We examined the patterns of care for male breast cancer patients diagnosed in 2003 and 2004 in a population-based sample of men treated in communities throughout the United States. The majority of men with breast cancer received a mastectomy and nearly 60% received hormonal therapy. In multivariate models, the use of chemotherapy among men with invasive breast cancer was influenced by tumor characteristics, age and marital status. Larger tumors and being currently unmarried was associated with an increased mortality in men with ER positive/borderline invasive tumors. The use of tamoxifen decreased the risk of death from cancer. However, there was no decrease in mortality in men who received AIs.
Yabroff reported that 52% of women diagnosed with invasive breast cancer were diagnosed on mammography.13
Mammography is not a screening tool used for men; self-discovered lumps were a primary form of detection among men with in situ
and invasive breast cancer. In contrast, women with DCIS are usually screen detected.14
Giordano reported that majority of the men, between 50% and 97%, presented with a breast mass.7
Mastectomy for men with in situ
and invasive disease was most common. Although men with stage IV were less likely to receive a mastectomy than men with stages I-III, surgery is unlikely to be curative in men with stage IV disease. The NCCN guidelines suggest that men with breast cancer should be treated using the guidelines for post-menopausal women with consideration of patient preference.9
Men have less breast tissue than women and the involved tissue is smaller, therefore surgical margins may also be smaller. Re-excision was performed more frequently in men with in situ
than in men with invasive disease. It is possible that the surgeons were trying to obtain an adequate margin and because of the small tumor size and lack of definition of the tumor it required re-excision.15
In a British Columbia study of men and women with breast cancer, men receiving mastectomies were more likely to be treated with radiation than were women.16
Men in the current study were also more likely to receive radiation following a mastectomy than were women registered in SEER and diagnosed at the same stage and years, and treated with mastectomy.
Approximately one-third of men with in situ
carcinoma had nodal surgical procedures. Since nodal dissection is not indicated in DCIS for women, this may represent an overuse with the associated risks of the nodal procedure itself including lymphedema. However, 14 of 17 men who had a nodal surgical procedure had a mastectomy, considered an acceptable option.9
The use of sentinel node biopsy has not been well studied in men with breast cancer. In the current study nearly 36% of men with invasive breast cancer who had a sentinel node biopsy had at least one positive node. While Rushby found in a study of 31 men with breast cancer 61% of the sentinel nodes were positive,17
a study by Boughey reported a rate of 37%.18
Male breast cancer is largely hormone-receptor positive.7,19
Giordano reported that 81% of men had ER positive tumors, similar to this study, (83%).7
Nearly 64% of women with early stage breast cancer have ER-positive tumors, substantially lower than reported for men.20
Giordano also reported that about 37% of men overexpressed HER2, much higher than observed in our data. 7
Men with stage III breast cancer had the highest percentage of HER2-overexpression, but this was less than half that reported by Giordano, although our data are more recent and included a combination of IHC and FISH tests. This difference in hormone receptor status between men and women in breast cancer phenotype is likely related to meaningful biological variation.
Perou identified 2 subtypes of hormone receptor positive female breast cancer that have very different prognosis.21
An unanswered question is whether male breast cancer has a molecular profile similar to female hormone positive-breast cancer or whether males develop a unique subtype of hormone receptor positive breast cancer. Even if the molecular profile of male breast cancer is identical to that of female breast cancer, the hormonal milieu in men cannot be assumed to be the same as in post-menopausal women. For systemic treatment, tamoxifen is a mainstay of therapy. With the publication of studies that show a small improvement in disease free survival,22,23,24,25
AIs have become recommended adjuvant treatment in post-menopausal women.26
The current study indicates that AIs are also being used in men either as sole initial therapy or after tamoxifen. However, AIs are not the standard of care and the endocrine physiology of men and women differ; this is one instance where treating hormone positive breast cancer in men as one would in women is not scientifically supported. The hormonal effects of AIs in men have not been adequately studied. The NCCN guidelines suggest that treatment of male breast cancer should be similar to that for post-menopausal breast cancer except that the use of AIs “is ineffective without concomitant suppress of testicular steroidogenesis.” 9
A trial of AIs in healthy men demonstrating a marked increase in circulating testosterone with only a 50% decrease in estradiol is consistent with this hypothesis.27
Therefore, the benefits of AIs alone in the treatment of male breast cancer should not be extrapolated from data in females as the efficacy may vary. Some investigators have suggested administering a gonadotropin-releasing hormone concurrently with an AI in men with breast cancer, but this requires further study.28
The decrease in mortality observed with tamoxifen and the lack of a mortality decrease in men treated with an AI supports the use of tamoxifen as the hormonal agent of choice in men with breast cancer. AI should not be used for the treatment of men with breast cancer outside the context of a clinical trial. The use of AIs in men in the present study suggests that additional research into the role and effect of AIs in men with breast cancer is urgently needed.
Almost 10% of men with DCIS received tamoxifen. There are no data to support the use of tamoxifen in men with in situ
breast cancer. In 2000 72% of women with node negative, ER positive invasive early stage breast cancer received tamoxifen,15
about 10% more than received hormonal therapy in this male breast cancer cohort.
Few men in this study received trastuzumab. However, trastuzumab was only approved by the Federal Drug Administration for use in metastatic disease during the study period. Approval for early stage disease was not granted until November 2006.
The factors associated with chemotherapy use were those associated with prognosis. Men with an increased risk of recurrence were more likely to receive chemotherapy. Approximately 65% of women diagnosed with positive nodes and ER positive early stage breast cancer received chemotherapy 15
compared to 66% of men diagnosed at stages I-III positive nodes and ER positive/borderline tumors.The chemotherapy regimens were similar to those used in women, with anthracycline- and taxane-based regimens preferred. In addition, married men were more likely to receive chemotherapy than men who were single, widowed, divorced or separated. This “marriage” effect has been noted in other studies, but is not well understood.29,30
Perhaps it is due to the increased social support of married individuals.
The study has several limitations. Orchiectomy as a treatment option cannot be ruled out. We do not expect that orchiectomy was a major therapy for male breast cancer in 2003-2004. We did not have physician specialties which might influence therapeutic decision-making. Patient preference for therapy was unknown, although we did know whether specific treatments were refused by the patient. Follow-up time was relatively short, especially for the early stage patients, a maximum of 47 months. This may limit the findings from the mortality data.
Notwithstanding these limitations, this population-based study among men with breast cancer representing communities across the US provides a unique perspective on the treatment of this uncommon malignancy. POC studies are helpful in evaluating dissemination of clinical trials into the community practice, treatment patterns across racial/ethnic and socioeconomic groups and community practice for the treatment of rare tumors, such as male breast cancer, for which there are no evidence based treatment recommendations. Future POC studies should address: 1) AI’s with and without GnRH analogues 2) non-anthracycline, 3) molecular profiling tools, 4) hormonal therapy alone, especially lymph node negative breast cancer, 5) biological therapies and 6) the risk of osteoporosis and the use of bisphosphonates.