July/August 2005

Fig.3

Fig4.

Fig5.

Diagnosis: Invasive Ductal Carcinoma of the Breast

Histopathology:
Infiltrating ductal carcinoma was demonstrated with tubular formation in 20% of the specimen(Fig3). There is marked variation in the size of the nuclei with chromatin clumping and prominent nucleoli. Occasional mitosis may be demonstrated (Figure 4). Vascular and lymphatic invasion is present. Lymph node examination demonstrated 7 positive nodes out of 15 evaluated. Immunohistochemical staining demonstrated estrogen receptor (ER) positivity in 70% (Fig. 5), progesterone receptor (PR) positivity in 80%, Ki67 (a proliferation marker) positivity in 10%, and negative staining for the c-erb2 (HER2/neu) oncogene marker.

Discussion: In the US, male breast cancer accounts for approximately 1% of all breast cancers, with 1300 cases diagnosed in 2003, and it accounts for 0.2% of all malignancies in men. It is staged similarly to that of female breast cancer, and prognosis is linked to nodal status, tumor size, and presence of metastasis. Survival rates are similar between men and women for each individual stage. Unfortunately, due to delayed detection in males, the disease is usually more advanced at diagnosis. Node positive disease occurs in 28-60% of males, and metastases have a predilection for the liver, lung, and bone.

The greatest incidence occurs during the 6th decade of life, and a positive family history occurs in up to 30%. Females are 100 times more likely to develop breast cancer as opposed to their male counterparts.

Carcinomas comprise 96% of malignant breast neoplasms in males, a majority of which are invasive ductal carcinomas and <5% invasive papillary carcinomas. Lobular carcinoma is rare in males due to lack of terminal lobules in the male breast. Less common neoplasms include sarcomas, primary basal cell carcinomas of the nipple, medullary and squamous carcinomas and ductal carcinoma in situ. Estrogen receptor positivity occurs more commonly in males with breast cancer than in women, occurring in 75-94% of males. c-erb2 (HER2/neu) staining is associated with a poorer prognosis in women, and limited data in men suggest that there are lower rates of HER2/neu expression in male breast tumors.

Risk factors:
Risk factors for development of breast cancer in men include Klinefelter syndrome, infertility, orchiectomy, and history of bilateral orchitis, testicular injury and radiation exposure. It has also been suggested that prostate cancer patients treated with estrogen therapy are at an elevated risk, although firm data is currently not available. The BRCA2 gene has been linked to male breast cancer and can be used to identify males at higher risk, but no such link exists for the BRCA1 gene.

Clinical Presentation:
Typically, male breast cancer presents as a painless retroareolar mass, frequently eccentric to the nipple, with the upper outer quadrant being the second most common site. Unfortunately, 40-55% of patients have axillary involvement at the time of diagnosis. Ulceration, serous discharge, nipple inversion, retraction, edema, and an eczematous-like dermatitis occur in up to 30% of patients. It is important to note that nipple discharge in men is associated with carcinomas in nearly 75% of the cases and requires a malignancy workup.

Diagnostic Work-Up:
Mammography has a sensitivity and specificity of approximately 90% in detecting breast cancers in males. Ultrasound can also be utilized in specific cases that need additional diagnostic work-up. Fine needle aspiration (FNA) for tissue diagnosis followed by a core biopsy if FNA is inconclusive is mandatory in highly suspicious cases.

Treatment:
Treatment is similar to female breast cancer. Surgical resection and nodal staging is the most important treatment modality. Prognosis is dependent upon the stage of the disease at diagnosis. Since most male breast cancers are estrogen and progesterone receptor positive, hormonal therapy is promising. In several small studies tamoxifen has been demonstrated to improve survival in male patients with stage II and stage III disease. Radiotherapy can also be considered depending on the stage and nodal status.

References:

1. Giordano SH, Buzdar AU, Hortobagy GN: Breast Cancer in Men. Ann Intern Med. 2002; 137:678-687
2. Buzdar AU: Breast Cancer in Men. Oncology. 2003; 17(10):1361-1370.
3. Peppercorn J, Winer E: The Buzdar Article Reviewed. 2003; 17(10): 1370-1371.
4. Gennari R, Curigliano G, Jereczek-Fossa BA, Zurrida S, Renne G, Intra M, Galimberti V, Luini A, Orecchia R, Viale G, Goldhrisch A, Veronesi U: Male breast cancer: A special therapeutic problem. Anything new? Int J Oncology. 2004. 24:663-670.
5. Roubidoux MA, Patterson SK: Breast Cancer, Male. 2005. eMedicine.com
6. Volm MD: Male breast cancer. Curr Treatment Options in Oncology. 2003. 4(2):159-64.

This case is presented by Drs. Amy Cheng and David Kawamura.