age 35, with larger, grade 3 tumors, and/or node-positive disease – should subsequently undergo ovarian suppression combined with either exemestane or tamoxifen, with the choice being individualized based upon drug side effect profiles and tolerance. Those with low-risk disease not treated with adjuvant chemotherapy can be well treated with tamoxifen alone for at least 5 years.

The SOFT trial didn’t provide guidance regarding management of premenopausal women with intermediate-risk disease – those with low-grade but larger and/or node-positive tumors – but other evidence suggests ovarian suppression combined with exemestane or tamoxifen is a reasonable strategy there, too, said Dr. Rugo, professor of medicine at the University of California, San Francisco.

American Association for Cancer Research President Dr. Carlos L. Arteaga said he suspects a substantial number of premenopausal women who have undergone chemotherapy for high-risk hormone receptor–positive breast cancer and have embarked on a planned 10 years of adjuvant tamoxifen which they’re not looking forward to will be interested in the shorter SOFT alternative consisting of 5 years of exemestane plus ovarian suppression.

Simultaneous with Dr. Francis’ presentation in San Antonio, the SOFT results were published online in the New England Journal of Medicine (doi:10.1056/NEJMoa1412379).

The trial was conducted by the International Breast Cancer Study Group and funded by the National Cancer Institute and Pfizer. Dr. Francis reported having no financial conflicts.

[email protected]

SAN ANTONIO – Adding ovarian suppression to 5 years of tamoxifen in women with hormone receptor–positive early breast cancer who remain premenopausal following chemotherapy provides a markedly greater reduction in breast cancer recurrence, compared with standard adjuvant therapy with tamoxifen alone – and combining ovarian suppression with an aromatase inhibitor instead of tamoxifen further improves outcomes, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

This was a key finding of SOFT (Suppression of Ovarian Function Trial), a randomized comparison of adjuvant tamoxifen or exemestane plus ovarian suppression versus tamoxifen alone in 3,047 patients in 25 countries, making this the largest randomized trial ever conducted in premenopausal women with hormone receptor–positive breast cancer.

The other key finding in SOFT was that not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy based upon a decision made with their physician had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. In these patients, who were typically closer to the age of natural menopause onset and had cancers with a more favorable pathology than women who underwent chemotherapy, adding ovarian suppression offered no further advantage over tamoxifen alone, added Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, Australia.

Bruce Jancin/Frontline Medical News

She called the SOFT results practice changing, and other experts agreed.

“For me, when I go back to my practice on Monday and I see a woman under age 35 with a hormone-sensitive breast cancer, I will now know what to advise that woman,” Dr. Francis said. “The strength of my recommendation for exemestane plus ovarian function suppression following chemotherapy will be greater in that woman; I’ll feel like maybe I should be recommending it rather than discussing it, because the advantage is so great. And when I see a premenopausal woman who is 48 and who’s got a small, screen-detected, nonaggressive breast cancer, I will feel very comfortable that she can do quite well with tamoxifen alone.”

The SOFT trial was unique in that it mandated that only women with documented recovery of ovarian function within 8 months of completing chemotherapy were eligible for enrollment.

At a median follow-up of 5.6 years, the 5-year disease-free survival rate was 84.7% in patients randomized to tamoxifen alone and not significantly different at 86.6% in those assigned to tamoxifen combined with ovarian function suppression. But the study design included two distinct populations – 53% who received chemotherapy and 47% who didn’t – and their outcomes were distinctly different.

The group who had undergone chemotherapy tended to have a higher baseline recurrence risk. They were younger – average age 40 – and typically had larger, higher-grade tumors and were more likely to be node positive. Their 5-year rate of freedom from breast cancer recurrence was 78% with tamoxifen alone, 82.5% with tamoxifen and ovarian suppression, and 85.7% with exemestane combined with ovarian suppression. That translates to a 22% decrease in the relative risk of recurrence in women on tamoxifen plus ovarian suppression. The absolute 7.7% difference in freedom from recurrent breast cancer at 5 years between women on exemestane plus ovarian suppression, compared with tamoxifen alone equated to a 35% relative risk reduction.

The advantage of ovarian suppression was most dramatic in the 350 study participants under age 35. Their 5-year rate of freedom from recurrent breast cancer was 67.7% with tamoxifen alone, 78.9% with tamoxifen combined with ovarian suppression, and 83.4% with exemestane and ovarian suppression, for a hefty absolute difference of 15.7%, compared with tamoxifen only.

Prior studies suggested that women diagnosed with hormone receptor–positive breast cancer before age 35 are at particularly high risk of disease recurrence. This was borne out in SOFT. One in three women under age 35 assigned to tamoxifen alone had further breast cancer within 5 years, compared with just one in six on exemestane plus ovarian suppression, Dr. Francis reported.

