Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-...

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Published in:	BMC medicine 2024-01, Vol.22 (1), p.9-9, Article 9
Main Authors:	Wang, Yuwei, Dackus, Gwen M H E, Rosenberg, Efraim H, Cornelissen, Sten, de Boo, Leonora W, Broeks, Annegien, Brugman, Wim, Chan, Terry W S, van Diest, Paul J, Hauptmann, Michael, Ter Hoeve, Natalie D, Isaeva, Olga I, de Jong, Vincent M T, Jóźwiak, Katarzyna, Kluin, Roelof J C, Kok, Marleen, Koop, Esther, Nederlof, Petra M, Opdam, Mark, Schouten, Philip C, Siesling, Sabine, van Steenis, Charlaine, Voogd, Adri C, Vreuls, Willem, Salgado, Roberto F, Linn, Sabine C, Schmidt, Marjanka K
Format:	Article
Language:	eng
Subjects:	Adjuvants, Immunologic Adult Analysis Biomarkers BRCA1 protein BRCA1 Protein - genetics BRCA1 status Breast cancer Cancer Cancer patients Cancer therapies Chemotherapy Chemotherapy-naïve Clinical outcomes Complications and side effects Diagnosis DNA methylation Ethnicity Female Formaldehyde Gene mutations Genetic aspects Genetic transcription Genomes Humans Instrument industry Long-term outcomes Lymphocytes Medical prognosis Methylation Mutation Neoplasms, Second Primary Nodes Patient outcomes Prognosis Regression analysis Risk Risk classification Subgroups Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - genetics Triple-negative breast cancer Tumor-infiltrating lymphocytes Tumors
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Summary:	Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and
ISSN:	1741-7015 1741-7015