Breast Cancer

CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.

Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.

Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.

Click here to hear more about these practice-changing results.

The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.

pwendling@frontlinemedcom.com

Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.

CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.

Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.

Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.

Click here to hear more about these practice-changing results.

The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.

pwendling@frontlinemedcom.com

Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.

CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.

Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.

Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.

Click here to hear more about these practice-changing results.

The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.

pwendling@frontlinemedcom.com

Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.

Adjuvant endocrine therapy should be extended from 5 to 10 years in women with hormone receptor–positive breast cancer, according to an updated clinical practice guideline published online May 27 in the Journal of Clinical Oncology.

"For decades, tamoxifen taken for 5 years was the standard adjuvant endocrine treatment. More recently, patients who are postmenopausal also have been offered the option of taking an aromatase inhibitor (AI) as an alternative to tamoxifen or in sequence after tamoxifen," said Dr. Harold J. Burstein, cochair of the American Society of Clinical Oncology expert panel that wrote the update.

However, since the last update (2010) of this clinical practice guideline, emerging research from international randomized trials has demonstrated that women who continue adjuvant endocrine therapy for an additional 5 years have a modest gain in overall survival, as well as lower rates of recurrence and contralateral breast cancer, the panel noted.

Now, pre- and perimenopausal women diagnosed with hormone receptor–positive breast cancer should be offered a total of 10 years of adjuvant endocrine therapy. Which agents they should take depends on their menopausal status. Pre- and perimenopausal women can be given tamoxifen but not aromatase inhibitors; postmenopausal women can be given either agent, but the total duration of aromatase inhibitors shouldn’t exceed 5 years, Dr. Burstein and his associates said (J. Clin. Oncol. 2014 May 27 [doi:10.1200/JCO.2013.54.2258]).

"It is not known which strategy is preferred; tamoxifen and AIs have different adverse effect profiles that might reasonably inform that choice, and patient preferences based on the tolerability of these agents in individual women should be considered," the guideline states.

The known adverse effects of both treatments, which include menopausal symptoms and rare cases of endometrial cancer and thromboembolism, persist with longer duration of treatment. But no new adverse effects specific to that increased duration have been identified to date, Dr. Burstein and his associates said.

Given the importance of adjuvant endocrine therapy to patient survival and quality of life, "clinicians are encouraged to inquire diligently about treatment compliance and treatment-related adverse effects, and to pursue interventions known to mitigate adverse effects and enhance adherence," the guideline says.

The updated recommendations, along with other explanatory information, can be obtained at www.asco.org/guidelines/endocrinebreast. Patient information is available at www.cancer.net.

Adjuvant endocrine therapy should be extended from 5 to 10 years in women with hormone receptor–positive breast cancer, according to an updated clinical practice guideline published online May 27 in the Journal of Clinical Oncology.

"For decades, tamoxifen taken for 5 years was the standard adjuvant endocrine treatment. More recently, patients who are postmenopausal also have been offered the option of taking an aromatase inhibitor (AI) as an alternative to tamoxifen or in sequence after tamoxifen," said Dr. Harold J. Burstein, cochair of the American Society of Clinical Oncology expert panel that wrote the update.

However, since the last update (2010) of this clinical practice guideline, emerging research from international randomized trials has demonstrated that women who continue adjuvant endocrine therapy for an additional 5 years have a modest gain in overall survival, as well as lower rates of recurrence and contralateral breast cancer, the panel noted.

Now, pre- and perimenopausal women diagnosed with hormone receptor–positive breast cancer should be offered a total of 10 years of adjuvant endocrine therapy. Which agents they should take depends on their menopausal status. Pre- and perimenopausal women can be given tamoxifen but not aromatase inhibitors; postmenopausal women can be given either agent, but the total duration of aromatase inhibitors shouldn’t exceed 5 years, Dr. Burstein and his associates said (J. Clin. Oncol. 2014 May 27 [doi:10.1200/JCO.2013.54.2258]).

"It is not known which strategy is preferred; tamoxifen and AIs have different adverse effect profiles that might reasonably inform that choice, and patient preferences based on the tolerability of these agents in individual women should be considered," the guideline states.

The known adverse effects of both treatments, which include menopausal symptoms and rare cases of endometrial cancer and thromboembolism, persist with longer duration of treatment. But no new adverse effects specific to that increased duration have been identified to date, Dr. Burstein and his associates said.

