Breast Cancer

SAN FRANCISCO – Injectable fulvestrant and oral anastrozole were the top picks for first-, second- and third-line treatment of metastatic breast cancer in women enrolled in Medicare Part D, based on a retrospective study of 681 women.

Total treatment costs averaged $102,000/patient, including costs for physicians, inpatient and outpatient care, hospice, skilled nursing, and durable medical equipment, reported Dr. Hope S. Rugo and her associates.

Their analysis updates a similar previous study that did not include data on oral medications. Thus, this study provides a more complete picture of treatment patterns and costs for patients with metastatic breast cancer. Oral medications now comprise three of the five most common first-, second- or third-line therapies in women who developed metastatic breast cancer, according to the researchers.

The investigators analyzed SEER (Surveillance Epidemiology and End Results) cancer registry data and Medicare data for 7,905 women who were diagnosed with breast cancer in 2001-2007 with concurrent or subsequent metastases and were enrolled in Medicare from 12 months prior to diagnosis through 2009 or death. Of these, 82% received first-line treatment. Data on oral therapies were available only for the 681 patients enrolled in Medicare Part D, the federal program that subsidizes the costs of prescription drugs for Medicare beneficiaries.

In the overall sample, 48% of the women went on to second-line therapy and 26% had third-line therapy. In the Part D subgroup, 63% went on to second-line therapy and 45% had third-line therapy, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The mean total cost per patient in the cohort as a whole was $127,000. Fulvestrant was the top choice for first-line therapy, used in 19%. Injectable vinorelbine was the most common second-line chemotherapy, used in 18% of those who got second-line treatment and in 16% of those who got third-line therapy, she reported in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The findings were similar to those from a previous report presented by another group of investigators at the 2011 Breast Cancer Symposium. Those researchers used SEER data on women diagnosed in 2001-2005 and enrolled in Medicare until 2008 or death. Fulvestrant was most common as first-line therapy and vinorelbine was most common for second- and third-line treatment. The mean per-patient cost in that study was $110,000.

In the current analysis of the 681 patients enrolled in Medicare Part D, fulvestrant still was the most common first-line treatment given to 9.1% of patients, but oral anastrozole was a close second at 8.7%. The next most common choices were oral letrozole (7%), any taxane drug (5%), and oral tamoxifen (4%).

Of the 427 patients in the Part D subgroup who got second-line therapy, 19% received fulvestrant, 9% got anastrozole, 8% got letrozole, 7% received vinorelbine, and 4% took tamoxifen.

For third-line treatment of 309 patients in the Part D subgroup, anastrozole and fulvestrant tied for top choice (11% each), tamoxifen or letrozole was used in 7% each, and vinorelbine was used in 6%.

The total costs per drug were highest for vinorelbine: a mean of $155,000 in second-line treatment and $134,000 in third-line treatment. In comparison, mean costs for the other top second-line therapies were $111,000 for fulvestrant, $106,000 for anastrozole, $108,000 for letrozole, and $107,000 for tamoxifen. Mean costs for other third-line treatments were $110,000 for anastrozole, $100,000 for fulvestrant, $101,000 for tamoxifen, and $71,000 for letrozole.

The study excluded patients with a history of other cancers before a diagnosis of breast cancer, patients who were not eligible for Medicare Part A or Part B benefits, patients enrolled in health maintenance organizations, and those who were first diagnosed with metastatic breast cancer at the time of death or autopsy.

The data did not identify disease progression, so the investigators used a published algorithm to identify the date of metastases. They also created an algorithm to identify first-, second- and third-line treatments in the data, based on factors such as the length of time before administering a new agent. These methods may have misclassified some treatments. Other limitations of the study include using Medicare data from 2001-2007, which may not reflect recent advances in treatment. SEER data cover just 28% of the U.S. population, and 90% of the study population was 65 years in age or older, so the cohort may not be representative of all patients with metastatic breast cancer.

The symposium was co-sponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Eisai funded the study and one of the investigators was an employee of the company. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Injectable fulvestrant and oral anastrozole were the top picks for first-, second- and third-line treatment of metastatic breast cancer in women enrolled in Medicare Part D, based on a retrospective study of 681 women.

Total treatment costs averaged $102,000/patient, including costs for physicians, inpatient and outpatient care, hospice, skilled nursing, and durable medical equipment, reported Dr. Hope S. Rugo and her associates.

Their analysis updates a similar previous study that did not include data on oral medications. Thus, this study provides a more complete picture of treatment patterns and costs for patients with metastatic breast cancer. Oral medications now comprise three of the five most common first-, second- or third-line therapies in women who developed metastatic breast cancer, according to the researchers.

The investigators analyzed SEER (Surveillance Epidemiology and End Results) cancer registry data and Medicare data for 7,905 women who were diagnosed with breast cancer in 2001-2007 with concurrent or subsequent metastases and were enrolled in Medicare from 12 months prior to diagnosis through 2009 or death. Of these, 82% received first-line treatment. Data on oral therapies were available only for the 681 patients enrolled in Medicare Part D, the federal program that subsidizes the costs of prescription drugs for Medicare beneficiaries.

In the overall sample, 48% of the women went on to second-line therapy and 26% had third-line therapy. In the Part D subgroup, 63% went on to second-line therapy and 45% had third-line therapy, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The mean total cost per patient in the cohort as a whole was $127,000. Fulvestrant was the top choice for first-line therapy, used in 19%. Injectable vinorelbine was the most common second-line chemotherapy, used in 18% of those who got second-line treatment and in 16% of those who got third-line therapy, she reported in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The findings were similar to those from a previous report presented by another group of investigators at the 2011 Breast Cancer Symposium. Those researchers used SEER data on women diagnosed in 2001-2005 and enrolled in Medicare until 2008 or death. Fulvestrant was most common as first-line therapy and vinorelbine was most common for second- and third-line treatment. The mean per-patient cost in that study was $110,000.

In the current analysis of the 681 patients enrolled in Medicare Part D, fulvestrant still was the most common first-line treatment given to 9.1% of patients, but oral anastrozole was a close second at 8.7%. The next most common choices were oral letrozole (7%), any taxane drug (5%), and oral tamoxifen (4%).

Of the 427 patients in the Part D subgroup who got second-line therapy, 19% received fulvestrant, 9% got anastrozole, 8% got letrozole, 7% received vinorelbine, and 4% took tamoxifen.

For third-line treatment of 309 patients in the Part D subgroup, anastrozole and fulvestrant tied for top choice (11% each), tamoxifen or letrozole was used in 7% each, and vinorelbine was used in 6%.

The total costs per drug were highest for vinorelbine: a mean of $155,000 in second-line treatment and $134,000 in third-line treatment. In comparison, mean costs for the other top second-line therapies were $111,000 for fulvestrant, $106,000 for anastrozole, $108,000 for letrozole, and $107,000 for tamoxifen. Mean costs for other third-line treatments were $110,000 for anastrozole, $100,000 for fulvestrant, $101,000 for tamoxifen, and $71,000 for letrozole.

The study excluded patients with a history of other cancers before a diagnosis of breast cancer, patients who were not eligible for Medicare Part A or Part B benefits, patients enrolled in health maintenance organizations, and those who were first diagnosed with metastatic breast cancer at the time of death or autopsy.

The data did not identify disease progression, so the investigators used a published algorithm to identify the date of metastases. They also created an algorithm to identify first-, second- and third-line treatments in the data, based on factors such as the length of time before administering a new agent. These methods may have misclassified some treatments. Other limitations of the study include using Medicare data from 2001-2007, which may not reflect recent advances in treatment. SEER data cover just 28% of the U.S. population, and 90% of the study population was 65 years in age or older, so the cohort may not be representative of all patients with metastatic breast cancer.

The symposium was co-sponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Eisai funded the study and one of the investigators was an employee of the company. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Injectable fulvestrant and oral anastrozole were the top picks for first-, second- and third-line treatment of metastatic breast cancer in women enrolled in Medicare Part D, based on a retrospective study of 681 women.

Total treatment costs averaged $102,000/patient, including costs for physicians, inpatient and outpatient care, hospice, skilled nursing, and durable medical equipment, reported Dr. Hope S. Rugo and her associates.

Their analysis updates a similar previous study that did not include data on oral medications. Thus, this study provides a more complete picture of treatment patterns and costs for patients with metastatic breast cancer. Oral medications now comprise three of the five most common first-, second- or third-line therapies in women who developed metastatic breast cancer, according to the researchers.

The investigators analyzed SEER (Surveillance Epidemiology and End Results) cancer registry data and Medicare data for 7,905 women who were diagnosed with breast cancer in 2001-2007 with concurrent or subsequent metastases and were enrolled in Medicare from 12 months prior to diagnosis through 2009 or death. Of these, 82% received first-line treatment. Data on oral therapies were available only for the 681 patients enrolled in Medicare Part D, the federal program that subsidizes the costs of prescription drugs for Medicare beneficiaries.

In the overall sample, 48% of the women went on to second-line therapy and 26% had third-line therapy. In the Part D subgroup, 63% went on to second-line therapy and 45% had third-line therapy, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The mean total cost per patient in the cohort as a whole was $127,000. Fulvestrant was the top choice for first-line therapy, used in 19%. Injectable vinorelbine was the most common second-line chemotherapy, used in 18% of those who got second-line treatment and in 16% of those who got third-line therapy, she reported in a poster presentation at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The findings were similar to those from a previous report presented by another group of investigators at the 2011 Breast Cancer Symposium. Those researchers used SEER data on women diagnosed in 2001-2005 and enrolled in Medicare until 2008 or death. Fulvestrant was most common as first-line therapy and vinorelbine was most common for second- and third-line treatment. The mean per-patient cost in that study was $110,000.

In the current analysis of the 681 patients enrolled in Medicare Part D, fulvestrant still was the most common first-line treatment given to 9.1% of patients, but oral anastrozole was a close second at 8.7%. The next most common choices were oral letrozole (7%), any taxane drug (5%), and oral tamoxifen (4%).

Of the 427 patients in the Part D subgroup who got second-line therapy, 19% received fulvestrant, 9% got anastrozole, 8% got letrozole, 7% received vinorelbine, and 4% took tamoxifen.

For third-line treatment of 309 patients in the Part D subgroup, anastrozole and fulvestrant tied for top choice (11% each), tamoxifen or letrozole was used in 7% each, and vinorelbine was used in 6%.

The total costs per drug were highest for vinorelbine: a mean of $155,000 in second-line treatment and $134,000 in third-line treatment. In comparison, mean costs for the other top second-line therapies were $111,000 for fulvestrant, $106,000 for anastrozole, $108,000 for letrozole, and $107,000 for tamoxifen. Mean costs for other third-line treatments were $110,000 for anastrozole, $100,000 for fulvestrant, $101,000 for tamoxifen, and $71,000 for letrozole.

The study excluded patients with a history of other cancers before a diagnosis of breast cancer, patients who were not eligible for Medicare Part A or Part B benefits, patients enrolled in health maintenance organizations, and those who were first diagnosed with metastatic breast cancer at the time of death or autopsy.

The data did not identify disease progression, so the investigators used a published algorithm to identify the date of metastases. They also created an algorithm to identify first-, second- and third-line treatments in the data, based on factors such as the length of time before administering a new agent. These methods may have misclassified some treatments. Other limitations of the study include using Medicare data from 2001-2007, which may not reflect recent advances in treatment. SEER data cover just 28% of the U.S. population, and 90% of the study population was 65 years in age or older, so the cohort may not be representative of all patients with metastatic breast cancer.

The symposium was co-sponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Eisai funded the study and one of the investigators was an employee of the company. Dr. Rugo reported having financial associations with Merck, Novartis, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – In patients who had hormone receptor–positive, HER2-negative advanced breast cancer, everolimus plus exemestane was just as effective among women who had a recurrence during or within a year of adjuvant therapy.

The results were seen in a secondary, subgroup analysis of 137 patients in the BOLERO-2 (Breast Cancer Trials of Oral Everolimus 2) study. The subset that had recurrences during or within a year of adjuvant therapy comprised 19% of the patients in the study, and their outcomes were similar to the overall results of the trial, which support the use of everolimus plus exemestane as first-line therapy in postmenopausal patients with hormone receptor–positive advanced breast cancer that recurs after adjuvant therapy, Dr. Hope S. Rugo and her associates reported in a poster session at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In the women who had a recurrence during or within 12 months of adjuvant therapy, everolimus plus exemestane improved median progression-free survival to 11.5 months, compared with 4.1 months with placebo plus exemestane.

