Male breast cancer: a 20-year multicenter experience

Background-. Male breast cancer (MaBC) is a rare disease and accounts for approximately 1% of breast cancer. Treatment is largely extrapolated from female breast cancer (FeBC) due to lack of data in MaBC. However, there are distinct features of MaBC that warrant different treatment approach. We aim to better characterize the risk factors, clinicopathologic features, treatment and outcome of MaBC patients from 6 hospitals across Steward Healthcare Network. Methods-. 107 men with breast cancer were identified from the respective cancer registry at Steward and 64 patients were included with complete medical records. Their clinical, histopathological and treatment records were retrospectively reviewed. Results-. Of these 64 patients, median age at diagnosis was 68 years, 58 patients were white (90.6%), 13 patients had family history of breast or ovarian cancer (20.3%), 4 patients tested positive for BRCA2 (6.25%), 1 patient had liver cirrhosis, and no patient had Klinefelter syndrome or testicular dysfunction. 57 patients (89%) presented with a breast mass with 4 of these patients having nipple changes (6.25%). 59 patients (92.2%) had invasive ductal carcinoma, 42 patients (65.6%) had grade 2 tumors, 31 patients (48.4%) had tumor size between 2-5 cm, and 31 patients (48.4%) had lymph node involvement at time of diagnosis. 62 patients (96.8%) had M0 disease at time of diagnosis. 97% of patients had ER positive cancer, 87.5% of patients had PR positive cancer, and 7.8% of patients had HER2 positive cancer. Most patients underwent mastectomy (87.5%). Only 16% of patients with T1 tumors (5/31) underwent breast conserving surgery. 10 patients (15.6%) received neoadjuvant chemotherapy, 35 patients (54.6%) received adjuvant radiation therapy, 19 patients (30%) received adjuvant chemotherapy, and 98.4% of patients received adjuvant hormonal therapy. The median follow up was 71.5 months (range 6-250 months), 5-year survival rate was 86.9% (95% CI, 74.5% to 93.6%), 5-year relapse free survival rate was 89.9% (95% CI, 77.4% to 95.7%) and 10-year survival rate was 58.1% (95% CI, 41.0% to 71.8%). The presence of distant metastasis at the time of initial diagnosis was the only factor associated with shorter overall survival (hazard ratio 22.54, p <0.0001). Conclusion-. Majority of MaBC patients present with palpable breast mass and the tumors are almost exclusively hormone receptor positive. Majority of patients present without distant metastasis and received surgical therapy however only a small subset of patients received breast conserving surgery for T1 tumor. Almost all patients received adjuvant hormonal therapy. Overall survival and relapse free survival in our cohort is similar to historic reports in female breast cancer. Citation Format: Guoliang Zheng, Haoyang Wang, Fang-Yu Liu, Jose Pablo Leone. Male breast cancer- a 20 year multi-center experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-23-01.