Given the importance of adjuvant endocrine therapy to patient survival and quality of life, "clinicians are encouraged to inquire diligently about treatment compliance and treatment-related adverse effects, and to pursue interventions known to mitigate adverse effects and enhance adherence," the guideline says.

The updated recommendations, along with other explanatory information, can be obtained at www.asco.org/guidelines/endocrinebreast. Patient information is available at www.cancer.net.

Adjuvant endocrine therapy should be extended from 5 to 10 years in women with hormone receptor–positive breast cancer, according to an updated clinical practice guideline published online May 27 in the Journal of Clinical Oncology.

"For decades, tamoxifen taken for 5 years was the standard adjuvant endocrine treatment. More recently, patients who are postmenopausal also have been offered the option of taking an aromatase inhibitor (AI) as an alternative to tamoxifen or in sequence after tamoxifen," said Dr. Harold J. Burstein, cochair of the American Society of Clinical Oncology expert panel that wrote the update.

However, since the last update (2010) of this clinical practice guideline, emerging research from international randomized trials has demonstrated that women who continue adjuvant endocrine therapy for an additional 5 years have a modest gain in overall survival, as well as lower rates of recurrence and contralateral breast cancer, the panel noted.

Now, pre- and perimenopausal women diagnosed with hormone receptor–positive breast cancer should be offered a total of 10 years of adjuvant endocrine therapy. Which agents they should take depends on their menopausal status. Pre- and perimenopausal women can be given tamoxifen but not aromatase inhibitors; postmenopausal women can be given either agent, but the total duration of aromatase inhibitors shouldn’t exceed 5 years, Dr. Burstein and his associates said (J. Clin. Oncol. 2014 May 27 [doi:10.1200/JCO.2013.54.2258]).

"It is not known which strategy is preferred; tamoxifen and AIs have different adverse effect profiles that might reasonably inform that choice, and patient preferences based on the tolerability of these agents in individual women should be considered," the guideline states.

The known adverse effects of both treatments, which include menopausal symptoms and rare cases of endometrial cancer and thromboembolism, persist with longer duration of treatment. But no new adverse effects specific to that increased duration have been identified to date, Dr. Burstein and his associates said.

Given the importance of adjuvant endocrine therapy to patient survival and quality of life, "clinicians are encouraged to inquire diligently about treatment compliance and treatment-related adverse effects, and to pursue interventions known to mitigate adverse effects and enhance adherence," the guideline says.

The updated recommendations, along with other explanatory information, can be obtained at www.asco.org/guidelines/endocrinebreast. Patient information is available at www.cancer.net.

1. Abstract LBA1, Olivia Pagani et al.

Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs. tamoxifen (T) plus OFS in premenopausal women with hormone receptor–positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. http://abstracts.asco.org/144/AbstView_144_129398.html

2. Abstract LBA4, Martine J. Piccart-Gebhart et al.

First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T?L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).

http://abstracts.asco.org/144/AbstView_144_128258.html

3. Abstract LBA505, Halle C.F. Moore et al.

Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor–negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).

http://abstracts.asco.org/144/AbstView_144_129172.html

4. Abstract 503, Hongchao Pan et al.

Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials.

http://abstracts.asco.org/144/AbstView_144_133648.html

Covered at premeeting press briefing, Oncology Practice report here.

5. Abstract 1005, Gunter Von Minckwitz et al.

Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto.

http://abstracts.asco.org/144/AbstView_144_131770.html

6. Abstract 516, Ingrid A. Mayer et al.

SU2C phase Ib study of the PI3K-alpha inhibitor BYL719 with letrozole in ER+/HER2– metastatic breast cancer (MBC).

http://abstracts.asco.org/144/AbstView_144_130044.html

7. Abstract 1016, G. Thomas Budd et al.

Outcome of male patients and black patients enrolled in S0221, an intergroup chemotherapy study.

http://abstracts.asco.org/144/AbstView_144_128157.html

Dr. Hope S. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

1. Abstract LBA1, Olivia Pagani et al.

Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs. tamoxifen (T) plus OFS in premenopausal women with hormone receptor–positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. http://abstracts.asco.org/144/AbstView_144_129398.html

2. Abstract LBA4, Martine J. Piccart-Gebhart et al.

First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T?L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).

http://abstracts.asco.org/144/AbstView_144_128258.html

3. Abstract LBA505, Halle C.F. Moore et al.

Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor–negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).

http://abstracts.asco.org/144/AbstView_144_129172.html

4. Abstract 503, Hongchao Pan et al.

Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials.

http://abstracts.asco.org/144/AbstView_144_133648.html

Covered at premeeting press briefing, Oncology Practice report here.

