DOI: 10.1148/radiol.2302030360
(Radiology 2004;230:553-555.)
© RSNA, 2004
Screening-detected Breast Cancer in a Man with BRCA2 Mutation: Case Report1
R. James Brenner, MD,
Jeffrey N. Weitzel, MD,
Nora Hansen, MD and
Peter Boasberg, MD
1 From the Eisenberg Keefer Breast Center (R.J.B.), Department of Surgical Oncology (N.H.), and Department of Medical Oncology (P.B.), John Wayne Cancer Institute, Saint Johns Health Center, 1328 22nd St, Santa Monica, CA 90404; Department of Radiologic Science, UCLA-Geffen School of Medicine, Los Angeles, Calif (R.J.B.); and Department of Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, Calif (J.N.W.). Received February 28, 2003; revision requested May 7; revision received June 10; accepted July 23. Address correspondence to R.J.B. (e-mail: james.brenner@stjohns.org).
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ABSTRACT
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Current indications for breast cancer screening in the male population are lacking, although family history of breast cancer may be such an indication. The authors describe a man with a history of clinically diagnosed right breast cancer who subsequently tested positive for the breast cancer susceptibility gene BRCA2 and received a diagnosis of mammographically detected left breast cancer at screening. The authors discuss the clinical implications of this approach to detecting male breast cancer.
© RSNA, 2004
Index terms: Breast neoplasms, male, 00.32 • Cancer screening • Genes and genetics
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INTRODUCTION
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Male breast cancer accounts for substantially less than 1% of cancers diagnosed in the United States; the estimated incidence in 2002 was 1,500 cases (1). Most cases of male breast cancer are considered sporadic, with various risk factors described (2,3). There is no consensus as to what, if any, subgroup of men might benefit from screening mammography to facilitate the reduction in mortality rates that has been achieved in the female population (4,5). The purpose of this report is to describe an asymptomatic man with a history of prior right breast cancer in whom a BRCA2 gene mutation was subsequently identified and who underwent unilateral screening mammography of the contralateral breast.
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Case Report
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The institutional review board of Saint Johns Health Center granted us exemption from their review for this report. However, the patient did give written informed consent for the publication of this case.
A 65-year-old man 2 years prior to presenting to our clinic received a diagnosis of a 1.5-cm infiltrating ductal carcinoma of the right breast following removal of a palpable retroareolar mass and subsequent mastectomy. The tumor was positive for estrogen and progesterone receptors, contained microscopic foci of both ductal carcinoma in situ and lobular carcinoma in situ, and was stage IIA, with one of 33 axillary lymph nodes containing a 1-cm metastatic deposit and no evidence of distant disease. He received a 6-month course of chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, followed by tamoxifen.
Although none of the patient’s five siblings and neither parent had a history of breast cancer and he was not of Jewish ancestry, it was determined on the basis of previous reports (1,2) that there was a 4%–21% probability that he had a BRCA mutation. He therefore underwent BRCA1 and BRCA2 testing with use of sequencing (Myriad Genetics Laboratory, Salt Lake City, Utah), which revealed a deleterious germ line BRCA2 mutation. Consequently, it was recommended that he follow a heightened surveillance regimen that included annual screening, physical, and mammographic examinations.
At the patient’s second annual mammographic examination, a new 8-mm nonpalpable mass with lobulated margins was detected in the lower inner retroareolar region of the left breast (Figure). Physical examination results suggested mild gynecomastia that had not changed from prior findings, and minimal mammographic findings of gynecomastia, as evidenced by slight nonfocal tissue density in the subareolar regions, were noted. He underwent stereotactic percutaneous core-needle biopsy, which revealed the mass to represent infiltrating ductal carcinoma. The lesion was thought to be a new primary cancer on the basis of the different hormone receptor profile (the first cancer was progesterone receptor positive, and the second cancer was progesterone receptor negative), the rarity of breast metastases to the contralateral breast as the sole site of disease, and the absence of circumscribed margins of the mammographic mass, which characterize breast metastases (6). Mastectomy of the left breast and dissection of two left axillary sentinel nodes were performed, and neither revealed other sites of malignant disease or metastatic disease in the lymph nodes.
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Figure a. (a) Mediolateral oblique and (b) craniocaudal views of left breast on baseline mammograms (right) obtained at the time of right breast mastectomy and on second annual screening follow-up mammograms (left). Black arrow points to a new lobulated mass, which represented nonpalpable carcinoma, at the 6-o’clock position. White arrows point to noncancerous lymph nodes, which were unchanged between the two examinations.
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Figure b. (a) Mediolateral oblique and (b) craniocaudal views of left breast on baseline mammograms (right) obtained at the time of right breast mastectomy and on second annual screening follow-up mammograms (left). Black arrow points to a new lobulated mass, which represented nonpalpable carcinoma, at the 6-o’clock position. White arrows point to noncancerous lymph nodes, which were unchanged between the two examinations.