The multicenter, double-blind BOLERO-2 study randomized 724 postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. Patients received open-label exemestane plus blinded therapy with either placebo or everolimus, which inhibits the mammalian target of rapamycin (mTOR) signaling pathway. At 18 months of follow-up, patients in the exemestane-plus-everolimus group had a significantly longer median progression-free survival of 11 months as compared to 4 months for the control group (N. Engl. J. Med. 2012;366:520-529).

Similar efficacy was found in various analyses of subgroups in the study, including patients with visceral metastases, patients with bone-only metastases, and patients whose disease recurred after adjuvant therapy.

In the subgroup analysis of patients who entered the study after a recurrence during or within a year of adjuvant therapy, 100 patients received everolimus plus exemestane and 37 received placebo and exemestane. Almost all of the 137 patients had received nonsteroidal aromatase inhibitor therapy as their last therapy before entering the BOLERO-2 trial.

The median progression-free survival rates of 11.5 months with the everolimus combination and 4.1 months with the placebo combination were based on investigators’ local radiologic assessments. Central radiologic assessment by an independent radiology committee confirmed these results, finding that median progression-free survival reached 15.2 months in the everolimus group, compared with 4.2 months in the placebo group. Hazard ratios were 0.39 under the local assessment and 0.32 under the central assessment, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

Rates of the most common grade 3 or 4 adverse events seen in the everolimus-plus-exemestane group in the subset analysis – hyperglycemia in 8%, stomatitis in 4%, diarrhea in 4%, and fatigue in 3% – were similar to rates seen in the overall BOLERO-2 population and were within the known safety profile of everolimus. Some patients in the everolimus group (but not the placebo group) developed pneumonitis or interstitial lung disease, but these were mostly low grade and manageable by conventional strategies.

Baseline characteristics were well balanced in the randomized groups in the subset analysis.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals, which markets everolimus, funded the study, and some of the investigators were company employees. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – In patients who had hormone receptor–positive, HER2-negative advanced breast cancer, everolimus plus exemestane was just as effective among women who had a recurrence during or within a year of adjuvant therapy.

The results were seen in a secondary, subgroup analysis of 137 patients in the BOLERO-2 (Breast Cancer Trials of Oral Everolimus 2) study. The subset that had recurrences during or within a year of adjuvant therapy comprised 19% of the patients in the study, and their outcomes were similar to the overall results of the trial, which support the use of everolimus plus exemestane as first-line therapy in postmenopausal patients with hormone receptor–positive advanced breast cancer that recurs after adjuvant therapy, Dr. Hope S. Rugo and her associates reported in a poster session at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In the women who had a recurrence during or within 12 months of adjuvant therapy, everolimus plus exemestane improved median progression-free survival to 11.5 months, compared with 4.1 months with placebo plus exemestane.

The multicenter, double-blind BOLERO-2 study randomized 724 postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. Patients received open-label exemestane plus blinded therapy with either placebo or everolimus, which inhibits the mammalian target of rapamycin (mTOR) signaling pathway. At 18 months of follow-up, patients in the exemestane-plus-everolimus group had a significantly longer median progression-free survival of 11 months as compared to 4 months for the control group (N. Engl. J. Med. 2012;366:520-529).

Similar efficacy was found in various analyses of subgroups in the study, including patients with visceral metastases, patients with bone-only metastases, and patients whose disease recurred after adjuvant therapy.

In the subgroup analysis of patients who entered the study after a recurrence during or within a year of adjuvant therapy, 100 patients received everolimus plus exemestane and 37 received placebo and exemestane. Almost all of the 137 patients had received nonsteroidal aromatase inhibitor therapy as their last therapy before entering the BOLERO-2 trial.

The median progression-free survival rates of 11.5 months with the everolimus combination and 4.1 months with the placebo combination were based on investigators’ local radiologic assessments. Central radiologic assessment by an independent radiology committee confirmed these results, finding that median progression-free survival reached 15.2 months in the everolimus group, compared with 4.2 months in the placebo group. Hazard ratios were 0.39 under the local assessment and 0.32 under the central assessment, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

Rates of the most common grade 3 or 4 adverse events seen in the everolimus-plus-exemestane group in the subset analysis – hyperglycemia in 8%, stomatitis in 4%, diarrhea in 4%, and fatigue in 3% – were similar to rates seen in the overall BOLERO-2 population and were within the known safety profile of everolimus. Some patients in the everolimus group (but not the placebo group) developed pneumonitis or interstitial lung disease, but these were mostly low grade and manageable by conventional strategies.

Baseline characteristics were well balanced in the randomized groups in the subset analysis.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals, which markets everolimus, funded the study, and some of the investigators were company employees. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – In patients who had hormone receptor–positive, HER2-negative advanced breast cancer, everolimus plus exemestane was just as effective among women who had a recurrence during or within a year of adjuvant therapy.

The results were seen in a secondary, subgroup analysis of 137 patients in the BOLERO-2 (Breast Cancer Trials of Oral Everolimus 2) study. The subset that had recurrences during or within a year of adjuvant therapy comprised 19% of the patients in the study, and their outcomes were similar to the overall results of the trial, which support the use of everolimus plus exemestane as first-line therapy in postmenopausal patients with hormone receptor–positive advanced breast cancer that recurs after adjuvant therapy, Dr. Hope S. Rugo and her associates reported in a poster session at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In the women who had a recurrence during or within 12 months of adjuvant therapy, everolimus plus exemestane improved median progression-free survival to 11.5 months, compared with 4.1 months with placebo plus exemestane.

The multicenter, double-blind BOLERO-2 study randomized 724 postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. Patients received open-label exemestane plus blinded therapy with either placebo or everolimus, which inhibits the mammalian target of rapamycin (mTOR) signaling pathway. At 18 months of follow-up, patients in the exemestane-plus-everolimus group had a significantly longer median progression-free survival of 11 months as compared to 4 months for the control group (N. Engl. J. Med. 2012;366:520-529).

Similar efficacy was found in various analyses of subgroups in the study, including patients with visceral metastases, patients with bone-only metastases, and patients whose disease recurred after adjuvant therapy.

In the subgroup analysis of patients who entered the study after a recurrence during or within a year of adjuvant therapy, 100 patients received everolimus plus exemestane and 37 received placebo and exemestane. Almost all of the 137 patients had received nonsteroidal aromatase inhibitor therapy as their last therapy before entering the BOLERO-2 trial.

The median progression-free survival rates of 11.5 months with the everolimus combination and 4.1 months with the placebo combination were based on investigators’ local radiologic assessments. Central radiologic assessment by an independent radiology committee confirmed these results, finding that median progression-free survival reached 15.2 months in the everolimus group, compared with 4.2 months in the placebo group. Hazard ratios were 0.39 under the local assessment and 0.32 under the central assessment, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

Rates of the most common grade 3 or 4 adverse events seen in the everolimus-plus-exemestane group in the subset analysis – hyperglycemia in 8%, stomatitis in 4%, diarrhea in 4%, and fatigue in 3% – were similar to rates seen in the overall BOLERO-2 population and were within the known safety profile of everolimus. Some patients in the everolimus group (but not the placebo group) developed pneumonitis or interstitial lung disease, but these were mostly low grade and manageable by conventional strategies.

Baseline characteristics were well balanced in the randomized groups in the subset analysis.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals, which markets everolimus, funded the study, and some of the investigators were company employees. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

ATLANTA – Five common radiation therapy practices are not adequately supported by evidence and may not be the best choice for many patients, radiation oncology experts said at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The evidence-based recommendations on radiation therapy for breast cancer, prostate cancer, and bone metastases are part of the national "Choosing Wisely" campaign, which is aimed at improving the quality of care by reducing or eliminating overuse of tests and procedures. This campaign is about "removal of waste to improve quality and safety, and doing no harm to patients," said Daniel Wolfson, executive vice president and chief operating officer of the American Board of Internal Medicine (ABIM) Foundation, which is leading the Choosing Wisely campaign.

Medical societies in various disciplines have released recommendations geared toward individual clinical disciplines, and now it’s ASTRO’s turn, said Dr. Michael L. Steinberg, chairman of ASTRO’s board of directors, in a briefing announcing the guidelines. "The list serves only as a starting point for a detailed conversation between a patient and physician, and to ensure patient-centered care, which is a core principle of ASTRO."

The five recommendations are:

• Don’t initiate whole-breast radiotherapy as a part of breast conservation therapy in women aged 50 years and older with early-stage invasive breast cancer without considering shorter treatment schedules.

"We’ve known for years that whole-breast radiation improves local control and improves survival, and has cosmetic advantages over mastectomy," Dr. Steinberg said. In recent years, however, randomized clinical trials have demonstrated that shorter courses of therapy – less than 4 weeks, compared with 5 weeks for conventionally fractionated radiation – produce equivalent tumor control and cosmetic outcomes.

• Don’t initiate management of patients who have low-risk prostate cancer without discussing active surveillance.

Patients with low-risk prostate cancer should discuss "reasonable management options" with their physicians, including active surveillance. With this recommendation, ASTRO is "reinforcing the shared decision-making model," Dr. Steinberg said.

• Don’t routinely use extended fractionation schemes (more than 10 fractions) for palliation of bone metastases.

Patients with bone metastases may derive equivalent pain relief from 30 Gy in 10 fractions, 20 Gy over 5 fractions, or even a single 8-Gy fraction, studies suggest. The single-fraction option is more convenient for patients, but it may be associated with a marginally higher need for retreatment of the same site. Patients who are not ambulatory, have transportation problems, or a limited prognosis may be good candidates for the single-fraction option, the guidelines say.

• Don’t routinely recommend proton-beam therapy for prostate cancer outside of a prospective clinical trial or registry.

"There is no clear evidence that proton-beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy," the Choosing Wisely guidelines state.

At ASTRO 2012, investigators reported that men who receive proton-beam radiotherapy for prostate cancer have modestly better bowel function in the short term than do those who receive conformal or intensity-modulated radiation, but the effect is transient. In addition, proton-beam therapy is estimated to cost about 70% more than external-beam radiotherapy for the treatment of prostate cancer.

• Don’t routinely use intensity-modulated radiation therapy (IMRT) to deliver whole-breast radiotherapy as part of breast conservation therapy.

"Clinical trials have suggested lower rates of skin toxicity after using modern 3D conformal techniques relative to older methods of 2D planning. In these trials, the term ‘IMRT’ has generally been applied to describe methods that are more accurately defined as field-in-field 3D conformal radiotherapy. While IMRT may be of benefit in select cases where the anatomy is unusual, its routine use has not been demonstrated to provide significant clinical advantage," the guidelines note.

The cost difference between 3D conformal radiotherapy and IMRT for whole-breast radiotherapy is approximately $7,000, according to Dr. Steinberg.

"These are not ‘never do this’ recommendations, these are ‘engage the patient in the shared-decision paradigm’ guidelines, because there may be patients that are better treated with, let’s say, IMRT [for whole-breast radiotherapy]," he said.

Asked whether the Choosing Wisely guidelines in radiation oncology and other disciplines might be used by insurers to justify denying reimbursement for certain procedures, Mr. Wolfson said that "we haven’t seen that, and whether it comes to be will be the question, but we would sharply criticize that [approach]."

ATLANTA – Five common radiation therapy practices are not adequately supported by evidence and may not be the best choice for many patients, radiation oncology experts said at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The evidence-based recommendations on radiation therapy for breast cancer, prostate cancer, and bone metastases are part of the national "Choosing Wisely" campaign, which is aimed at improving the quality of care by reducing or eliminating overuse of tests and procedures. This campaign is about "removal of waste to improve quality and safety, and doing no harm to patients," said Daniel Wolfson, executive vice president and chief operating officer of the American Board of Internal Medicine (ABIM) Foundation, which is leading the Choosing Wisely campaign.

Medical societies in various disciplines have released recommendations geared toward individual clinical disciplines, and now it’s ASTRO’s turn, said Dr. Michael L. Steinberg, chairman of ASTRO’s board of directors, in a briefing announcing the guidelines. "The list serves only as a starting point for a detailed conversation between a patient and physician, and to ensure patient-centered care, which is a core principle of ASTRO."

The five recommendations are:

• Don’t initiate whole-breast radiotherapy as a part of breast conservation therapy in women aged 50 years and older with early-stage invasive breast cancer without considering shorter treatment schedules.

