Clinicopathologic Characteristics of Male Breast Cancer : A Report of 21 Cases in Radiotherapy Center of Hamedan , Iran

Male breast cancer accounts for less than 1% of all cancer in men and around 1% of all diagnosed breast cancer. Despite a significant raise in the last 25 years , among male patients, it still remains a rare disease (Cutuli et al., 2010). Given its low incidence, few studies have assessed risk and prognosis The literature about male breast cancer consists of retrospective studies and there are no randomized prospective data so the therapy is based on standards admitted from female breast cancer. Data obtained from retrospective analysis demonstrate that male breast cancer is not exactly the same disease as female breast cancer and notable differences have emerged (Bourthafour et al., 2011). Men tend to be diagnosed at an older age and higher estrogen receptor (ER) and progesterone receptor (PR) expression is notable in men. Male breast cancer exhibits more frequent lymph node involvement and more than 40% of individuals having stage 3 or 4 disease (Voney et al., 2009). Invasive ductal carcinoma is a predominant pathologic


Introduction
Male breast cancer accounts for less than of all cancer in men and around 1% of all diagnosed breast cancer.Despite a significant raise in the last 25 years , among male patients, it still remains a rare disease (Cutuli et al., 2010).Given its low incidence, few studies have assessed risk and prognosis The literature about male breast cancer consists of retrospective studies and there are no randomized prospective data so the therapy is based on standards admitted from female breast cancer.Data obtained from retrospective analysis demonstrate that male breast cancer is not exactly the same disease as female breast cancer and notable differences have emerged (Bourthafour et al., 2011).Men tend to be diagnosed at an older age and higher estrogen receptor (ER) and progesterone receptor (PR) expression is notable in men.Male breast cancer exhibits more frequent lymph node involvement and more than 40% of individuals having stage 3 or 4 disease (Voney et al., 2009).
Invasive ductal carcinoma is a predominant pathologic

Materials and Methods
We conducted a retrospective study from 2004-2011 with 21 male breast cancer patients.Inclusion criteria were male gender and histological confirmation of breast cancer and we excluded patients with insufficient follow up from this study.We analyzed epidemiologic data (age, personal and family history), tumor characteristics (size, histological type ,location, TNM stage, receptors), surgery, adjuvant chemotherapy and radiation therapy, hormonal therapy and survival (relapse, follow up, death).
The American joint committee on cancer (AJCC, 6 th , edition) TNM classification system was used for staging of the tumors.Immunohistochemical analysis to determine estrogen (ER) and Progesterone receptor (PR), Her-2(neu) and P53 status established in the line with word health organization criteria.All the patient were followed at 3-month intervals during the first and second years, 6-month intervals in the third to fifth year and yearly there after.

Results
Twenty one male patients at the mahdieh institute of oncology in Hamadan, Iran with a diagnosis of brest cancer between December 2004 and April 2011 were analyzed retros pectively.The median age was 49.24±14.15years.(range 30-83 years).A family history of breast cancer was noted in four cases.The main clinical complaint was a retroareolar mass in 85.7% of patients (n=18).The mean time before visiting by a doctor was 18 months (range 2-48 month).
Table 1 shows the general characteristics of the patients.Table 2 shows the tumor characteristic including, tumor stage, LN status, LN involvement.
Histologically, 85.7% (n=18) of pathological records report invasive ductal carcinoma and 4.7% (n=1) had ductal carcinoma insitu and 9.4% (n=2) had mixed histology including invasive medullary and ductal carcinoma.ER, PR and HER-2 (neu) status were evaluated in all patients and P53 status reported in 10 patients.
Table 3 shows the immunohistochemical characteristics of the patients.The treatment consisted of modified radical mastectomy in 85.7% (18 cases)of patients, Lumpectomy in 14.29% (3 cases) and 95.2% (n=20) of patients received adjuvant radiotherapy following surgery and chemotherapy.
As noticed before, 3 cases were at stage 1 but according to breast conservative surgery, we prescribed radiotherapy to them.The median dose of radiation was 50 GY, to chest wall and regional lymph nodes if indicated.
Chemotherapy with TAC, ACgT or CEF regimens have been delivered to 18 cases (85.7%).Hormonal therapy was delivered to 16 cases (76.1%) due to ER or PR positivity situation.One patient received palliative chemotherapy due to bone metastases at presentation.During median follow up of 30 months (3-84 month); we found distant metastasis in 4 case (19% ).The site of metastasis were in bone in 2 cases, Lung in 1 case and liver in 1 patient.During follow-up period, only one patient died due to metastatic disease.The mean time to recurrence detection was 30 months.

Discussion
According to very low incidence of male breast cancer, very few investigations have been conducted in Iran.In the past decade's according to Epidemiology and End results data (SEER), a rise in the incidence of male breast cancer from 1 to 1.2 per 100000 men have been reported from 1970to 2004(Speirv and Shaaba, 2008).The mean age at diagnosis is 60-67 years in different studies (Tawil et al., 2011), the mean age in our study is 49 years, this lower age correlate with lower age at diagnosis of breast cancer among Iranian woman with breast cancer.
Some of the main risk factors includes, genetic risk factor like BRCA-2 mutations, occupational risk factors include high temperature environments, gonadal dysfunction (Klienfelter syndrome) and Obesity.we could not define any occupational specify in this study unless the history of breast cancer in 4 patients family history (Cutuli et al., 2010;Bourthafour and Belbarake, 2011).
Positively of hormonal receptors is more frequent in men than woman (75-93%) (Davda et al., 2011;Tawil et al., 2011) and our data is comparable to other studies (76.1%,ER or PR positive).P53 expression has been detected in 0-54% of patient with male breast cancer by immunohistochemistry (Davda et al., 2011) and In our patient 4 (19%) were positive for P53.Tamoxifen has proved increasing survival rates in women with hormone positive receptors and is the standard treatment in both males and female breast cancer.In our study the mean time for recurrence for ER negative patient was 12 month and 36 month for ER positive patients.The tolerance of treatment was acceptable in our patients and no specific important known side effects of tamoxifen like deep venous thrombosis or impotence occurred.
According to small sample size in the current study, multivariate analysis was not done to explore the independent effects of the prognostic factors.
In conclusion, the percentage of cases of male breast cancer is very low compared to breast cancer in female.Limited studies in the literature make gender-specific finding difficult so future research of this entity involving multi institutional studies and longer follow up is essential to provide new insights about the biological and clinical factors of this rare cancer.