Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been...

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Detalles Bibliográficos
Autores: Schettini, Francesco, Blondeaux, Eva, Molinelli, Chiara, Bas, Raphaëlle, Kim, Hee Jeong, Di Meglio, Antonio, Bernstein Molho, Rinat, Linn, Sabine C, Pogoda, Katarzyna, Carrasco, Estela, Punie, Kevin, Agostinetto, Elisa, Lopetegui-Lia, Nerea, Phillips, Kelly-Anne, Toss, Angela, Rousset-Jablonski, Christine, Acheritogaray, Marion, Ferrari, Alberta, Paluch-Shimon, Shani, Fruscio, Robert, Cui, Wanda, Wong, Stephanie M, Vernieri, Claudio, Dieci, Maria Vittoria, Matikas, Alexios, Rozenblit, Mariya, Villarreal-Garza, Cynthia, De Marchis, Laura, Puglisi, Fabio, Vasconcelos de Matos, Leonor, Mariño, Monica, Teixeira, Luis, Graffeo, Rossella, Rognone, Alessia, Chirco, Alessandra, Antone, Nicoleta, Abdou, Yara, Marhold, Maximilian, Božović-Spasojević, Ivana, Cortés Salgado, Alfonso, Carmisciano, Luca, Bruzzone, Marco, Curigliano, Giuseppe, Prat, Aleix, Lambertini, Matteo
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/20984
Acceso en línea:https://hdl.handle.net/20.500.13003/20984
Access Level:acceso abierto
Palabra clave:Breast Neoplasms
Disease-Free Survival
Prognosis
Receptor, ErbB-2
Germ-Line Mutation
Young Adult
Female
Adult
Humans
BRCA2 Protein
BRCA1 Protein
Retrospective Studies
Proteína BRCA1
Humanos
Adulto Joven
Pronóstico
Receptor ErbB-2
Femenino
Mutación de Línea Germinal
Neoplasias de la Mama
Estudios Retrospectivos
Adulto
Supervivencia sin Enfermedad
Proteína BRCA2
Descripción
Sumario:Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS. In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

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