"We’ve known for years that whole-breast radiation improves local control and improves survival, and has cosmetic advantages over mastectomy," Dr. Steinberg said. In recent years, however, randomized clinical trials have demonstrated that shorter courses of therapy – less than 4 weeks, compared with 5 weeks for conventionally fractionated radiation – produce equivalent tumor control and cosmetic outcomes.

• Don’t initiate management of patients who have low-risk prostate cancer without discussing active surveillance.

Patients with low-risk prostate cancer should discuss "reasonable management options" with their physicians, including active surveillance. With this recommendation, ASTRO is "reinforcing the shared decision-making model," Dr. Steinberg said.

• Don’t routinely use extended fractionation schemes (more than 10 fractions) for palliation of bone metastases.

Patients with bone metastases may derive equivalent pain relief from 30 Gy in 10 fractions, 20 Gy over 5 fractions, or even a single 8-Gy fraction, studies suggest. The single-fraction option is more convenient for patients, but it may be associated with a marginally higher need for retreatment of the same site. Patients who are not ambulatory, have transportation problems, or a limited prognosis may be good candidates for the single-fraction option, the guidelines say.

• Don’t routinely recommend proton-beam therapy for prostate cancer outside of a prospective clinical trial or registry.

"There is no clear evidence that proton-beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy," the Choosing Wisely guidelines state.

At ASTRO 2012, investigators reported that men who receive proton-beam radiotherapy for prostate cancer have modestly better bowel function in the short term than do those who receive conformal or intensity-modulated radiation, but the effect is transient. In addition, proton-beam therapy is estimated to cost about 70% more than external-beam radiotherapy for the treatment of prostate cancer.

• Don’t routinely use intensity-modulated radiation therapy (IMRT) to deliver whole-breast radiotherapy as part of breast conservation therapy.

"Clinical trials have suggested lower rates of skin toxicity after using modern 3D conformal techniques relative to older methods of 2D planning. In these trials, the term ‘IMRT’ has generally been applied to describe methods that are more accurately defined as field-in-field 3D conformal radiotherapy. While IMRT may be of benefit in select cases where the anatomy is unusual, its routine use has not been demonstrated to provide significant clinical advantage," the guidelines note.

The cost difference between 3D conformal radiotherapy and IMRT for whole-breast radiotherapy is approximately $7,000, according to Dr. Steinberg.

"These are not ‘never do this’ recommendations, these are ‘engage the patient in the shared-decision paradigm’ guidelines, because there may be patients that are better treated with, let’s say, IMRT [for whole-breast radiotherapy]," he said.

Asked whether the Choosing Wisely guidelines in radiation oncology and other disciplines might be used by insurers to justify denying reimbursement for certain procedures, Mr. Wolfson said that "we haven’t seen that, and whether it comes to be will be the question, but we would sharply criticize that [approach]."

ATLANTA – Five common radiation therapy practices are not adequately supported by evidence and may not be the best choice for many patients, radiation oncology experts said at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The evidence-based recommendations on radiation therapy for breast cancer, prostate cancer, and bone metastases are part of the national "Choosing Wisely" campaign, which is aimed at improving the quality of care by reducing or eliminating overuse of tests and procedures. This campaign is about "removal of waste to improve quality and safety, and doing no harm to patients," said Daniel Wolfson, executive vice president and chief operating officer of the American Board of Internal Medicine (ABIM) Foundation, which is leading the Choosing Wisely campaign.

Medical societies in various disciplines have released recommendations geared toward individual clinical disciplines, and now it’s ASTRO’s turn, said Dr. Michael L. Steinberg, chairman of ASTRO’s board of directors, in a briefing announcing the guidelines. "The list serves only as a starting point for a detailed conversation between a patient and physician, and to ensure patient-centered care, which is a core principle of ASTRO."

The five recommendations are:

• Don’t initiate whole-breast radiotherapy as a part of breast conservation therapy in women aged 50 years and older with early-stage invasive breast cancer without considering shorter treatment schedules.

"We’ve known for years that whole-breast radiation improves local control and improves survival, and has cosmetic advantages over mastectomy," Dr. Steinberg said. In recent years, however, randomized clinical trials have demonstrated that shorter courses of therapy – less than 4 weeks, compared with 5 weeks for conventionally fractionated radiation – produce equivalent tumor control and cosmetic outcomes.

• Don’t initiate management of patients who have low-risk prostate cancer without discussing active surveillance.

Patients with low-risk prostate cancer should discuss "reasonable management options" with their physicians, including active surveillance. With this recommendation, ASTRO is "reinforcing the shared decision-making model," Dr. Steinberg said.

• Don’t routinely use extended fractionation schemes (more than 10 fractions) for palliation of bone metastases.

Patients with bone metastases may derive equivalent pain relief from 30 Gy in 10 fractions, 20 Gy over 5 fractions, or even a single 8-Gy fraction, studies suggest. The single-fraction option is more convenient for patients, but it may be associated with a marginally higher need for retreatment of the same site. Patients who are not ambulatory, have transportation problems, or a limited prognosis may be good candidates for the single-fraction option, the guidelines say.

• Don’t routinely recommend proton-beam therapy for prostate cancer outside of a prospective clinical trial or registry.

"There is no clear evidence that proton-beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy," the Choosing Wisely guidelines state.

At ASTRO 2012, investigators reported that men who receive proton-beam radiotherapy for prostate cancer have modestly better bowel function in the short term than do those who receive conformal or intensity-modulated radiation, but the effect is transient. In addition, proton-beam therapy is estimated to cost about 70% more than external-beam radiotherapy for the treatment of prostate cancer.

• Don’t routinely use intensity-modulated radiation therapy (IMRT) to deliver whole-breast radiotherapy as part of breast conservation therapy.

"Clinical trials have suggested lower rates of skin toxicity after using modern 3D conformal techniques relative to older methods of 2D planning. In these trials, the term ‘IMRT’ has generally been applied to describe methods that are more accurately defined as field-in-field 3D conformal radiotherapy. While IMRT may be of benefit in select cases where the anatomy is unusual, its routine use has not been demonstrated to provide significant clinical advantage," the guidelines note.

The cost difference between 3D conformal radiotherapy and IMRT for whole-breast radiotherapy is approximately $7,000, according to Dr. Steinberg.

"These are not ‘never do this’ recommendations, these are ‘engage the patient in the shared-decision paradigm’ guidelines, because there may be patients that are better treated with, let’s say, IMRT [for whole-breast radiotherapy]," he said.

Asked whether the Choosing Wisely guidelines in radiation oncology and other disciplines might be used by insurers to justify denying reimbursement for certain procedures, Mr. Wolfson said that "we haven’t seen that, and whether it comes to be will be the question, but we would sharply criticize that [approach]."

SAN FRANCISCO – Among postmenopausal women with advanced hormone receptor–positive breast cancer, everolimus appeared to be more effective in the patients with one or no alterations in four key genes.

In a secondary analysis of data from the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2) study, one or no alterations in the PIK3CA; CCND1; FGFR1 and FGFR2 genes were seen in 76% of 227 tumor samples from women who took everolimus. These patients had significantly better progression-free survival than did patients with two or more alterations in these genes, Dr. Hope S. Rugo reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The number of patients with multiple gene alterations was admittedly small, but "potentially we have identified a population of patients who are less likely to benefit from everolimus," Dr. Rugo said.

She and her associates performed next-generation sequencing on DNA extracted tumor samples taken at diagnosis in BOLERO-2. Point mutations, short insertions or deletions, copy number alterations, or gene rearrangements were assessed in 219 tumors. Each tumor averaged 4 somatic mutations, with a range of 0-15 somatic mutations. Of the 182 genes sequenced, 104 had at least one known somatic mutation.

In the primary data analysis, all patients on everolimus had a 55% improvement in progression-free survival. In the secondary analysis of patients with minimal or no genetic alterations, 73% had an improvement in progression-free survival, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The genetic analysis found alterations in PIK3CA in 48% of samples, altered CCND1 in 31% of samples, altered P53 in 23%, and altered FGFR1 in 18%, so the researchers used these common alterations to seek predictors of treatment response. The four most commonly altered genes and the overall "tumor genetic landscape" in the current analysis were similar to those seen in previous large analyses such as The Cancer Genome Atlas Network (Nature 2012;490:61-70).

There was a hint that patients with alterations of FGFR1 or FGFR2 might be less likely to benefit from everolimus therapy. These numbers were small, however, and so the finding is only a hypothesis-generating observation, she said.

The sample group comprised approximately one-third of the cohort in BOLERO-2, the trial data that was the basis for the approval of everolimus. Baseline characteristics and outcomes were similar between the subgroup in the secondary analysis and the overall cohort.

The BOLERO-2 study comprised 724 postmenopausal women with advanced hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. The women were randomized to treatment with exemestane plus everolimus or placebo. At 18 months of follow-up, median progression-free survival was 11 months in the patients in the exemestane-plus-everolimus group, significantly longer than the 4-month median progression-free survival seen in the exemestane-plus-placebo group (N. Engl. J. Med. 2012;366:520-29).

As in other recent trials, most of the tumor samples for the genetic analysis were archived from the time of initial diagnosis rather than after metastasis. "Although the impact on the results shown here is unknown, we do know that additional mutations in these pathways are acquired with metastatic progression," Dr. Rugo said. "I think it’s important for all of us to try to obtain metastatic tumor tissue for these analyses moving forward."

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals Corp., which markets everolimus (Afinitor), funded the study. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Among postmenopausal women with advanced hormone receptor–positive breast cancer, everolimus appeared to be more effective in the patients with one or no alterations in four key genes.

In a secondary analysis of data from the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2) study, one or no alterations in the PIK3CA; CCND1; FGFR1 and FGFR2 genes were seen in 76% of 227 tumor samples from women who took everolimus. These patients had significantly better progression-free survival than did patients with two or more alterations in these genes, Dr. Hope S. Rugo reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The number of patients with multiple gene alterations was admittedly small, but "potentially we have identified a population of patients who are less likely to benefit from everolimus," Dr. Rugo said.

She and her associates performed next-generation sequencing on DNA extracted tumor samples taken at diagnosis in BOLERO-2. Point mutations, short insertions or deletions, copy number alterations, or gene rearrangements were assessed in 219 tumors. Each tumor averaged 4 somatic mutations, with a range of 0-15 somatic mutations. Of the 182 genes sequenced, 104 had at least one known somatic mutation.

In the primary data analysis, all patients on everolimus had a 55% improvement in progression-free survival. In the secondary analysis of patients with minimal or no genetic alterations, 73% had an improvement in progression-free survival, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The genetic analysis found alterations in PIK3CA in 48% of samples, altered CCND1 in 31% of samples, altered P53 in 23%, and altered FGFR1 in 18%, so the researchers used these common alterations to seek predictors of treatment response. The four most commonly altered genes and the overall "tumor genetic landscape" in the current analysis were similar to those seen in previous large analyses such as The Cancer Genome Atlas Network (Nature 2012;490:61-70).

There was a hint that patients with alterations of FGFR1 or FGFR2 might be less likely to benefit from everolimus therapy. These numbers were small, however, and so the finding is only a hypothesis-generating observation, she said.

The sample group comprised approximately one-third of the cohort in BOLERO-2, the trial data that was the basis for the approval of everolimus. Baseline characteristics and outcomes were similar between the subgroup in the secondary analysis and the overall cohort.

The BOLERO-2 study comprised 724 postmenopausal women with advanced hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. The women were randomized to treatment with exemestane plus everolimus or placebo. At 18 months of follow-up, median progression-free survival was 11 months in the patients in the exemestane-plus-everolimus group, significantly longer than the 4-month median progression-free survival seen in the exemestane-plus-placebo group (N. Engl. J. Med. 2012;366:520-29).

As in other recent trials, most of the tumor samples for the genetic analysis were archived from the time of initial diagnosis rather than after metastasis. "Although the impact on the results shown here is unknown, we do know that additional mutations in these pathways are acquired with metastatic progression," Dr. Rugo said. "I think it’s important for all of us to try to obtain metastatic tumor tissue for these analyses moving forward."

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals Corp., which markets everolimus (Afinitor), funded the study. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Among postmenopausal women with advanced hormone receptor–positive breast cancer, everolimus appeared to be more effective in the patients with one or no alterations in four key genes.

