![]() Given the multiple signaling-driven features, treatment of TPBC with multi-targeted agents may block the complex network more effectively. However, the curative efficacy of this combinatory regimen remains unsatisfactory. In the TBCRC 023 study, patients with ER-positive, HER2-positive breast cancer receiving 12-week or 24-week treatment had a bpCR of 9% or 33% with minimal side effects 9. In the TBCRC 006 study, the pCR rate of neoadjuvant lapatinib and trastuzumab plus letrozole was 18% in patients with ER-positive, HER2-positive breast cancer 8. Clinical trials have shown that the combination of HER2-targeted therapy with endocrine therapy achieved a moderate therapeutic efficacy in HR-positive, HER2-positive breast cancer 8, 9. However, few studies have focused on the treatment exploration for TPBC in the neoadjuvant setting.Īmple evidence has unveiled that complex crosstalk between HER2 and ER signaling lays the foundation for poor response to current therapies in patients with TPBC and for a rationale to block them simultaneously 6, 7. A retrospective study reported that neoadjuvant chemotherapy combined with trastuzumab treatment only resulted in a pathological complete response (pCR) rate of 20% in patients with TPBC, the lowest among all subgroups of HER2-positive breast cancers 5, indicating that optimized therapeutic strategies are urgently required for the management of TPBC. TPBC displays unique biological behaviors and manifests a poorer response to standard neoadjuvant therapy than hormone receptor (HR)-negative, HER2-positive breast cancer 3, 4. More than 50% of HER2-positive breast cancers express intact estrogen receptor (ER) and progesterone receptor (PR), termed triple-positive breast cancer (TPBC) 2. Human epidermal growth factor receptor 2 (HER2) overexpression is found in approximately 15–20% of breast cancer patients with an aggressive phenotype and detrimental outcome 1. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC. There is no serious adverse event- or treatment-related death. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. ![]() The mean Ki67 expression reduces from 40.4% at baseline to 17.9% ( P < 0.001) at time of surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79 95% confidence interval (CI), 21.3–41.3). The secondary endpoints include residual cancer burden (RCB)−0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II–III TPBC with a Karnofsky score of ≥70 (NCT04486911). Nature Communications volume 13, Article number: 7043 ( 2022)Ĭurrent therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer
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