Introduction Male breast cancer (MBC) is extremely rare and represents less than 1% of breast cancer (BC). There are limited studies investigating clinical outcomes of MBC. Although the survival of female breast cancer (FBC) has increased over the years; there is a substantial knowledge gap regarding survival trends of MBC. Given the rarity of MBC, recommendations on the treatment of MBC are scarce and mainly extrapolated from the data from FBC. We aim to analyze the clinical characteristics and annual trend in the survival of MBC compared to FBC. Methods We queried the National Cancer Database for BC patients (pts) diagnosed during 2004-2020. The demographic, clinicopathological and treatment characteristics were summarized by sex. An inverse-propensity weighted cox regression model was used to assess the association between sex and overall survival. Propensity weights were based on age, race, insurance, T, N, M-stages, subtype, grade, chemotherapy (CT), radiation (RT), hormone therapy (HT), and time to definitive treatment. To compare survival trends over time, year of diagnosis and its interaction with sex were included in the model. All analyses were performed at a significance level of 0.05. Results A total of 24, 055 MBC and 2,532,470 FBC pts were identified. MBC pts were older (mean age: 65.6 vs 61.4 years), Blacks (12.8 vs 11.2%) and had more government insurance (55.7% vs 45.8%) compared to FBC (all p< 0.001). Compared with FBC, more MBC pts had stage IV (7% vs 4.7%), fewer pts had stage I (33.4% vs 44.8%), more pts had larger tumors (cT4: 6% vs 3.7%), and node positive disease (18.5% vs 15.5%) (all p< 0.001). MBC were more likely estrogen (ER) (88.5% vs 78.5%) and progesterone receptor (PR) (79.6% vs 68%) positive and less likely HER2 receptor positive (7.9% vs 9.3%) or triple negative (2.8% vs 7.6%) compared to FBC (all p < 0.001). Male pts with BC received less CT (38.7% vs 41.2%), RT (32% vs 52.6%), HT (59.8% vs 62.5%) compared to females with BC (p < 0.001). The overall survival (OS) rates were lower in MBC compared to FBC (5-year: 73% vs 83%; 10-year: 54% vs 70%, p < 0.001). In the propensity weighted cox-regression model, males had higher mortality compared to females with BC (HR 2.8, 95% CI 2.88 - 2.9, p < 0.001). This difference in OS was observed in TNBC (HR 1.2, 95% CI 1.21 - 1.24) and HER2+ (HR 2, 95% CI 1.9 - 2.0), but not in ER/PR+ HER2- BC (HR 0.78, 95% CI 0.78 - 0.79), all p < 0.001. The 5-year and 10-year OS of early-stage MBC and advanced MBC was lower compared to FBC (Early-stage:- 5-year: 77% vs 86%, 10-year: 57% vs 72%, HR 2.9, 95% CI 2.9-2.92; Advanced: 5-year: 23% vs 28%, 10-year: 8% vs 13%, HR 1.14, 95% CI 1.14 – 1.2, both p < 0.001) The 5-year OS rates increased steadily for FBC from 2004-2015; however, the survival rates were not improved for MBC (Table 1) (p-value for interaction of sex and year of diagnosis was 0.02). Conclusion MBC pts have higher mortality rates and poor clinical outcomes compared to FBC pts. We demonstrate that the survival of MBC pts has not improved over the last decade, even after adjusting for clinicopathological and treatment characteristics. These findings suggest the need to investigate personalized treatment interventions for male breast cancer pts, especially given the disparate trends in survival among male and female BC over a period of time. Table 1: Survival trend by sex - overall BC cohort Citation Format: Arya Mariam Roy, Anthony George, Archit Patel, Malak Alharbi, Kristopher Attwood, Shipra Gandhi. Clinical characteristics and survival trends of male breast cancer in the United States: A propensity score matched analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-03.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

BackgroundTo investigate the clinicopathological features and prognostic factors of male breast cancer (MBC) and female breast cancer (FBC) patients.MethodsA total of 90 MBC and 180 FBC patients were included in this retrospective study. The clinicopathological features, disease-free survival rate (DFSR), and overall survival rate (OSR) were compared between the two groups. Cox proportional hazard model was used to analyze the factors affecting the survival rates.ResultsMost MBC were invasive ductal carcinoma (70/90, 77.8%) and luminal type (83/90, 92.2%), and were treated with modified radical mastectomy (78/90, 86.7%). Compared with women, there were more patients with one-set age of ≥70 years old, having family history of cancer, comorbid with underlying diseases in the male patients. They also had higher portion of patients at T3 and T4 stages. The rates of male patients receiving adjuvant radiotherapy, chemotherapy and endocrine therapy were lower (P<0.05) than female patients. OSR and DFSR were lower in the male patients than in the female patients (P<0.05). T stage, TNM stage, the status of progesterone receptor and endocrine therapy were independent prognostic factors for survival of MBC (P<0.05); TNM stage, chemotherapy or endocrine therapy were independent factors for survival of FBC (P<0.05).ConclusionsCompared with FBC, MBC occurs later with more underlying diseases and lower survival rates. MBC is less active in adjuvant therapy and endocrine therapy. Since MBC has more luminal type, increased endocrine therapy may improve the survival.

