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Review
. 2022 Feb 21;12(2):323.
doi: 10.3390/jpm12020323.

Homologous Recombination Deficiency (HRD) and BRCA 1/2 Gene Mutation for Predicting the Effect of Platinum-Based Neoadjuvant Chemotherapy of Early-Stage Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis

Yue Chai  1 , Yujie Chen  2 , Di Zhang  1 , Yuce Wei  1 , Zhijun Li  1 , Qiao Li  1 , Binghe Xu  1
Affiliations
Review

Homologous Recombination Deficiency (HRD) and BRCA 1/2 Gene Mutation for Predicting the Effect of Platinum-Based Neoadjuvant Chemotherapy of Early-Stage Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis

Yue Chai et al. J Pers Med. .

Abstract

Background: Platinum-based agents may benefit patients with triple-negative breast cancer (TNBC) whose tumors are dysfunctional in DNA repair mechanisms associated with the homologous recombination repair (HRR) genes. The purpose of this meta-analysis was to assess the values of BRCA1/2 and homologous recombination deficiency (HRD) in the prediction of the pathological complete response (pCR) rates of patients with TNBC treated with platinum-based neoadjuvant chemotherapy (NAC).

Patients and methods: Patients with TNBC with BRCA or HRD status from platinum-based NAC trials were analyzed. The odds ratios (ORs) with 95% confidence intervals (CI) for the identified studies were calculated.

Results: 13 eligible studies between January 2000 and September 2021 were included through systematic literature searches of Embase, PubMed, Cochrane, and Web of Science databases. In 12 trials with BRCA status, 629 of 1266 (49.7%) patients with TNBC achieved pCR with platinum-based NAC, including 134 out of 222 (60.4%) BRCA1/2-mutated patients and 495 out of 1044 (47.4%) BRCA wildtype patients (OR, 1.62; 95% CI, 1.20-2.20). The prevalence of HRD was higher than BRCA1/2 mutations in patients with TNBC (69.2% vs. 17.5%). In six trials with HRD information, pCR rates of HRD-positive patients with TNBC were significantly higher than those of HRD-negative patients with TNBC (241/412, 58.5% vs. 60/183, 32.8%, OR, 3.01; 95% CI, 2.07-4.39, p < 0.001).

Conclusions: BRCA1/2-mutated and HRD-positive patients with TNBC could benefit from platinum-based NAC. In the future, a prospective study using unified HRD testing criteria is warranted for further investigation.

Keywords: BRCA; homologous recombination deficiency; neoadjuvant chemotherapy; platinum agents; triple-negative breast cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Funnel plot showing publication bias among the studies included in the analysis.
Figure 2
Figure 2
Flowchart of the literature search.
Figure 3
Figure 3
Forest plot for comparison of pCR rates: (A) patients with BRCA 1/2 mutation vs. patients with BRCA1/2 wildtype; (B) HRD-positive vs. HRD-negative patients in 6 HRD-predefined studies.
See this image and copyright information in PMC

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References

    1. Dent R., Rugo H.S. Most neoadjuvant chemotherapy for triple-negative breast cancer should include platinum. Lancet Oncol. 2021;22:27–28. doi: 10.1016/S1470-2045(20)30747-6. - DOI - PubMed
    1. Liedtke C., Mazouni C., Hess K.R., André F., Tordai A., Mejia J.A., Symmans W.F., Gonzalez-Angulo A.M., Hennessy B., Green M., et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J. Clin. Oncol. 2008;26:1275–1281. doi: 10.1200/JCO.2007.14.4147. - DOI - PubMed
    1. Cortazar P., Zhang L., Untch M., Mehta K., Costantino J.P., Wolmark N., Bonnefoi H., Cameron D., Gianni L., Valagussa P., et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet. 2014;384:164–172. doi: 10.1016/S0140-6736(13)62422-8. - DOI - PubMed
    1. Saleh R.R., Nadler M.B., Desnoyers A., Meti N., Fazelzad R., Amir E. Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis. Cancer Treat Rev. 2021;100:102283. doi: 10.1016/j.ctrv.2021.102283. - DOI - PubMed
    1. Kalra M., Tong Y., Jones D.R., Walsh T., Danso M.A., Ma C.X., Silverman P., King M.C., Badve S.S., Perkins S.M., et al. Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer. NPJ Breast Cancer. 2021;7:29. doi: 10.1038/s41523-021-00240-w. - DOI - PMC - PubMed

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