In a secondary analysis of data from the Breast Cancer Trials of Oral Everolimus–2 (BOLERO-2) study, one or no alterations in the PIK3CA; CCND1; FGFR1 and FGFR2 genes were seen in 76% of 227 tumor samples from women who took everolimus. These patients had significantly better progression-free survival than did patients with two or more alterations in these genes, Dr. Hope S. Rugo reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The number of patients with multiple gene alterations was admittedly small, but "potentially we have identified a population of patients who are less likely to benefit from everolimus," Dr. Rugo said.

She and her associates performed next-generation sequencing on DNA extracted tumor samples taken at diagnosis in BOLERO-2. Point mutations, short insertions or deletions, copy number alterations, or gene rearrangements were assessed in 219 tumors. Each tumor averaged 4 somatic mutations, with a range of 0-15 somatic mutations. Of the 182 genes sequenced, 104 had at least one known somatic mutation.

In the primary data analysis, all patients on everolimus had a 55% improvement in progression-free survival. In the secondary analysis of patients with minimal or no genetic alterations, 73% had an improvement in progression-free survival, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.

The genetic analysis found alterations in PIK3CA in 48% of samples, altered CCND1 in 31% of samples, altered P53 in 23%, and altered FGFR1 in 18%, so the researchers used these common alterations to seek predictors of treatment response. The four most commonly altered genes and the overall "tumor genetic landscape" in the current analysis were similar to those seen in previous large analyses such as The Cancer Genome Atlas Network (Nature 2012;490:61-70).

There was a hint that patients with alterations of FGFR1 or FGFR2 might be less likely to benefit from everolimus therapy. These numbers were small, however, and so the finding is only a hypothesis-generating observation, she said.

The sample group comprised approximately one-third of the cohort in BOLERO-2, the trial data that was the basis for the approval of everolimus. Baseline characteristics and outcomes were similar between the subgroup in the secondary analysis and the overall cohort.

The BOLERO-2 study comprised 724 postmenopausal women with advanced hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. The women were randomized to treatment with exemestane plus everolimus or placebo. At 18 months of follow-up, median progression-free survival was 11 months in the patients in the exemestane-plus-everolimus group, significantly longer than the 4-month median progression-free survival seen in the exemestane-plus-placebo group (N. Engl. J. Med. 2012;366:520-29).

As in other recent trials, most of the tumor samples for the genetic analysis were archived from the time of initial diagnosis rather than after metastasis. "Although the impact on the results shown here is unknown, we do know that additional mutations in these pathways are acquired with metastatic progression," Dr. Rugo said. "I think it’s important for all of us to try to obtain metastatic tumor tissue for these analyses moving forward."

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Novartis Pharmaceuticals Corp., which markets everolimus (Afinitor), funded the study. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

The U.S. Preventive Services Task Force has issued updated recommendations on the use of chemoprevention for breast cancer that emphasize the need for informed, shared decision-making.

"It’s a complicated decision, and there are a lot of moving parts, if you will," USPSTF member Dr. Mark Ebell said in an interview.

New research since the original 2002 guidance, including updates from the pivotal STAR trial (Cancer Prev. Res. 2010;3:696-706) and a recent meta-analysis of risk-reducing medications (Ann. Intern. Med. 2013;158:604-14), have helped clarify the balance of benefits and harms by a woman’s age, breast cancer risk, race, and whether she’s had a hysterectomy.

Alexander Raths/Fotolia.com

The 2013 guidelines, published in Annals of Internal Medicine, plug those data into a series of tables that present the net benefit as stratified by those risk factors. For example, Table 1 is for white, non-Hispanic women who have a uterus.

"So, you’d go there, look up [the patient’s] 5-year projected risk, look up [the patient’s] age, and it provides a general color-coded assessment of whether there are more risks or harms," Dr. Ebell said. "It’s a tough decision, and two women with similar risk factors may make different decisions, and that’s perfectly okay. Everyone’s different; everyone assesses risk differently and has different values. We just wanted to make sure they have the best possible information when they make their decision."

Both the original and updated versions carry the same overall recommendation: Women who are at an average or low risk should not use chemoprevention, while women at high risk should consider therapy if they don’t have any contraindications.

The 2013 recommendations are trying, however, to be a bit more explicit about which medications have been approved by the Food and Drug Administration (FDA) for breast cancer chemoprevention, said Dr. Ebell, a family physician with the College of Public Health, University of Georgia, Athens.

The USPSTF recommends the use of the selective estrogen receptor modulators tamoxifen and raloxifene (Evista) to reduce the incidence of invasive breast cancer in asymptomatic women aged 35 years and older who are without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ and who are at increased risk of breast cancer. The daily doses are 20 mg and 60 mg, respectively, for 5 years.

Tamoxifen is FDA approved for this use in women aged 35 years and older, while raloxifene is approved for this indication in postmenopausal women.

In a draft version of the guidance released this April, the target audience for the recommendation was asymptomatic women aged 40 years and older, but the age limit was lowered to 35 years in the final version because the Breast Cancer Prevention Trial enrolled women over age 35, Dr. Ebell said.

Notably absent in the new guidelines is an endorsement of the aromatase inhibitor exemestane (Aromasin). Updated chemoprevention guidelines issued earlier this year by the American Society of Clinical Oncology recommend that exemestane be discussed as an alternative to reduce the risk of invasive, estrogen receptor–positive breast cancer in postmenopausal women (J. Clin. Onc. 2013;31:2942-62).

The task force only considers FDA-approved medications for the indication of breast cancer chemoprevention, and exemestane is only approved for breast cancer treatment, Dr. Ebell explained.

The aromatase inhibitor anastrozole (Arimidex) is not recommended by either ASCO or the USPSTF, with data awaited from the ongoing phase III, placebo-controlled British IBIS II (Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer) study.

Dr. Joanna Cain, professor of obstetrics/gynecology at the University of Massachusetts, Worcester, said the task force made the decision regarding exemestane on the basis of the present evidence.

"UPSTF has a level of standards that exemestane does not yet meet, while ASCO is willing to move with less evidence," she said in an interview. "They are not ruling it out but saying by their criteria, it does not yet meet this. Having said all that, if a patient is intolerant of tamoxifen and raloxifene and needs chemopreventive therapy, we would consider using exemestane as an alternative."

Dr. Cain noted that she welcomes the 2013 guidance, particularly the appropriate caution about individual patient risks for these medications such as age, venous thrombosis, and endometrial cancer, which also includes the risk conferred by obesity and genetics such as Lynch syndrome.

"In particular, the clarity around benefit, and therefore, use only for those at increased risk, is helpful," she said.

The use of risk-reducing medications is quite low, but that’s because only about 5% of women are really appropriate candidates and only a minority of these actually take the medication, Dr. Ebell said.

Just 12% of high-risk women opted to take tamoxifen to reduce their risk for breast cancer in a national survey highlighted by the task force, with 77% of women declining primarily because of concerns about serious adverse events and small therapeutic benefit (Arch. Intern. Med. 2006;166:2260-5).

Further, only 27% of the 350 primary care physicians surveyed had prescribed tamoxifen for breast cancer prevention at least once in the prior 12 months.

"We do need to engage the primary care community more broadly, not just ob.gyns., in this informed decision-making and make sure they are comfortable and confident when they have a patient with questions about chemoprevention," Dr. Ebell said.

Dr. Ebell reported having no financial disclosures.

pwendling@frontlinemedcom.com

The U.S. Preventive Services Task Force has issued updated recommendations on the use of chemoprevention for breast cancer that emphasize the need for informed, shared decision-making.

"It’s a complicated decision, and there are a lot of moving parts, if you will," USPSTF member Dr. Mark Ebell said in an interview.

New research since the original 2002 guidance, including updates from the pivotal STAR trial (Cancer Prev. Res. 2010;3:696-706) and a recent meta-analysis of risk-reducing medications (Ann. Intern. Med. 2013;158:604-14), have helped clarify the balance of benefits and harms by a woman’s age, breast cancer risk, race, and whether she’s had a hysterectomy.

Alexander Raths/Fotolia.com

The 2013 guidelines, published in Annals of Internal Medicine, plug those data into a series of tables that present the net benefit as stratified by those risk factors. For example, Table 1 is for white, non-Hispanic women who have a uterus.

"So, you’d go there, look up [the patient’s] 5-year projected risk, look up [the patient’s] age, and it provides a general color-coded assessment of whether there are more risks or harms," Dr. Ebell said. "It’s a tough decision, and two women with similar risk factors may make different decisions, and that’s perfectly okay. Everyone’s different; everyone assesses risk differently and has different values. We just wanted to make sure they have the best possible information when they make their decision."

Both the original and updated versions carry the same overall recommendation: Women who are at an average or low risk should not use chemoprevention, while women at high risk should consider therapy if they don’t have any contraindications.

The 2013 recommendations are trying, however, to be a bit more explicit about which medications have been approved by the Food and Drug Administration (FDA) for breast cancer chemoprevention, said Dr. Ebell, a family physician with the College of Public Health, University of Georgia, Athens.

The USPSTF recommends the use of the selective estrogen receptor modulators tamoxifen and raloxifene (Evista) to reduce the incidence of invasive breast cancer in asymptomatic women aged 35 years and older who are without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ and who are at increased risk of breast cancer. The daily doses are 20 mg and 60 mg, respectively, for 5 years.

Tamoxifen is FDA approved for this use in women aged 35 years and older, while raloxifene is approved for this indication in postmenopausal women.

In a draft version of the guidance released this April, the target audience for the recommendation was asymptomatic women aged 40 years and older, but the age limit was lowered to 35 years in the final version because the Breast Cancer Prevention Trial enrolled women over age 35, Dr. Ebell said.

Notably absent in the new guidelines is an endorsement of the aromatase inhibitor exemestane (Aromasin). Updated chemoprevention guidelines issued earlier this year by the American Society of Clinical Oncology recommend that exemestane be discussed as an alternative to reduce the risk of invasive, estrogen receptor–positive breast cancer in postmenopausal women (J. Clin. Onc. 2013;31:2942-62).

The task force only considers FDA-approved medications for the indication of breast cancer chemoprevention, and exemestane is only approved for breast cancer treatment, Dr. Ebell explained.

The aromatase inhibitor anastrozole (Arimidex) is not recommended by either ASCO or the USPSTF, with data awaited from the ongoing phase III, placebo-controlled British IBIS II (Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer) study.

Dr. Joanna Cain, professor of obstetrics/gynecology at the University of Massachusetts, Worcester, said the task force made the decision regarding exemestane on the basis of the present evidence.

"UPSTF has a level of standards that exemestane does not yet meet, while ASCO is willing to move with less evidence," she said in an interview. "They are not ruling it out but saying by their criteria, it does not yet meet this. Having said all that, if a patient is intolerant of tamoxifen and raloxifene and needs chemopreventive therapy, we would consider using exemestane as an alternative."

Dr. Cain noted that she welcomes the 2013 guidance, particularly the appropriate caution about individual patient risks for these medications such as age, venous thrombosis, and endometrial cancer, which also includes the risk conferred by obesity and genetics such as Lynch syndrome.

"In particular, the clarity around benefit, and therefore, use only for those at increased risk, is helpful," she said.

The use of risk-reducing medications is quite low, but that’s because only about 5% of women are really appropriate candidates and only a minority of these actually take the medication, Dr. Ebell said.

Just 12% of high-risk women opted to take tamoxifen to reduce their risk for breast cancer in a national survey highlighted by the task force, with 77% of women declining primarily because of concerns about serious adverse events and small therapeutic benefit (Arch. Intern. Med. 2006;166:2260-5).

Further, only 27% of the 350 primary care physicians surveyed had prescribed tamoxifen for breast cancer prevention at least once in the prior 12 months.

"We do need to engage the primary care community more broadly, not just ob.gyns., in this informed decision-making and make sure they are comfortable and confident when they have a patient with questions about chemoprevention," Dr. Ebell said.

Dr. Ebell reported having no financial disclosures.

pwendling@frontlinemedcom.com

The U.S. Preventive Services Task Force has issued updated recommendations on the use of chemoprevention for breast cancer that emphasize the need for informed, shared decision-making.

"It’s a complicated decision, and there are a lot of moving parts, if you will," USPSTF member Dr. Mark Ebell said in an interview.

