Genetic and functional homologous repair deficiency as biomarkers for platinum sensitivity in TNBC: A case report
| Autor: | Gomez-Puerto, Diego, Llop Guevara, Alba, Cruellas Lapeña, Mara, Torres Esquius, Sara, De la Torre Fdez de Vega, Fco Javier, Peg Camara, Vicente, Balmaña Gelpí, Judith, Pimentel, Isabel |
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| Přispěvatelé: | Institut Català de la Salut, [Gomez-Puerto D] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Llop-Guevara A] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Barcelona Hospital Universitari, Barcelona, Spain. [Cruellas M, Torres-Esquius S, Balmaña J] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [De La Torre J] Unitat de Ginecologia Oncològica i Patologia Mamària, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Peg V] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pimentel I] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
ADN - Reparació
Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Cancer Research Genetic Phenomena::DNA Repair [PHENOMENA AND PROCESSES] Oncology Mama - Càncer - Tractament Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Quimioteràpia combinada fenómenos genéticos::reparación del ADN [FENÓMENOS Y PROCESOS] neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES] |
| Zdroj: | Scientia |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2022.963728 |
| Popis: | HRD-biomarkers; Pathological complete response; Triple-negative breast cancer Biomarcadores HRD; Respuesta patológica completa; Cáncer de mama triple negativo Biomarcadors HRD; Resposta patològica completa; Càncer de mama triple negatiu Triple-negative breast cancer is the most aggressive subtype of mammary carcinoma. In the early stage, neoadjuvant chemotherapy (NAC) is the standard of care for prognostic stratification and the best adjuvant treatment strategy. A 30-year-old female presented in the emergency room because of a gigantic right breast associated with an ulcerated lump at the upper quadrants. The right axillary nodes were palpable. An ultrasound was performed, showing the ulcerated neoformation with enlarged right axillary lymph nodes observed to level III. A core biopsy of the breast lesion was performed, and the pathological examination revealed a nonspecial type, grade 3, invasive, triple-negative breast cancer. No distant disease was found in the PET-CT scan. A germline genetic panel by next-generation sequencing identified a likely pathogenic variant in RAD51D (c.898C>T). Assessment of the functionality of the DNA homologous recombination repair pathway by RAD51 foci in the tumor revealed a profile of homologous recombination deficiency. NAC consisting of weekly carboplatin and paclitaxel followed by dose-dense doxorubicin/cyclophosphamide was performed with a complete metabolic response achieved in the PET-CT scan. The patient underwent a modified radical mastectomy plus axillary lymphadenectomy with a pathological complete response in the breast and axilla and remains disease-free after 2 years of follow-up. We report a young female with a triple-negative breast cancer stage cT4bN3M0 and a hereditary pathogenic mutation in RAD51D. The tumor was highly proliferative and homologous recombination-deficient by RAD51. The patient received platinum-based NAC, achieving a pathologic complete response. More effort should be made to identify predictive functional biomarkers of treatment response, such as RAD51 foci, for platinum sensitivity. |
| Databáze: | OpenAIRE |
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