Systematic assessment of quality of life and treatment toxicities featured prominently in the SOFT trial. Add-on ovarian suppression was associated with increased rates of menopausal symptoms, insomnia, hypertension, diabetes, osteoporosis, and depression. The endocrine toxicities became less pronounced after 2 years. Patient reports of sexual dysfunction were more prominent and longer lasting in the exemestane group. Fifteen percent of women stopped ovarian suppression by 2 years, and 22% by 3 years.

Discussant Dr. Hope S. Rugo noted that while only 4.7% of breast cancers are diagnosed in women under age 40, that still adds up to roughly 11,000 new cases per year in the United States alone.

The SOFT results inspired Dr. Rugo to propose a new treatment algorithm for women with premenopausal hormone receptor–positive early-stage breast cancer. Patients who receive chemotherapy for high-risk disease – that is, women who are younger and especially those under age 35, with larger, grade 3 tumors, and/or node-positive disease – should subsequently undergo ovarian suppression combined with either exemestane or tamoxifen, with the choice being individualized based upon drug side effect profiles and tolerance. Those with low-risk disease not treated with adjuvant chemotherapy can be well treated with tamoxifen alone for at least 5 years.

The SOFT trial didn’t provide guidance regarding management of premenopausal women with intermediate-risk disease – those with low-grade but larger and/or node-positive tumors – but other evidence suggests ovarian suppression combined with exemestane or tamoxifen is a reasonable strategy there, too, said Dr. Rugo, professor of medicine at the University of California, San Francisco.

American Association for Cancer Research President Dr. Carlos L. Arteaga said he suspects a substantial number of premenopausal women who have undergone chemotherapy for high-risk hormone receptor–positive breast cancer and have embarked on a planned 10 years of adjuvant tamoxifen which they’re not looking forward to will be interested in the shorter SOFT alternative consisting of 5 years of exemestane plus ovarian suppression.

Simultaneous with Dr. Francis’ presentation in San Antonio, the SOFT results were published online in the New England Journal of Medicine (doi:10.1056/NEJMoa1412379).

The trial was conducted by the International Breast Cancer Study Group and funded by the National Cancer Institute and Pfizer. Dr. Francis reported having no financial conflicts.

[email protected]

SAN ANTONIO – Adding ovarian suppression to 5 years of tamoxifen in women with hormone receptor–positive early breast cancer who remain premenopausal following chemotherapy provides a markedly greater reduction in breast cancer recurrence, compared with standard adjuvant therapy with tamoxifen alone – and combining ovarian suppression with an aromatase inhibitor instead of tamoxifen further improves outcomes, Dr. Prudence Francis reported at the San Antonio Breast Cancer Symposium.

This was a key finding of SOFT (Suppression of Ovarian Function Trial), a randomized comparison of adjuvant tamoxifen or exemestane plus ovarian suppression versus tamoxifen alone in 3,047 patients in 25 countries, making this the largest randomized trial ever conducted in premenopausal women with hormone receptor–positive breast cancer.

The other key finding in SOFT was that not all premenopausal patients obtained benefit from ovarian suppression. Those who didn’t receive chemotherapy based upon a decision made with their physician had excellent outcomes with 5 years of tamoxifen alone, with a 95.8% disease-free survival at 5 years. In these patients, who were typically closer to the age of natural menopause onset and had cancers with a more favorable pathology than women who underwent chemotherapy, adding ovarian suppression offered no further advantage over tamoxifen alone, added Dr. Francis, who is head of breast medical oncology at the Peter MacCallum Cancer Center, Melbourne, Australia.

Bruce Jancin/Frontline Medical News

She called the SOFT results practice changing, and other experts agreed.

“For me, when I go back to my practice on Monday and I see a woman under age 35 with a hormone-sensitive breast cancer, I will now know what to advise that woman,” Dr. Francis said. “The strength of my recommendation for exemestane plus ovarian function suppression following chemotherapy will be greater in that woman; I’ll feel like maybe I should be recommending it rather than discussing it, because the advantage is so great. And when I see a premenopausal woman who is 48 and who’s got a small, screen-detected, nonaggressive breast cancer, I will feel very comfortable that she can do quite well with tamoxifen alone.”

The SOFT trial was unique in that it mandated that only women with documented recovery of ovarian function within 8 months of completing chemotherapy were eligible for enrollment.

At a median follow-up of 5.6 years, the 5-year disease-free survival rate was 84.7% in patients randomized to tamoxifen alone and not significantly different at 86.6% in those assigned to tamoxifen combined with ovarian function suppression. But the study design included two distinct populations – 53% who received chemotherapy and 47% who didn’t – and their outcomes were distinctly different.

The group who had undergone chemotherapy tended to have a higher baseline recurrence risk. They were younger – average age 40 – and typically had larger, higher-grade tumors and were more likely to be node positive. Their 5-year rate of freedom from breast cancer recurrence was 78% with tamoxifen alone, 82.5% with tamoxifen and ovarian suppression, and 85.7% with exemestane combined with ovarian suppression. That translates to a 22% decrease in the relative risk of recurrence in women on tamoxifen plus ovarian suppression. The absolute 7.7% difference in freedom from recurrent breast cancer at 5 years between women on exemestane plus ovarian suppression, compared with tamoxifen alone equated to a 35% relative risk reduction.