Background: Male breast cancer (MaBC) is rare, comprising &amp;lt;1% of all breast cancers in the United States. The low incidence of MaBC limits the ability to conduct clinical trials specifically for this population. Due to the paucity of research on MaBC, current understanding regarding MaBC biology, pathology, and treatment strategies has been primarily based on evidence extrapolated from research on female breast cancer (FBC) patients. Traditional diagnostic biomarkers such as ER, PR, and HER2, as well as newer multi-gene prognostic signatures, are employed when making treatment decisions for both MaBC and FBC. However, limited empirical data is available to support the use of identical laboratory biomarkers and molecular signatures in both MaBC and FBC. The 70-gene risk of distant recurrence signature, MammaPrint (MP), and the 80-gene molecular subtyping signature, BluePrint (BP), are commonly used to help make treatment decisions for both MaBC and FBC patients. To support the clinical utility of MP and BP in MaBC, this study aims to elucidate whether significant molecular biological differences exist between MaBC and FBC. To address this knowledge gap, we evaluated and compared 1) MP index results within Low Risk (LR) and High Risk (HR) groups, 2) MP and BP gene expression, and 3) differentially expressed genes within the full genome and their associated biological pathways between tumors from MaBC and FBC. Methods: This analysis included a total of 817 breast tumor samples sent to Agendia, Inc. (Irvine, CA) for MP and BP testing. Full-transcriptome microarray data were available for 1) a subset of 400 post-menopausal FBC patients enrolled in the FLEX Registry (NCT03053193) and 2) 80 MaBC pateints, 32 of whom enrolled in the FLEX registry and 48 non-study patients for whom data were limited to metadata and quality metrics routinely captured for diagnostic testing. Data from all patients were de-indentified. Differences in mean MP indices between FBC (N=400) and MaBC (N=417) according to MP Risk classification (LR or HR) were analyzed using a Z-test. Differential gene expression analysis was performed using the R-limma package in which gene expression data were quantile normalized. Pathway analyses were performed using GOseq. Differentially expressed genes (DEGs) were identified between FBC (N=400) and MaBC (N=80) for whom full transcriptome microarray data were available. DEGs were defined as those with a fold change of &amp;gt; 2 and an adjusted P value of &amp;lt; 0.05. Results: All patients in this study had hormone positive, HER2 negative early-stage breast cancer. There was no statistical difference in the average MP index between MaBC and FBC classified as MP LR (P=0.273) or those classified as MP HR (P=0.692). Gene expression comparison revealed 166 DEGs between MaBC (N=80) and FBC (N=400), 99 DEGs between MP HR MaBC (N=42) and MP HR FBC (N=200), and 290 DEGs between MP LR MaBC (N=38) and MP LR FBC (N=200). Pathway analyses revealed that downregulated genes in MaBC compared to FBC enriched to immune-related functions, including B-cell mediated immunity, whereas upregulated genes were associated with hormone metabolic processes. In all comparisons, expression of MP or BP genes was not significantly different. Conclusions: We found similar MP index distributions between MaBC and FBC. Importantly, differential gene expression between MaBC and FBC provides novel insight into the mechanisms underlying MaBC. Although these data reveal biological distinctions between male and female breast cancer, MP and BP assay performance is preserved across both groups. Further studies are needed to assess clinical outcomes; however, these findings support the use of MP risk of recurrence assay and BP molecular subtyping assay for prognosis and informing treatment decisions in MaBC. Citation Format: Jennifer Crozier, Julie Barone, Kalyan Banda, Beth Lesnikoski, Robert Maganini, Sami Diab, Ian Grady, Thomas Lomis, Charles Cox, Amy Truitt, Benjamin Nota, Andrea Menicucci, Erin Yoder, William Audeh, FLEX Investigators Group. Differential gene expression analysis and clinical utility of MammaPrint and BluePrint in male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-11.

Male breast cancer (MBC) is a rare disease, with clinical and prognostic features still controversial. The aim of this study was to discuss the clinical characteristics and prognosis of MBC. Clinical data related to 71 MBC patients was reviewed. The radio of MBC to female breast cancer (FBC) was 42:10 000. Age related to the diagnosis of MBC ranged from 43 to 84 years with the median age as 62 years old, older than the FBC patients (t = 6.355, P = 0.000). The percentage of invasive ductal carcinoma in MBC patients was much higher than in FBC patients (χ(2) = 29.875, P = 0.000). The positive rate of estrogen receptor (ER) was significantly higher than those in FBC patients and the positive rates of human epidermal growth factor receptor-2 (HER-2) were less frequently (χ(2) = 3.741, P = 0.048 and χ(2) = 12.845, P = 0.002) seen. Data from the univariate and multivariate analysis showed that the 3-, 5- and 10-year survival rates of MBC were 82.6%, 74.0% and 47.4% respectively, significantly higher than those in FBC patients (P = 0.004, P = 0.046). Patients with positive HER-2 showed worse prognosis than HER-2 negative patients in MBC patients (χ(2) = 4.219, P = 0.040). There were significant clinic-pathologic and prognostic differences between FBC and MBC patients. The HER-2 positivity seemed to be an important factor for the prognosis and treatment of patients with MBC.