New research since the original 2002 guidance, including updates from the pivotal STAR trial (Cancer Prev. Res. 2010;3:696-706) and a recent meta-analysis of risk-reducing medications (Ann. Intern. Med. 2013;158:604-14), have helped clarify the balance of benefits and harms by a woman’s age, breast cancer risk, race, and whether she’s had a hysterectomy.

Alexander Raths/Fotolia.com

The 2013 guidelines, published in Annals of Internal Medicine, plug those data into a series of tables that present the net benefit as stratified by those risk factors. For example, Table 1 is for white, non-Hispanic women who have a uterus.

"So, you’d go there, look up [the patient’s] 5-year projected risk, look up [the patient’s] age, and it provides a general color-coded assessment of whether there are more risks or harms," Dr. Ebell said. "It’s a tough decision, and two women with similar risk factors may make different decisions, and that’s perfectly okay. Everyone’s different; everyone assesses risk differently and has different values. We just wanted to make sure they have the best possible information when they make their decision."

Both the original and updated versions carry the same overall recommendation: Women who are at an average or low risk should not use chemoprevention, while women at high risk should consider therapy if they don’t have any contraindications.

The 2013 recommendations are trying, however, to be a bit more explicit about which medications have been approved by the Food and Drug Administration (FDA) for breast cancer chemoprevention, said Dr. Ebell, a family physician with the College of Public Health, University of Georgia, Athens.

The USPSTF recommends the use of the selective estrogen receptor modulators tamoxifen and raloxifene (Evista) to reduce the incidence of invasive breast cancer in asymptomatic women aged 35 years and older who are without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ and who are at increased risk of breast cancer. The daily doses are 20 mg and 60 mg, respectively, for 5 years.

Tamoxifen is FDA approved for this use in women aged 35 years and older, while raloxifene is approved for this indication in postmenopausal women.

In a draft version of the guidance released this April, the target audience for the recommendation was asymptomatic women aged 40 years and older, but the age limit was lowered to 35 years in the final version because the Breast Cancer Prevention Trial enrolled women over age 35, Dr. Ebell said.

Notably absent in the new guidelines is an endorsement of the aromatase inhibitor exemestane (Aromasin). Updated chemoprevention guidelines issued earlier this year by the American Society of Clinical Oncology recommend that exemestane be discussed as an alternative to reduce the risk of invasive, estrogen receptor–positive breast cancer in postmenopausal women (J. Clin. Onc. 2013;31:2942-62).

The task force only considers FDA-approved medications for the indication of breast cancer chemoprevention, and exemestane is only approved for breast cancer treatment, Dr. Ebell explained.

The aromatase inhibitor anastrozole (Arimidex) is not recommended by either ASCO or the USPSTF, with data awaited from the ongoing phase III, placebo-controlled British IBIS II (Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer) study.

Dr. Joanna Cain, professor of obstetrics/gynecology at the University of Massachusetts, Worcester, said the task force made the decision regarding exemestane on the basis of the present evidence.

"UPSTF has a level of standards that exemestane does not yet meet, while ASCO is willing to move with less evidence," she said in an interview. "They are not ruling it out but saying by their criteria, it does not yet meet this. Having said all that, if a patient is intolerant of tamoxifen and raloxifene and needs chemopreventive therapy, we would consider using exemestane as an alternative."

Dr. Cain noted that she welcomes the 2013 guidance, particularly the appropriate caution about individual patient risks for these medications such as age, venous thrombosis, and endometrial cancer, which also includes the risk conferred by obesity and genetics such as Lynch syndrome.

"In particular, the clarity around benefit, and therefore, use only for those at increased risk, is helpful," she said.

The use of risk-reducing medications is quite low, but that’s because only about 5% of women are really appropriate candidates and only a minority of these actually take the medication, Dr. Ebell said.

Just 12% of high-risk women opted to take tamoxifen to reduce their risk for breast cancer in a national survey highlighted by the task force, with 77% of women declining primarily because of concerns about serious adverse events and small therapeutic benefit (Arch. Intern. Med. 2006;166:2260-5).

Further, only 27% of the 350 primary care physicians surveyed had prescribed tamoxifen for breast cancer prevention at least once in the prior 12 months.

"We do need to engage the primary care community more broadly, not just ob.gyns., in this informed decision-making and make sure they are comfortable and confident when they have a patient with questions about chemoprevention," Dr. Ebell said.

Dr. Ebell reported having no financial disclosures.

pwendling@frontlinemedcom.com

SAN FRANCISCO – A change in the status of any breast cancer tumor biomarker after neoadjuvant therapy was independently associated with a 37% decreased likelihood of recurrence in 5 years, a multivariate analysis showed.

The subtyping of breast cancer by receptor status changed in 41% of 398 samples between the initial tumor and residual disease after neoadjuvant chemotherapy.

In patients with any change in the status of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), after neoadjuvant chemotherapy, 63% were relapse free 5 years later as compared with 48% of patients with no receptor change, a significant difference.

Overall survival at 5 years, however, did not differ significantly based on receptor status change, Dr. Napa Parinyanitikul and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology. At 5 years, 73% of patients with a receptor status change and 63% with no change were alive.

The study analyzed data on patients treated at her institution in 1992-2012 who had tumor biomarker results from pretreatment biopsies and from samples of residual disease after neoadjuvant chemotherapy. Most patients in the study were white, with clinical stage II or III disease.

Of the tumors, 49% were hormone receptor–positive and HER2 negative; 18% were HER2 positive, and 33% were negative for all three receptors (triple-negative breast cancer). Neoadjuvant chemotherapy consisted of a taxane-based regimen in 10%, an anthracycline-based regimen in 19%, an anthracycline/taxane-based regimen in 71%, and trastuzumab-based chemotherapy in 49%. The 88% of patients with hormone receptor-positive disease received adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor.

After a median of 40 months of follow-up, 32% of women had died and 42% had a recurrence of breast cancer, reported Dr. Parinyanitikul, a fellow at the University of Texas MD Anderson Cancer Center, Houston.

The likelihood of receptor status changes differed significantly by the subtype of breast cancer. Of hormone receptor–positive cancers, 51% had a change in receptor status, compared with 27% of HER2-positive cancers and 22% of triple-negative breast cancers.

Other factors did not significantly affect the likelihood of receptor status change, including patient age or race, histology, tumor stage or grade, the presence of lymphovascular invasion, or the class of neoadjuvant chemotherapeutic agents.

Of ER-positive tumors, 11% changed to ER negative after neoadjuvant chemotherapy; of ER-negative tumors, 21% changed to ER positive. Of the PR-positive tumors, 35% changed to PR-negative; of PR-negative tumors, 12% changed to PR positive. Of HER2-positive tumors, 40% changed to HER2 negative; of HER2-negative tumors, 3% changed to HER2 positive. Among 35 patients treated with trastuzumab, the HER2 status changed in 16 (46%).

Patients who had tumors with an ER-negative status that did not change had the worst 5-year rates for overall survival (47%) and relapse-free survival (40%), compared with patients whose tumors had an ER-positive status did not change (81% overall survival and 63% relapse-free survival), patients whose ER status changed from positive to negative (67% and 66% survival rates, respectively), and patients whose ER status changed from negative to positive (75% and 59%, respectively).

Similarly, patients who had PR-negative tumors whose status did not change had significantly lower rates of overall survival (51%) and relapse-free survival (41%), compared with patients whose PR-positive tumor status did not change (87% and 67%, respectively), those who changed from PR positive to PR negative (78% and 73%, respectively), and patients whose PR-negative status changed to PR positive (69% and 55%, respectively).

Changes or lack of change in HER2 subgroups were not significantly associated with varying outcomes.

The investigators also looked at the absolute percent changes in ER or PR status using cutoffs in 10% increments from 10% to 50%. The 5-year overall survival rate was significantly greater in ER-positive patients who had at least a 20% change in ER status, compared with those with less than a 20% change (87% vs. 73%, respectively). The 5-year relapse-free survival rate also was significantly greater if the ER status changed by at least 20% (71%), compared with smaller ER changes (59%).

Of cancers that were hormone receptor–positive and HER2 negative before neoadjuvant chemotherapy, 20% changed to HER2-positive or triple-negative breast cancer after treatment, 12% of tumors that had been HER2 positive changed to triple negative tumors, and 2% of triple negative breast cancers changed to HER2-positive after treatment. These changes produced only one significant effect on outcomes: 5-year overall survival rates were significantly lower in patients who changed from HER2-positive to triple-negative breast cancer (23%), compared with those whose HER2-positive cancer did not change to triple negative (71%).

Larger prospective studies are needed to confirm the findings and to determine any impact of biomarker changes on long-term survival, she said.

Previous studies have reported discordance in hormone receptor status in up to 51% of breast cancers between the primary tumor and residual disease and changes in HER2 status in up to 43% of cases. Conclusions about associations between changes in receptor status and clinical outcomes have been inconsistent.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Parinyanitikul reported having no financial disclosures.

sherryboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – A change in the status of any breast cancer tumor biomarker after neoadjuvant therapy was independently associated with a 37% decreased likelihood of recurrence in 5 years, a multivariate analysis showed.

The subtyping of breast cancer by receptor status changed in 41% of 398 samples between the initial tumor and residual disease after neoadjuvant chemotherapy.

In patients with any change in the status of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), after neoadjuvant chemotherapy, 63% were relapse free 5 years later as compared with 48% of patients with no receptor change, a significant difference.

Overall survival at 5 years, however, did not differ significantly based on receptor status change, Dr. Napa Parinyanitikul and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology. At 5 years, 73% of patients with a receptor status change and 63% with no change were alive.

The study analyzed data on patients treated at her institution in 1992-2012 who had tumor biomarker results from pretreatment biopsies and from samples of residual disease after neoadjuvant chemotherapy. Most patients in the study were white, with clinical stage II or III disease.

Of the tumors, 49% were hormone receptor–positive and HER2 negative; 18% were HER2 positive, and 33% were negative for all three receptors (triple-negative breast cancer). Neoadjuvant chemotherapy consisted of a taxane-based regimen in 10%, an anthracycline-based regimen in 19%, an anthracycline/taxane-based regimen in 71%, and trastuzumab-based chemotherapy in 49%. The 88% of patients with hormone receptor-positive disease received adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor.

After a median of 40 months of follow-up, 32% of women had died and 42% had a recurrence of breast cancer, reported Dr. Parinyanitikul, a fellow at the University of Texas MD Anderson Cancer Center, Houston.

The likelihood of receptor status changes differed significantly by the subtype of breast cancer. Of hormone receptor–positive cancers, 51% had a change in receptor status, compared with 27% of HER2-positive cancers and 22% of triple-negative breast cancers.

Other factors did not significantly affect the likelihood of receptor status change, including patient age or race, histology, tumor stage or grade, the presence of lymphovascular invasion, or the class of neoadjuvant chemotherapeutic agents.

Of ER-positive tumors, 11% changed to ER negative after neoadjuvant chemotherapy; of ER-negative tumors, 21% changed to ER positive. Of the PR-positive tumors, 35% changed to PR-negative; of PR-negative tumors, 12% changed to PR positive. Of HER2-positive tumors, 40% changed to HER2 negative; of HER2-negative tumors, 3% changed to HER2 positive. Among 35 patients treated with trastuzumab, the HER2 status changed in 16 (46%).

Patients who had tumors with an ER-negative status that did not change had the worst 5-year rates for overall survival (47%) and relapse-free survival (40%), compared with patients whose tumors had an ER-positive status did not change (81% overall survival and 63% relapse-free survival), patients whose ER status changed from positive to negative (67% and 66% survival rates, respectively), and patients whose ER status changed from negative to positive (75% and 59%, respectively).

Similarly, patients who had PR-negative tumors whose status did not change had significantly lower rates of overall survival (51%) and relapse-free survival (41%), compared with patients whose PR-positive tumor status did not change (87% and 67%, respectively), those who changed from PR positive to PR negative (78% and 73%, respectively), and patients whose PR-negative status changed to PR positive (69% and 55%, respectively).

Changes or lack of change in HER2 subgroups were not significantly associated with varying outcomes.

The investigators also looked at the absolute percent changes in ER or PR status using cutoffs in 10% increments from 10% to 50%. The 5-year overall survival rate was significantly greater in ER-positive patients who had at least a 20% change in ER status, compared with those with less than a 20% change (87% vs. 73%, respectively). The 5-year relapse-free survival rate also was significantly greater if the ER status changed by at least 20% (71%), compared with smaller ER changes (59%).

