Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial

Abstract

Purpose: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC).

Patients and methods: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery.

Results: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%).

Conclusion: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

FIG 1

Kaplan-Meier analysis with the log-rank test of the overall survival of MPBCS patients assigned to the neoadjuvant arm, according to RCB. OS, overall survival; RCB, residual cancer burden.

FIG 2

RCB according to the breast cancer subtype in the neoadjuvant arm of the MPBCS cohort. Distribution of RCB by immunohistochemical subtypes is shown in the left panel and by PAM50 subtypes in the right panel. Numbers within circles are the number of patients in each category. Positive Pearson residuals (red hues) specified an attraction (positive association), and negative residuals (blue hues) implied a repulsion (negative association) between the corresponding row and column variables. HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; MPBCS, Molecular Profiling of Breast Cancer Study; RCB, residual cancer burden.

FIG 3

Overall survival of MPBCS patients according to the type of surgery (BCS or total mastectomy). Kaplan-Meier survival curves with log-rank analysis (above) and univariate and IPTW-corrected Cox proportional hazards regression model hazard ratios with their correspondent 95% CIs and P values (below). ^aThe model considered (1) the type of surgery as the main predictor of survival, (2) variables that affect the type of surgery decision as weights from IPTW analysis, and (3) radiotherapy (yes/no) as a covariable. Analyses were performed only with the patients with no missing values in any of the variables involved. BCS, breast-conserving surgery; IPTW, inverse probability of treatment weighting; MPBCS, Molecular Profiling of Breast Cancer Study; OS, overall survival.

FIG A1

Covariance balance plot for all variables considered in the IPTW model. IPTW, inverse probability of treatment weighting.

FIG A2

CONSORT diagram for MPBCS patients analyzed in this work. MPBCS, Molecular Profiling of Breast Cancer Study.

FIG A3

Kaplan-Meier analysis with the log-rank test of the OS of MPBCS participants according to their (A) immunohistochemical and (B) PAM50 subtypes. MPBCS, Molecular Profiling of Breast Cancer Study; OS, overall survival.