Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 10, 2018; 9(2): 33-41
Published online Apr 10, 2018. doi: 10.5306/wjco.v9.i2.33
Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy
Marco Galvez, Carlos A Castaneda, Joselyn Sanchez, Miluska Castillo, Lia Pamela Rebaza, Gabriela Calderon, Miguel De La Cruz, Jose Manuel Cotrina, Julio Abugattas, Jorge Dunstan, Henry Guerra, Omar Mejia, Henry L Gomez
Marco Galvez, Carlos A Castaneda, Henry L Gomez, Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
Carlos A Castaneda, Faculty of Medicine, Universidad Peruana San Juan Bautista, Lima 15067, Peru
Joselyn Sanchez, Miluska Castillo, Lia Pamela Rebaza, Omar Mejia, Department of Research, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
Gabriela Calderon, Miguel De La Cruz, Jose Manuel Cotrina, Julio Abugattas, Jorge Dunstan, Department of Breast Cancer Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
Henry Guerra, Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
Author contributions: Galvez M, Castaneda CA and Rebaza LP contributed to the conception and design of the study , performed data analysis and interpretation; Galvez M, Castaneda CA, Sanchez J, Castillo M, Rebaza LP and Mejia O performed data acquisition, as well as provided administrative, technical and material support; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Institutional review board statement: This study was reviewed and approved by the Instituto Nacional de Enfermedades Neoplasicas Institutional Review Board. Personal and filiation data including identity of every patient was protected with an added code in the Excel table. This is a retrospective case series that did not have any activity or contact with the patients.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All of the authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Carlos A Castaneda, MD, MSc, Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520 Surquillo, Lima 15038, Peru. ccastaneda@inen.sld.pe
Telephone: +51-1-6204991
Received: June 28, 2017
Peer-review started: July 3, 2017
First decision: December 7, 2017
Revised: December 19, 2017
Accepted: February 5, 2018
Article in press: February 5, 2018
Published online: April 10, 2018
Abstract
AIM

To investigate the survival impact of clinicopathological factors, including pathological complete response (pCR) and tumor-infiltrating lymphocytes (sTIL) levels according to subtypes, in breast cancer (BC) patients who received neo-adjuvant chemotherapy (NAC).

METHODS

We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. sTIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preNAC core biopsy. pCR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, sTIL, pCR and survival were carried out using SPSSvs19.

RESULTS

Median age was 49 years (range 24-84 years) and the most frequent clinical stage was IIIB (58.3%). Luminal A, Luminal B, HER2-enriched and (triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. pCR was observed in 11% and median percentage of sTIL was 40% (2%-95%) in the whole population. pCR was associated to Ct1-2 (P = 0.045) and to high sTIL (P = 0.029) in the whole population. There was a slight trend towards significance for sTIL (P = 0.054) in Luminal A. sTIL was associated with grade III (P < 0.001), no-Luminal A subtype (P < 0.001), RE-negative (P < 0.001), PgR-negative (P < 0.001), HER2-positive (P = 0.002) and pCR (P = 0.029) in the whole population. Longer disease-free survival was associated with grade I-II (P = 0.006), cN0 (P < 0.001), clinical stage II (P = 0.004), ER-positive (P < 0.001), PgR-positive (P < 0.001), luminal A (P < 0.001) and pCR (P = 0.002). Longer disease-free survival was associated with grade I-II in Luminal A (P < 0.001), N0-1 in Luminal A (P = 0.045) and TNBC (P = 0.01), clinical stage II in Luminal A (P = 0.003) and TNBC (P = 0.038), and pCR in TNBC (P < 0.001). Longer overall survival was associated with grade I-II (P < 0.001), ER-positive (P < 0.001), PgR-positive (P < 0.001), Luminal A (P < 0.001), cN0 (P = 0.002) and pCR (P = 0.002) in the whole population. Overall survival was associated with clinical stage II (P = 0.017) in Luminal A, older age (P = 0.042) in Luminal B, and pCR in TNBC (P = 0.005).

CONCLUSION

Predictive and prognostic values of clinicopathological features, like pCR and sTIL, differ depending on the evaluated molecular subtype

Keywords: Breast cancer, Subtype, Tumor-infiltrating lymphocytes, Neoadjuvant therapy, Pathological complete response, Survival

Core tip: The authors evaluated a series of 435 breast cancer (BC) patients who received neoadjuvant chemotherapy. They evaluated the association between stromal tumor-infiltrating lymphocytes levels and pCR in preneoadjuvant chemotherapy samples according to molecular subtypes. The results confirm differences in the predictive and prognostic role of stromal tumor-infiltrating lymphocytes and pathological complete response depending on the tumor subtype. Additionally, the authors evaluate the value of traditional prognostic features in every BC subset. The results increase the understanding of biomarkers in the heterogeneous scenario of BC.