The first study, a phase 2 trial in 100 to 150 patients, will evaluate a new drug to treat male breast cancer. She said negotiations with a pharmaceutical company are currently ongoing.
Dr. Cardoso presented initial results from part one of the program, a joint effort by the EORTC, Translational Breast Cancer Research Consortium, Breast International Group, and the North American Breast Cancer Group, at the 2014 San Antonio Breast Cancer Symposium in December.4
For the 1,822 patients enrolled, clinical data, long term outcomes, and local pathology were centrally analyzed at EORTC. Of these, 1,473 (1,384 from the European Union and 89 from the United States), had formalin-fixed, paraffin-embedded (FFPE) samples available that were analyzed for histology, grade, and estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, and Ki67 status at one of three central labs located in the United Kingdom, the Netherlands, and the United States.4
Median age at diagnosis was 68.5; about 90% were between ages 57 and 79 or older, and 63% were diagnosed from 2001 to 2010.4
The results showed that “male breast cancer is usually ER-positive, PR-positive, and AR-positive and of luminal A-like subtype; 5% were HER2-positive and less than 1% were triple-negative breast cancer,” she reported.
A total of 56% of patients had T1 tumors at diagnosis but only 4% had undergone breast-conserving surgery. Although estrogen receptor was highly positive in 90% of patients, adjuvant endocrine therapy, primarily tamoxifen, was given in only 77% of patients.4
Median overall survival (OS) was 10.4 years for patients with nonmetastatic node-negative disease; 8.4 years for those with nonmetastatic node-positive disease; and 2.6 years for those with metastatic disease. A significant improvement in OS was observed over time.
High expression of ER and PR were prognostic for better outcome, whereas tumor grade, Ki67 expression, and immunohistochemistry subtypes were not prognostic. “In-depth characterization of samples is ongoing,” she noted.4
Risk factors for breast cancer in males include obesity, family history of male or female breast cancer, exogenous estrogen or testosterone use, BRCA gene mutations, Klinefelter syndrome, radiation exposure, and testicular disorders.5 Due to its low incidence, mammography is not recommended to detect breast cancer in men.6
By age 70, the estimated cumulative risk of breast cancer for men carrying germline mutations in the BRCA2 gene is 6.8%, for BRCA1 mutation carriers it is 1.2%.7
Incidence of breast cancer in males increases with age, with rates higher in African American men than in white men.8
Since 2000, death rates for male breast cancer have decreased 1.8% per year.6 A population-based study found that male patients with breast cancer have later disease onset and more advanced disease compared with female patients; however, they have lower risk of death from breast cancer than comparable female patients.9
A recent study documented a higher risk of death in black men diagnosed with early-stage breast cancer age 18 to 64 compared with white men that “was significantly reduced after accounting for differences in insurance and income,” as this did not hold true for older black men, possibly because of uniform health coverage through Medicare. The authors said these findings suggest “that poverty may play an important role in racial disparities in breast cancer mortality.”10
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Dr. Cardoso credits the BCRF with being one of her earliest supporters, providing funding for research on breast cancer in men since 2007. Results of this research led to a 2008 workshop, proceedings of which were published in the Journal of Clinical Oncology in 2010.11
Further networking between the Breast International Group and The North American Breast Cancer Group resulted in creation of the International Breast Cancer Program.
She has two important messages for her colleagues: given the available data, it’s no longer acceptable to treat male patients with breast cancer as if they were postmenopausal females—and especially not with aromatase inhibitors, as these agents may actually hurt patients—and that everyone needs to continue to advocate for males to enter clinical trials of new agents.
- American Cancer Society. Breast Cancer in Men. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003091-pdf. Accessed May 8, 2015.
- Anderson WF, Devesa SS. Breast carcinoma in men. Cancer. 2005;103(2):432-433.
- ClinicalTrials.gov. Male breast cancer: understanding the biology for improved patient care. NCT01101425. Available at: https://clinicaltrials.gov/ct2/show/NCT01101425. Accessed May 8, 2015.
- Cardoso F, Bartlett J, Slaets L, et al. Characterization of male breast cancer: First results of the EORTC10085/TBCRC/BIG/NABCG International Male BC Program. S6-05. Presented at: 2014 San Antonio Breast Cancer Symposium; p48.
- Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol. 2013;24(6):1434-1443.
- American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society, Inc. 2013. Available at: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-042725.pdf. Accessed May 8, 2015.
- Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99(23):1811-1814.
- Goodman MT, Tung KH, Wilkens LR. Comparative epidemiology of breast cancer among men and women in the US, 1996 to 2000. Cancer Causes Control. 2006;17(2):127-136.
- Miao H, Verkooijen HM, Chia KS, et al. Incidence and outcome of male breast cancer: an international population-based study. J Clin Oncol. 2011;29(33):4381-4386.
- Sineshaw HM, Freedman RA, Ward EM, et al. Black/White Disparities in Receipt of Treatment and Survival Among Men With Early-Stage Breast Cancer. J Clin Oncol. May 4, 2015. [Epub ahead of print] pii: JCO.2014.60.5584.
- Korde LA, Zujewski JA, Kamin L, et al. Multidisciplinary meeting on male breast cancer: Summary and research recommendations. J Clin Oncol. 2010;28(12):2114-2122.