Triple negative breast cancer and platinum-based systemic treatment: a meta-analysis and systematic review

Abstract

BackgroundTriple negative breast cancer (TNBC) represents 15–20% of breast cancers. Due to its heterogeneity and high rates of relapse, there is a need to optimize treatment efficacy. Platinum chemotherapy is still controversial and currently not recommended as first-line treatment for TNBC. Recent studies have shown promising activity of this regimen. This study was done to evaluate the effect of platinum chemotherapy on pathologic complete response (pCR) after neoadjuvant treatment for early TNBC and progression-free survival (PFS) in metastatic TNBC.MethodsA systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were done to identify randomized controlled trials (RCTs) investigating the use of platinum-based chemotherapy in adults with TNBC. Studies were appraised using the Cochrane Collaboration tool. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) for pCR, and Hazard Ratios (HRs) with 95%CI for PFS were analyzed.ResultsEleven RCTs were included (N = 2946). Platinum-based chemotherapy showed pCR benefit of 40%vs27% (OR1.75,95% CI 1.46–2.62,p < 0.0001) in the neo-adjuvant setting. Subgroup analysis showed increased pCR rates (44.6%vs27.8%) with platinum plus taxane regimen (p < 0.0001). In metastatic TNBC, three RCTs were analyzed (N = 531), platinum treatment did not show PFS advantage (HR1.16,95%CI 0.90–1.49,p = 0.24).ConclusionPlatinum chemotherapy is associated with increased pCR rates in TNBC, hence it is a viable option for patients in the neoadjuvant setting. Subgroup analysis showed that the combination of platinum and taxanes (Carboplatin/Paclitaxel) improved pCR. However, no PFS advantage was seen in metastatic TNBC. Given the current conflicting data in metastatic TNBC, further exploration with additional powered studies is needed.

Time trends of neoadjuvant chemotherapy for early breast cancer

“…Our study reports routine clinical data that are comparable for HR+ HER2− (16.3%) and HR− HER2+ (51.4%) but higher for HR+ HER2+ (41.0%) and TN (42.5%) (Figure 5). These rates are consistent with recent data reported for TN39 and HER2 positive40 subtypes. For those subtypes, increasing pCR rates have been achieved in routine clinical practice during the past decade, based on results from randomized trials (eg, on carboplatin for TN tumors,41 on trastuzumab in the neoadjuvant setting for HER2 positive tumors,42…”

Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies

“…In contrast, high-risk and locally advanced TNBC necessitate aggressive treatment with a variety of chemotherapy schedules and drug combinations. Since cytotoxic chemotherapy is often the only available systemic option to treat TNBC in order to reduce and prevent tumor relapse and systemic metastasis, a vast majority of TNBC patients with high-risk and locally advanced disease have no choices but to endure standard chemotherapies as prescribed [ 21 , 22 , 78 , 79 , 80 ]. Ineffective chemotherapy and chemo-toxicity increases the burden of treatment, and often leads to undesirable side effects and long-term adverse health consequences, adversely impacting the patient’s quality of life.…”

Platinum-based neoadjuvant chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis

“…Anthracyclines, taxanes, cyclophosphamide, fluorouracil, and platinumbased drugs are the most widely used, easily available, and low-cost drugs. Compared with the previous meta-analysis, 21,22 the current meta-analysis found that the above drugs alone could achieve better clinical effect, i.e. similar pCR rates but a lower incidence of hematologic toxicities such as anemia and neutropenia.…”