Breast Cancer

CHICAGO – There has been a clear and abrupt decline in screening mammography in the wake of the controversial breast cancer screening recommendations by the U.S. Preventive Services Task Force.

After climbing steadily at a rate of about 1% per year since 2001, breast mammography among women on Medicare declined 4.3% in 2010, the first full year after the USPSTF recommendations came out.

The reasons for the decline aren’t entirely clear, but it may be that women over age 74 years began to follow the task force recommendations and no longer got screened, or that women aged 50-74 years extended their screening interval from 1 to 2 years, again according to task force recommendations, lead author Dr. David C. Levin said at the annual meeting of the Radiological Society of North America.

Patrice Wendling/IMNG Medical Media

"What is clear is that the introduction of those recommendations in late 2009 had a chilling effect on the willingness of women to get screened," he said. "It remains to be seen whether this trend is going to continue and whether it will affect breast cancer mortality."

For the analysis, Dr. Levin reviewed film and digital screening mammography codes in the Medicare Part B Physician/Supplier Procedure Summary Master Files for 2005 to 2010. The database provides volumes for each code each year.

From these data, he calculated that the screening mammography rate per 1,000 female Medicare beneficiaries had been growing in small increments each year from 311.6 in 2005 to 312.4 in 2006, 316.2 in 2007, 320.1 in 2008, and 322.9 in 2009. This represents a compound annual growth rate of 0.9%.

After the recommendations came out, the screening mammography rate fell to 309.1/1,000 women in 2010, representing a decline of 4.3% in a single year, said Dr. Levin, a radiologist and founder of the center for research on utilization of imaging services at Thomas Jefferson University Hospital in Philadelphia.

He pointed out that earlier this year, Mayo Clinic researchers reported a 5.7% decline in screening mammography in 2010 among women aged 40-64, based on data from almost 7.9 million women enrolled in nearly 100 health plans.

In a separate presentation at the meeting, investigators analyzed the outcomes of 43,351 screening mammograms performed between 2007 and 2010 to determine how the new USPSTF recommendations against screening in women 40-49 years could impact this age group.

The cross-sectional analysis included all patients presenting for a screening mammogram without clinical findings at New York Presbyterian Hospital–Weill Cornell Medical College (NYPH-WCMC) in New York City. Women aged 40-49 comprised 33.5% of the screening population.

During the 4 years, 205 breast cancers were detected (4.7/1,000). Women in their forties accounted for 19% of the cancers found, which would represent a substantial degree of underdiagnoses if they had been missed, reported Dr. Elizabeth Arleo, a radiologist at NYPH-WCMC.

Notably, only three of the women in their forties with screen-detected breast cancer had a first-degree relative with premenopausal breast cancer, thereby placing them at higher risk. More than half of the cancers in this subgroup, however, were invasive (21/39).

If the USPSTF recommendations had been enforced during the study years, these cancers may not have been detected until the patients’ baseline screening at age 50 or until the cancers had progressed to clinically evident, palpable disease, Dr. Arleo coauthors said.

Dr. Levin reported relationships with HealthHelp and Outpatient Imaging Affiliates. Dr. Arleo said she had no relevant financial disclosures.

CHICAGO – There has been a clear and abrupt decline in screening mammography in the wake of the controversial breast cancer screening recommendations by the U.S. Preventive Services Task Force.

After climbing steadily at a rate of about 1% per year since 2001, breast mammography among women on Medicare declined 4.3% in 2010, the first full year after the USPSTF recommendations came out.

The reasons for the decline aren’t entirely clear, but it may be that women over age 74 years began to follow the task force recommendations and no longer got screened, or that women aged 50-74 years extended their screening interval from 1 to 2 years, again according to task force recommendations, lead author Dr. David C. Levin said at the annual meeting of the Radiological Society of North America.

Patrice Wendling/IMNG Medical Media

"What is clear is that the introduction of those recommendations in late 2009 had a chilling effect on the willingness of women to get screened," he said. "It remains to be seen whether this trend is going to continue and whether it will affect breast cancer mortality."

For the analysis, Dr. Levin reviewed film and digital screening mammography codes in the Medicare Part B Physician/Supplier Procedure Summary Master Files for 2005 to 2010. The database provides volumes for each code each year.

From these data, he calculated that the screening mammography rate per 1,000 female Medicare beneficiaries had been growing in small increments each year from 311.6 in 2005 to 312.4 in 2006, 316.2 in 2007, 320.1 in 2008, and 322.9 in 2009. This represents a compound annual growth rate of 0.9%.

After the recommendations came out, the screening mammography rate fell to 309.1/1,000 women in 2010, representing a decline of 4.3% in a single year, said Dr. Levin, a radiologist and founder of the center for research on utilization of imaging services at Thomas Jefferson University Hospital in Philadelphia.

He pointed out that earlier this year, Mayo Clinic researchers reported a 5.7% decline in screening mammography in 2010 among women aged 40-64, based on data from almost 7.9 million women enrolled in nearly 100 health plans.

In a separate presentation at the meeting, investigators analyzed the outcomes of 43,351 screening mammograms performed between 2007 and 2010 to determine how the new USPSTF recommendations against screening in women 40-49 years could impact this age group.

The cross-sectional analysis included all patients presenting for a screening mammogram without clinical findings at New York Presbyterian Hospital–Weill Cornell Medical College (NYPH-WCMC) in New York City. Women aged 40-49 comprised 33.5% of the screening population.

During the 4 years, 205 breast cancers were detected (4.7/1,000). Women in their forties accounted for 19% of the cancers found, which would represent a substantial degree of underdiagnoses if they had been missed, reported Dr. Elizabeth Arleo, a radiologist at NYPH-WCMC.

Notably, only three of the women in their forties with screen-detected breast cancer had a first-degree relative with premenopausal breast cancer, thereby placing them at higher risk. More than half of the cancers in this subgroup, however, were invasive (21/39).

