ABSTRACT
Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II-III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%-84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0-I was 75% (95% CI, 46.8%-91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5%-70.5%) at baseline to 17.2% (95% CI, 0.7%-33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment-related deaths occurred. This four-drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.
ABSTRACT
Background: The role of neoadjuvant chemotherapy (NAC) in the prognosis of breast cancer among patients with grade 2 tumors remains unclear. As such, we aimed to explore the relationships between NAC and survival outcomes among patients with grade 2 breast cancer. Materials and Methods: We collected data on 726 breast cancer patients with grade 2 tumors and at least 5-years of follow-up from the date of diagnosis. We then conducted survival analyses to examine the association between NAC and disease-free survival (DFS) and overall survival (OS). The role of NAC in prognosis was further examined in subgroup analyses, with patients stratified according to molecular subtypes, histological grade, ER status, PR status, HER2 status and Ki67 index. We also determined the main sites of local recurrence, as well as these organs involved in distant metastasis among patients receiving NAC. Finally, we analyzed independent predictive factors for DFS and OS using Cox regression analyses. Results: Among patients who received NAC, the prevalence of pathologic complete response (pCR) was 9.87% (23/233), with 32.6% of patients (76/233) experiencing partial response. Survival analyses demonstrated that NAC had an overall adverse effect on DFS and OS. Subgroup analyses showed that patients who received NAC had shorter DFS in all molecular subgroups of breast cancer, with exception of triple negative breast cancer (TNBC) patients. NAC was also associated with shorter OS among patients with histological grade of 2 and a low Ki67 index. The main recurrence site was the chest well, while distant metastasis occurred in the bone, liver and lung. In Cox regression analyses, we found that NAC was an independent predictor for DFS, but not for OS. Conclusions: NAC may have an adverse effect on breast cancer prognosis among patients with grade 2 tumors. These patients need not receive NAC, except when the patient has a strong desire for breast conservation, and this is unlikely to be achieved in the absence of NAC.