The advantage of ovarian suppression was most dramatic in the 350 study participants under age 35. Their 5-year rate of freedom from recurrent breast cancer was 67.7% with tamoxifen alone, 78.9% with tamoxifen combined with ovarian suppression, and 83.4% with exemestane and ovarian suppression, for a hefty absolute difference of 15.7%, compared with tamoxifen only.

Prior studies suggested that women diagnosed with hormone receptor–positive breast cancer before age 35 are at particularly high risk of disease recurrence. This was borne out in SOFT. One in three women under age 35 assigned to tamoxifen alone had further breast cancer within 5 years, compared with just one in six on exemestane plus ovarian suppression, Dr. Francis reported.

Systematic assessment of quality of life and treatment toxicities featured prominently in the SOFT trial. Add-on ovarian suppression was associated with increased rates of menopausal symptoms, insomnia, hypertension, diabetes, osteoporosis, and depression. The endocrine toxicities became less pronounced after 2 years. Patient reports of sexual dysfunction were more prominent and longer lasting in the exemestane group. Fifteen percent of women stopped ovarian suppression by 2 years, and 22% by 3 years.

Discussant Dr. Hope S. Rugo noted that while only 4.7% of breast cancers are diagnosed in women under age 40, that still adds up to roughly 11,000 new cases per year in the United States alone.

The SOFT results inspired Dr. Rugo to propose a new treatment algorithm for women with premenopausal hormone receptor–positive early-stage breast cancer. Patients who receive chemotherapy for high-risk disease – that is, women who are younger and especially those under age 35, with larger, grade 3 tumors, and/or node-positive disease – should subsequently undergo ovarian suppression combined with either exemestane or tamoxifen, with the choice being individualized based upon drug side effect profiles and tolerance. Those with low-risk disease not treated with adjuvant chemotherapy can be well treated with tamoxifen alone for at least 5 years.

The SOFT trial didn’t provide guidance regarding management of premenopausal women with intermediate-risk disease – those with low-grade but larger and/or node-positive tumors – but other evidence suggests ovarian suppression combined with exemestane or tamoxifen is a reasonable strategy there, too, said Dr. Rugo, professor of medicine at the University of California, San Francisco.

American Association for Cancer Research President Dr. Carlos L. Arteaga said he suspects a substantial number of premenopausal women who have undergone chemotherapy for high-risk hormone receptor–positive breast cancer and have embarked on a planned 10 years of adjuvant tamoxifen which they’re not looking forward to will be interested in the shorter SOFT alternative consisting of 5 years of exemestane plus ovarian suppression.

Simultaneous with Dr. Francis’ presentation in San Antonio, the SOFT results were published online in the New England Journal of Medicine (doi:10.1056/NEJMoa1412379).

The trial was conducted by the International Breast Cancer Study Group and funded by the National Cancer Institute and Pfizer. Dr. Francis reported having no financial conflicts.

[email protected]

SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.

Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.

The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.

[email protected]

On Twitter @nikolaideslaura

SAN ANTONIO– Roughly one in five women with heavily pretreated, advanced triple-negative breast cancer experienced a response to monotherapy using the novel immune checkpoint inhibitor pembrolizumab in KEYNOTE-012, a small proof-of-concept study.

In a video interview at the San Antonio Breast Cancer Symposium, Dr. Rita Nanda, who presented the results, describes the long duration of that response, more than 40 weeks in most of the women, all of whom had received multiple lines of chemotherapy. Dr. Nanda of the University of Chicago also commented on the possible study of pembrolizumab against other subtypes of breast cancer and on possible combination regimens.

[email protected]

SAN ANTONIO– Roughly one in five women with heavily pretreated, advanced triple-negative breast cancer experienced a response to monotherapy using the novel immune checkpoint inhibitor pembrolizumab in KEYNOTE-012, a small proof-of-concept study.

In a video interview at the San Antonio Breast Cancer Symposium, Dr. Rita Nanda, who presented the results, describes the long duration of that response, more than 40 weeks in most of the women, all of whom had received multiple lines of chemotherapy. Dr. Nanda of the University of Chicago also commented on the possible study of pembrolizumab against other subtypes of breast cancer and on possible combination regimens.

[email protected]

SAN ANTONIO– Roughly one in five women with heavily pretreated, advanced triple-negative breast cancer experienced a response to monotherapy using the novel immune checkpoint inhibitor pembrolizumab in KEYNOTE-012, a small proof-of-concept study.

In a video interview at the San Antonio Breast Cancer Symposium, Dr. Rita Nanda, who presented the results, describes the long duration of that response, more than 40 weeks in most of the women, all of whom had received multiple lines of chemotherapy. Dr. Nanda of the University of Chicago also commented on the possible study of pembrolizumab against other subtypes of breast cancer and on possible combination regimens.

[email protected]