Of cancers that were hormone receptor–positive and HER2 negative before neoadjuvant chemotherapy, 20% changed to HER2-positive or triple-negative breast cancer after treatment, 12% of tumors that had been HER2 positive changed to triple negative tumors, and 2% of triple negative breast cancers changed to HER2-positive after treatment. These changes produced only one significant effect on outcomes: 5-year overall survival rates were significantly lower in patients who changed from HER2-positive to triple-negative breast cancer (23%), compared with those whose HER2-positive cancer did not change to triple negative (71%).

Larger prospective studies are needed to confirm the findings and to determine any impact of biomarker changes on long-term survival, she said.

Previous studies have reported discordance in hormone receptor status in up to 51% of breast cancers between the primary tumor and residual disease and changes in HER2 status in up to 43% of cases. Conclusions about associations between changes in receptor status and clinical outcomes have been inconsistent.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Parinyanitikul reported having no financial disclosures.

sherryboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – A change in the status of any breast cancer tumor biomarker after neoadjuvant therapy was independently associated with a 37% decreased likelihood of recurrence in 5 years, a multivariate analysis showed.

The subtyping of breast cancer by receptor status changed in 41% of 398 samples between the initial tumor and residual disease after neoadjuvant chemotherapy.

In patients with any change in the status of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), after neoadjuvant chemotherapy, 63% were relapse free 5 years later as compared with 48% of patients with no receptor change, a significant difference.

Overall survival at 5 years, however, did not differ significantly based on receptor status change, Dr. Napa Parinyanitikul and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology. At 5 years, 73% of patients with a receptor status change and 63% with no change were alive.

The study analyzed data on patients treated at her institution in 1992-2012 who had tumor biomarker results from pretreatment biopsies and from samples of residual disease after neoadjuvant chemotherapy. Most patients in the study were white, with clinical stage II or III disease.

Of the tumors, 49% were hormone receptor–positive and HER2 negative; 18% were HER2 positive, and 33% were negative for all three receptors (triple-negative breast cancer). Neoadjuvant chemotherapy consisted of a taxane-based regimen in 10%, an anthracycline-based regimen in 19%, an anthracycline/taxane-based regimen in 71%, and trastuzumab-based chemotherapy in 49%. The 88% of patients with hormone receptor-positive disease received adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor.

After a median of 40 months of follow-up, 32% of women had died and 42% had a recurrence of breast cancer, reported Dr. Parinyanitikul, a fellow at the University of Texas MD Anderson Cancer Center, Houston.

The likelihood of receptor status changes differed significantly by the subtype of breast cancer. Of hormone receptor–positive cancers, 51% had a change in receptor status, compared with 27% of HER2-positive cancers and 22% of triple-negative breast cancers.

Other factors did not significantly affect the likelihood of receptor status change, including patient age or race, histology, tumor stage or grade, the presence of lymphovascular invasion, or the class of neoadjuvant chemotherapeutic agents.

Of ER-positive tumors, 11% changed to ER negative after neoadjuvant chemotherapy; of ER-negative tumors, 21% changed to ER positive. Of the PR-positive tumors, 35% changed to PR-negative; of PR-negative tumors, 12% changed to PR positive. Of HER2-positive tumors, 40% changed to HER2 negative; of HER2-negative tumors, 3% changed to HER2 positive. Among 35 patients treated with trastuzumab, the HER2 status changed in 16 (46%).

Patients who had tumors with an ER-negative status that did not change had the worst 5-year rates for overall survival (47%) and relapse-free survival (40%), compared with patients whose tumors had an ER-positive status did not change (81% overall survival and 63% relapse-free survival), patients whose ER status changed from positive to negative (67% and 66% survival rates, respectively), and patients whose ER status changed from negative to positive (75% and 59%, respectively).

Similarly, patients who had PR-negative tumors whose status did not change had significantly lower rates of overall survival (51%) and relapse-free survival (41%), compared with patients whose PR-positive tumor status did not change (87% and 67%, respectively), those who changed from PR positive to PR negative (78% and 73%, respectively), and patients whose PR-negative status changed to PR positive (69% and 55%, respectively).

Changes or lack of change in HER2 subgroups were not significantly associated with varying outcomes.

The investigators also looked at the absolute percent changes in ER or PR status using cutoffs in 10% increments from 10% to 50%. The 5-year overall survival rate was significantly greater in ER-positive patients who had at least a 20% change in ER status, compared with those with less than a 20% change (87% vs. 73%, respectively). The 5-year relapse-free survival rate also was significantly greater if the ER status changed by at least 20% (71%), compared with smaller ER changes (59%).

Of cancers that were hormone receptor–positive and HER2 negative before neoadjuvant chemotherapy, 20% changed to HER2-positive or triple-negative breast cancer after treatment, 12% of tumors that had been HER2 positive changed to triple negative tumors, and 2% of triple negative breast cancers changed to HER2-positive after treatment. These changes produced only one significant effect on outcomes: 5-year overall survival rates were significantly lower in patients who changed from HER2-positive to triple-negative breast cancer (23%), compared with those whose HER2-positive cancer did not change to triple negative (71%).

Larger prospective studies are needed to confirm the findings and to determine any impact of biomarker changes on long-term survival, she said.

Previous studies have reported discordance in hormone receptor status in up to 51% of breast cancers between the primary tumor and residual disease and changes in HER2 status in up to 43% of cases. Conclusions about associations between changes in receptor status and clinical outcomes have been inconsistent.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Parinyanitikul reported having no financial disclosures.

sherryboschert@frontlinemedcom.com

On Twitter @sherryboschert

This year has already been a busy one for the two genes most commonly linked to hereditary breast cancer: BRCA1 and BRCA2.

First, BRCA1/2 entered the spotlight after the actress Angelina Jolie revealed she had tested positive for a hereditary breast cancer mutation and had opted for prophylactic surgery to mitigate her cancer risks.

Because breast cancer risk is an important topic to many women and families, patient calls to our genetic services and to others increased during this national conversation (The 'Jolie effect' on BRCA risks, Internal Medicine News, July 2013, p. 13). Although these types of health-interest stories may lead some readers or listeners to overestimate their own risks of hereditary breast cancer, the temporary focus on family histories may induce some patients with concerning family histories to seek genetic counseling.

Shortly after the Angelina Jolie story, another BRCA-related event occurred that is likely to have far broader and longer-lasting effects.

On June 13, 2013, the U.S. Supreme Court ruled on the legitimacy of gene patenting of the BRCA1 and BRCA2 genes. The case pitted Utah-based Myriad Genetics, a genetic testing company, against a coalition of physicians, researchers, and advocacy groups (Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 12-398 [2013]). At stake was the question of whether human genes can be patented and protected under intellectual property laws, or if genes are more akin to "products of nature" and should not be subject to patent protection.

Although the case centered on the roughly $3,000 BRCA1/2 Myriad Genetics test, it had potential implications for many other genetic tests and for roughly 3,000 other patents issued by the U.S. Patent Office related to granted human genetic patents.

In a move hailed by many outside the entrepreneurial and business realms, the Supreme Court ruled unanimously against Myriad Genetics, invalidating five intellectual property claims around the BRCA1/2 patents. The court argued that genomic DNA is a "product of nature" and that "separating that [BRCA1/2] gene from its surrounding genetic material is not an act of invention."

On the surface, this ruling seemed straightforward for many of us in the clinical genetics field. It clarifies that discovering something biologically inherent in all of us (we all carry two copies each of the BRCA1 and BRCA2 genes) was not tantamount to an "invention" deserving of patent protection and commercial control by one company or individual.

Within hours of the ruling, several other laboratories released statements that they would immediately be offering BRCA1/2 testing – with the implication that costs of the expensive test would drop and become more affordable for many patients and clinics. Ambry Genetics briefly displayed a sign on its website that said, "Your Genes Have Been Freed." As prior efforts by clinical labs and even some research labs to sequence BRCA1/2 had been challenged by Myriad Genetics as patent infringement, the "freeing" of the genes was praised by many.

One immediate expectation is that the proliferation of multigene panels – which previously had to exclude patented genes – will likely occur. Whether and how this ruling will affect other aspects of previously patented genetic tests remain to be seen.

Thus, on first glance, the short-term winner would appear to be the patient, who shortly will be able to access less costly genetic testing. In spite of this victory for the patient, legitimate concerns will need to be addressed about the quality of testing by other laboratories that engage in BRCA testing.

From a technical standpoint, there is little reason to doubt the quality of laboratories that add BRCA testing to their menus. However, for more than a decade, Myriad Genetics provided the bulk of hereditary breast cancer testing – and in doing so accumulated invaluable experience from the interpretation of more than 1 million tests.

Initially, the genetic variants discovered were deposited into publicly available databases, but Myriad Genetics halted this practice in 2004, perhaps to further protect their interpretative expertise. Lack of access to the known pathogenic and benign BRCA1/2 variants may hamper other laboratories’ interpretation of some results.

The Supreme Court did not address this lack of data parity between Myriad Genetics and other laboratories. It’s possible Myriad Genetics could argue that, although BRCA1/2 testing has been liberated across the diagnostic laboratory spectrum, Myriad Genetics still offers optimal interpretation of BRCA1/2 test results.

Beyond the ruling on the BRCA1/2 question, there are some other interesting potential fallouts from the court’s actions.

One such area relates to patentability of cDNA. These are DNA sequences typically generated from processed RNA sequences; they differ from DNA principally in their lack of introns. Traditionally, cDNA is generated from the processed RNA transcripts and contains largely just the protein-coding portions of the genetic information.

Although processed RNA can be found in nature, the Supreme Court determined that the generated (think "invented") cDNA products are not naturally occurring and do merit patent protection. The legitimacy of this argument comes from noting that RNA does occur in nature, but cDNA has to be coaxed from the naturally occurring processed RNA.

From the biotechnology field’s perspective, this distinction between genomic DNA and cDNA is of paramount importance. Many biologically based therapeutics rely on cDNA technology, and invalidation of these patents would have irrevocably changed the biopharmaceutical landscape.

While cDNA’s patentability had been assumed (as had DNA by some), the Supreme Court’s ruling solidifies for now that cDNA products can be protected. On some level, knowing that cDNA intellectual property is inherently protectable may help pharmaceutical companies rest easier.

Outside the realm of human genetic considerations, the ruling provides some optimism for those wishing to challenge gene patents from other organisms, including many bacterial and viral patents. However, the excitement of being able to contest other patents should be tempered with concerns over how invalidating other gene patents could affect other areas of the biotechnology industry. For example, other patents related to products produced by nonhuman organisms might be subject to challenges, thereby broadening the impact of the BRCA1/2 decision into other areas, including pharmaceuticals, nutraceuticals, and genetically modified foods.

These broader possibilities imply that the BRCA1/2 patent ruling may be just an important chapter in a longer story of biological patents that will be worth following in coming years.

Dr. Matthew R.G. Taylor is trained in both internal medicine and clinical genetics and is associate professor and director of the Adult Clinical Genetics Clinic at the University of Colorado, Denver.

This year has already been a busy one for the two genes most commonly linked to hereditary breast cancer: BRCA1 and BRCA2.

First, BRCA1/2 entered the spotlight after the actress Angelina Jolie revealed she had tested positive for a hereditary breast cancer mutation and had opted for prophylactic surgery to mitigate her cancer risks.

Because breast cancer risk is an important topic to many women and families, patient calls to our genetic services and to others increased during this national conversation (The 'Jolie effect' on BRCA risks, Internal Medicine News, July 2013, p. 13). Although these types of health-interest stories may lead some readers or listeners to overestimate their own risks of hereditary breast cancer, the temporary focus on family histories may induce some patients with concerning family histories to seek genetic counseling.

Shortly after the Angelina Jolie story, another BRCA-related event occurred that is likely to have far broader and longer-lasting effects.

On June 13, 2013, the U.S. Supreme Court ruled on the legitimacy of gene patenting of the BRCA1 and BRCA2 genes. The case pitted Utah-based Myriad Genetics, a genetic testing company, against a coalition of physicians, researchers, and advocacy groups (Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 12-398 [2013]). At stake was the question of whether human genes can be patented and protected under intellectual property laws, or if genes are more akin to "products of nature" and should not be subject to patent protection.

Although the case centered on the roughly $3,000 BRCA1/2 Myriad Genetics test, it had potential implications for many other genetic tests and for roughly 3,000 other patents issued by the U.S. Patent Office related to granted human genetic patents.