5. Abstract 1005, Gunter Von Minckwitz et al.

Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto.

http://abstracts.asco.org/144/AbstView_144_131770.html

6. Abstract 516, Ingrid A. Mayer et al.

SU2C phase Ib study of the PI3K-alpha inhibitor BYL719 with letrozole in ER+/HER2– metastatic breast cancer (MBC).

http://abstracts.asco.org/144/AbstView_144_130044.html

7. Abstract 1016, G. Thomas Budd et al.

Outcome of male patients and black patients enrolled in S0221, an intergroup chemotherapy study.

http://abstracts.asco.org/144/AbstView_144_128157.html

Dr. Hope S. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

1. Abstract LBA1, Olivia Pagani et al.

Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs. tamoxifen (T) plus OFS in premenopausal women with hormone receptor–positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. http://abstracts.asco.org/144/AbstView_144_129398.html

2. Abstract LBA4, Martine J. Piccart-Gebhart et al.

First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T?L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).

http://abstracts.asco.org/144/AbstView_144_128258.html

3. Abstract LBA505, Halle C.F. Moore et al.

Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor–negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).

http://abstracts.asco.org/144/AbstView_144_129172.html

4. Abstract 503, Hongchao Pan et al.

Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials.

http://abstracts.asco.org/144/AbstView_144_133648.html

Covered at premeeting press briefing, Oncology Practice report here.

5. Abstract 1005, Gunter Von Minckwitz et al.

Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto.

http://abstracts.asco.org/144/AbstView_144_131770.html

6. Abstract 516, Ingrid A. Mayer et al.

SU2C phase Ib study of the PI3K-alpha inhibitor BYL719 with letrozole in ER+/HER2– metastatic breast cancer (MBC).

http://abstracts.asco.org/144/AbstView_144_130044.html

7. Abstract 1016, G. Thomas Budd et al.

Outcome of male patients and black patients enrolled in S0221, an intergroup chemotherapy study.

http://abstracts.asco.org/144/AbstView_144_128157.html

Dr. Hope S. Rugo is a professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center.

Fear seems to be a major driver of contralateral prophylactic mastectomy after initial breast cancer surgery.

Almost two-thirds of those who had the procedure had no clinical indication for it, Sarah T. Hawley, Ph.D., and her colleagues wrote in the May 21 online issue of JAMA Surgery (doi:10.1001/jamasurg.2013.5689). The women choosing contralateral prophylactic mastectomy (CPM) for which there was no clinical indication were more highly educated than were those who didn’t elect the surgery, more likely to be white, and two to four times more likely to be worried about a recurrence.

Fear of recurrence was a "powerful nonclinical factor" in the analysis, wrote Dr. Hawley of the University of Michigan, Ann Arbor – and education may be the best way to overcome it.

"A patient’s decision to undergo contralateral prophylactic mastectomy based on a strong fear of recurrence in the absence of clinical indications presents an important clinical challenge for surgeons," she and her colleagues wrote. "Growing literature supports the notion that patients have a difficult time assessing and interpreting their own risk and that fear and anxiety related to disease recurrence often supersede accurate risk perceptions to drive health decisions."

Dr. Hawley and her coinvestigators extracted their data from the Surveillance, Epidemiology, and End Results (SEER) registries for Los Angeles and Detroit. They included records from 1,447 women aged 20-79 years who had been diagnosed with a first incident primary ductal carcinoma in situ or invasive breast cancer of stages I-IIIa.

About half of the sample was white; 21% was black, and 30% Hispanic. Other groups made up the balance. More than half (59%) had achieved some college-level education.

About half the respondents (57%) underwent breast-conserving surgery (BCS). Other surgical treatments included unilateral mastectomy (UM; 34%), and contralateral prophylactic mastectomy (8%).