If the USPSTF recommendations had been enforced during the study years, these cancers may not have been detected until the patients’ baseline screening at age 50 or until the cancers had progressed to clinically evident, palpable disease, Dr. Arleo coauthors said.

Dr. Levin reported relationships with HealthHelp and Outpatient Imaging Affiliates. Dr. Arleo said she had no relevant financial disclosures.

CHICAGO – There has been a clear and abrupt decline in screening mammography in the wake of the controversial breast cancer screening recommendations by the U.S. Preventive Services Task Force.

After climbing steadily at a rate of about 1% per year since 2001, breast mammography among women on Medicare declined 4.3% in 2010, the first full year after the USPSTF recommendations came out.

The reasons for the decline aren’t entirely clear, but it may be that women over age 74 years began to follow the task force recommendations and no longer got screened, or that women aged 50-74 years extended their screening interval from 1 to 2 years, again according to task force recommendations, lead author Dr. David C. Levin said at the annual meeting of the Radiological Society of North America.

Patrice Wendling/IMNG Medical Media

"What is clear is that the introduction of those recommendations in late 2009 had a chilling effect on the willingness of women to get screened," he said. "It remains to be seen whether this trend is going to continue and whether it will affect breast cancer mortality."

For the analysis, Dr. Levin reviewed film and digital screening mammography codes in the Medicare Part B Physician/Supplier Procedure Summary Master Files for 2005 to 2010. The database provides volumes for each code each year.

From these data, he calculated that the screening mammography rate per 1,000 female Medicare beneficiaries had been growing in small increments each year from 311.6 in 2005 to 312.4 in 2006, 316.2 in 2007, 320.1 in 2008, and 322.9 in 2009. This represents a compound annual growth rate of 0.9%.

After the recommendations came out, the screening mammography rate fell to 309.1/1,000 women in 2010, representing a decline of 4.3% in a single year, said Dr. Levin, a radiologist and founder of the center for research on utilization of imaging services at Thomas Jefferson University Hospital in Philadelphia.

He pointed out that earlier this year, Mayo Clinic researchers reported a 5.7% decline in screening mammography in 2010 among women aged 40-64, based on data from almost 7.9 million women enrolled in nearly 100 health plans.

In a separate presentation at the meeting, investigators analyzed the outcomes of 43,351 screening mammograms performed between 2007 and 2010 to determine how the new USPSTF recommendations against screening in women 40-49 years could impact this age group.

The cross-sectional analysis included all patients presenting for a screening mammogram without clinical findings at New York Presbyterian Hospital–Weill Cornell Medical College (NYPH-WCMC) in New York City. Women aged 40-49 comprised 33.5% of the screening population.

During the 4 years, 205 breast cancers were detected (4.7/1,000). Women in their forties accounted for 19% of the cancers found, which would represent a substantial degree of underdiagnoses if they had been missed, reported Dr. Elizabeth Arleo, a radiologist at NYPH-WCMC.

Notably, only three of the women in their forties with screen-detected breast cancer had a first-degree relative with premenopausal breast cancer, thereby placing them at higher risk. More than half of the cancers in this subgroup, however, were invasive (21/39).

If the USPSTF recommendations had been enforced during the study years, these cancers may not have been detected until the patients’ baseline screening at age 50 or until the cancers had progressed to clinically evident, palpable disease, Dr. Arleo coauthors said.

Dr. Levin reported relationships with HealthHelp and Outpatient Imaging Affiliates. Dr. Arleo said she had no relevant financial disclosures.

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – Five years of adjuvant tamoxifen in women with estrogen receptor–positive early breast cancer is well established as being excellent therapy with a long-term carryover effect. Now 10 years has been shown to be even better.

A new analysis from the large international ATLAS trial demonstrated that participants randomized to 10 years of adjuvant tamoxifen had a 25% reduction in recurrences and a 29% lower mortality due to breast cancer in years 10-14 after diagnosis, compared with women who stopped the drug after the standard 5 years, Richard Gray, M.Sc., reported at the San Antonio Breast Cancer Symposium.

These findings from ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) are all the more impressive in light of the 2011 Early Breast Cancer Trialists’ Collaborative Group overview analysis, which features 15 years of follow-up of more than 10,000 women in randomized trials pitting 5 years of tamoxifen versus no tamoxifen (Lancet 2011;378:771-84). The meta-analysis showed that 5 years of tamoxifen reduced deaths due to breast cancer by 34% during the first 5 years after treatment ended and by 27% in the subsequent 5 years.

Thus, 10 years of tamoxifen had to compete against a big carryover effect of 5 years of the drug, noted Mr. Gray, professor of medical statistics at the University of Oxford (U.K.).

By multiplying the risk reduction ratios from ATLAS and the Oxford overview, he estimated that 10 years of tamoxifen reduces breast cancer mortality by one-third in the first decade following diagnosis and by fully half in the second decade, compared with no tamoxifen.

Benefits Far Outweigh Risks

The ATLAS analysis involved 6,846 randomized women with estrogen receptor–positive disease. The cumulative risk of recurrence during years 5-14 after diagnosis was 21.4% in women assigned to 10 years of tamoxifen and 25.1% in controls. Breast cancer mortality during years 5-14 was 12.2% in patients on 10 years of tamoxifen and 15.0% in those who stopped after 5 years, for an absolute mortality reduction of 2.8%.

The benefits of 10 years of tamoxifen compared with 5 far outweighed the risks, Prof. Gray continued. The cumulative risk of endometrial cancer in years 5-14 was 3.1% for women randomized to continue therapy for 10 years, compared with 1.6% for controls. Mortality due to endometrial cancer was rare, however: 0.4% in the extended therapy group and 0.2% in controls.

"I think these ATLAS results are relevant to quite a wide range of women. And the findings encourage one to think that aromatase inhibitors, too, might be more effective with longer therapy," he said.

Indeed, ongoing clinical trials are comparing outcomes with 10 versus the standard 5 years of adjuvant aromatase inhibitor therapy.