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 Information@Karger.de www.karger.com treated with tamoxifen in the adjuvant setting for an estrogenreceptor positive tumor. This choice is a reasonable selection, since retrospective studies show that tamoxifen is active in metastatic male breast cancer and suggest that adjuvant tamoxifen may improve survival [5]. Despite appropriate adjuvant therapy, the patient described in this case developed a relapse while on tamoxifen and was treated with an aromatase inhibitor. Although aromatase inhibitors have excellent activity in post-menopausal women with breast cancer, the data regarding the effectiveness of aromatase inhibitors in male patients are scant. Several case reports have described male patients who responded to aromatase inhibitors. One male patient with locally advanced disease experienced tumor shrinkage on letrozole [6], and a male patient with metastatic breast cancer had a complete response to letrozole after previously receiving tamoxifen [7]. In our series of 5 male patients with metastatic disease treated with aromatase inhibitors, none had a clinical response but 2 had stable disease for greater than 6 months [8]. It is unclear whether aromatase inhibition results in complete estrogen suppression in men. In small studies of healthy male volunteers, anastrozole was found to lower estrogen levels, but not as effectively as in women [9]. Additionally, testosterone levels increased by 58% among men treated with anastrozole. Among men on aromatase inhibitors, it is possible that the hypothalamic-pituitary feedback loop results in an increase substrate for aromatization, and thus prevents complete estrogen suppression. By adding a gonadotropin-releasing hormone analog, such as leuprolide, the negative feedback loop would be interrupted and complete estrogen suppression may be achieved. We have reported on 2 patients who responded to such combination, including one who did not respond to an aromatase inhibitor without a GNRH analog [10]. Unfortunately, a clinical trial sponsored through the Southwest Oncology Group designed to test the combination of goserelin Approximately 1% of all breast cancers are diagnosed in men. In 2008, an estimated 1,990 new cases will be diagnosed in the United States [1]. Although the disease remains relatively rare, the incidence of breast cancer in men has been increasing [2]. Men tend to present with more advanced disease than women, probably due to both lack of awareness of male breast cancer and the fact that women are being screened with mammography. Considerable uncertainty still exists as to the optimal management of breast cancer in men. In the article by Bauerschmitz in this issue of ONKOLOGIE, a case of male breast cancer is described [3]. The presenting features of this tumor display some of the typical features of male breast cancer. It is an invasive ductal carcinoma, which is the most frequent histology seen in male patients. All other histologies (lobular, mucinous, medullary, and papillary) account for only 5% of cases [2]. The tumor is also strongly estrogen receptor positive. Although somewhat counterintuitive, male breast cancers are more likely than female breast cancers to express estrogen and progesterone receptors: over 90% of male breast cancers are estrogen receptor positive. Conversely, cancers of the male breast are less likely to be HER2 positive. One series of 99 male breast cancers reported that only about 10% of tumors had HER2 amplification [4]. Thus, the rates of HER2 amplification are substantially lower in male versus female breast cancers. Recommending a particular therapy for men with breast cancer is challenging, because no randomized trials have been done to determine optimal treatment. Due to the rarity of this disease, most treatment recommendations are based on retrospective series or are extrapolated from clinical trials in women with breast cancer. Using data generated from clinical trials conducted with women is probably reasonable when making chemotherapy decisions, but may be more problematic when choosing hormonal therapies given the different hormonal milieu. The patient described in this case report was Male Breast Cancer: It’s Time for Evidence Instead of Extrapolation

