Male breast cancer: a multicenter study to provide a guide for proper management.

INTRODUCTION: To offer an extensive retrospective experience on the management of male breast cancer. METHODS: A multicenter retrospective observational cohort study was conducted, including male patients diagnosed with breast cancer (invasive or in situ) in 12 Italian breast units from January 1975 to December 2019. Patients aged 18 years or older were assessed for eligibility. Exclusion criteria were metastatic cancer at diagnosis, previous cancer(s), received neoadjuvant treatment, incomplete data on (neo) adjuvant treatment(s), and/or follow-up data. Data on radiological examinations, demographic characteristics, risk factors, histological features, receptor status, treatments, and follow-up were collected. RESULTS: In a series of 671 male patients with breast cancer assessed for eligibility, 403 (28 in situ and 375 invasive neoplasms) were included in the study. All included patients underwent surgery. The median age at surgery was 63.8 years (IQR 56.1-72.1). In 68% of cases, patients underwent echography, and in 55.1%, a mammography. Most patients were ER and PR positive (63.8%), HER2 negative (80.4%), with high (≥ 20%) Ki67 values (61.3%), and luminal B subtype (51.1%). The 10-year overall survival was 73.6% (95% CI 67.0-79.1) for invasive breast cancer and 90% (95% CI 65.6-97.4) for in situ breast cancer. In patients with invasive breast cancer, at univariable analysis, having a G3 tumor (vs. G1), pT2/3/4 (vs. pT1), pN2/3 (vs. pN0), luminal B subtype with Ki67 ≥ 20% (vs. Luminal A), were significantly associated with a higher risk of death. In multivariable analyses, pT2/3/4 (vs. pT1) remained significantly associated with a higher risk of death (HR 3.14, 95% CI 1.83-5.39), and having a HER2 positive or a triple-negative subtype (vs. Luminal A) was also significantly associated with a higher risk of mortality (HR 4.76, 95% CI 1.26-18.1). CONCLUSION: Male breast cancer is a rare disease, the better understanding of which is necessary for a more effective diagnostic and therapeutic approach.

Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft.

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4 years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches.

Infiltrating Epitheliosis of the Breast: Fine Needle Aspiration Cytology.

Epitheliosis (or usual duct hyperplasia) is a proliferation of epithelial and myoepithelial cells located within enlarged acini and small ducts, which is characterized by irregular and peripheral fenestration. Infiltrating epitheliosis (IE) is a specific lesion, characterized by classical epitheliosis flowing out into the adjacent stroma. The stroma is desmoplastic and shows keloid appearance with irregular elastosis. IE can mimic malignancy both on radiological and histological grounds. The aim of the present study is to describe the fine needle aspiration cytological features of 6 consecutive cases of IE, with histological correlation. IE cases presenting as screen detected lesions and preoperatively diagnosed on fine needle aspiration cytology (FNAC) were reviewed. All patients had radiologically breast lesions suspicious for malignancy that underwent FNAC followed by surgical resection. The FNAC smears presented some features that could lead to a misdiagnosis of malignancy, such as bloody background, high cellularity, and stromal fragments containing epithelial cells. Nevertheless, malignancy was excluded, due to the absence of atypia and the presence of myoepithelial cells in the cell clusters. IE presents a special FNAC pattern that can be misinterpreted as malignancy. Therefore, knowledge is necessary to avoid patient overtreatment.