Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status
- Author(s)
- Wang, Y; Dackus, GMHE; Rosenberg, EH; Cornelissen, S; de Boo, LW; Broeks, A; Brugman, W; Chan, TWS; van Diest, PJ; Hauptmann, M; Ter Hoeve, ND; Isaeva, OI; de Jong, VMT; Jóźwiak, K; Kluin, RJC; Kok, M; Koop, E; Nederlof, PM; Opdam, M; Schouten, PC; Siesling, S; van Steenis, C; Voogd, AC; Vreuls, W; Salgado, RF; Linn, SC; Schmidt, MK;
- Details
- Publication Year 2024-01-09,Volume 22,Issue #1,Page 9
- Journal Title
- BMC Medicine
- Publication Type
- Research article
- Abstract
- BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. CONCLUSIONS: Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.
- Publisher
- BioMed Central
- Keywords
- Humans; Female; Adult; *Triple Negative Breast Neoplasms/drug therapy/genetics; *Neoplasms, Second Primary; Adjuvants, Immunologic; Ethnicity; Biomarkers; BRCA1 Protein/genetics; BRCA1 status; Chemotherapy-naïve; Long-term outcomes; Risk classification; Triple-negative breast cancer; Tumor-infiltrating lymphocytes
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1186/s12916-023-03233-7
- Open Access at Publisher's Site
https://doi.org/10.1186/s12916-023-03233-7- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-02-22 12:10:33
Last Modified: 2024-02-22 12:19:10