Background: Male breast cancer (MBC) is a very rare disease. There are ambiguous opinions about treatment outcomes and survival outcome. This study aimed to investigate the incidence and survival outcome of male breast cancer in Korea. Additionally, we evaluated the differences between male and female breast cancer (FBC). Method: We identified 226,612 breast cancer cases diagnosed between 1999 and 2016 in the Korea Central Cancer Registry (KCCR). We retrospectively analyzed the data that patient demographics and clinical information between MBC and FBC. Overall survival (OS) was estimated according to sex, age, histologic type, stage. Results: Of the 226,612 patients, 1,052 had male breast cancer patient and 225,560 had female breast cancer patients. The ratio of male to female was 0.0047. MBC patients were diagnosed the most frequently in those aged 60-69 years. In contrast, FBC was diagnosed the most frequently in those aged 40-49 years (p&amp;lt;.0001). Male patient received less adjuvant therapy than female patients (radiotherapy, MBC vs. FBC = 8% vs. 22%, chemotherapy, 41.9% vs. 55.7%, p&amp;lt;.0001). The 5-years OS rates after the diagnosis of breast cancer were 88.8% for all patients. MBC has a lower 5-years OS rate than FBC (76.2% for men, and 88.9% for women, p&amp;lt;.0001). Both groups showed lower survival in patients aged ≥60 years. The 5-years OS rates of invasive type were 75.8% for men and 89% for women. The OS rate was lower in both groups as the stage increased. Conclusion: We found that there is a difference between MBC and FBC. The survival outcomes in MBC were worse than that of FBC. This study showed the different OS patterns according to the age, histology, and stage. Based on these results, clinicians need to recognize the difference from FBC when treating MBC. Citation Format: Eungyeong Lee, Heein Jo, Jai Hong Han, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Myong Cheol Lim, Young-Joo Won, Eun Sook Lee, Eun Sook Lee. Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-05.

Immunohistochemical profiling studies carried out on female breast cancer has been extrapolated to breast cancer in males. Although, we do not know if it really reflects the reality of this pathology in males patients since the studies are often retrospective and studying a limited number of patients. The objectives was to describe particualrities of breast cancer in males and analyze the evolutionary characteristics and study the molecular profile of this rare disease in Tunisian men. It is a retrospective, descriptive and analytic study carried out over a period of 15 years in the departments of gynecology-obstetrics, general surgery, medical carcinology and anatomopathology of the Farhat Hached Teaching Hospital in Sousse, Tunisia. Fourty five patients were included.The most common histological type was invasive ductal carcinoma (95% of our patients). Our series was divided into 3 immunohistochemical groups with a majority group: luminal A (68.2%), followed by luminal B (27.3%) and only one patient had a triple negative type tumor (4.5%).The Overall survival rate (OSR) at 5 and 10 years was 83.2% and 76.8% respectively. Recurrence-free survival (RFS) at 5 and 10 years was 64.5% and 58.6%, respectively. The OSR was influenced significantly by age, clinical and histological size of the tumor, the presence of distant metastases and the occurrence of recurrence. Recurrence-free survival (RFS) was influenced by age, clinical and histological size of the tumor, and infiltration of the dermis. Breast cancer in males has similarities with women's breast cancer. However, it remains diagnosed at a later stage.

Male breast cancer is a rare neoplasm, and its treatments are based on those of female breast cancer. This study aimed to analyze 20 years of male breast cancer clinical characteristics and treatment results from the Middle Black Sea Region of Turkey. A retrospective analysis of 16 male breast cancer patients treated in our tertiary hospital between 1994 and 2014 was performed. Epidemiologic data, tumor characteristics, and treatments were recorded and compared with 466 female breast cancer ((premenopausal; n=230)+(postmenopausal n=236)) patients. The 5-year disease-free and overall survival rates were calculated. Male breast cancer constituted 0.1% of all malignant neoplasms in both sexes, 0.2% of all malignant neoplasms in males, and 0.7% of all breast cancers. The mean patient age in this study was 59.8±9.5 (39-74) years. The mean time between first symptom and diagnosis was 32.4±5.3 (3-60) months. Histology revealed infiltrative ductal carcinoma in 81.3% of patients. The most common detected molecular subtype was luminal A, in 12 (75%) patients. Estrogen receptor rate (93.8%) in male breast cancer patients was significantly higher than that in female breast cancer (70.8% in all females, p=0.003; 68.2% in postmenopausal females, p=0.002) patients. Most of the tumors (56.3%) were grade 2. Tumor stage was T4 in 50% of males. The majority (56.3%) of the patients were stage III at diagnosis. Surgery, chemotherapy, radiotherapy and endocrine-therapy were applied to 62.5%, 62.5%, 81.2% and 73.3%, respectively. Loco-regional failure did not occur in any of the cases. All recurrences were metastastic. The 5-year disease-free and overall survival rates in male breast cancer patients were 58% and 68%, respectively. Tumors found in male breast cancer patients were similar in size to tumors found in females, but they advanced to T4 stage more rapidly because of the lack of breast parenchymal tissues. The rate of estrogen receptor expression tended to be higher in male breast cancer patients than in female breast cancer patients. Metastasis is the most important problem in initially non-metastatic male breast cancer patients.