But aromatase inhibitors are not an option in premenopausal patients because they’re ineffective in that setting. In addition, some postmenopausal breast cancer patients can’t tolerate aromatase inhibitors due to arthralgias, bone pain, or other side effects. And while aromatase inhibitors are now the standard of care for adjuvant therapy in postmenopausal patients in the United States and Europe, tamoxifen remains widely used in developing countries because it’s so much less expensive, he added.

Data Are Compelling

Dr. Peter Ravdin called the ATLAS data compelling.

"I think the results of this trial will have a major immediate impact on premenopausal women. For women who are now approaching 5 years of therapy, up until this point we’d have told them we’re going to be stopping the drug. Now we’re going to be telling them that there’s clinical evidence that 10 years is superior to 5 years. And I’m going to be comfortable doing that," said Dr. Ravdin, director of the breast health clinic at the Cancer Therapy and Research Center of the University of Texas, San Antonio.

"One of the things that I think is profoundly important about this study is that the biology of the disease shows that there are some women fated to have late relapse that our early treatments aren’t effective in blocking, but that we can do better by treating women with hormonal therapy beyond 5 years," he added.

Women with a relatively high risk of late relapse – that is, those with larger tumors and/or positive lymph nodes – will definitely be strong candidates for continuation of therapy. Those with small grade 1 tumors and a very low risk of both early and late relapse might rationally decide they don’t want to take tamoxifen for longer than 5 years, according to the oncologist.

The risk of tamoxifen-related endometrial cancer in premenopausal patients is negligible. But some women experience such problematic tamoxifen-induced hot flashes or vaginal symptoms that they may balk at continuing treatment beyond 5 years.

"I think that the amount of benefit they’ll get in continuing will be small enough that that would be a perfectly rational decision. An additional one-third reduction in a very small risk is still a very small benefit," Dr. Ravdin observed.

Simultaneous with Prof. Gray’s presentation in San Antonio, the ATLAS results were published online (Lancet 2012 Dec. 5 [doi: 10.1016/S0140-6736(12)61963-1]).

The ATLAS trial was funded by Cancer Research UK, the UK Medical Research Council, AstraZeneca, the U.S. Army, and EU Biomed. Dr. Gray reported having no financial conflicts.

SAN ANTONIO – Five years of adjuvant tamoxifen in women with estrogen receptor–positive early breast cancer is well established as being excellent therapy with a long-term carryover effect. Now 10 years has been shown to be even better.

A new analysis from the large international ATLAS trial demonstrated that participants randomized to 10 years of adjuvant tamoxifen had a 25% reduction in recurrences and a 29% lower mortality due to breast cancer in years 10-14 after diagnosis, compared with women who stopped the drug after the standard 5 years, Richard Gray, M.Sc., reported at the San Antonio Breast Cancer Symposium.

These findings from ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) are all the more impressive in light of the 2011 Early Breast Cancer Trialists’ Collaborative Group overview analysis, which features 15 years of follow-up of more than 10,000 women in randomized trials pitting 5 years of tamoxifen versus no tamoxifen (Lancet 2011;378:771-84). The meta-analysis showed that 5 years of tamoxifen reduced deaths due to breast cancer by 34% during the first 5 years after treatment ended and by 27% in the subsequent 5 years.

Thus, 10 years of tamoxifen had to compete against a big carryover effect of 5 years of the drug, noted Mr. Gray, professor of medical statistics at the University of Oxford (U.K.).

By multiplying the risk reduction ratios from ATLAS and the Oxford overview, he estimated that 10 years of tamoxifen reduces breast cancer mortality by one-third in the first decade following diagnosis and by fully half in the second decade, compared with no tamoxifen.

Benefits Far Outweigh Risks

The ATLAS analysis involved 6,846 randomized women with estrogen receptor–positive disease. The cumulative risk of recurrence during years 5-14 after diagnosis was 21.4% in women assigned to 10 years of tamoxifen and 25.1% in controls. Breast cancer mortality during years 5-14 was 12.2% in patients on 10 years of tamoxifen and 15.0% in those who stopped after 5 years, for an absolute mortality reduction of 2.8%.

The benefits of 10 years of tamoxifen compared with 5 far outweighed the risks, Prof. Gray continued. The cumulative risk of endometrial cancer in years 5-14 was 3.1% for women randomized to continue therapy for 10 years, compared with 1.6% for controls. Mortality due to endometrial cancer was rare, however: 0.4% in the extended therapy group and 0.2% in controls.

"I think these ATLAS results are relevant to quite a wide range of women. And the findings encourage one to think that aromatase inhibitors, too, might be more effective with longer therapy," he said.

Indeed, ongoing clinical trials are comparing outcomes with 10 versus the standard 5 years of adjuvant aromatase inhibitor therapy.

But aromatase inhibitors are not an option in premenopausal patients because they’re ineffective in that setting. In addition, some postmenopausal breast cancer patients can’t tolerate aromatase inhibitors due to arthralgias, bone pain, or other side effects. And while aromatase inhibitors are now the standard of care for adjuvant therapy in postmenopausal patients in the United States and Europe, tamoxifen remains widely used in developing countries because it’s so much less expensive, he added.

Data Are Compelling

Dr. Peter Ravdin called the ATLAS data compelling.

"I think the results of this trial will have a major immediate impact on premenopausal women. For women who are now approaching 5 years of therapy, up until this point we’d have told them we’re going to be stopping the drug. Now we’re going to be telling them that there’s clinical evidence that 10 years is superior to 5 years. And I’m going to be comfortable doing that," said Dr. Ravdin, director of the breast health clinic at the Cancer Therapy and Research Center of the University of Texas, San Antonio.

"One of the things that I think is profoundly important about this study is that the biology of the disease shows that there are some women fated to have late relapse that our early treatments aren’t effective in blocking, but that we can do better by treating women with hormonal therapy beyond 5 years," he added.

Women with a relatively high risk of late relapse – that is, those with larger tumors and/or positive lymph nodes – will definitely be strong candidates for continuation of therapy. Those with small grade 1 tumors and a very low risk of both early and late relapse might rationally decide they don’t want to take tamoxifen for longer than 5 years, according to the oncologist.

