Abstract
Platinum (Pt)-based chemo-regimens have been proved effective in neoadjuvant and salvage chemotherapy of triple negative breast cancer (TNBC). However, the survival benefit of Pt-based regimens in early stage TNBC(eTNBC) treatment has remained unclear. We conducted a meta-analysis to explore its role in improving the clinical outcomes of eTNBC. We carried out a comprehensive literature search on 15 March 2021 for randomized controlled trials (RCTs) comparing ajuvant/neoadjuvant Pt-based and Pt-free chemo-regimens in eTNBC patients, according to PRISMA 2020. We extracted the survival data and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS). Seven eligible RCTs enrolling a total of 2,027 eTNBC patients were identified in this meta-analysis, with 1,007 receiving Pt-free regimens, and the other 1,020 patients receiving Pt-based regimens, respectively. Patients in Pt-based regimens arm were associated with significant improved DFS (HR = 0.70, 95% CI: 0.58–0.84), and OS (HR = 0.78, 95% CI: 0.61–1.00). The survival benefits of DFS remained consistent in both the two strategies of Pt usage, either adding Pt to standard anthracyclines&taxanes based regimens (A&T + Pt), or combination of Pt and taxanes alone (TPt). The survival benefits also remained consistent in either neoadjuvant or adjuvant use of Pt. The present meta-analysis of RCTs revealed that Pt-based chemo-regimens could significantly improve both DFS and OS for eTNBC patients. Based on efficiency and toxicity, we recommend Pt-based regimens for eTNBC, especially the “A&T + Pt” mode if the toxicities are tolerable, which may lead TNBC therapy into a new era.
Highlights
Triple negative breast cancer (TNBC), i.e., ER, PR, and HER-2, accounting for 15−20% in breast cancer, is a highly aggressive subtype with a significantly inferior prognosis than non-TNBC1
The CREATE-X trial demonstrated that adjuvant capecitabine could significantly ameliorate the prognosis in those early stage TNBC (eTNBC) with non-pCR after standard neoadjuvant chemotherapy (NACT)
Indications for NACT have been extended to eTNBC patients with risk factors (i.e., T > 2 cm, or LN+, or young-onset (
Summary
Triple negative breast cancer (TNBC), i.e., ER (estrogen receptor)-, PR (progesterone receptor)-, and HER-2 (human epithelial growth factor receptor-2)-, accounting for 15−20% in breast cancer, is a highly aggressive subtype with a significantly inferior prognosis than non-TNBC1. Due to insensitivity to endocrine therapy and anti-HER2 therapy, chemotherapy is the dominant systemic treatment for TNBC in general. Anthracyclines (A/E) and taxanes(T) based chemo-regimens, administrated in various combinations and schedules, have been widely accepted as the standard regimens for early stage TNBC (eTNBC)[2,3]. Dose-dense regimens have been proved to be more effective in adjuvant treatments of high-risk BC patients[4,5]. Neoadjuvant chemotherapy (NACT) has provided more information in tailoring subsequent treatments for BC patients. Adjuvant addition of capecitabine for those TNBC patients with non-pCR (pathological complete response) after standard NACT has been recommended in most guidelines[6]. Even with the assistance of dose-dense regimens and guidance of NACT, the improvement of long-term survival is still critical for eTNBC
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