Neoadjuvant Chemotherapy In HER2-positive Breast Cancer Research Articles

The Add-On Effect of Fluorouracil, Epirubicin, and Cyclophosphamide Regimens for Neoadjuvant Chemotherapy in Human Epidermal Receptor 2 (HER2)-Positive Breast Cancer: A Single-Center Retrospective Study.

The addition of pertuzumab to trastuzumab in neoadjuvant chemotherapy (NAC) for anti-human epidermal receptor 2 (HER2) positive breast cancer has shown a significant improvement in the pathologic complete response (pCR) rate. However, the add-on effect of an anthracycline-based regimen (standard-of-care regimen) remains unclear. In this retrospective, observational study, participants received pertuzumab combination therapy as NAC for HER2-positive primary breast cancer. This study was conducted from January 1, 2020, to December 31, 2022. Patients who had not received at least three courses of pertuzumab owing to adverse events or those who had received preoperative radiotherapy were excluded. The pCR rate was 35.3% (12/34 patients). The pCR group had a significantly higher percentage of histopathologic grade III (1/11 patients, p=0.030) and a significantly higher percentage of hormone receptor-negative patients (7/12 patients, p=0.015) than the non-pCR group. The non-pCR group had a significantly higher incidence of vascular invasion than the pCR group (7/22 patients, p=0.036). Menopausal status, stage, and ki-67 values were not significantly different between the two groups. This study suggests an unlikely add-on effect of an anthracycline-based regimen for NAC in HER2-positive breast cancer. Moreover, our results support that the pCR rate is high in patients with hormone receptor-negative, HER2-positive breast cancer.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04)

BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC).MethodsIn this multicenter phase II clinical trial (January 2019–July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples.ResultsIn total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6–64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1–86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1–61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples.ConclusionNab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Value of radiomics based on CE-MRI for predicting the efficacy of neoadjuvant chemotherapy in invasive breast cancer

To establish and validate a radiomics nomogram based on contrast-enhanced (CE)-MRI for predicting the efficacy of neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer with non-mass enhancement (NME). A cohort comprising 117 HER2-positive breast cancer patients showing NME on CE-MRI between January 2012 and December 2019 were retrospectively analysed in our study. Patients were classified as pathological complete respone (pCR) according to surgical specimens and axillary lymph nodes without invasive tumour cells. Clinicopathological data were recorded, and images were assessed by two radiologists. A total of 1130 radiomics features were extracted from the primary tumour and six radiomics features were selected by the maximal relevance and minimal redundancy and least absolute shrinkage and selection operator algorithms. Univariate logistic regression was used to screen meaningful clinical and imaging features. The rad-score and independent risk factors were incorporated to build a nomogram model. Calibration and receiver operator characteristic curves were used to confirm the performance of the nomogram in the training and testing cohorts. The clinical usefulness of the nomogram was evaluated by decision curve analysis. The difference in the rad-score between the pCR and non-pCR groups was significant in the training and testing cohorts (p < 0.01). The nomogram model showed good calibration and discrimination, with AUCs of 0.900 and 0.810 in the training and testing cohorts. Decision curve analysis indicated that the radiomics-based model was superior in terms of patient clinical benefit. The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer patients showing NME. HER2-positive breast cancer showing segmental enhancement on CE-MRI was more likely to achieve pCR after NAC than regional enhancement and diffuse enhancement.The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer that showed NME.

PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis.

PurposePIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers.MethodsA total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients.ResultsPIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001–12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016).ConclusionPIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

Optimal threshold for stromal tumor-infiltrating lymphocytes: its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy.

The purpose of the present study was to determine the optimal threshold for stromal tumor-infiltrating lymphocytes (TILs) and investigate its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). Levels of stromal TILs were evaluated using hematoxylin and eosin-stained sections of core biopsies from 116 patients. We investigated the correlation between stromal TILs and pathological response to identify its optimal threshold. Using receiver operating characteristic curve analysis, a 30% threshold best discriminated pathological complete response (pCR) from non-pCR subgroups (P<0.001). Lymphocyte-rich breast cancer (LRBC) was defined as having ≥30% stromal TILs level, and was used for analysis. For analyses of predictive factors, multivariate analysis indicated that LRBC was a strong predictor of pCR with an odds ratio of 5.23 (P<0.001). Negative hormone receptor (HR) status was also significantly associated with pCR (P=0.028). LRBC significantly predicted pCR in both HR-positive and HR-negative tumors (P=0.016 and 0.006, respectively). For survival analyses, LRBC was the only independent predictor of improved event-free survival (EFS) among baseline clinicopathological factors in multivariate analysis (P=0.012). When pathological response was included, both LRBC and pCR were independent predictors of better EFS (P=0.040 and 0.045, respectively). LRBC significantly predicted longer EFS in the non-pCR subgroup (P=0.018), whereas LRBC was not significantly associated with EFS in the pCR subgroup (P=0.825). A 30% threshold for stromal TILs optimally identified response to trastuzumab-based NAC in HER2-positive breast cancer; its predictive and prognostic value was also validated in our study.