The risk of tamoxifen-related endometrial cancer in premenopausal patients is negligible. But some women experience such problematic tamoxifen-induced hot flashes or vaginal symptoms that they may balk at continuing treatment beyond 5 years.

"I think that the amount of benefit they’ll get in continuing will be small enough that that would be a perfectly rational decision. An additional one-third reduction in a very small risk is still a very small benefit," Dr. Ravdin observed.

Simultaneous with Prof. Gray’s presentation in San Antonio, the ATLAS results were published online (Lancet 2012 Dec. 5 [doi: 10.1016/S0140-6736(12)61963-1]).

The ATLAS trial was funded by Cancer Research UK, the UK Medical Research Council, AstraZeneca, the U.S. Army, and EU Biomed. Dr. Gray reported having no financial conflicts.

SAN ANTONIO – Five years of adjuvant tamoxifen in women with estrogen receptor–positive early breast cancer is well established as being excellent therapy with a long-term carryover effect. Now 10 years has been shown to be even better.

A new analysis from the large international ATLAS trial demonstrated that participants randomized to 10 years of adjuvant tamoxifen had a 25% reduction in recurrences and a 29% lower mortality due to breast cancer in years 10-14 after diagnosis, compared with women who stopped the drug after the standard 5 years, Richard Gray, M.Sc., reported at the San Antonio Breast Cancer Symposium.

These findings from ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) are all the more impressive in light of the 2011 Early Breast Cancer Trialists’ Collaborative Group overview analysis, which features 15 years of follow-up of more than 10,000 women in randomized trials pitting 5 years of tamoxifen versus no tamoxifen (Lancet 2011;378:771-84). The meta-analysis showed that 5 years of tamoxifen reduced deaths due to breast cancer by 34% during the first 5 years after treatment ended and by 27% in the subsequent 5 years.

Thus, 10 years of tamoxifen had to compete against a big carryover effect of 5 years of the drug, noted Mr. Gray, professor of medical statistics at the University of Oxford (U.K.).

By multiplying the risk reduction ratios from ATLAS and the Oxford overview, he estimated that 10 years of tamoxifen reduces breast cancer mortality by one-third in the first decade following diagnosis and by fully half in the second decade, compared with no tamoxifen.

Benefits Far Outweigh Risks

The ATLAS analysis involved 6,846 randomized women with estrogen receptor–positive disease. The cumulative risk of recurrence during years 5-14 after diagnosis was 21.4% in women assigned to 10 years of tamoxifen and 25.1% in controls. Breast cancer mortality during years 5-14 was 12.2% in patients on 10 years of tamoxifen and 15.0% in those who stopped after 5 years, for an absolute mortality reduction of 2.8%.

The benefits of 10 years of tamoxifen compared with 5 far outweighed the risks, Prof. Gray continued. The cumulative risk of endometrial cancer in years 5-14 was 3.1% for women randomized to continue therapy for 10 years, compared with 1.6% for controls. Mortality due to endometrial cancer was rare, however: 0.4% in the extended therapy group and 0.2% in controls.

"I think these ATLAS results are relevant to quite a wide range of women. And the findings encourage one to think that aromatase inhibitors, too, might be more effective with longer therapy," he said.

Indeed, ongoing clinical trials are comparing outcomes with 10 versus the standard 5 years of adjuvant aromatase inhibitor therapy.

But aromatase inhibitors are not an option in premenopausal patients because they’re ineffective in that setting. In addition, some postmenopausal breast cancer patients can’t tolerate aromatase inhibitors due to arthralgias, bone pain, or other side effects. And while aromatase inhibitors are now the standard of care for adjuvant therapy in postmenopausal patients in the United States and Europe, tamoxifen remains widely used in developing countries because it’s so much less expensive, he added.

Data Are Compelling

Dr. Peter Ravdin called the ATLAS data compelling.

"I think the results of this trial will have a major immediate impact on premenopausal women. For women who are now approaching 5 years of therapy, up until this point we’d have told them we’re going to be stopping the drug. Now we’re going to be telling them that there’s clinical evidence that 10 years is superior to 5 years. And I’m going to be comfortable doing that," said Dr. Ravdin, director of the breast health clinic at the Cancer Therapy and Research Center of the University of Texas, San Antonio.

"One of the things that I think is profoundly important about this study is that the biology of the disease shows that there are some women fated to have late relapse that our early treatments aren’t effective in blocking, but that we can do better by treating women with hormonal therapy beyond 5 years," he added.

Women with a relatively high risk of late relapse – that is, those with larger tumors and/or positive lymph nodes – will definitely be strong candidates for continuation of therapy. Those with small grade 1 tumors and a very low risk of both early and late relapse might rationally decide they don’t want to take tamoxifen for longer than 5 years, according to the oncologist.

The risk of tamoxifen-related endometrial cancer in premenopausal patients is negligible. But some women experience such problematic tamoxifen-induced hot flashes or vaginal symptoms that they may balk at continuing treatment beyond 5 years.

"I think that the amount of benefit they’ll get in continuing will be small enough that that would be a perfectly rational decision. An additional one-third reduction in a very small risk is still a very small benefit," Dr. Ravdin observed.

Simultaneous with Prof. Gray’s presentation in San Antonio, the ATLAS results were published online (Lancet 2012 Dec. 5 [doi: 10.1016/S0140-6736(12)61963-1]).

The ATLAS trial was funded by Cancer Research UK, the UK Medical Research Council, AstraZeneca, the U.S. Army, and EU Biomed. Dr. Gray reported having no financial conflicts.

IMNG Medical News reporter Michele Sullivan asks attendees of the San Antonio Breast Cancer Symposium what they found interesting at the meeting today.

IMNG Medical News reporter Michele Sullivan asks attendees of the San Antonio Breast Cancer Symposium what they found interesting at the meeting today.