CPM was pondered more frequently than it was an executed, the investigators said, with 19% of the entire sample considering it "strongly or very strongly."

Most of the women who had CPM said that they did it to prevent recurrence, with 78% citing that worry as a very important driver of their decision. However, the authors said, of the 106 women who underwent CPM, only 31% had clinical indications, while the majority (67%) did not.

A multivariate analysis determined the relationships between patient characteristics and breast surgery,

Those with some college-level education were five times more likely to have CPM than UM, and four times more likely to have that than BCS. Those with high worry were almost three times more likely to have CPM than UM, and four times more likely to have CPM than BCS.

Women who had positive genetic testing were 10 times more likely to have contralateral prophylactic mastectomy than unilateral mastectomy, and 19 times more likely to have CPM than BCS. But those with negative results were still twice as likely to have the CPM as either of the other surgeries.

Having at least two close relatives with breast or ovarian cancer also significantly increased the likelihood of a CMP vs. UM (relative risk = 5) or BCS (RR = 4). Having had a diagnostic MRI doubled the chance of having CPM, compared with the other surgeries.

"Our results provide evidence that decisions about CPM represent a clear case in which better strategies to increase patient knowledge about their own risk of developing contralateral cancer as well as the net benefit of treatment are needed and should be made only after patients are accurately informed about these issues," Dr. Hawley and her coauthors said, adding that such patients need to clearly understand the consequences of CMP, "including lengthy recovery time and increased risk for serious operative complications."

The National Institutes of Health and the University of Michigan supported the study. Neither Dr. Hawley nor her coauthors had any financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Fear seems to be a major driver of contralateral prophylactic mastectomy after initial breast cancer surgery.

Almost two-thirds of those who had the procedure had no clinical indication for it, Sarah T. Hawley, Ph.D., and her colleagues wrote in the May 21 online issue of JAMA Surgery (doi:10.1001/jamasurg.2013.5689). The women choosing contralateral prophylactic mastectomy (CPM) for which there was no clinical indication were more highly educated than were those who didn’t elect the surgery, more likely to be white, and two to four times more likely to be worried about a recurrence.

Fear of recurrence was a "powerful nonclinical factor" in the analysis, wrote Dr. Hawley of the University of Michigan, Ann Arbor – and education may be the best way to overcome it.

"A patient’s decision to undergo contralateral prophylactic mastectomy based on a strong fear of recurrence in the absence of clinical indications presents an important clinical challenge for surgeons," she and her colleagues wrote. "Growing literature supports the notion that patients have a difficult time assessing and interpreting their own risk and that fear and anxiety related to disease recurrence often supersede accurate risk perceptions to drive health decisions."

Dr. Hawley and her coinvestigators extracted their data from the Surveillance, Epidemiology, and End Results (SEER) registries for Los Angeles and Detroit. They included records from 1,447 women aged 20-79 years who had been diagnosed with a first incident primary ductal carcinoma in situ or invasive breast cancer of stages I-IIIa.

About half of the sample was white; 21% was black, and 30% Hispanic. Other groups made up the balance. More than half (59%) had achieved some college-level education.

About half the respondents (57%) underwent breast-conserving surgery (BCS). Other surgical treatments included unilateral mastectomy (UM; 34%), and contralateral prophylactic mastectomy (8%).

CPM was pondered more frequently than it was an executed, the investigators said, with 19% of the entire sample considering it "strongly or very strongly."

Most of the women who had CPM said that they did it to prevent recurrence, with 78% citing that worry as a very important driver of their decision. However, the authors said, of the 106 women who underwent CPM, only 31% had clinical indications, while the majority (67%) did not.

A multivariate analysis determined the relationships between patient characteristics and breast surgery,

Those with some college-level education were five times more likely to have CPM than UM, and four times more likely to have that than BCS. Those with high worry were almost three times more likely to have CPM than UM, and four times more likely to have CPM than BCS.

Women who had positive genetic testing were 10 times more likely to have contralateral prophylactic mastectomy than unilateral mastectomy, and 19 times more likely to have CPM than BCS. But those with negative results were still twice as likely to have the CPM as either of the other surgeries.

