Clinical, histomorphological, and therapeutic prognostic factors in patients with triple-negative invasive breast cancer / Fatores prognósticos clínicos, histomorfológicos e terapêuticos em pacientes com câncer de mama invasivo triplo negativo

ABSTRACT Introduction: Breast cancer is the most common visceral malignancy in women, the leading cause of cancer death among women worldwide. The triple negative subgroup has poor prognosis and aggressive biological behavior. Objectives: To outline the clinical and histopathological aspects, the treatment profile, and to suggest which factors may predict poor prognosis in patients with triple-negative invasive breast cancer in the Campos Gerais region of Paraná. Methods: A retrospective observational cohort study, longitudinal, comparative, performed in a clinic of anatomic pathology in the Instituto Sul Paranaense de Oncologia, in Ponta Grossa, Paraná. The inclusion criteria were female patients with pathology report of invasive breast carcinoma, whose immunohistochemistry showed negative for hormone receptors and human epidermal growth factor receptor (HER2), diagnosed in the period between January 1, 2002 and December 31, 2012. The patients were divided into two groups, living women and patients who have died. Results: The recurrence rate, chemotherapy type, angiolymphatic invasion, tumor size, lymph node invasion, and type of surgery performed were significant variables in the univariate analysis between the groups. After Cox regression for multivariate analysis, only the angiolymphatic invasion (p = 0.012, relative risk [RR] 5.0518, confidence interval [CI] 95% 1.4261-17.8952), and tumor size (p = 0.0385, RR 1.2605, CI 95% 1.0123-1.5695) remained significant. Conclusion: The angiolymphatic invasion and tumor size proved to be risk factors for death, from all causes, in patients with triple-negative breast cancer. Differences between groups can indicate different molecular subtypes within the triple-negative phenotype.

RESUMO Introdução: O câncer de mama é a neoplasia maligna visceral mais frequente em mulheres, sendo a principal causa de morte por câncer no sexo feminino em todo o mundo. O subgrupo triplo negativo apresenta prognóstico pobre e comportamento biológico agressivo. Objetivos: Delinear os aspectos clínicos e histomorfológicos e o perfil de tratamento, além de sugerir quais fatores podem predizer pior prognóstico nas pacientes com câncer de mama invasivo triplo negativo na região dos Campos Gerais do Paraná. Métodos: Estudo de corte retrospectivo observacional, longitudinal e comparativo, realizado em uma clínica de anatomia patológica e no Instituto Sul Paranaense de Oncologia, em Ponta Grossa, Paraná. Os critérios de inclusão foram pacientes do sexo feminino com laudo anatomopatológico de carcinoma de mama invasor, cuja imuno-histoquímica apresentou-se negativa para os receptores hormonais e receptor de crescimento epidérmico humano 2 (HER2), diagnosticadas no período entre 01 de janeiro de 2002 a 31 de dezembro de 2012. As pacientes foram divididas em dois grupos, mulheres vivas e as que faleceram. Resultados: O índice de recidiva, o tipo de quimioterapia, a invasão angiolinfática, o tamanho do tumor, a invasão linfonodal e os tipos de cirurgia realizadas foram variáveis significativas na análise univariada entre os grupos. Após a regressão de cox para análise multivariada, apenas a invasão angiolinfática (p = 0,012, risco relativo [RR] 5,0518, intervalo de confiança [IC] 95% 1,4261-17,8952) e o tamanho do tumor permaneceram significativos (p = 0,0385, RR 1,2605, IC 95% 1,0123-1,5695). Conclusão: A invasão angiolinfática e o tamanho do tumor mostraram-se fatores de risco para óbito, por todas as causas, em pacientes com câncer de mama triplo negativo. Diferenças entre os grupos podem indicar diferentes subtipos moleculares dentro do fenótipo triplo negativo.

Sexual maturation and fertility of mice exposed to triphenyltin during prepubertal and pubertal periods.

This study investigated the effects of pre- and peripubertal exposure (PND 15-45) to triphenyltin hydroxide (TPT: 0, 1.875, 3.75, 7.5 and 15 mg/kg bw/d po) on mouse sexual maturation and fertility. Half of the mice were euthanized on PND 46 and the remaining mice were submitted to fertility tests on PND 65-75. TPT caused a transient decrease of weight gain at 3.75 mg/kg bw/d, and deaths and body weight deficits at higher doses. Delays of testes descent (TD), vaginal opening (VO) and first estrus (FE) occurred at doses ≥3.75 (TD) and ≥7.5 mg/kg bw/d (VO, FE), respectively. Body weight on the days of TD, VO and FE did not differ among groups. TPT at doses ≥3.75 mg/kg decreased sperm and spermatid counts at the end of treatment (PND 46) but no alteration was noted later on PND 75. Testicular histopathology (PND 46) showed a dose-dependent reduction of seminiferous tubules diameter, a greater degree of vacuolation in Sertoli cells and germ cell degeneration and necrosis in TPT-treated mice. TPT did not affect the outcome of fertility tests. Study-derived NOAEL was 1.875 mg TPT/kg bw/d for males and 3.75 mg TPT/kg bw/d for females. The detrimental effects of TPT on spermatogenesis were reversed after treatment discontinuation.