Breast  Joint  clinic ( Tumor board)       May 14 , 2016

(Case presentation) Male Breast Cancer

  35yrs male, FH negative , PMH: negative
CC: Neck Pain (after falling down)
PE: Lt breast ill-defined mass in UUQ – cervical spine tenderness
MRI of spine: Vertebral pathologic fracture (C5-C6) with cord compression
US: Lt breast lobulated mass 30*33 mm in UUQ , Lt axillary suspicious LN
MG: Lt irregular mass
CNBx (Lt Br Mass) : IDC , G I , LVI + , ER + , PR + , HER2 negative , Ki-67  30-40%
Mets workup: Metastatic involvement in whole body bone scan in lower cervical, mid thoracic and lumbar                       
 spine & skull & Lt  4th ,  6th and 12th rib

Question: 1-Plan of treatment ? 2-Tamoxifen or Aromataz Inhibitor? Her2 directed therapy

Joint recommendation:

 Internal fixation of cervical vertebral body & Radiotherapy
(Hormon therapy with tamoxifen (no agreement on Trastuzumab

Discussion:
Male breast cancer (MBC) accounts for less than 1% of all breast cancers and less than 0.5% of all male cancer deaths in the United States. The worldwide female-to-male incidence rate ratio of breast cancer is 122:1. MBC compared to female breast cancers occur later in life with higher stage, higher grade, and more estrogen receptor–positive tumors [1, 2]. The median age of onset of MBC is 72 years of age, compared to 61 years in women [1]. The risk of male breast cancer is related to an increased lifelong exposure to estrogen (as with female breast cancer) or to reduced androgen. The strongest association is in men with Klinefelter syndrome (XXY); they have a 14- to 50-fold increased risk of developing male breast cancer and account for about 3% of all male breast cancer cases [2]. Also, men who carry a BRCA1 or, particularly, a BRCA2 mutation, have an increased risk of developing breast cancer. The following conditions have been reported to be associated with an increased risk of breast cancer in men: chronic liver disorders, such as cirrhosis, chronic alcoholism, and schistosomiasis; a history of mumps orchitis, undescended testes, or testicular injury; and feminization, genetically or by environmental exposure. In contrast, gynecomastia alone does not appear to be a risk factor men often present with more advanced stage than do women 
(2) .
All known histopathologic types of breast cancer have been described in men, with infiltrating ductal carcinoma accounting for at least 70% of cases. However, ILC in men is rare. A majority of male breast cancers are ER/PR+, and the percentage positive is greater than for female breast cancer [2]. Primary local treatment is typically total mastectomy. In some patients with early disease, BCT can be considered. However, the subareolar location of most male breast cancers and the small amount of breast tissue present in most men limits eligibility for BCT(2).
The same considerations regarding nodal surgery pertain for men as for women, with sentinel node biopsy the preferred treatment in clinically node-negative patients. The use of postmastectomy RT follows the same guidelines as for female breast cancer. Similarly, the use of systemic therapy follows the same guidelines as for women with postmenopausal
breast cancer[2].  
Metastatic breast cancer in men is treated identically to metastatic disease in women [2]. Hormonal manipulation has played a central role in the initial management of metastatic MBC due to the high incidence of hormone receptor- positivity. Multiple reports of orchiectomy as treatment of metastatic MBC indicate response rates between 32% and 67%, with a median survival of 56 months in responding patients versus 38 months in non-responding patients [1].
 Other ablative surgical procedures have been evaluated in metastatic MBC, either as primary treatment or at the time of disease progression after orchiectomy. Adrenalectomy and hypophysectomy are associated with response rates of 76% and 58%, respectively. These surgical procedures are rarely used today due to the associated morbidity and the introduction of medical management of metastatic disease[1].
Tamoxifen is the endocrine treatment of choice in metastatic disease. Objective response rates as high as 81% have been reported in ER-positive MBC with tamoxifen treatment [1]. Tamoxifen is the mainstay for adjuvant systemic therapy in ER+ male breast cancer; a study of 257 male breast cancer patients demonstrated a 1.5-fold increase in mortality in those treated with an AI versus tamoxifen[2].
Other agents, including aminoglutethimide, megestrol acetate, androgens, antiandrogens, steroids, and luteinizing hormone-releasing hormone (LHRH) analogs are associated with 50% to 70% response rates in ER-positive MBC [1].
Aromatase inhibitors are very active in women with hormone receptor-positive metastatic breast cancer, but their roles for men are less clear. Current data suggest that aromatase inhibitors may be considered following progression on tamoxifen. The role of fulvestrant, a selective estrogen receptor downregulator,is less clear [1].
Treatment with chemotherapy should be considered for patients with ER-negative tumors, for those with rapidly progressing disease, and for patients refractory to hormone therapy, similar to principles for initiating chemotherapy in women. HER2-directed therapies including trastuzumab, pertuzumab and lapatinib, have not been formally studied in metastatic MBC [1].
Eggemann et al, analyzed 257 male patients with hormone-receptor-positive breast cancer from numerous German population-based cancer registries treated with tamoxifen (N = 207) or aromatase inhibitors (N = 50). After the adjustment for the patient’s age, tumor size, node status, and tumor grading, the AI treatment was linked to a 1.5-fold increase in risk of mortality compared to tamoxifen. They decided that the overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. They recommended the tamoxifen as the treatment of choice for hormonereceptor-positive male breast cancer [3]. 
The incidence of HER2 overexpression/amplification in MBC appears to be low, and there are no prospective data evaluating survival outcomes with adjuvant trastuzumab in MBC. In a study with 147 stage 1 to 3 MBC cases, 9 patients were known to overexpress HER2, and only 5 of these patients received trastuzumab with chemotherapy . Nonetheless, its use should be considered in men with HER2-positive breast cancer.
 
References:
1-Jay R Harris,Monica Moro.”Diseases of the breast”. 5th ed. ,2014

2-DeVita et al,Cancer: Principles & Practice of Oncology, 10th ed. 2015

3-H. Eggemann,A Ignatov,BJ. Smith et al, Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breastcancer patients. Breast Cancer Res Treat   (2013) 137:465–470

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