ObjectiveWith the emergence of new antibody coupled drugs, the treatment decisions of patients with low and ultra-low HER2 expression have been reshaped. However, the epidemiological characteristics of relatively rare male breast cancer are still unclear. This study discusses the clinicopathological and immunophenotypic characteristics of male invasive breast cancer with low and ultra-low HER2 expression.MethodsThe clinicopathological and immunophenotypic features of 106 cases of male invasive breast cancer were retrospectively analyzed. HER2 was evaluated according to ASCO/CAP guidelines. The cutoff value of HER2 positive cell staining was > 10%. HER2 negative cases were divided into HER2 low expression (IHC = 1+/2 + and ISH without amplification) and HER2-0 (IHC-0, HER2 null and < 10% weak staining of cell membrane). The clinicopathological characteristics and prognosis of the cases were collected.Results106 male patients with invasive breast cancer from 2015 to 2024 were included in this study, and more than 85% of male breast cancer histological types were invasive ductal carcinoma. Immunophenotype: There were 23 cases of HER2-zero (including 13 cases of HER2 ultra-low), 72 cases of HER2 low, 11 cases of HER2 positive, and the HER2 positive rate was 10.38%, and the incidence of low expression was 67.93%; The incidence of HER2 low in male breast cancer was significantly higher than that in female breast cancer, and the difference was statistically significant (P < 0.05). In terms of prognosis, there was no statistical difference between HER2 low male breast cancer and female breast cancer (P > 0.05). There was no statistical difference in survival prognosis between different HER2 status in the male breast cancer cohort.ConclusionMale invasive breast cancer is rare, and it is more common in the elderly over 60 years old. The positive rate of ER and PR is high, and the incidence of HER2 low is high. The high HER2 low expression rate of male breast cancer can provide a new anti-HER2 treatment decision.

