Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

Abstract

The purpose of this study was to retrospectively review the pathologic complete response (pCR) rate from patients (n=86) with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012). Stage II patients achieved a higher response rate compared to stage III (P=0.03). The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively) and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively). Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03) and death (HR=0.21; P=0.02). In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial

“…While it is difficult to compare pCR rates with historical data due to different grouping strategies, in this study, the pCR rate in trastuzumab-treated patients was not affected by region, or by age, in line with some previous observations [9]. A lower pCR rate was observed among patients with later stage disease, per other reports [10, 11]. Nevertheless, pCR rates were similar between trastuzumab and CT-P6 groups, across subgroups.…”

Is There a Role for Post-Mastectomy Radiotherapy for T1-2N1 Breast Cancers With Node-Positive Pathology After Patients Become Node-Negative Pathology Following Neoadjuvant Chemotherapy?

“…NAC has been shown to modify the extent of pathological disease found in axillary lymph nodes in ~20–40% of patients ( 2 , 3 ). The trastuzumab-based NAC regimen has shown a greater pCR rate ( 16 , 17 ). A potential down-staging represents a challenge to the indications for PMRT.…”

“…The newer NAC regimens have increased the percentage of pCR ( 16 , 17 , 22 ). One study reported that 46.8% of HER2-positive breast cancer patients subjected to neoadjuvant chemotherapy with trastuzumab achieved a pCR ( 16 ). However, few published studies have demonstrated how pCR status affects locoregional treatment choices.…”

Amino Acid‐Based Advanced Liquid Formulation Development for Highly Concentrated Therapeutic Antibodies Balances Physical and Chemical Stability and Low Viscosity

“…The therapeutic antibody trastuzumab (Herceptin®) was used as a model substance for studying the molecular integrity during the application of different kinds of thermal stresses, for example, during thermal unfolding and during liquid storage at elevated temperatures.…”