In a move hailed by many outside the entrepreneurial and business realms, the Supreme Court ruled unanimously against Myriad Genetics, invalidating five intellectual property claims around the BRCA1/2 patents. The court argued that genomic DNA is a "product of nature" and that "separating that [BRCA1/2] gene from its surrounding genetic material is not an act of invention."

On the surface, this ruling seemed straightforward for many of us in the clinical genetics field. It clarifies that discovering something biologically inherent in all of us (we all carry two copies each of the BRCA1 and BRCA2 genes) was not tantamount to an "invention" deserving of patent protection and commercial control by one company or individual.

Within hours of the ruling, several other laboratories released statements that they would immediately be offering BRCA1/2 testing – with the implication that costs of the expensive test would drop and become more affordable for many patients and clinics. Ambry Genetics briefly displayed a sign on its website that said, "Your Genes Have Been Freed." As prior efforts by clinical labs and even some research labs to sequence BRCA1/2 had been challenged by Myriad Genetics as patent infringement, the "freeing" of the genes was praised by many.

One immediate expectation is that the proliferation of multigene panels – which previously had to exclude patented genes – will likely occur. Whether and how this ruling will affect other aspects of previously patented genetic tests remain to be seen.

Thus, on first glance, the short-term winner would appear to be the patient, who shortly will be able to access less costly genetic testing. In spite of this victory for the patient, legitimate concerns will need to be addressed about the quality of testing by other laboratories that engage in BRCA testing.

From a technical standpoint, there is little reason to doubt the quality of laboratories that add BRCA testing to their menus. However, for more than a decade, Myriad Genetics provided the bulk of hereditary breast cancer testing – and in doing so accumulated invaluable experience from the interpretation of more than 1 million tests.

Initially, the genetic variants discovered were deposited into publicly available databases, but Myriad Genetics halted this practice in 2004, perhaps to further protect their interpretative expertise. Lack of access to the known pathogenic and benign BRCA1/2 variants may hamper other laboratories’ interpretation of some results.

The Supreme Court did not address this lack of data parity between Myriad Genetics and other laboratories. It’s possible Myriad Genetics could argue that, although BRCA1/2 testing has been liberated across the diagnostic laboratory spectrum, Myriad Genetics still offers optimal interpretation of BRCA1/2 test results.

Beyond the ruling on the BRCA1/2 question, there are some other interesting potential fallouts from the court’s actions.

One such area relates to patentability of cDNA. These are DNA sequences typically generated from processed RNA sequences; they differ from DNA principally in their lack of introns. Traditionally, cDNA is generated from the processed RNA transcripts and contains largely just the protein-coding portions of the genetic information.

Although processed RNA can be found in nature, the Supreme Court determined that the generated (think "invented") cDNA products are not naturally occurring and do merit patent protection. The legitimacy of this argument comes from noting that RNA does occur in nature, but cDNA has to be coaxed from the naturally occurring processed RNA.

From the biotechnology field’s perspective, this distinction between genomic DNA and cDNA is of paramount importance. Many biologically based therapeutics rely on cDNA technology, and invalidation of these patents would have irrevocably changed the biopharmaceutical landscape.

While cDNA’s patentability had been assumed (as had DNA by some), the Supreme Court’s ruling solidifies for now that cDNA products can be protected. On some level, knowing that cDNA intellectual property is inherently protectable may help pharmaceutical companies rest easier.

Outside the realm of human genetic considerations, the ruling provides some optimism for those wishing to challenge gene patents from other organisms, including many bacterial and viral patents. However, the excitement of being able to contest other patents should be tempered with concerns over how invalidating other gene patents could affect other areas of the biotechnology industry. For example, other patents related to products produced by nonhuman organisms might be subject to challenges, thereby broadening the impact of the BRCA1/2 decision into other areas, including pharmaceuticals, nutraceuticals, and genetically modified foods.

These broader possibilities imply that the BRCA1/2 patent ruling may be just an important chapter in a longer story of biological patents that will be worth following in coming years.

Dr. Matthew R.G. Taylor is trained in both internal medicine and clinical genetics and is associate professor and director of the Adult Clinical Genetics Clinic at the University of Colorado, Denver.

This year has already been a busy one for the two genes most commonly linked to hereditary breast cancer: BRCA1 and BRCA2.

First, BRCA1/2 entered the spotlight after the actress Angelina Jolie revealed she had tested positive for a hereditary breast cancer mutation and had opted for prophylactic surgery to mitigate her cancer risks.

Because breast cancer risk is an important topic to many women and families, patient calls to our genetic services and to others increased during this national conversation (The 'Jolie effect' on BRCA risks, Internal Medicine News, July 2013, p. 13). Although these types of health-interest stories may lead some readers or listeners to overestimate their own risks of hereditary breast cancer, the temporary focus on family histories may induce some patients with concerning family histories to seek genetic counseling.

Shortly after the Angelina Jolie story, another BRCA-related event occurred that is likely to have far broader and longer-lasting effects.

On June 13, 2013, the U.S. Supreme Court ruled on the legitimacy of gene patenting of the BRCA1 and BRCA2 genes. The case pitted Utah-based Myriad Genetics, a genetic testing company, against a coalition of physicians, researchers, and advocacy groups (Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 12-398 [2013]). At stake was the question of whether human genes can be patented and protected under intellectual property laws, or if genes are more akin to "products of nature" and should not be subject to patent protection.

Although the case centered on the roughly $3,000 BRCA1/2 Myriad Genetics test, it had potential implications for many other genetic tests and for roughly 3,000 other patents issued by the U.S. Patent Office related to granted human genetic patents.

In a move hailed by many outside the entrepreneurial and business realms, the Supreme Court ruled unanimously against Myriad Genetics, invalidating five intellectual property claims around the BRCA1/2 patents. The court argued that genomic DNA is a "product of nature" and that "separating that [BRCA1/2] gene from its surrounding genetic material is not an act of invention."

On the surface, this ruling seemed straightforward for many of us in the clinical genetics field. It clarifies that discovering something biologically inherent in all of us (we all carry two copies each of the BRCA1 and BRCA2 genes) was not tantamount to an "invention" deserving of patent protection and commercial control by one company or individual.

Within hours of the ruling, several other laboratories released statements that they would immediately be offering BRCA1/2 testing – with the implication that costs of the expensive test would drop and become more affordable for many patients and clinics. Ambry Genetics briefly displayed a sign on its website that said, "Your Genes Have Been Freed." As prior efforts by clinical labs and even some research labs to sequence BRCA1/2 had been challenged by Myriad Genetics as patent infringement, the "freeing" of the genes was praised by many.

One immediate expectation is that the proliferation of multigene panels – which previously had to exclude patented genes – will likely occur. Whether and how this ruling will affect other aspects of previously patented genetic tests remain to be seen.

Thus, on first glance, the short-term winner would appear to be the patient, who shortly will be able to access less costly genetic testing. In spite of this victory for the patient, legitimate concerns will need to be addressed about the quality of testing by other laboratories that engage in BRCA testing.

From a technical standpoint, there is little reason to doubt the quality of laboratories that add BRCA testing to their menus. However, for more than a decade, Myriad Genetics provided the bulk of hereditary breast cancer testing – and in doing so accumulated invaluable experience from the interpretation of more than 1 million tests.

Initially, the genetic variants discovered were deposited into publicly available databases, but Myriad Genetics halted this practice in 2004, perhaps to further protect their interpretative expertise. Lack of access to the known pathogenic and benign BRCA1/2 variants may hamper other laboratories’ interpretation of some results.

The Supreme Court did not address this lack of data parity between Myriad Genetics and other laboratories. It’s possible Myriad Genetics could argue that, although BRCA1/2 testing has been liberated across the diagnostic laboratory spectrum, Myriad Genetics still offers optimal interpretation of BRCA1/2 test results.

Beyond the ruling on the BRCA1/2 question, there are some other interesting potential fallouts from the court’s actions.

One such area relates to patentability of cDNA. These are DNA sequences typically generated from processed RNA sequences; they differ from DNA principally in their lack of introns. Traditionally, cDNA is generated from the processed RNA transcripts and contains largely just the protein-coding portions of the genetic information.

Although processed RNA can be found in nature, the Supreme Court determined that the generated (think "invented") cDNA products are not naturally occurring and do merit patent protection. The legitimacy of this argument comes from noting that RNA does occur in nature, but cDNA has to be coaxed from the naturally occurring processed RNA.

From the biotechnology field’s perspective, this distinction between genomic DNA and cDNA is of paramount importance. Many biologically based therapeutics rely on cDNA technology, and invalidation of these patents would have irrevocably changed the biopharmaceutical landscape.

While cDNA’s patentability had been assumed (as had DNA by some), the Supreme Court’s ruling solidifies for now that cDNA products can be protected. On some level, knowing that cDNA intellectual property is inherently protectable may help pharmaceutical companies rest easier.

Outside the realm of human genetic considerations, the ruling provides some optimism for those wishing to challenge gene patents from other organisms, including many bacterial and viral patents. However, the excitement of being able to contest other patents should be tempered with concerns over how invalidating other gene patents could affect other areas of the biotechnology industry. For example, other patents related to products produced by nonhuman organisms might be subject to challenges, thereby broadening the impact of the BRCA1/2 decision into other areas, including pharmaceuticals, nutraceuticals, and genetically modified foods.

These broader possibilities imply that the BRCA1/2 patent ruling may be just an important chapter in a longer story of biological patents that will be worth following in coming years.

Dr. Matthew R.G. Taylor is trained in both internal medicine and clinical genetics and is associate professor and director of the Adult Clinical Genetics Clinic at the University of Colorado, Denver.

Capecitabine, first approved for treating metastatic breast cancer in 1998, now will be available in a generic formulation, the Food and Drug Administration announced Sept. 16.

The FDA has approved generic capecitabine (150 mg and 500 mg), manufactured by Teva Pharmaceuticals USA, the first generic formulation of this drug to be approved, the agency said in a written statement.

Capecitabine also has been approved for treating metastatic colorectal cancer (2001) and Dukes’ C colon cancer (2005). It is a nucleoside metabolic inhibitor with antineoplastic activity, and the trade formulation is marketed by Genentech as Xeloda.

Teva is not disclosing launch plans for the product at this time, a Teva spokesperson said.

To view the label for the trade formulation, click here.

emechcatie@frontlinemedcom.com

*This story was updated 9/17/2013

Capecitabine, first approved for treating metastatic breast cancer in 1998, now will be available in a generic formulation, the Food and Drug Administration announced Sept. 16.

The FDA has approved generic capecitabine (150 mg and 500 mg), manufactured by Teva Pharmaceuticals USA, the first generic formulation of this drug to be approved, the agency said in a written statement.

Capecitabine also has been approved for treating metastatic colorectal cancer (2001) and Dukes’ C colon cancer (2005). It is a nucleoside metabolic inhibitor with antineoplastic activity, and the trade formulation is marketed by Genentech as Xeloda.

Teva is not disclosing launch plans for the product at this time, a Teva spokesperson said.

To view the label for the trade formulation, click here.

emechcatie@frontlinemedcom.com

*This story was updated 9/17/2013

Capecitabine, first approved for treating metastatic breast cancer in 1998, now will be available in a generic formulation, the Food and Drug Administration announced Sept. 16.

The FDA has approved generic capecitabine (150 mg and 500 mg), manufactured by Teva Pharmaceuticals USA, the first generic formulation of this drug to be approved, the agency said in a written statement.

Capecitabine also has been approved for treating metastatic colorectal cancer (2001) and Dukes’ C colon cancer (2005). It is a nucleoside metabolic inhibitor with antineoplastic activity, and the trade formulation is marketed by Genentech as Xeloda.

Teva is not disclosing launch plans for the product at this time, a Teva spokesperson said.

To view the label for the trade formulation, click here.

emechcatie@frontlinemedcom.com

*This story was updated 9/17/2013

Young women who elect contralateral prophylactic mastectomy do so, in part, because they want to improve their chances for survival, even though they realize there is no convincing evidence of a survival benefit, based on results from a survey.

Moreover, many women, particularly those without a known BRCA mutation, substantially overestimate their risk of developing cancer in the unaffected breast, Shoshana M. Rosenberg, Sc.D., of the Dana-Farber Cancer Institute and the Harvard School of Public Health, both in Boston, and her colleagues reported in the Sept. 17 issue of Annals of Internal Medicine.

