Different Pathological Complete Response Rates According to PAM50 Subtype in HER2+ Breast Cancer Patients Treated With Neoadjuvant Pertuzumab/Trastuzumab vs. Trastuzumab Plus Standard Chemotherapy: An Analysis of Real-World Data

Abstract

Background: Double blockade with pertuzumab and trastuzumab combined with chemotherapy is the standard neoadjuvant treatment for HER2-positive early breast cancer. Data derived from clinical trials indicates that the response rates differ among intrinsic subtypes of breast cancer. The aim of this study is to determine if these results are valid in real-world patients.Methods: A total of 259 patients treated in eight Spanish hospitals were included and divided into two cohorts: Cohort A (132 patients) received trastuzumab plus standard neoadjuvant chemotherapy (NAC), and Cohort B received pertuzumab and trastuzumab plus NAC (122 patients). Pathological complete response (pCR) was defined as the complete disappearance of invasive tumor cells. Assignment of the intrinsic subtype was realized using the research-based PAM50 signature.Results: There were more HER2-enriched tumors in Cohort A (70 vs. 56%) and more basal-like tumors in Cohort B (12 vs. 2%), with similar luminal cases in both cohorts (luminal A 12 vs. 14%; luminal B 14 vs. 18%). The overall pCR rate was 39% in Cohort A and 61% in Cohort B. Better pCR rates with pertuzumab plus trastuzumab than with trastuzumab alone were also observed in all intrinsic subtypes (luminal PAM50 41 vs. 11.4% and HER2-enriched subtype 73.5 vs. 50%) but not in basal-like tumors (53.3 vs. 50%). In multivariate analysis the only significant variables related to pCR in both luminal PAM50 and HER2-enriched subtypes were treatment with pertuzumab plus trastuzumab (Cohort B) and histological grade 3.Conclusions: With data obtained from patients treated in clinical practice, it has been possible to verify that the addition of pertuzumab to trastuzumab and neoadjuvant chemotherapy substantially increases the rate of pCR, especially in the HER2-enriched subtype but also in luminal subtypes, with no apparent benefit in basal-like tumors.

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

“…Interestingly, the classic classification of BC by IHC had a lower predictive potential than intrinsic subtypes (IHC-luminal subtype, p = 0.03 and IHQ-HER2+ subtype, p = 0.06). Again, the clinical benefit of dual anti-HER2 therapy is exemplified by the differences in pCR achievement between Group A and B when the intrinsic subtype is considered; whereas luminal PAM50 subtypes and the HER2-enriched subtype present higher pCR rates in Cohort B (41% vs. 11.4%, p < 0.01, and 73.5% vs. 50%, p < 0.01, respectively), the rate of pCR is not significantly different in basal-like subtypes (53.3% vs. 50%), consistent with the absence of HER2 targets in basal-like tumors [ 32 ].…”

“…In univariate analysis, tumor grade was noticeably associated with pCR status in patients with G1 and G2 tumors, where pCR rarely occurs, while 31.3% of G3 tumors had pCR ( p < 0.0001) [ 31 ]. Finally, in 2019, Diaz-Redondo et al, in a HER2+ cohort of 259 patients treated with NAC-Trastuzumab ± Pertuzumab, determined that histological grade 3 was significantly related to pCR in a multivariate analysis [ 32 ].…”

Real-World Clinical Outcomes of Biosimilar Trastuzumab (CT-P6) in HER2-Positive Early-Stage and Metastatic Breast Cancer

“…In the phase III randomized controlled trial that established the equivalence of CT-P6 and the reference product, no pertuzumab was added to the neoadjuvant regimen (16). However, since the dual HER2-targeted approach may further improve pCR rates compared with use of either RTZ alone (19,23,26,27), most patients with HER2-positive breast cancer who received neoadjuvant chemotherapy at our institutions were treated with TCHP from 2018, when CT-P6 was approved. For this reason, we compared the efficacy of CT-P6 and RTZ among patients with HER2-positive EBC who received neoadjuvant TCHP.…”

Real-World Comparison of CT-P6 and Reference Trastuzumab for the Treatment of HER2-Positive Early-Stage and Metastatic Breast Cancer

“…In the phase III randomized controlled trial that established the equivalence of CT-P6 and the reference product, no pertuzumab was added to the neoadjuvant regimen. [16] However, since the dual HER2targeted approach may further improve pCR rates compared with use of either monoclonal antibody alone, [20,24,27,28] most patients with HER2-positive breast cancer who received neoadjuvant chemotherapy at our institution were treated with TCHP from 2018, when CT-P6 was approved. For this reason, we compared the e cacy of CT-P6 and RTZ among patients with HER2-positive EBC who received TCHP in the neoadjuvant setting.…”