Abstract | Background: Patients and methods: In total, 425 TNBC patients were identified from S9313. HRD score, tumor BRCA1/2 sequencing, and BRCA1 PM were carried out on DNA isolated from formalin-fixed paraffin-embedded tissue. Positive HRD status was defined as either a deleterious tumor BRCA1/2 (tBRCA) mutation or a pre-defined HRD score ≥42. Markers were tested for prognostic value on disease-free survival (DFS) and overall survival (OS) using Cox regression models adjusted for treatment assignment and nodal status. Results: HRD status was determined in 89% (379/425) of cases. Of these, 67% were HRD positive (27% with tBRCA mutation, 40% tBRCA-negative but HRD score ≥42). HRD-positive status was associated with a better DFS [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.51-1.00; P = 0.049] and non-significant trend toward better OS (HR = 0.71; 95% CI 0.48-1.03; P = 0.073). High HRD score (≥42) in tBRCA-negative patients (n = 274) was also associated with better DFS (HR = 0.64; 95% CI 0.43-0.94; P = 0.023) and OS (HR = 0.65; 95% CI 0.42-1.00; P = 0.049). BRCA1 PM was evaluated successfully in 82% (348/425) and detected in 32% of cases. The DFS HR for BRCA1 PM was similar to that for HRD but did not reach statistical significance (HR = 0.79; 95% CI 0.54-1.17; P = 0.25). Conclusions: HRD positivity was observed in two-thirds of TNBC patients receiving adjuvant AC and was associated with better DFS. HRD status may identify TNBC patients who receive greater benefit from AC-based chemotherapy and should be evaluated further in prospective studies. Clinical Trials Number: Int0137 (The trial pre-dates Clinicaltrial.Gov website establishment).
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Authors | P Sharma, W E Barlow, A K Godwin, H Pathak, K Isakova, D Williams, K M Timms, A R Hartman, R J Wenstrup, H M Linden, D Tripathy, G N Hortobagyi, D F Hayes |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 29
Issue 3
Pg. 654-660
(03 01 2018)
ISSN: 1569-8041 [Electronic] England |
PMID | 29293876
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- BRCA1 Protein
- BRCA1 protein, human
- Biomarkers, Tumor
- Doxorubicin
- Cyclophosphamide
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- BRCA1 Protein
(genetics)
- Biomarkers, Tumor
(genetics)
- Chemotherapy, Adjuvant
(methods)
- Cyclophosphamide
(administration & dosage)
- Disease-Free Survival
- Doxorubicin
(administration & dosage)
- Female
- Genomic Instability
(genetics)
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Recombinational DNA Repair
(genetics)
- Treatment Outcome
- Triple Negative Breast Neoplasms
(drug therapy, genetics, mortality)
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