Corrigendum: PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution.

[This corrects the article DOI: 10.3389/fonc.2019.00707.].

PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution.

Introduction: HER2-enriched subtype has been associated with higher response to neoadjuvant anti-HER2-based therapy across various clinical trials. However, limited data exist in real-world practice and regarding residual disease. Here, we evaluate the association of HER2-enriched with pathological response (pCR) and gene expression changes in pre- and post-treatment paired samples in HER2-positive breast cancer patients treated outside of a clinical trial. Methods: We evaluated clinical-pathological data from a consecutive series of 150 patients with stage II-IIIC HER2-positive breast cancer treated from August 2004 to December 2012 with trastuzumab-based neoadjuvant chemotherapy. Expression of 105 breast cancer-related genes, including the PAM50 genes, was determined in available pre-and post-treatment formalin-fixed paraffin-embedded tumor samples using the nCounter platform. Intrinsic molecular subtypes were determined using the research-based PAM50 predictor. Association of genomic variables with total pCR was performed. Results: The pCR rate was 53.3%, with higher pCR among hormonal receptor (HR)-negative tumors (70 vs. 39%; P < 0.001). A total of 89 baseline and 28 residual tumors were profiled, including pre- and post-treatment paired samples from 26 patients not achieving a pCR. HER2-enriched was the predominant baseline subtype not only in the overall and HR-negative cohorts (64 and 75%, respectively), but also in the HR-positive cohort (55%). HER2-enriched was associated with higher pCR rates compared to non-HER2-enriched subtypes (65 vs. 31%; OR = 4.07, 95% CI 1.65-10.61, P < 0.002) and this association was independent of HR status. In pre- and post-treatment paired samples from patients not achieving a pCR, a lower proportion of HER2-enriched and twice the number of luminal tumors were observed at baseline, and luminal A was the most frequent subtype in residual tumors. Interestingly, most (81.8%) HER2-enriched tumors changed to non-HER2-enriched, whereas most luminal A samples maintained the same subtype in residual tumors. Conclusions: Outside of a clinical trial, PAM50 HER2-enriched subtype predicts pCR beyond HR status following trastuzumab-based chemotherapy in HER2-positive disease. The clinical value of intrinsic molecular subtype in residual disease warrants further investigation.

Factores asociados con la respuesta patológica a la quimioterapia neoadyuvante en el cáncer triple negativo / Factors associated with pathologic response to neoadjuvant chemotherapy in triple negative cancer

Introducción: Los tumores de mama triple negativo (TN) representan aproximadamente entre el 20% al 25% de todos los cánceres de mama. El manejo clínico de estos tumores ha cambiado dramáticamente y se ha evaluado el rol de la neoadyuvancia. Nuestros objetivos fueron determinar las tasas de respuesta completa patológica (RCp) y su influencia en la sobrevida global (SG) y sobrevida libre de enfermedad (SLE). Métodos: Se realizó una revisión retrospectiva de 89 casos con tumores de mama TN diagnosticados y tratados con quimioterapia neodayuvante en el Instituto Nacional de Enfermedades Neoplásicas (Lima-Perú) durante el 2002-2007. Se evaluó la asociación entre las principales variables clinicopatológicas con la respuesta patológica y se calcularon las tasas de SLE, el tiempo a la progresión y la SG según el tipo de respuesta patológica. Resultados: La mediana de edad al diagnóstico fue de 40 años, 56 pacientes (62.95) solo recibieron quimioterapia en neoadyuvancia, 23 (25.8%) recibieron quimioterapia seguida de radioterapia y 10 (11.2%) quimioterapia y radioterapia concurrentes. Once paciente (17.7%) presentaron respuesta patológica completa. Los factores asociados con enfermedad residual fueron: grupo de edad <40 años (riesgo relativo [RR]=4.2; P=0.001), nulípara o un hijo (RR=4.5; P=0.042) y edad al primer embarazo mayor o igual a 30 años (RR=4.7; P=0.031). Con una mediana de seguimiento de 3.4 años, la SG fue de 87.3% al primer año fue y 51.8% en el tercer año. La SLE para las pacientes con RCp fue de 90.9% al tercer año y del 54.6% para pacientes con enfermedad residual (P=0.043); la SG al tercer año fue año 100% para pacientes con RCp, y del 54.6% para pacientes con enfermedad residual (P=0.035). Conclusiones: Se observaron las tasas de respuesta similares a algunos reportes publicados previamente y se encontraron algunas variables que estarían asociadas a la enfermedad residual. La RCp predijo altas tasas de SLE y SG.

Introduction: Triple negative (TN) breast tumors occur in approximately 20% to 25% of all breast cancers. The clinical management of these tumors has dramatically changed and the role of neoadjuvancy has been evaluated. Our aims were determine the pathologic complete response (pCR) rates and its influence in the overall survival (OS) and disease-free survival (DFS). Methods: We realized a retrospective review of 89 cases with TN breast tumors diagnosed and treated with neoadjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima – Perú) in the period 2002 – 2007. Association between the main clinicopathologic variables and pathological response was evaluated; also was calculated the rates of DFS and OS according to type of pathological response. Results: The median age at diagnosis was 40 years, 56 patients (62.9% received only neoadjuvant chemotherapy, 23 (25.8%) received chemotherapy then radiotherapy and 10 (11.2%) received concurrent chemotherapy and radiotherapy. Eleven patients (17.7%) achieved pCR. Factors associated with residual disease were: <40 years age group (relative risk [RR]=4.2; P=0.001), nulliparous or 1 child (RR=4.5; P=0.042) and age to first pregnancy more than years (RR=4.7; P=0.031). With a median of follow-up of 3.4 years, OS for all patients was 87.3% at first year and 51.8 at third year. Three years-DFS for patients achieving pCR was 90.9% and 54.6% to patients with residual disease (P=0.043); 3-years OS was 100% for patients with pCR and 54.6% for patients with residual disease (P=0.035). Conclusions: We observe similar response rates to some reports published previously and we found some variables associated to residual disease, pCR predicted high rates of DFS and OS.