Prognostic significance of tumor subtypes in male breast cancer: a population-based study Abstract # 1072 GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR J.P. Leone1, J. Leone2, A.O. Zwenger2, J. Iturbe2, C.T. Vallejo2, B.A. Leone2 Background Results Male breast cancer (MaBC) is an uncommon disease representing less than 1% of all breast cancers in the United States. Although both male and female breast cancer patients (pts) have significantly improved their mortality and survival rates, the progress in men has lagged behind. Information about prognostic factors and treatment strategies in MaBC is controversial, with most data extrapolated from female breast cancer. The classification of breast cancer according to tumor subtypes has been one of the major achievements towards our knowledge of this neoplasm in women. This classification has been a challenge in MaBC; although this topic has gained much attention in recent years, few reports have described the incidence of each tumor subtype and its role in prognosis with significant discrepancies. A better understanding of MaBC tumor subtypes would be critical to improve our assessment of prognosis and our treatment recommendations for these pts. A total of 657 patients were included in this study. Median age was 65 years (range 29- 97). Median follow-up was 10 months (range 0-23). There were 34 deaths reported. At diagnosis, 52% were 65 years or older, 82.6% were ductal, 46.4% were T1, 56.1% were N0, 7.6% were M1, 14% had breast conservation and 22% adjuvant radiotherapy. Median number of positive LNs was 0 (range 0-39). Table 1 shows the patient characteristics according to tumor subtype. Patients with TN tumors were younger (p=0.007), had higher grade (p=0.0001), presented with more advanced stage (p=0.01), more likely to have a mastectomy (p=0.001) and to die from breast cancer (p=0.0003). Unadjusted models revealed a decreased OS in those patients with stage IV (p<0.0001), T4 tumors (p=0.0081), M1 (p<0.0001), no surgery (p<0.0001), no radiation therapy (p=0.0347), ER- (p=0.0004), PR- (p=0.0002), HER2+ (p=0.04) and TN subtype (p<0.0001). In multivariate analysis, patients who had no surgery, those with stage IV and those with TN tumors had a significantly worse OS. Table 2. Univariate and Multivariate Analysis Variable Log-Rank P Wald Cox P HR 95.0% CI for HR Lower Upper Stage <0.0001 13.59 0.004   IV Reference I 9.294 0.002 0.126 0.033 0.478 II 10.196 0.001 0.186 0.066 0.523 III 4.223 0.04 0.254 0.069 0.939 Surgery 10.042 0.007 No Surgery Partial Mastectomy 3.395 0.065 0.219 0.043 1.102 Mastectomy 9.565 0.217 0.083 0.572 Radiation 0.0347 No Radiation Adjuvant Radiation 1.605 0.205 0.434 0.119 1.578 Tumor Subtype 15.706 Triple Negative HR+/HER2+ 7.727 0.005 0.165 0.046 0.588 HR-/HER2+ 1.264 0.261 0.281 0.031 2.572 HR+/HER2- 15.388 <0.001 0.104 0.034 0.323 Age at diagnosis 0.7006 Race 0.1425 Year of diagnosis 0.3746 Grade 0.1618 Histology 0.6715 T 0.0081 N 0.1095 M ER 0.0004 PR 0.0002 HER2 0.044 Marital status 0.3328 Table 1. Patient Characteristics   Tumor subtype: HR+/ HER2- HER2+ HR-/HER2+ Triple negative Total N % P All patients 552 84.0% 80 12.2% 8 1.2% 17 2.6% 657 Age at diagnosis, y <50 50-64 >64 65 185 302 77.4% 80.1% 88.3% 11 38 31 13.1% 16.5% 9.1% 2 4 2.4% 0.9% 6 5 7.1% 1.5% 84 231 342 0.007 Race White Black Other* Unknown 454 27 84.7% 87.1% 100.0% 62 16 11.6% 19.0% 6.5% 0.0% 1 1.1% 3.2% 14 536 0.448 Year of diagnosis 2010 2011 258 294 82.2% 85.7% 47 33 15.0% 9.6% 1.3% 12 1.6% 3.5% 314 343 0.088 Histology Ductal Lobular Other 87 83.6% 91.7% 85.3% 72 7 13.3% 8.3% 6.9% 3 2.9% 2.2% 4.9% 543 102 0.147 Grade I II III/IV 81 293 155 23 95.3% 89.3% 72.8% 74.2% 32 37 4.7% 9.8% 17.4% 22.6% 0.3% 2.8% 15 0.6% 7.0% 85 328 213 <0.0001 Stage III IV 218 189 97 35 13 90.1% 82.9% 81.5% 70.0% 72.2% 19 30 7.9% 13.2% 13.4% 22.0% 22.2% 1.8% 1.7% 2.0% 5.6% 2.1% 3.4% 6.0% 242 228 119 50 18 0.01 Surgery No surgery Partial mastectomy Mastectomy 78 441 63.5% 84.8% 86.0% 9 57 26.9% 11.1% 5.8% 0.8% 3.8% 4.3% 52 92 513 0.001 Radiation No radiation Adjuvant radiation 432 120 84.4% 82.8% 61 11.9% 1.4% 2.5% 512 145 0.894 Vital status Alive Dead 531 21 85.2% 61.8% 23.5% 11.8% 623 34 Cause of Death Breast cancer 45.0% 30.0% 14.3% 5.0% 20.0% 20 0.0003 Analysis of OS according to stage showed that pts with stage IV had significantly shorter survival (p<0.0001). Objective The aim of this population-based study was to analyze the characteristics of each tumor subtype in MaBC and its association with prognosis compared with other factors. Materials and Methods We obtained data from the National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) program, using the 18 registry (1973- 2011) database. We extracted all cases of men with microscopically confirmed invasive breast cancer diagnosed between 2010 and 2011 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status. Pts with other primary either before or after breast cancer were excluded. We analyzed the following variables: age at diagnosis, race, year of diagnosis, grade histology, ER, PR, HER2, T, N, M, stage, type of surgery, radiation therapy, laterality, number of lymph nodes (LN) examinined, number of positive LN, insurance, marital status, survival months, vital status and cause of death. Tumor subtypes were classified as: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple negative (TN). Pt characteristics were compared between tumor subtypes using chi2 or Fisher’s exact tests. Survival probabilities were estimated using the Kaplan Meier method. Log-Rank test analyzed differences in overall survival (OS) between groups. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. OS was shorter for pts with HER2 positive tumors compared with those who had HER2 negative disease (p=0.044). Conclusions In this cohort, we observed significant differences in patient characteristics according to tumor subtype. Most patients were diagnosed at age 65 or older and with early stages of disease. Although HER2+ and TN patients represented a small proportion of cases, it is important to recognize their worse prognosis. In addition to stage and surgery, tumor subtype has a clear influence on OS in MaBC. Finally, analysis of OS according to tumor subtype showed significantly longer survival for pts with HR+/HER2- breast cancers (p<0.0001). *American Indian/AK Native, Asian/Pacific Islander 1University of Iowa Holden Comprehensive Cancer Center, 2Grupo Oncológico Cooperativo del Sur email: jose-leone@uiowa.edu