Abstract
PurposeBreast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis.MethodsPublic databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies.ResultsSeventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 – 0.79), platinum (HR: 0.45; 95% CI: 0.22 – 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 – 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 – 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo.ConclusionThe PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.
Highlights
Breast cancer (BC) is one of the three most common cancers in the world [1] and is the most common cancer and the leading cause of cancer-related death in women globally [2]
125 documents were excluded for the following reasons: duplicate reports [64], studies with no inclusion of a population with germline BRCA1 (gBRCA) mutation in the entire population or subgroups [30], studies with no report of the above outcomes or use of the above protocols [16], reviews or comments [9], studies with non-randomized controlled trials (RCTs) designs [4], studies reporting gBRCA mutation-related BC risk [1], and studies researching populations with mutations in other homologous recombination repair (HRR)-related genes [1]
The progression-free survival (PFS) analysis suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, triple-negative breast cancer (TNBC), and advanced BC patients with gBRCA mutations
Summary
Breast cancer (BC) is one of the three most common cancers in the world [1] and is the most common cancer and the leading cause of cancer-related death in women globally [2]. Germline BRCA1/2 mutation reduces gene expression and has been considered an important risk factor for the onset of BC; in addition, mutant BRCA1/2 allele carriers have a lifetime risk of BC as high as 80%-85% [5]. 75% of BC patients with germline BRCA1 (gBRCA) mutations are classified as having triple-negative breast cancer (TNBC), and the TNBC rate among patients with gBRCA2 mutations is reported to be 20%-25% [6, 7], which often has a high nuclear grade and a larger tumor burden [8]. In addition to the risk of BC, BRCA mutations are considered predive of prognosis, and BC patients with gBRCA mutations have worse survival outcomes than those without gBRCA mutations [9, 10]. Screening for gBRCA mutation carriers may help formulate therapeutic strategies to improve survival outcomes
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