Background: Hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) breast cancer (BC) is more prevalent in male patients compared to female counterparts. Gender associated differences along with molecular differences, immune system, and other factors might play a crucial role in disease management. Here, we characterized molecular and immune differences between HR+/HER2- MaBC and FeBC. Methods: 8156 female (HR+/HER2-, n = 5232) and 121 male (HR+/HER2-, n = 97) BC samples were analysed by next-generation sequencing (NextSeq; WES, NovaSeq) and Whole Transcriptome Sequencing (WTS; NovaSeq) (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) (high ≥10 mt/MB) was calculated. Microsatellite-instability (MSI) was tested by IHC and NGS. Statistical significance was determined using chi-square and Mann-Whitney U test with p-values adjusted for multiple comparisons (q &amp;lt; 0.05). Results: The proportion of HR+/HER2- subtype was significantly higher in MaBC (80.17% vs 64.14%, p&amp;lt;0.05) compared with FeBC. HR+/HER2- MaBC had higher frequency of BRCA2 (10.64% vs 4.38%, p&amp;lt;0.05), GATA3 (22.68% vs 14.11%, p&amp;lt;0.05), but lower frequency of TP53 (3.45% vs 30.76%, q&amp;lt;0.05), ESR1 (4.12% vs 13.62%, p&amp;lt;0.05) and CDH1 (1.06% vs 17.43%, q&amp;lt;0.05) compared to HR+/HER2- FeBC. Compared to HR+/HER2- FeBC, MaBC had lower frequency of TMB-high (2.2% vs 9.08%, p&amp;lt;0.05), but there was no difference in dMMR/MSI-high (0% vs 0.61%, p=1) or PD-L1 (IHC, 22C3) positivity (21.21% vs 19.47%, p=0.72). HR+/HER2- MaBC had lower expression of AR-RNA (fold change (FC): 1.4, q&amp;lt;0.05), higher AR-protein (IHC) positivity (97.94% vs 84.03%, q&amp;lt;0.05), but no difference was noted in the frequency of fusion variant-AR (1.04% vs 3.19%, p=0.37) compared to FeBC. HR+/HER2- MaBC had increased expression of MHC class I gene HLA-B (FC: 1.2, p&amp;lt;0.05), MHC class II gene HLA-DQB2 (FC: 1.6, q&amp;lt;0.05), but decreased expression of drug efflux gene ABCC2 (FC: 1.4, q&amp;lt;0.05), and stem cell-related genes (KLF4, SOX2, POU5F1, PROM1, ALDH1A1, FC: 1.3-1.9, q&amp;lt;0.05) compared to HR+/HER2- FeBC. Conclusions: These data indicate that HR+/HER2- MaBC has a differential mutational spectrum and TMB-high frequency, MHC Class I and MHC class II, drug efflux and stem cell-related gene expression compared to their HR+/HER2- FeBC counterparts. These suggest important differences in tumor biology between men and women with HR+/HER2- breast cancer. A better understanding of these differences with additional research may help in design future clinical trials and treatments for men with HR+/HER2- BC. Citation Format: Dario Trapani, Sachin Kumar Deshmukh, Sharon Wu, Joanne Xiu, Pooja Advani, Daniel L. Abravanel, Nancy U. Lin, Giuseppe Curigliano, William Flood, Stephanie L. Graff, Maryam Lustberg, Philip Spanheimer, George W. Sledge, Sara M. Tolaney, Jose P. Leone. Molecular landscape of HR+/HER2- male breast cancer (MaBC) compared with female breast cancer (FeBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-01-16.

Purpose: Because of its rarity, male breast cancer is often compared to female breast cancer.Materials and Methods: To compare and contrast male and female breast cancers, we obtained case and population data from the NCI's Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses.Results: Men with breast cancer comprised less than 1% of all breast cancers. Male compared to female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, both overall and within each age group, but these trends were greater for women than men. Comparing cases diagnosed in 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (p = 0.03) and by 42% among women (p ∼ 0).Conclusion: There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled the late-onset and hormone sensitive type of female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially hormone positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for male breast cancer, but progress has lagged behind for men compared to women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2075.

The aim of this study is to review the characteristics and the survival rate in male breast cancer (MBC) patients in Korea over a 31-year period. Additionally, we analyzed the overall survival (OS) rate of a group of MBC matched to females with breast cancer.We retrospectively analyzed the data from 400 Korean patients who were treated for MBC from 1978 to 2009. Patient demographics and clinical information were routinely documented throughout the study period. Survival and prognostic factors were evaluated. Each MBC patient was matched with 5 female breast cancer (FBC) patients based on 7 characteristics and we compared the OS rates between the 2 groups.For MBC cases, the median follow-up was 72 months and the 5-year OS rate was 85.9%. In univariate analyses, the prognostic factors influencing OS were age (more than 60 years, P <0.001), tumor size (>2 cm, P = 0.007), and having a negative progesterone receptor (PR) status (P = 0.042). Only the age (P = 0.028) and tumor size (P = 0.024) were significant prognostic factors for OS in multivariate analysis. After matching, we had 260 male patients matched to 1300 female patients for analysis. Compared with cases among females, the rate of mastectomy was higher among MBC cases and tumors, which were almost invasive ductal carcinomas (IDCs), were more likely to be located in the central part of the breast. For MBC cases, the percentage of adjuvant radiation therapy was low compared with female cases. The primary hormone therapy agent used was tamoxifen. The 5-year OS rates were similar in MBC compared with FBC (91.0% vs. 92.6%, P = 0.300).We found that only the age (more than 60 years) and tumor size were independent prognostic factors of survival in MBC. The prognosis for MBC is similar to that for FBC given similar stage and hormone-receptor status.

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the nishinihon cooperative study group of adjuvant chemoendocrine therapy for breast cancer (ACETBC) of Japan