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Discussion
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Male patients are usually referred for mammographic evaluation because of physical signs or symptoms—most commonly palpable lumps, nipple discharge, or both. Mammographic features that help distinguish the more common condition of gynecomastia from malignancy have been described (7). Mammographic screening for male breast cancer has not been advocated, in part because of the relatively low incidence of the disease and the inability to sufficiently define specific variables that help identify groups of patients at substantial risk; however, several risk factors have been described. Despite SEER (Surveillance, Epidemiology, and End-Results) data indicating a significantly increased empiric risk (standardized incidence ratio, 30; 95% CI: 15, 52) of contralateral new primary breast cancer in such male patients, the absolute risk is less than that for women who have had unilateral breast cancer previously (3).
The described patient had infiltrating ductal carcinoma with ductal carcinoma in situ, as well as lobular carcinoma in situ. Although unusual histologic findings of male breast cancer have been reported (7,8), most of these cancers are of ductal origin. Lobular development in the male breast is unusual in the absence of an estrogen stimulus, which may come from exogenous sources such as hormonal treatment for prostate cancer. Lobular malignancy is rare without a known source of estrogen stimulus, and the presence of lobular carcinoma in situ in this patient could not be explained. However, estrogen receptor–positive breast cancer in male patients is not uncommon and is typically responsive to hormonal treatment such as that with tamoxifen, which was prescribed in this case following chemotherapy for the first tumor. The effect of adjuvant tamoxifen on the incidence of new primary breast cancer in BRCA carriers is uncertain, although the results of one retrospective analysis suggest that it has a protective effect (4).
Although a family history of breast cancer and Jewish ancestry are among the risk factors for male breast cancer, mutations of the recently discovered BRCA2 gene may account for a substantial proportion of cases. Current estimates suggest that 4%–21% of unselected cases of male breast cancer (ie, cases of patients with none of the primary risk factors such as Jewish ancestry or family history) may be attributable to BRCA2 gene mutations, and a more recent report suggests that BRCA1 also may be seen in some male patients with breast cancer (1,2,9). A substantially higher probability of a BRCA mutation exists when the patient has the additional characteristic of a family history of early-onset breast cancer or ovarian cancer. There are few available data on the risk of new primary breast cancer among men who have had breast cancer and have a BRCA2 mutation, although women with a BRCA2 mutation have an up to 52% lifetime risk of having subsequent contralateral breast cancer (4).
Although there has been editorial comment regarding screening mammographic evaluations of men, to our knowledge, no evidence-based data are available (10). Similar to the patient described in this report, two male patients from the same institution who were reported on separately had cancer that was detected at screening mammography; however, since their genetic status is unknown, one can only speculate about their BRCA status (7,11).
The prognosis associated with male breast cancer is similar to that associated with female breast cancer when the prognosis is adjusted for stage. In the absence of screening, most male patients with breast cancer present with clinical symptoms and more advanced disease. Because this disease affects so few men, we believe the diagnosis of breast cancer in male patients should prompt genetic counseling and screening. The identification of a gene mutation may affect the treatment of not only the patient but also other family members (2,12).
The discovery of the BRCA2 mutation in the described patient prompted increased surveillance and resulted in the identification of a small screening-detected cancer with no spread to the lymph nodes, unlike his previous tumor, which was node positive. Cancer risk counseling and heightened surveillance are recommended in the setting of male breast cancer, regardless of the presence or absence of a family history (13). Although the use of screening mammography is more commonly recommended primarily for men who are at risk and have gynecomastia (13) or any identifiable parenchyma on a baseline mammogram, we believe it should be considered for any male patient with a BRCA mutation.
In conclusion, male breast cancer may be the presenting feature indicating that a family has a BRCA mutation and in our opinion warrants referral for cancer risk assessment. The presence of a gene mutation probably indicates substantial risk for a subsequent new primary breast cancer and should prompt increased surveillance, including consideration of screening mammography. The findings in the described case illustrate the potential to have an important and positive prognostic effect on a subsequent cancer diagnosis.
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ACKNOWLEDGMENTS
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The authors acknowledge Monica Y. Almanza, MD, for her assistance in this report.
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FOOTNOTES
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Author contributions: Guarantor of integrity of entire study, R.J.B.; study concepts and design, all authors; literature research, R.J.B.; clinical studies, all authors; data acquisition, R.J.B., N.H., P.B.; data analysis/interpretation, R.J.B., J.N.W.; manuscript preparation, R.J.B., J.N.W.; manuscript definition of intellectual content, editing, revision/review, and final version approval, all authors
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REFERENCES
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ABSTRACT
INTRODUCTION
