{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:12:10Z","timestamp":1785507130491,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR24992814"],"award-info":[{"award-number":["BR24992814"]}]},{"award":["BR24992814"],"award-info":[{"award-number":["BR24992814"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Germline PALB2 variants are associated with hereditary breast cancer risk, but their clinical impact in Central Asian populations remains largely uncharacterized. This case study aims to evaluate the clinical significance of PALB2 variants in two Kazakh women with early-onset breast cancer. Methods: Molecular genetic testing identified germline PALB2 pathogenic variants (NM_024675.4:c.18_22delGAAGC and NM_024675.4:c.1034T&gt;G) in two Kazakh women with early-onset invasive ductal carcinoma. Clinical courses, treatment responses, and outcomes were followed. Results: Neither patient had a reported family history of breast or other malignancies. Patient 1, a 26-year-old pregnant woman, was diagnosed with stage IIIB luminal B, HER2-negative invasive ductal carcinoma and received neoadjuvant chemotherapy, radical surgery, radiotherapy, endocrine therapy, and subsequent treatment for metastatic disease. Despite an initial response, she developed extensive skeletal metastases and died from metastatic breast cancer. Patient 2, a 33-year-old woman, presented with de novo stage IV luminal B, HER2-negative invasive ductal carcinoma with hepatic metastases. Following multimodal treatment, including chemotherapy, surgery, radiotherapy, endocrine suppression, and systemic therapy for disease progression, she experienced further metastatic spread and ultimately died from breast cancer-related complications. Conclusions: Both patients exhibited aggressive clinical courses characterized by early disease onset, metastatic progression, and poor outcomes despite comprehensive treatment. These cases highlight the potential clinical significance of germline PALB2 variants in apparently sporadic breast cancer and underscore the importance of genetic testing, risk assessment, and genetic counselling in young breast cancer patients, particularly in underrepresented.<\/jats:p>","DOI":"10.3390\/genes17080913","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:23:20Z","timestamp":1785504200000},"page":"913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Germline PALB2 Genetic Variant Associated with Rapid Metastatic Progression and Poor Survival in Two Kazakh Women with Breast Cancer: A Case Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-9577","authenticated-orcid":false,"given":"Gulnur","family":"Zhunussova","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazgul","family":"Omarbayeva","sequence":"additional","affiliation":[{"name":"Oncology Department, Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan"},{"name":"Department of Mammology, Kazakh Institute of Oncology and Radiology, Almaty 050022, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aigul","family":"Zhunussova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Abdullayeva","sequence":"additional","affiliation":[{"name":"Oncology Department, Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-2244","authenticated-orcid":false,"given":"Liliya","family":"Skvortsova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-7211","authenticated-orcid":false,"given":"Nursultan","family":"Nurdinov","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medical Disciplines, Faculty of Dentistry, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkestan 161200, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-5465","authenticated-orcid":false,"given":"Ainash","family":"Oshibayeva","sequence":"additional","affiliation":[{"name":"Department of Public Health and Scientific Research, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkestan 161200, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/1541-7786.MCR-23-0411","article-title":"Updating the Definition of Cancer","volume":"21","author":"Brown","year":"2023","journal-title":"Mol. 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