Ki67 as a prognostic factor in male breast cancer (male BC): Results from a large GEICAM Spanish cohort of male BC.
Authors: Ander Urruticoechea, Purificacion Martinez, Cristina Hernando, Sabela Recalde, Alfonso Sanchez Munoz, David Morales, Marta Santisteban, Isaura Fernández, Sonia Del Barco, Esther Zamora, Vega Iranzo, Tamara Martos, Eduardo Martinez, Silvia Antolín Novoa, Alfonso Modolell, Mirta Garcia Alonso, Elisa García, Pilar Bueso, Montserrat Llobera, Noelia Martinez-Jañez
Journal: Journal of Clinical Oncology (2024)

556 Background: Male BC management is based, by default, on evidence produced from female BC. There is a high need to validate gender specific performance of established prognostic biomarkers. We present here descriptive results from a large, country specific, registry of Male BC. Methods: GEICAM/2016-04 (NCT03800355) is a retrospective, observational study including Male BC pts diagnosed from 2000 to 2019 in 51 Spanish sites. Data from BC diagnosis until 10-Mar-2020 was collected from medical charts; biological specimens were obtained. Pts and tumors characteristics, therapies, and outcomes were analyzed. Molecular subtypes were categorized as hormonal receptor positive (HR+)/HER2 negative (HER2−), triple negative (TN) (HR−/HER2−), and HER2+ (any HR). Results: 773 pts were analyzed, at first diagnosis, 721 (93%) had early BC (EBC) (stages I [28%], II [41%], III [21%]), and 52 (7%) de novo metastatic BC; median age was 66 (23-96) years; median body mass index was 28 (18-50) Kg/m 2 (overweight), with obesity in 4% as prior medical history. Previous history of other cancers: 20 (3%) pts were diagnosed with prostate cancer (PC) and 20 (3%) pts with skin cancer (melanoma and non-melanoma). BC family history was reported in 212 (35%) pts, 56 (9%) PC, and 35 (6%) ovarian cancer. Germline genetic testing for hereditary risk was performed in 238 (31%) pts, with BRCA1/2 mutations present in 46 (19%) pts (BRCA1 in 6, BRCA2 in 39, and both in 1); BRCA1/2 mutations were observed in 9 (33%) HER2+ pts and 32 (18%) HR+/HER2− pts. Of EBC pts, 322 (45%) were node-positive, 274 (38%) had T2 tumors; 4% had breast conserving surgery, and 42% sentinel lymph node biopsy; 42% received adjuvant radiation therapy; 336 (47%) adjuvant and 44 (6%) neoadjuvant chemotherapy, 609 (84%) adjuvant endocrine therapy, mainly tamoxifen (72%); and 6% pts did not receive any systemic therapy. Morphologically, invasive carcinoma of no special type was reported in 89% pts, and 52% were grade 2. Per local pathological assessment, 97% estrogen receptor positive (ER+), 90% progesterone receptor positive (PgR+), 84% androgen receptor positive; 51% presented Ki67 index expression ≥20%, and 11% HER2+. Frequency according to molecular subtype: 599 (77%) HR+/HER2−, 75 (10%) HER2+, 6 (1%) TN, and 93 (12%) unknown. With a median follow-up of 64 months, medians of invasive disease-free survival (iDFS) and distant DFS (dDFS) were not statistically different in HR+/HER2− vs HER2+ pts and according to levels of Ki67 index expression (&lt;20% vs. ≥20%). In a Cox multivariate model, stage I-II vs III and age were statistically significant (p&lt;0.05) for both iDFS and dDFS. Conclusions: HR+/HER2− is the most common Male BC subtype, with ER and PgR highly positive, and 20% as median Ki67 index. No statistically significant differences were observed in terms of iDFS and dDFS based on level of Ki67 index expression. Clinical trial information: NCT03800355 .