Browsing by Author "Fruscio, Robert (16042230300)"

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.

Objectives: This study aimed to provide timely and effective guidance for pregnant women and health care providers to optimize maternal treatment and fetal protection and to promote effective management of the mother, fetus, and neonate when administering potentially teratogenic medications. New insights and more experience were gained since the first consensus meeting 5 years ago. Methods: Members of the European Society of Gynecological Oncology task force "Cancer in Pregnancy" in concert with other international experts reviewed the existing literature on their respective areas of expertise. The summaries were subsequently merged into a complete article that served as a basis for discussion during the consensus meeting. All participants approved the final article. Results: In the experts' view, cancer can be successfully treated during pregnancy in collaboration with a multi-disciplinary team, optimizing maternal treatment while considering fetal safety. To maximize the maternal outcome, cancer treatment should follow a standard treatment protocol as for non pregnant patients. Iatrogenic pre-maturity should be avoided. Individualization of treatment and effective psychologic support is imperative to provide throughout the pregnancy period. Diagnostic procedures, including staging examinations and imaging, such as magnetic resonance imaging and sonography, are preferable. Pelvic surgery, either open or laparoscopic, as part of a treatment protocol, may reveal beneficial outcomes and is preferably performed by experts. Most standard regimens of chemotherapy can be administered from 14 weeks gestational age onward. Apart from cervical and vulvar cancer, as well as important vulvar scarring, the mode of delivery is determined by the obstetrician. Term delivery is aimed for. Breast-feeding should be considered based on individual drug safety and neonatologist-breast-feeding expert's consult. Conclusions: Despite limited evidence-based information, cancer treatment during pregnancy can succeed. State-of-the-art treatment should be provided for this vulnerable population to preserve maternal and fetal prognosis. Supplementary Information: Supplementary data on teratogenic effects, ionizing examinations, sentinel lymph node biopsy, tumor markers during pregnancy, as well as additional references and tables are available at the extended online version of this consensus article, go to http://links.lww.com/ IGC/A197. Copyright © 2014 by IGCS and ESGO.