IMNG Medical News reporter Michele Sullivan asks attendees of the San Antonio Breast Cancer Symposium what they found interesting at the meeting today.

SAN ANTONIO – Fulvestrant administered at 500 mg in women with locally advanced or metastatic breast cancer results in clinically meaningful improvement in survival without increased toxicity compared with the formerly standard monthly 250-mg dose, according to the final analysis of overall survival in the CONFIRM trial.

CONFIRM (Comparison of Faslodex in Recurrence of Metastatic Breast Cancer) was a phase III, randomized, double-blind clinical trial involving 736 postmenopausal women at 128 centers in 17 countries. All had estrogen receptor–positive locally advanced or metastatic disease. They were randomized to 250 mg of intramuscular fulvestrant (Faslodex) every 28 days, which was then the approved dose, or to 500 mg on days 0, 14, and 28 and every 28 days thereafter.

"Based on the results of the present trial, we believe that whenever fulvestrant is considered for the treatment of postmenopausal patients with estrogen receptor-positive advanced breast cancer, the recommended dose is 500 mg," Dr. Angelo Di Leo declared in presenting the CONFIRM update at the annual San Antonio Breast Cancer Symposium.

The final data confirm an earlier interim analysis (J. Clin. Oncol. 2010;28:4594-600), which also showed a survival advantage for the doubled dose. Observers commented that the new analysis provides clinicians with reassurance that the Food and Drug Administration was correct in 2010 when, on the strength of the interim CONFIRM analysis, the agency replaced the 250-mg dose with 500 mg as the approved dose.

The final overall survival analysis was performed when 75% of study participants had died. Fulvestrant at 500 mg was associated with a "clinically meaningful" 4.1-month increase in overall survival: 26.4 months as compared with 22.3 months in the 250-mg group (P = .016). This translated to a 19% reduction in the risk of death, said Dr. Di Leo, head of the department of medical oncology at the Tuscan Tumor Institute at the Hospital of Prato (Italy).

The safety findings were particularly striking. The high and low doses of fulvestrant were associated with similar rates of serious adverse events. There were five serious adverse events leading to death in the 500-mg group and seven in the 250-mg group. Coupled with the survival advantage, the safety data show "without any doubt" that 500 mg monthly is the correct dose, he noted in an interview with this publication.

The CONFIRM trial was sponsored by AstraZeneca. Dr. Di Leo reported that he serves as an adviser to the pharmaceutical company.

SAN ANTONIO – Fulvestrant administered at 500 mg in women with locally advanced or metastatic breast cancer results in clinically meaningful improvement in survival without increased toxicity compared with the formerly standard monthly 250-mg dose, according to the final analysis of overall survival in the CONFIRM trial.

CONFIRM (Comparison of Faslodex in Recurrence of Metastatic Breast Cancer) was a phase III, randomized, double-blind clinical trial involving 736 postmenopausal women at 128 centers in 17 countries. All had estrogen receptor–positive locally advanced or metastatic disease. They were randomized to 250 mg of intramuscular fulvestrant (Faslodex) every 28 days, which was then the approved dose, or to 500 mg on days 0, 14, and 28 and every 28 days thereafter.

"Based on the results of the present trial, we believe that whenever fulvestrant is considered for the treatment of postmenopausal patients with estrogen receptor-positive advanced breast cancer, the recommended dose is 500 mg," Dr. Angelo Di Leo declared in presenting the CONFIRM update at the annual San Antonio Breast Cancer Symposium.

The final data confirm an earlier interim analysis (J. Clin. Oncol. 2010;28:4594-600), which also showed a survival advantage for the doubled dose. Observers commented that the new analysis provides clinicians with reassurance that the Food and Drug Administration was correct in 2010 when, on the strength of the interim CONFIRM analysis, the agency replaced the 250-mg dose with 500 mg as the approved dose.

The final overall survival analysis was performed when 75% of study participants had died. Fulvestrant at 500 mg was associated with a "clinically meaningful" 4.1-month increase in overall survival: 26.4 months as compared with 22.3 months in the 250-mg group (P = .016). This translated to a 19% reduction in the risk of death, said Dr. Di Leo, head of the department of medical oncology at the Tuscan Tumor Institute at the Hospital of Prato (Italy).

The safety findings were particularly striking. The high and low doses of fulvestrant were associated with similar rates of serious adverse events. There were five serious adverse events leading to death in the 500-mg group and seven in the 250-mg group. Coupled with the survival advantage, the safety data show "without any doubt" that 500 mg monthly is the correct dose, he noted in an interview with this publication.

The CONFIRM trial was sponsored by AstraZeneca. Dr. Di Leo reported that he serves as an adviser to the pharmaceutical company.

SAN ANTONIO – Fulvestrant administered at 500 mg in women with locally advanced or metastatic breast cancer results in clinically meaningful improvement in survival without increased toxicity compared with the formerly standard monthly 250-mg dose, according to the final analysis of overall survival in the CONFIRM trial.

CONFIRM (Comparison of Faslodex in Recurrence of Metastatic Breast Cancer) was a phase III, randomized, double-blind clinical trial involving 736 postmenopausal women at 128 centers in 17 countries. All had estrogen receptor–positive locally advanced or metastatic disease. They were randomized to 250 mg of intramuscular fulvestrant (Faslodex) every 28 days, which was then the approved dose, or to 500 mg on days 0, 14, and 28 and every 28 days thereafter.

"Based on the results of the present trial, we believe that whenever fulvestrant is considered for the treatment of postmenopausal patients with estrogen receptor-positive advanced breast cancer, the recommended dose is 500 mg," Dr. Angelo Di Leo declared in presenting the CONFIRM update at the annual San Antonio Breast Cancer Symposium.

The final data confirm an earlier interim analysis (J. Clin. Oncol. 2010;28:4594-600), which also showed a survival advantage for the doubled dose. Observers commented that the new analysis provides clinicians with reassurance that the Food and Drug Administration was correct in 2010 when, on the strength of the interim CONFIRM analysis, the agency replaced the 250-mg dose with 500 mg as the approved dose.

