{Reference Type}: Journal Article
{Title}: Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.
{Author}: Schettini F;Blondeaux E;Molinelli C;Bas R;Kim HJ;Di Meglio A;Bernstein Molho R;Linn SC;Pogoda K;Carrasco E;Punie K;Agostinetto E;Lopetegui-Lia N;Phillips KA;Toss A;Rousset-Jablonski C;Acheritogaray M;Ferrari A;Paluch-Shimon S;Fruscio R;Cui W;Wong SM;Vernieri C;Dieci MV;Matikas A;Rozenblit M;Villarreal-Garza C;De Marchis L;Puglisi F;Vasconcelos de Matos L;Mariño M;Teixeira L;Graffeo R;Rognone A;Chirco A;Antone N;Abdou Y;Marhold M;Božović-Spasojević I;Cortés Salgado A;Carmisciano L;Bruzzone M;Curigliano G;Prat A;Lambertini M;
{Journal}: Cancer
{Volume}: 130
{Issue}: 16
{Year}: 2024 Aug 15
{Factor}: 6.921
{DOI}: 10.1002/cncr.35323
{Abstract}: BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.