Having at least two close relatives with breast or ovarian cancer also significantly increased the likelihood of a CMP vs. UM (relative risk = 5) or BCS (RR = 4). Having had a diagnostic MRI doubled the chance of having CPM, compared with the other surgeries.

"Our results provide evidence that decisions about CPM represent a clear case in which better strategies to increase patient knowledge about their own risk of developing contralateral cancer as well as the net benefit of treatment are needed and should be made only after patients are accurately informed about these issues," Dr. Hawley and her coauthors said, adding that such patients need to clearly understand the consequences of CMP, "including lengthy recovery time and increased risk for serious operative complications."

The National Institutes of Health and the University of Michigan supported the study. Neither Dr. Hawley nor her coauthors had any financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Fear seems to be a major driver of contralateral prophylactic mastectomy after initial breast cancer surgery.

Almost two-thirds of those who had the procedure had no clinical indication for it, Sarah T. Hawley, Ph.D., and her colleagues wrote in the May 21 online issue of JAMA Surgery (doi:10.1001/jamasurg.2013.5689). The women choosing contralateral prophylactic mastectomy (CPM) for which there was no clinical indication were more highly educated than were those who didn’t elect the surgery, more likely to be white, and two to four times more likely to be worried about a recurrence.

Fear of recurrence was a "powerful nonclinical factor" in the analysis, wrote Dr. Hawley of the University of Michigan, Ann Arbor – and education may be the best way to overcome it.

"A patient’s decision to undergo contralateral prophylactic mastectomy based on a strong fear of recurrence in the absence of clinical indications presents an important clinical challenge for surgeons," she and her colleagues wrote. "Growing literature supports the notion that patients have a difficult time assessing and interpreting their own risk and that fear and anxiety related to disease recurrence often supersede accurate risk perceptions to drive health decisions."

Dr. Hawley and her coinvestigators extracted their data from the Surveillance, Epidemiology, and End Results (SEER) registries for Los Angeles and Detroit. They included records from 1,447 women aged 20-79 years who had been diagnosed with a first incident primary ductal carcinoma in situ or invasive breast cancer of stages I-IIIa.

About half of the sample was white; 21% was black, and 30% Hispanic. Other groups made up the balance. More than half (59%) had achieved some college-level education.

About half the respondents (57%) underwent breast-conserving surgery (BCS). Other surgical treatments included unilateral mastectomy (UM; 34%), and contralateral prophylactic mastectomy (8%).

CPM was pondered more frequently than it was an executed, the investigators said, with 19% of the entire sample considering it "strongly or very strongly."

Most of the women who had CPM said that they did it to prevent recurrence, with 78% citing that worry as a very important driver of their decision. However, the authors said, of the 106 women who underwent CPM, only 31% had clinical indications, while the majority (67%) did not.

A multivariate analysis determined the relationships between patient characteristics and breast surgery,

Those with some college-level education were five times more likely to have CPM than UM, and four times more likely to have that than BCS. Those with high worry were almost three times more likely to have CPM than UM, and four times more likely to have CPM than BCS.

Women who had positive genetic testing were 10 times more likely to have contralateral prophylactic mastectomy than unilateral mastectomy, and 19 times more likely to have CPM than BCS. But those with negative results were still twice as likely to have the CPM as either of the other surgeries.

Having at least two close relatives with breast or ovarian cancer also significantly increased the likelihood of a CMP vs. UM (relative risk = 5) or BCS (RR = 4). Having had a diagnostic MRI doubled the chance of having CPM, compared with the other surgeries.

"Our results provide evidence that decisions about CPM represent a clear case in which better strategies to increase patient knowledge about their own risk of developing contralateral cancer as well as the net benefit of treatment are needed and should be made only after patients are accurately informed about these issues," Dr. Hawley and her coauthors said, adding that such patients need to clearly understand the consequences of CMP, "including lengthy recovery time and increased risk for serious operative complications."

The National Institutes of Health and the University of Michigan supported the study. Neither Dr. Hawley nor her coauthors had any financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

An analysis of recently available registry data including HER2 status for breast cancer patients confirms higher proportions of more aggressive breast cancer subtypes among younger women, black women, and Hispanic women, and notable differences in clinical presentation across subtypes, investigators reported in the Journal of the National Cancer Institute.

