Browsing by Author "Božović-Spasojević, Ivana (22952876100)"

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. © 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

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. © 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Metastatic breast cancer (mBC) carries a huge burden for patients and healthcare systems globally. Optimal treatment is of paramount importance to streamline the treatment journey. In HR+/HER2− mBC, at disease progression on first-line therapy, the choice of next treatment lines should be guided not only by the presence of specific targetable mutations, but also by evidence of efficacy and safety from clinical trials and access to genetic testing and medications. The aim of the Delphi process is to gain consensus (at least 70% agreement) on the perspective of treatment strategies from experts in the field. The outcome of Delphi discussions is an algorithm for the second line in HR+/HER2− mBC. Clinicians may find it useful in their current practice and use it as a basis for the treatment individualization strategy, which must remain the core principle of our actions. © 2025 by the authors.

Metastatic breast cancer (mBC) carries a huge burden for patients and healthcare systems globally. Optimal treatment is of paramount importance to streamline the treatment journey. In HR+/HER2− mBC, at disease progression on first-line therapy, the choice of next treatment lines should be guided not only by the presence of specific targetable mutations, but also by evidence of efficacy and safety from clinical trials and access to genetic testing and medications. The aim of the Delphi process is to gain consensus (at least 70% agreement) on the perspective of treatment strategies from experts in the field. The outcome of Delphi discussions is an algorithm for the second line in HR+/HER2− mBC. Clinicians may find it useful in their current practice and use it as a basis for the treatment individualization strategy, which must remain the core principle of our actions. © 2025 by the authors.