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Associations between PIK3CA Mutations and Disease Free Survival in Patients with HR+, HER2− Tumors Treated with Adjuvant Hormonal Therapy: A Real‐World Study in Croatia

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Title: Associations between PIK3CA Mutations and Disease Free Survival in Patients with HR+, HER2− Tumors Treated with Adjuvant Hormonal Therapy: A Real‐World Study in Croatia
Authors: Dora Čerina Pavlinović, Natalija Dedić Plavetić, Ingrid Belac Lovasić, Robert Šeparović, Josipa Flam, Marija Pancirov, Žarko Bajić, Snježana Tomić, Eduard Vrdoljak
Source: Breast J
The Breast Journal, Vol 2024 (2024)
Publisher Information: Wiley, 2024.
Publication Year: 2024
Subject Terms: Breast Neoplasms / drug therapy, Receptor, ErbB-2, receptor, receptors, Receptor, ErbB-2 / metabolism, chemotherapy, Class I Phosphatidylinositol 3-Kinases / genetics, ErbB-2, 0302 clinical medicine, breast neoplasms, estrogen, antineoplastic agents, RC254-282, Breast Neoplasms / mortality, breast tumor, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Receptors, Estrogen / metabolism, Breast Neoplasms / therapy, Receptors, Progesterone / metabolism, Receptors, Estrogen, Chemotherapy, Adjuvant, Antineoplastic Agents, Hormonal / therapeutic use, Breast Neoplasms / pathology, Female, PIK3CA mutations, Public aspects of medicine, RA1-1270, Receptors, Progesterone, Research Article, Adult, tumor, disease-free survival, Antineoplastic Agents, Hormonal, Class I Phosphatidylinositol 3-Kinases, Croatia, Neoplasm Recurrence, Local / genetics, Breast Neoplasms, progesterone, Disease-Free Survival, 03 medical and health sciences, adjuvant, local, Biomarkers, Tumor, Humans, Retrospective Studies, Aged, Receptor, ErbB-2 / genetics, biomarkers, neoplasm recurrence, hormonal, Biomarkers, Tumor / genetics, Breast Neoplasms / genetics, Mutation, mutation, Neoplasm Recurrence, Local
Description: Introduction. Disease recurrence in patients with the early hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one‐quarter of patients with early‐stage disease will experience disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) gene are highly prevalent (30–40%) in HR+/HER2− advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine the association between and impact of PIK3CA mutation status on disease‐free survival (DFS) in HR+/HER2− early breast cancer patients. Methods. This cohort study was multicentric and retrospective in nature and was conducted at five Croatian institutions from July 2020 to December 2021. The study included initially early and locally advanced operable HR+/HER2− breast cancer patients who were diagnosed with disease recurrence during adjuvant hormonal treatment or within the first six years of follow‐up. Results. A total of 186 patients were included, 40.9% of whom tested positive for the PIK3CA mutation. Primary and adjuvant treatment, particularly adjuvant endocrine treatment, were similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with a positive PIK3CA status and the H1047 PIK3CA mutation had a significantly lower hazard of disease recurrence than patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; false discovery rate, FDR Conclusions. This study highlights the potential impact of PIK3CA mutations on disease recurrence during or following adjuvant endocrine therapy and potentially opens the door for further investigation of possibly more personalized treatment strategies.
Document Type: Article
Other literature type
Conference object
File Description: application/pdf
Language: English
ISSN: 1524-4741
1075-122X
DOI: 10.1155/2024/5648845
DOI: 10.1200/jco.2024.42.16_suppl.e12512
Access URL: https://pubmed.ncbi.nlm.nih.gov/39742376
https://doaj.org/article/58fd4feb40884d6bb8fd7ad6d6f40a50
https://onlinelibrary.wiley.com/doi/10.1155/2024/5648845
https://doi.org/10.1155/2024/5648845
https://ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.e12512
https://doi.org/10.1200/JCO.2024.42.16_suppl.e12512
https://urn.nsk.hr/urn:nbn:hr:105:788167
https://doi.org/10.1155/2024/5648845
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Accession Number: edsair.doi.dedup.....301b32a1a0bef7fe68b8052f67bc3eb7
Database: OpenAIRE
Description
Abstract:Introduction. Disease recurrence in patients with the early hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one‐quarter of patients with early‐stage disease will experience disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) gene are highly prevalent (30–40%) in HR+/HER2− advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine the association between and impact of PIK3CA mutation status on disease‐free survival (DFS) in HR+/HER2− early breast cancer patients. Methods. This cohort study was multicentric and retrospective in nature and was conducted at five Croatian institutions from July 2020 to December 2021. The study included initially early and locally advanced operable HR+/HER2− breast cancer patients who were diagnosed with disease recurrence during adjuvant hormonal treatment or within the first six years of follow‐up. Results. A total of 186 patients were included, 40.9% of whom tested positive for the PIK3CA mutation. Primary and adjuvant treatment, particularly adjuvant endocrine treatment, were similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with a positive PIK3CA status and the H1047 PIK3CA mutation had a significantly lower hazard of disease recurrence than patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; false discovery rate, FDR Conclusions. This study highlights the potential impact of PIK3CA mutations on disease recurrence during or following adjuvant endocrine therapy and potentially opens the door for further investigation of possibly more personalized treatment strategies.
ISSN:15244741
1075122X
DOI:10.1155/2024/5648845