The final overall survival analysis was performed when 75% of study participants had died. Fulvestrant at 500 mg was associated with a "clinically meaningful" 4.1-month increase in overall survival: 26.4 months as compared with 22.3 months in the 250-mg group (P = .016). This translated to a 19% reduction in the risk of death, said Dr. Di Leo, head of the department of medical oncology at the Tuscan Tumor Institute at the Hospital of Prato (Italy).

The safety findings were particularly striking. The high and low doses of fulvestrant were associated with similar rates of serious adverse events. There were five serious adverse events leading to death in the 500-mg group and seven in the 250-mg group. Coupled with the survival advantage, the safety data show "without any doubt" that 500 mg monthly is the correct dose, he noted in an interview with this publication.

The CONFIRM trial was sponsored by AstraZeneca. Dr. Di Leo reported that he serves as an adviser to the pharmaceutical company.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – An oral investigational agent that blocks cell cycle progression may expand treatment options for the most common type of breast cancer, the results of a randomized phase II trial suggest.

Combining the agent, called PD 0332991, with letrozole (Femara) as first-line therapy for advanced estrogen receptor (ER)-positive, HER2-negative disease more than tripled median progression-free survival, lead investigator Dr. Richard S. Finn reported at the San Antonio Breast Cancer Symposium.

The response rate also was better with the combination, but there were no complete responses.

PD 0332991 inhibits cyclin-dependent kinase 4/6, and thereby interferes with the action of the retinoblastoma (Rb) protein, arresting cells between the G1 and S phases of the cell cycle. Benefit appeared to be consistent regardless of the time to relapse, whether disease was recurrent or de novo, and irrespective of whether the tumor had cyclin D1 gene amplification or p16 gene loss (perturbations affecting the cell cycle).

There was an increase in grade 3/4 adverse events mainly driven by an increase in those of hematologic nature.

"PD 0332991 when added to letrozole provides a dramatic and unprecedented improvement in progression-free survival in this population," commented Dr. Finn of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

"These results confirm our observations made preclinically that PD 0332991 has activity in ER-positive breast cancer, as well as highlight the synergy that we observed in the laboratory. It is very important to remember that this molecule is well tolerated, that the toxicity profile was very manageable," he added.

On the basis of these positive findings, the investigators are planning a phase III trial that should open in 2013.

Many Questions for Investigator

The presentation drew comments and questions from breast cancer specialists in the audience.

Attendee Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center, New York, noted, "When one sees a disconnect between progression-free survival and response rate, one must think that maybe there is an effect on metastasis or new sites of disease. There’s two ways, obviously, that you can progress: in prior sites of disease vs. new sites of disease.

"Have you divided that out in this study, and are you having an antimetastatic effect?" he asked. "This pathway clearly relates to many mechanisms of metastasis."

"Certainly, that’s a potential mechanism," Dr. Finn replied. "We have not teased that out. I would say that if we are inducing cell cycle arrest and having a cytostatic effect, that could be having an effect in the metastatic sites or the measurable sites, regardless."

Another attendee noted that in such patients, letrozole monotherapy usually achieves a median progression-free survival on the order of 9.5 months, whereas the value in the trial was 7.5 months. "Why did the control arm do so badly?" he asked.

Dr. Finn noted that the values did not differ greatly, that the patient population was heterogeneous (including some who had previously received hormonal therapy), and that cross-trial comparisons are problematic. "Even with all that taken into consideration, the magnitude of benefit that we are seeing, even if the control arm did 9 or 11 or 12 months, this magnitude of benefit is so significant that this is clearly a signal that this molecule has a role in this disease," he maintained.

Dr. Frankie Ann Holmes of Texas Oncology in Houston, who also attended the session, wondered, "So if in all of the parameters you have studied, you couldn’t find a biomarker, do you have a hypothesis? Are you going to find a biomarker, or is it just such a big difference, we don’t really need to drill down?"

"We do have a biomarker: That biomarker is ER," Dr. Finn replied. "The most important genomic event that probably is related to sensitivity to this compound is having an intact Rb pathway. And it would appear that ER positivity is a marker for an intact Rb pathway and that explains part of the dramatic benefit that we are seeing."

Most Women Had Stage IV Disease

Women were eligible for the trial, formally known as TRIO-18, if they were postmenopausal and had previously untreated, locally recurrent or metastatic ER-positive, HER2-negative breast cancer.

The trial had two parts. In the first part, 66 otherwise unselected women were randomized evenly to the combination of PD 0332991 and letrozole or to letrozole alone. In the second, exploratory part, 99 patients also known to have cyclin D1 amplification and/or p16 loss were similarly randomized.

The women had a median age of 63 years, and most had stage IV disease. Roughly two-thirds had experienced their relapse within 12 months of adjuvant treatment or had de novo disease.

A first interim analysis, conducted in the unselected patient population and previously reported at the IMPAKT Breast Cancer Conference, showed that progression-free survival, the trial’s primary endpoint, was significantly better with the combination than with letrozole alone (hazard ratio, 0.35; P = .006).

A second interim analysis, conducted in the entire trial population and the one being reported in San Antonio, showed that median progression-free survival was 26.1 months with the combination versus 7.5 months with letrozole alone (hazard ratio, 0.37; P less than .001), according to Dr. Finn.

The combination was also associated with a better overall response rate both in the entire trial population (34% vs. 26%) and in the subset having measurable disease (45% vs. 31%).

Dose modifications were more common with addition of PD 0332991. The rate of treatment discontinuation because of adverse events was 10% with the combination vs. 1% with letrozole monotherapy.

Compared with monotherapy, the combination was associated with higher rates of grade 3/4 neutropenia (51% vs. 1%), leukopenia (14% vs. 0%), and anemia (5% vs. 0%).

However, "I need to stress that this was not clinically significant neutropenia," Dr. Finn commented. "There was no evidence of neutropenic fever, there was no use of growth factors in this study either."

Alopecia was more common with the combination as well, but all cases were of grade 1 severity.