Although the reasons underlying these ethnic and age differences are not yet clear, the new data "are directly relevant to individualized treatment decisions that influence clinical outcomes," said Nadia Howlader of the National Cancer Institute, Bethesda, Md., and her colleagues.

They analyzed nationally representative data from 17 population-based Surveillance, Epidemiology, and End Results (SEER) registries, identifying 36,810 women diagnosed as having invasive breast cancer in 2010, the first year for which SEER data regarding tumor HER2 status were available. In addition to information on tumor receptor status, stage, and grade, the database includes information on patient age, race/ethnicity, and socioeconomic status.

Ms. Howlader, a mathematical statistician in the division of cancer control and population sciences, and her associates found that 72.7% of these breast cancers were HR-positive (expressing either estrogen receptors or progesterone receptors) and HER2-negative (not expressing human epidermal growth factor 2-neu); 12.2% were triple-negative (negative for estrogen, progesterone, and HER2 receptors); 10.3% were HR-positive and HER2-positive; and 4.6% were HR-negative but HER2-positive (J. Natl. Cancer Inst. 2014 April 28 [doi: 10.1093/jnci/dju055]).

The receptor status was unknown for 12% of the invasive breast cancer cases in the registries.

Compared with HR-positive and HER2-negative patients, those diagnosed with the other three subtypes were somewhat more likely to be younger, belong to minority racial or ethnic groups, live in counties with higher poverty levels, and have later-stage and higher Bloom-Richardson grade disease, the investigators reported.

Non-Hispanic black women had the highest incidence rates of triple-negative breast cancer across all age groups, with the difference in rates reaching its widest point at ages 60-64 and 65-69 years, when non-Hispanic black women were much more likely to be diagnosed with this subtype than were the other racial/ethnic groups. Triple-negative cancers were substantially more likely to be high-grade tumors (75% vs. 17%) and to present at an advanced stage than was the predominant HR-positive HER2-negative subtype.

The HER2-overexpressing tumors were less common subtypes with fewer observed variations by race/ethnicity, compared with both the HR-positive and HER2-negative, and triple-negative subtypes.

Compared with the predominant HR-positive and HER2-negative subtype, the proportion of women with the other three subtypes decreased with advancing age; these subtypes comprised 35% of case patients under age 50, but represented only 20% of case patients among those aged 75 years and older, the investigators reported.

"Understanding of the biological basis for differences in breast cancer subtype incidence and mortality across population groups is limited and warrants continued intensive study," the authors wrote. SEER data will continue to support this research, Ms. Howlader and her colleagues said.

This study was supported by the National Cancer Institute and the participating SEER registries. Ms. Howlader and her associates reported no financial conflicts of interest.

An analysis of recently available registry data including HER2 status for breast cancer patients confirms higher proportions of more aggressive breast cancer subtypes among younger women, black women, and Hispanic women, and notable differences in clinical presentation across subtypes, investigators reported in the Journal of the National Cancer Institute.

Although the reasons underlying these ethnic and age differences are not yet clear, the new data "are directly relevant to individualized treatment decisions that influence clinical outcomes," said Nadia Howlader of the National Cancer Institute, Bethesda, Md., and her colleagues.

They analyzed nationally representative data from 17 population-based Surveillance, Epidemiology, and End Results (SEER) registries, identifying 36,810 women diagnosed as having invasive breast cancer in 2010, the first year for which SEER data regarding tumor HER2 status were available. In addition to information on tumor receptor status, stage, and grade, the database includes information on patient age, race/ethnicity, and socioeconomic status.

Ms. Howlader, a mathematical statistician in the division of cancer control and population sciences, and her associates found that 72.7% of these breast cancers were HR-positive (expressing either estrogen receptors or progesterone receptors) and HER2-negative (not expressing human epidermal growth factor 2-neu); 12.2% were triple-negative (negative for estrogen, progesterone, and HER2 receptors); 10.3% were HR-positive and HER2-positive; and 4.6% were HR-negative but HER2-positive (J. Natl. Cancer Inst. 2014 April 28 [doi: 10.1093/jnci/dju055]).

The receptor status was unknown for 12% of the invasive breast cancer cases in the registries.

Compared with HR-positive and HER2-negative patients, those diagnosed with the other three subtypes were somewhat more likely to be younger, belong to minority racial or ethnic groups, live in counties with higher poverty levels, and have later-stage and higher Bloom-Richardson grade disease, the investigators reported.

