Prospective Evaluation of Risk Factors for Male Breast Cancer

Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852-7234, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 10/2008; 100(20):1477-81. DOI: 10.1093/jnci/djn329
Source: PubMed


Most risk factors for male breast cancer have been derived from retrospective studies that may reflect selective recall. In
the prospective National Institutes of Health–AARP Diet and Health Study, we studied 324 920 men, among whom 121 developed
breast cancer. Men who reported a first-degree relative with breast cancer had an increased risk of breast cancer (relative
risk [RR] = 1.92, 95% confidence interval [CI] = 1.19 to 3.09). Among the medical conditions examined, a new finding emerged
regarding increased male breast cancer risk associated with a history of a bone fracture (RR = 2.20, 95% CI = 1.24 to 3.91).
Obesity was positively related to risk (RR = 1.79, 95% CI = 1.10 to 2.91, for body mass indices of ≥30 vs <25 kg/m2) and physical activity inversely related, even after adjustment for body mass index. Smokers were at somewhat elevated risk,
although trends with smoking characteristics were inconsistent. Alcohol consumption was not related to risk. The identified
risk factors show some commonalities with female breast cancer and indicate the importance of hormonal mechanisms. Differences
in risk factors may reflect unique mechanisms associated with androgens and their ratio to bioavailable estrogens.

Download full-text


Available from: Albert R Hollenbeck, Sep 29, 2015
  • Source
    • "Human epidermal growth factor receptor 2 (HER2) over-expression and/or amplification appear less frequent in MBC and the mean age at diagnosis is approximately five years older than for women [2,3,5,6]. Risk factors include hormonal imbalances (for example, caused by liver disease, Klinefelter's syndrome or obesity), genetic predisposition (mainly due to BRCA2 mutations) and environmental factors (for example, exposure to chronic heat or radiation) [7,8]. Survival rates have been debated, with some studies finding that men diagnosed with breast cancer have a worse prognosis than women [9,10], whereas other studies have reported similar prognoses [11,12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Male breast cancer (MBC) is a rare and inadequately characterized disease. The aim of the present study was to characterize MBC tumors transcriptionally, to classify them into comprehensive subgroups, and to compare them with female breast cancer (FBC). A total of 66 clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was constructed for validation using immunohistochemistry. Two external gene expression datasets were used for comparison purposes: 37 MBCs and 359 FBCs. Using an unsupervised approach, we classified the MBC tumors into two subgroups, luminal M1 and luminal M2, respectively, with differences in tumor biological features and outcome, and which differed from the intrinsic subgroups described in FBC. The two subgroups were recapitulated in the external MBC dataset. Luminal M2 tumors were characterized by high expression of immune response genes and genes associated with estrogen receptor (ER) signaling. Luminal M1 tumors, on the other hand, despite being ER positive by immunohistochemistry showed a lower correlation to genes associated with ER signaling and displayed a more aggressive phenotype and worse prognosis. Validation of two of the most differentially expressed genes, class 1 human leukocyte antigen (HLA) and the metabolizing gene N-acetyltransferase-1 (NAT1), respectively, revealed significantly better survival associated with high expression of both markers (HLA, hazard ratio (HR) 3.6, P = 0.002; NAT1, HR 2.5, P = 0.033). Importantly, NAT1 remained significant in a multivariate analysis (HR 2.8, P = 0.040) and may thus be a novel prognostic marker in MBC. We have detected two unique and stable subgroups of MBC with differences in tumor biological features and outcome. They differ from the widely acknowledged intrinsic subgroups of FBC. As such, they may constitute two novel subgroups of breast cancer, occurring exclusively in men, and which may consequently require novel treatment approaches. Finally, we identified NAT1 as a possible prognostic biomarker for MBC, as suggested by NAT1 positivity corresponding to better outcome.
    Full-text · Article · Feb 2012 · Breast cancer research: BCR
  • Source
    • "There are some professions which are connected to MBC such as work places with high temperatures and low frequency magnetic fields (Brinton et al., 2008). Prostate cancer is associated with MBC. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.
    Full-text · Article · Jan 2012 · Asian Pacific journal of cancer prevention: APJCP
  • Source
    • "Data obtained from [3-7]. These references include comprehensive discussion on other considered risk factors for male breast cancer (MBC). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Male breast carcinoma is a rare condition. Few male breast cancer-specific epidemiological or clinical trial data are available - our understanding of male breast cancer thus comes from studies of female breast cancer, painting an inaccurate picture when it comes to determining contributing factors. Clinicians report an increase in diagnoses of male breast cancer but this has not been formally reported. We therefore undertook a review of data obtained from four western nations: England, Scotland, Canada and Australia. When adjusted for age, this review clearly showed an increase in the incidence of male breast cancer over a 15-year period. Reasons for the increased incidence are discussed in the context of suggested risk factors such as BRCA2 and lifestyle changes over the past few decades. The clinical management of male breast carcinoma is considered, in particular the potential role of aromatase inhibitors and fulvestrant and targeting pathways involving prolactin and androgen receptor.
    Full-text · Article · Sep 2011 · Breast cancer research: BCR
Show more