Dr. Finn disclosed that he receives research from funding from Novartis Pharmaceuticals. The trial was sponsored by Pfizer.

SAN ANTONIO – An oral investigational agent that blocks cell cycle progression may expand treatment options for the most common type of breast cancer, the results of a randomized phase II trial suggest.

Combining the agent, called PD 0332991, with letrozole (Femara) as first-line therapy for advanced estrogen receptor (ER)-positive, HER2-negative disease more than tripled median progression-free survival, lead investigator Dr. Richard S. Finn reported at the San Antonio Breast Cancer Symposium.

The response rate also was better with the combination, but there were no complete responses.

PD 0332991 inhibits cyclin-dependent kinase 4/6, and thereby interferes with the action of the retinoblastoma (Rb) protein, arresting cells between the G1 and S phases of the cell cycle. Benefit appeared to be consistent regardless of the time to relapse, whether disease was recurrent or de novo, and irrespective of whether the tumor had cyclin D1 gene amplification or p16 gene loss (perturbations affecting the cell cycle).

There was an increase in grade 3/4 adverse events mainly driven by an increase in those of hematologic nature.

"PD 0332991 when added to letrozole provides a dramatic and unprecedented improvement in progression-free survival in this population," commented Dr. Finn of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

"These results confirm our observations made preclinically that PD 0332991 has activity in ER-positive breast cancer, as well as highlight the synergy that we observed in the laboratory. It is very important to remember that this molecule is well tolerated, that the toxicity profile was very manageable," he added.

On the basis of these positive findings, the investigators are planning a phase III trial that should open in 2013.

Many Questions for Investigator

The presentation drew comments and questions from breast cancer specialists in the audience.

Attendee Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center, New York, noted, "When one sees a disconnect between progression-free survival and response rate, one must think that maybe there is an effect on metastasis or new sites of disease. There’s two ways, obviously, that you can progress: in prior sites of disease vs. new sites of disease.

"Have you divided that out in this study, and are you having an antimetastatic effect?" he asked. "This pathway clearly relates to many mechanisms of metastasis."

"Certainly, that’s a potential mechanism," Dr. Finn replied. "We have not teased that out. I would say that if we are inducing cell cycle arrest and having a cytostatic effect, that could be having an effect in the metastatic sites or the measurable sites, regardless."

Another attendee noted that in such patients, letrozole monotherapy usually achieves a median progression-free survival on the order of 9.5 months, whereas the value in the trial was 7.5 months. "Why did the control arm do so badly?" he asked.

Dr. Finn noted that the values did not differ greatly, that the patient population was heterogeneous (including some who had previously received hormonal therapy), and that cross-trial comparisons are problematic. "Even with all that taken into consideration, the magnitude of benefit that we are seeing, even if the control arm did 9 or 11 or 12 months, this magnitude of benefit is so significant that this is clearly a signal that this molecule has a role in this disease," he maintained.

Dr. Frankie Ann Holmes of Texas Oncology in Houston, who also attended the session, wondered, "So if in all of the parameters you have studied, you couldn’t find a biomarker, do you have a hypothesis? Are you going to find a biomarker, or is it just such a big difference, we don’t really need to drill down?"

"We do have a biomarker: That biomarker is ER," Dr. Finn replied. "The most important genomic event that probably is related to sensitivity to this compound is having an intact Rb pathway. And it would appear that ER positivity is a marker for an intact Rb pathway and that explains part of the dramatic benefit that we are seeing."

Most Women Had Stage IV Disease

Women were eligible for the trial, formally known as TRIO-18, if they were postmenopausal and had previously untreated, locally recurrent or metastatic ER-positive, HER2-negative breast cancer.

The trial had two parts. In the first part, 66 otherwise unselected women were randomized evenly to the combination of PD 0332991 and letrozole or to letrozole alone. In the second, exploratory part, 99 patients also known to have cyclin D1 amplification and/or p16 loss were similarly randomized.

The women had a median age of 63 years, and most had stage IV disease. Roughly two-thirds had experienced their relapse within 12 months of adjuvant treatment or had de novo disease.

A first interim analysis, conducted in the unselected patient population and previously reported at the IMPAKT Breast Cancer Conference, showed that progression-free survival, the trial’s primary endpoint, was significantly better with the combination than with letrozole alone (hazard ratio, 0.35; P = .006).

A second interim analysis, conducted in the entire trial population and the one being reported in San Antonio, showed that median progression-free survival was 26.1 months with the combination versus 7.5 months with letrozole alone (hazard ratio, 0.37; P less than .001), according to Dr. Finn.

The combination was also associated with a better overall response rate both in the entire trial population (34% vs. 26%) and in the subset having measurable disease (45% vs. 31%).

Dose modifications were more common with addition of PD 0332991. The rate of treatment discontinuation because of adverse events was 10% with the combination vs. 1% with letrozole monotherapy.

Compared with monotherapy, the combination was associated with higher rates of grade 3/4 neutropenia (51% vs. 1%), leukopenia (14% vs. 0%), and anemia (5% vs. 0%).

However, "I need to stress that this was not clinically significant neutropenia," Dr. Finn commented. "There was no evidence of neutropenic fever, there was no use of growth factors in this study either."

Alopecia was more common with the combination as well, but all cases were of grade 1 severity.

Dr. Finn disclosed that he receives research from funding from Novartis Pharmaceuticals. The trial was sponsored by Pfizer.

SAN ANTONIO – An oral investigational agent that blocks cell cycle progression may expand treatment options for the most common type of breast cancer, the results of a randomized phase II trial suggest.

Combining the agent, called PD 0332991, with letrozole (Femara) as first-line therapy for advanced estrogen receptor (ER)-positive, HER2-negative disease more than tripled median progression-free survival, lead investigator Dr. Richard S. Finn reported at the San Antonio Breast Cancer Symposium.

The response rate also was better with the combination, but there were no complete responses.