Non-Hispanic black women had the highest incidence rates of triple-negative breast cancer across all age groups, with the difference in rates reaching its widest point at ages 60-64 and 65-69 years, when non-Hispanic black women were much more likely to be diagnosed with this subtype than were the other racial/ethnic groups. Triple-negative cancers were substantially more likely to be high-grade tumors (75% vs. 17%) and to present at an advanced stage than was the predominant HR-positive HER2-negative subtype.

The HER2-overexpressing tumors were less common subtypes with fewer observed variations by race/ethnicity, compared with both the HR-positive and HER2-negative, and triple-negative subtypes.

Compared with the predominant HR-positive and HER2-negative subtype, the proportion of women with the other three subtypes decreased with advancing age; these subtypes comprised 35% of case patients under age 50, but represented only 20% of case patients among those aged 75 years and older, the investigators reported.

"Understanding of the biological basis for differences in breast cancer subtype incidence and mortality across population groups is limited and warrants continued intensive study," the authors wrote. SEER data will continue to support this research, Ms. Howlader and her colleagues said.

This study was supported by the National Cancer Institute and the participating SEER registries. Ms. Howlader and her associates reported no financial conflicts of interest.

An analysis of recently available registry data including HER2 status for breast cancer patients confirms higher proportions of more aggressive breast cancer subtypes among younger women, black women, and Hispanic women, and notable differences in clinical presentation across subtypes, investigators reported in the Journal of the National Cancer Institute.

Although the reasons underlying these ethnic and age differences are not yet clear, the new data "are directly relevant to individualized treatment decisions that influence clinical outcomes," said Nadia Howlader of the National Cancer Institute, Bethesda, Md., and her colleagues.

They analyzed nationally representative data from 17 population-based Surveillance, Epidemiology, and End Results (SEER) registries, identifying 36,810 women diagnosed as having invasive breast cancer in 2010, the first year for which SEER data regarding tumor HER2 status were available. In addition to information on tumor receptor status, stage, and grade, the database includes information on patient age, race/ethnicity, and socioeconomic status.

Ms. Howlader, a mathematical statistician in the division of cancer control and population sciences, and her associates found that 72.7% of these breast cancers were HR-positive (expressing either estrogen receptors or progesterone receptors) and HER2-negative (not expressing human epidermal growth factor 2-neu); 12.2% were triple-negative (negative for estrogen, progesterone, and HER2 receptors); 10.3% were HR-positive and HER2-positive; and 4.6% were HR-negative but HER2-positive (J. Natl. Cancer Inst. 2014 April 28 [doi: 10.1093/jnci/dju055]).

The receptor status was unknown for 12% of the invasive breast cancer cases in the registries.

Compared with HR-positive and HER2-negative patients, those diagnosed with the other three subtypes were somewhat more likely to be younger, belong to minority racial or ethnic groups, live in counties with higher poverty levels, and have later-stage and higher Bloom-Richardson grade disease, the investigators reported.

Non-Hispanic black women had the highest incidence rates of triple-negative breast cancer across all age groups, with the difference in rates reaching its widest point at ages 60-64 and 65-69 years, when non-Hispanic black women were much more likely to be diagnosed with this subtype than were the other racial/ethnic groups. Triple-negative cancers were substantially more likely to be high-grade tumors (75% vs. 17%) and to present at an advanced stage than was the predominant HR-positive HER2-negative subtype.

The HER2-overexpressing tumors were less common subtypes with fewer observed variations by race/ethnicity, compared with both the HR-positive and HER2-negative, and triple-negative subtypes.

Compared with the predominant HR-positive and HER2-negative subtype, the proportion of women with the other three subtypes decreased with advancing age; these subtypes comprised 35% of case patients under age 50, but represented only 20% of case patients among those aged 75 years and older, the investigators reported.

"Understanding of the biological basis for differences in breast cancer subtype incidence and mortality across population groups is limited and warrants continued intensive study," the authors wrote. SEER data will continue to support this research, Ms. Howlader and her colleagues said.

This study was supported by the National Cancer Institute and the participating SEER registries. Ms. Howlader and her associates reported no financial conflicts of interest.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.