The findings suggest "some degree of cognitive dissonance," since almost all respondents cited both the desire to improve survival or extend life and a desire to prevent metastatic disease as extremely or very important reasons for choosing contralateral prophylactic mastectomy, while also demonstrating awareness that bilateral mastectomy would not extend survival, the researchers said. Anxiety and fear of recurrence likely influenced the decision-making process and led women to identify their desire to extend life and prevent metastatic disease as among the most important reasons for having contralateral prophylactic mastectomy.

Of 550 women diagnosed at age 40 years or younger with breast cancer in one breast, 123 (22%) who underwent bilateral mastectomy were included in the analysis. Of those women, 94% said the desire to improve survival was an extremely or very important factor in their decision to undergo contralateral prophylactic mastectomy. Yet 74% of mutation carriers and 84% of noncarriers acknowledged that most women who are diagnosed with early-stage breast cancer and undergo treatment will ultimately die of something other than breast cancer.

Also, 98% cited a desire to decrease their risk of contralateral breast cancer and 95% cited a desire for peace of mind as extremely or very important factors in their decision (Ann. Intern. Med. 2013;17:373-81).

Mutation carriers estimated their risk of developing cancer in the contralateral breast in the 5 years after unilateral treatment at 20%, noncarriers estimated that risk at 10%. The risk for women with BRCA mutations is estimated to be 24%-31%. The group without mutations overestimated their risk, which is actually about 2%-4% over 5 years. Women in both groups estimated the risk of chest wall recurrence after bilateral mastectomy at 5%, which is actually estimated at less than 1%, the researchers noted.

Survey participants were women whose median age was 37 years at cancer diagnosis and who were recruited from four academic and five community hospitals in Massachusetts, and from one academic site in Toronto between November 2006 and November 2010. The participants were recruited as part of the Helping Ourselves, Helping Others: Young Women’s Breast Cancer Study. Most had stage I or stage II breast cancer, and all were believed to have breast cancer only in one breast. About 60% of tumors were estrogen receptor–positive, and about 25% of the women were BRCAmutation carriers.

The survey was a one-time supplement to the ongoing prospective cohort study. It is one of the largest surveys to date to examine decision-making, risk perceptions, and psychosocial aspects of contralateral prophylactic mastectomy among young women with breast cancer, the investigators said. The survey findings are important, given that the rates of contralateral prophylactic mastectomy have increased dramatically in recent years, from 4%-6% in the late 1990s to 11%-25% in more recent reports, even though "the value of the procedure for most women with unilateral early-stage breast cancer is unclear," the researchers said.

The study was limited by the lack of validation of the survey, the possibility of recall bias (since the women were surveyed an average of 2 years following surgery), and the possibility of limited generalizability of the findings because the study population was primarily white, non-Hispanic, and college educated. Yet, the findings highlight a need for improved communication with patients, they said.

Although 96%-97% of participants believed they were clear about benefits and risks, and which mattered most, many women reported that several outcomes associated with surgery were worse than they had expected. For example, 33% reported needing a higher-than-expected number of operations or procedures, and 28% said that numbness or tingling in the chest was worse than expected.

"With respect to QOL outcomes, 42% reported that their sense of sexuality was worse than they expected after surgery, and nearly one-third indicated that self-consciousness about appearance was also worse than expected," the researchers reported.

Only about half of the participants indicated that their physicians had talked at least to some degree about reasons not to have contralateral prophylactic mastectomy, suggesting a potential role for "interventions that ensure women are sufficiently informed and the actual risk for contralateral disease is effectively communicated," the investigators said.

Additional clarification of these conflicting responses would be helpful, they said, suggesting that future investigation "might include focus groups or collection of qualitative data with the goal of elucidating the role of cognitive biases in making treatment decisions."

This study was primarily funded by Susan G. Komen for the Cure. Dr. Rosenberg reported receiving support from the National Cancer Institute.

Young women who elect contralateral prophylactic mastectomy do so, in part, because they want to improve their chances for survival, even though they realize there is no convincing evidence of a survival benefit, based on results from a survey.

Moreover, many women, particularly those without a known BRCA mutation, substantially overestimate their risk of developing cancer in the unaffected breast, Shoshana M. Rosenberg, Sc.D., of the Dana-Farber Cancer Institute and the Harvard School of Public Health, both in Boston, and her colleagues reported in the Sept. 17 issue of Annals of Internal Medicine.

The findings suggest "some degree of cognitive dissonance," since almost all respondents cited both the desire to improve survival or extend life and a desire to prevent metastatic disease as extremely or very important reasons for choosing contralateral prophylactic mastectomy, while also demonstrating awareness that bilateral mastectomy would not extend survival, the researchers said. Anxiety and fear of recurrence likely influenced the decision-making process and led women to identify their desire to extend life and prevent metastatic disease as among the most important reasons for having contralateral prophylactic mastectomy.

Of 550 women diagnosed at age 40 years or younger with breast cancer in one breast, 123 (22%) who underwent bilateral mastectomy were included in the analysis. Of those women, 94% said the desire to improve survival was an extremely or very important factor in their decision to undergo contralateral prophylactic mastectomy. Yet 74% of mutation carriers and 84% of noncarriers acknowledged that most women who are diagnosed with early-stage breast cancer and undergo treatment will ultimately die of something other than breast cancer.

Also, 98% cited a desire to decrease their risk of contralateral breast cancer and 95% cited a desire for peace of mind as extremely or very important factors in their decision (Ann. Intern. Med. 2013;17:373-81).

Mutation carriers estimated their risk of developing cancer in the contralateral breast in the 5 years after unilateral treatment at 20%, noncarriers estimated that risk at 10%. The risk for women with BRCA mutations is estimated to be 24%-31%. The group without mutations overestimated their risk, which is actually about 2%-4% over 5 years. Women in both groups estimated the risk of chest wall recurrence after bilateral mastectomy at 5%, which is actually estimated at less than 1%, the researchers noted.

Survey participants were women whose median age was 37 years at cancer diagnosis and who were recruited from four academic and five community hospitals in Massachusetts, and from one academic site in Toronto between November 2006 and November 2010. The participants were recruited as part of the Helping Ourselves, Helping Others: Young Women’s Breast Cancer Study. Most had stage I or stage II breast cancer, and all were believed to have breast cancer only in one breast. About 60% of tumors were estrogen receptor–positive, and about 25% of the women were BRCAmutation carriers.

The survey was a one-time supplement to the ongoing prospective cohort study. It is one of the largest surveys to date to examine decision-making, risk perceptions, and psychosocial aspects of contralateral prophylactic mastectomy among young women with breast cancer, the investigators said. The survey findings are important, given that the rates of contralateral prophylactic mastectomy have increased dramatically in recent years, from 4%-6% in the late 1990s to 11%-25% in more recent reports, even though "the value of the procedure for most women with unilateral early-stage breast cancer is unclear," the researchers said.

The study was limited by the lack of validation of the survey, the possibility of recall bias (since the women were surveyed an average of 2 years following surgery), and the possibility of limited generalizability of the findings because the study population was primarily white, non-Hispanic, and college educated. Yet, the findings highlight a need for improved communication with patients, they said.

Although 96%-97% of participants believed they were clear about benefits and risks, and which mattered most, many women reported that several outcomes associated with surgery were worse than they had expected. For example, 33% reported needing a higher-than-expected number of operations or procedures, and 28% said that numbness or tingling in the chest was worse than expected.

"With respect to QOL outcomes, 42% reported that their sense of sexuality was worse than they expected after surgery, and nearly one-third indicated that self-consciousness about appearance was also worse than expected," the researchers reported.

Only about half of the participants indicated that their physicians had talked at least to some degree about reasons not to have contralateral prophylactic mastectomy, suggesting a potential role for "interventions that ensure women are sufficiently informed and the actual risk for contralateral disease is effectively communicated," the investigators said.

Additional clarification of these conflicting responses would be helpful, they said, suggesting that future investigation "might include focus groups or collection of qualitative data with the goal of elucidating the role of cognitive biases in making treatment decisions."

This study was primarily funded by Susan G. Komen for the Cure. Dr. Rosenberg reported receiving support from the National Cancer Institute.

Young women who elect contralateral prophylactic mastectomy do so, in part, because they want to improve their chances for survival, even though they realize there is no convincing evidence of a survival benefit, based on results from a survey.

Moreover, many women, particularly those without a known BRCA mutation, substantially overestimate their risk of developing cancer in the unaffected breast, Shoshana M. Rosenberg, Sc.D., of the Dana-Farber Cancer Institute and the Harvard School of Public Health, both in Boston, and her colleagues reported in the Sept. 17 issue of Annals of Internal Medicine.

The findings suggest "some degree of cognitive dissonance," since almost all respondents cited both the desire to improve survival or extend life and a desire to prevent metastatic disease as extremely or very important reasons for choosing contralateral prophylactic mastectomy, while also demonstrating awareness that bilateral mastectomy would not extend survival, the researchers said. Anxiety and fear of recurrence likely influenced the decision-making process and led women to identify their desire to extend life and prevent metastatic disease as among the most important reasons for having contralateral prophylactic mastectomy.

Of 550 women diagnosed at age 40 years or younger with breast cancer in one breast, 123 (22%) who underwent bilateral mastectomy were included in the analysis. Of those women, 94% said the desire to improve survival was an extremely or very important factor in their decision to undergo contralateral prophylactic mastectomy. Yet 74% of mutation carriers and 84% of noncarriers acknowledged that most women who are diagnosed with early-stage breast cancer and undergo treatment will ultimately die of something other than breast cancer.

Also, 98% cited a desire to decrease their risk of contralateral breast cancer and 95% cited a desire for peace of mind as extremely or very important factors in their decision (Ann. Intern. Med. 2013;17:373-81).

Mutation carriers estimated their risk of developing cancer in the contralateral breast in the 5 years after unilateral treatment at 20%, noncarriers estimated that risk at 10%. The risk for women with BRCA mutations is estimated to be 24%-31%. The group without mutations overestimated their risk, which is actually about 2%-4% over 5 years. Women in both groups estimated the risk of chest wall recurrence after bilateral mastectomy at 5%, which is actually estimated at less than 1%, the researchers noted.

Survey participants were women whose median age was 37 years at cancer diagnosis and who were recruited from four academic and five community hospitals in Massachusetts, and from one academic site in Toronto between November 2006 and November 2010. The participants were recruited as part of the Helping Ourselves, Helping Others: Young Women’s Breast Cancer Study. Most had stage I or stage II breast cancer, and all were believed to have breast cancer only in one breast. About 60% of tumors were estrogen receptor–positive, and about 25% of the women were BRCAmutation carriers.

The survey was a one-time supplement to the ongoing prospective cohort study. It is one of the largest surveys to date to examine decision-making, risk perceptions, and psychosocial aspects of contralateral prophylactic mastectomy among young women with breast cancer, the investigators said. The survey findings are important, given that the rates of contralateral prophylactic mastectomy have increased dramatically in recent years, from 4%-6% in the late 1990s to 11%-25% in more recent reports, even though "the value of the procedure for most women with unilateral early-stage breast cancer is unclear," the researchers said.

The study was limited by the lack of validation of the survey, the possibility of recall bias (since the women were surveyed an average of 2 years following surgery), and the possibility of limited generalizability of the findings because the study population was primarily white, non-Hispanic, and college educated. Yet, the findings highlight a need for improved communication with patients, they said.

Although 96%-97% of participants believed they were clear about benefits and risks, and which mattered most, many women reported that several outcomes associated with surgery were worse than they had expected. For example, 33% reported needing a higher-than-expected number of operations or procedures, and 28% said that numbness or tingling in the chest was worse than expected.

"With respect to QOL outcomes, 42% reported that their sense of sexuality was worse than they expected after surgery, and nearly one-third indicated that self-consciousness about appearance was also worse than expected," the researchers reported.

Only about half of the participants indicated that their physicians had talked at least to some degree about reasons not to have contralateral prophylactic mastectomy, suggesting a potential role for "interventions that ensure women are sufficiently informed and the actual risk for contralateral disease is effectively communicated," the investigators said.

Additional clarification of these conflicting responses would be helpful, they said, suggesting that future investigation "might include focus groups or collection of qualitative data with the goal of elucidating the role of cognitive biases in making treatment decisions."

This study was primarily funded by Susan G. Komen for the Cure. Dr. Rosenberg reported receiving support from the National Cancer Institute.