PD 0332991 inhibits cyclin-dependent kinase 4/6, and thereby interferes with the action of the retinoblastoma (Rb) protein, arresting cells between the G1 and S phases of the cell cycle. Benefit appeared to be consistent regardless of the time to relapse, whether disease was recurrent or de novo, and irrespective of whether the tumor had cyclin D1 gene amplification or p16 gene loss (perturbations affecting the cell cycle).

There was an increase in grade 3/4 adverse events mainly driven by an increase in those of hematologic nature.

"PD 0332991 when added to letrozole provides a dramatic and unprecedented improvement in progression-free survival in this population," commented Dr. Finn of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

"These results confirm our observations made preclinically that PD 0332991 has activity in ER-positive breast cancer, as well as highlight the synergy that we observed in the laboratory. It is very important to remember that this molecule is well tolerated, that the toxicity profile was very manageable," he added.

On the basis of these positive findings, the investigators are planning a phase III trial that should open in 2013.

Many Questions for Investigator

The presentation drew comments and questions from breast cancer specialists in the audience.

Attendee Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center, New York, noted, "When one sees a disconnect between progression-free survival and response rate, one must think that maybe there is an effect on metastasis or new sites of disease. There’s two ways, obviously, that you can progress: in prior sites of disease vs. new sites of disease.

"Have you divided that out in this study, and are you having an antimetastatic effect?" he asked. "This pathway clearly relates to many mechanisms of metastasis."

"Certainly, that’s a potential mechanism," Dr. Finn replied. "We have not teased that out. I would say that if we are inducing cell cycle arrest and having a cytostatic effect, that could be having an effect in the metastatic sites or the measurable sites, regardless."

Another attendee noted that in such patients, letrozole monotherapy usually achieves a median progression-free survival on the order of 9.5 months, whereas the value in the trial was 7.5 months. "Why did the control arm do so badly?" he asked.

Dr. Finn noted that the values did not differ greatly, that the patient population was heterogeneous (including some who had previously received hormonal therapy), and that cross-trial comparisons are problematic. "Even with all that taken into consideration, the magnitude of benefit that we are seeing, even if the control arm did 9 or 11 or 12 months, this magnitude of benefit is so significant that this is clearly a signal that this molecule has a role in this disease," he maintained.

Dr. Frankie Ann Holmes of Texas Oncology in Houston, who also attended the session, wondered, "So if in all of the parameters you have studied, you couldn’t find a biomarker, do you have a hypothesis? Are you going to find a biomarker, or is it just such a big difference, we don’t really need to drill down?"

"We do have a biomarker: That biomarker is ER," Dr. Finn replied. "The most important genomic event that probably is related to sensitivity to this compound is having an intact Rb pathway. And it would appear that ER positivity is a marker for an intact Rb pathway and that explains part of the dramatic benefit that we are seeing."

Most Women Had Stage IV Disease

Women were eligible for the trial, formally known as TRIO-18, if they were postmenopausal and had previously untreated, locally recurrent or metastatic ER-positive, HER2-negative breast cancer.

The trial had two parts. In the first part, 66 otherwise unselected women were randomized evenly to the combination of PD 0332991 and letrozole or to letrozole alone. In the second, exploratory part, 99 patients also known to have cyclin D1 amplification and/or p16 loss were similarly randomized.

The women had a median age of 63 years, and most had stage IV disease. Roughly two-thirds had experienced their relapse within 12 months of adjuvant treatment or had de novo disease.

A first interim analysis, conducted in the unselected patient population and previously reported at the IMPAKT Breast Cancer Conference, showed that progression-free survival, the trial’s primary endpoint, was significantly better with the combination than with letrozole alone (hazard ratio, 0.35; P = .006).

A second interim analysis, conducted in the entire trial population and the one being reported in San Antonio, showed that median progression-free survival was 26.1 months with the combination versus 7.5 months with letrozole alone (hazard ratio, 0.37; P less than .001), according to Dr. Finn.

The combination was also associated with a better overall response rate both in the entire trial population (34% vs. 26%) and in the subset having measurable disease (45% vs. 31%).

Dose modifications were more common with addition of PD 0332991. The rate of treatment discontinuation because of adverse events was 10% with the combination vs. 1% with letrozole monotherapy.

Compared with monotherapy, the combination was associated with higher rates of grade 3/4 neutropenia (51% vs. 1%), leukopenia (14% vs. 0%), and anemia (5% vs. 0%).

However, "I need to stress that this was not clinically significant neutropenia," Dr. Finn commented. "There was no evidence of neutropenic fever, there was no use of growth factors in this study either."

Alopecia was more common with the combination as well, but all cases were of grade 1 severity.

Dr. Finn disclosed that he receives research from funding from Novartis Pharmaceuticals. The trial was sponsored by Pfizer.

Dr. Howard A. "Skip" Burris III, editor-in-chief of The Oncology Report, and associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss research highlights at the 2012 San Antonio Breast Cancer Symposium. The day-by-day conversation introduces new findings and how these experts apply the studies in their oncology practices.

The CONFIRM Trial
Fulvestrant: 250 mg vs. 500 mg

The ATLAS Trial
Tamoxifen: 5 years vs. 10 years

Dr. Howard A. "Skip" Burris III, editor-in-chief of The Oncology Report, and associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss research highlights at the 2012 San Antonio Breast Cancer Symposium. The day-by-day conversation introduces new findings and how these experts apply the studies in their oncology practices.

The CONFIRM Trial
Fulvestrant: 250 mg vs. 500 mg

The ATLAS Trial
Tamoxifen: 5 years vs. 10 years

Dr. Howard A. "Skip" Burris III, editor-in-chief of The Oncology Report, and associate editors Dr. William J. Gradishar and Dr. Hope S. Rugo discuss research highlights at the 2012 San Antonio Breast Cancer Symposium. The day-by-day conversation introduces new findings and how these experts apply the studies in their oncology practices.

The CONFIRM Trial
Fulvestrant: 250 mg vs. 500 mg

The ATLAS Trial
Tamoxifen: 5 years vs. 10 years

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.