Cáncer de mama triple negativo: terapias sistémicas actuales y experiencia local / Triple negative breast cancer: current systemic therapy and local experience

Resumen El cáncer de mama (CM) es la principal causa de muerte por cáncer en mujeres chilenas. Es una enfermedad heterogénea, en la cual se han identificado cuatro subtipos básicos, determinados según características clínicas, histológicas y moleculares, los que se relacionan a estrategias terapéuticas. El CM triple negativo (CMTN) se caracteriza por su agresividad, recaída temprana y mayor tendencia a presentarse en etapas avanzadas. Frecuentemente afecta a mujeres jóvenes o con antecedentes familiares de CM u ovario. La única terapia sistémica aprobada para el CMTN es la quimioterapia; sin embargo, recientemente terapias moleculares con inhibidores de puntos de control inmune e inhibidores de la poli-adenosina difosfato ribosa polimerasa, han mostrado eficacia en pacientes seleccionados, y se han agregado al arsenal terapéutico para CMTN. Dada la aparición de estas nuevas estrategias, parece relevante entender la heterogeneidad de esta enfermedad, los mecanismos de acción de las nuevas terapias, resultados clínicos y criterios de selección de pacientes para terapias moleculares. Presentamos una revisión de la terapia sistémica actual del CMTN.

Breast cancer is the leading cause of cancer death in Chilean women and worldwide. It is a heterogeneous disease and four different subtypes have been identified based on clinical, histological and molecular features, which correlate with different treatment tumor sensitivity. Triple negative breast cancer is characterized by its aggressiveness, early relapse, and a greater tendency to present in advanced stages. It frequently affects young women, with cancer family history, especially breast or ovarian cancer. The approved systemic therapy for triple negative breast cancer is chemotherapy; however, recently, targeted therapies with checkpoint inhibitors and polyadenosine diphosphate ribose polymerase inhibitors have been shown to be effective in selected patients and have been added to the therapeutic arsenal for triple negative breast cancer. Given the appearance of these new strategies, it seems relevant to understand the heterogeneity of this disease, the mechanisms of action behind new therapies, clinical results, and the criteria to select patients for molecular therapies. We present a review of the current systemic therapy of this breast cancer subtype.

Cáncer de mama triple negativo: otra enfermedad y nuevo reto / Triple negative breast cancer: another disease and a new challenge

El cáncer de mama Triple Negativo es un subtipo molecular que se caracteriza por ausencia de expresión de receptores de estrógeno, progesterona y proteína HER2. Representa el 10 % a 15 % de todos los subtipos de cáncer de mama con impacto en el pronóstico y en las líneas de tratamiento; siendo negativo para receptores hormonales y HER2, la terapéutica hormonal y anti-HER2 no cuentan para su manejo. Aún no se dispone de productos dirigidos a blancos específicos para esta categoría.(AU)

The Triple Negative breast cancer is a molecular subtype characterized by no expression of the estrogen, the progesterone and the HER2 protein receptors. They represents 10 % to 15 % of all the breast cancer subtypes with an impact on the prognosis and in the treatment lines; is negative for the hormone receptors and for the HER2, hormonal and the anti-HER2 therapeutics do not count for the management of them. The products targeting specific to this category are not yet available(AU)

Triple‑negative breast cancer: An institutional analysis.

AIM: Triple‑negative breast cancer (TNBC) is defined by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER 2)/neu. It has been identified as an independent poor prognostic factor for survival. The aim of this study was to compare the clinico‑pathological characteristics and treatment outcomes of patients with TNBC and non‑TNBC. MATERIALS AND METHODS: We carried out an analysis of 706 patients with invasive breast cancer between January 2007 and December 2011 in whom information on the status of ER, PR, and HER2/neu were available. RESULTS: One hundred and fifty‑five patients (21.9%) patients had TNBC. Patients with TNBC had a significantly lower median age [46.2 vs. 49.8 years; P = 0.005, 95% confidence interval (CI): 0.98 to 2.38] and a higher proportion of high‑grade tumors as compared to the non‑TNBC group (43 vs. 24%; P < 0.0001). After a median follow‑up of 30 months, the three‑year relapse‑free survival (RFS) was significantly lower in the TNBC group (76 vs. 64%; log rank P = 0.002). Three‑year overall survival (OS) was lower in the TNBC group but not statistically significant. Age <49 years, higher nodal stage, and larger tumor size (>5 cm) were associated with poor outcome. CONCLUSION: TNBC is significantly associated with younger age and high‑grade tumors and constitutes 21.9% of all breast cancers in our institute. Triple negativity was a significantly poor prognostic factor for RFS but not OS.

Cáncer de mama triple negativo: una enfermedad de difícil diagnóstico y tratamiento / Triple negative breast cancer: a difficult disease to diagnose and treat

El cáncer de mama triple negativo (CMTN) es una neoplasia maligna caracterizada por la ausencia de la expresión de los receptores de estrógeno, de progesterona y HER2. Estudios recientes han señalado que el CMTN es un grupo heterogéneo de distintas neoplasias, con pronósticos diferentes. Sin embargo, debido a que la realización de perfiles genéticos no es una práctica estándar para el diagnóstico convencional del cáncer de mama, se dificulta la apropiada identificación de este subtipo de cáncer de mama. El CMTN se caracteriza por tener patrones epidemiológicos de alta incidencia en poblaciones afroamericanas y latinas, y de menor incidencia en población caucásica y constituye un problema de salud pública por su elevada morbilidad y mortalidad. Ante la ausencia de blancos terapéuticos, la quimioterapia cumple un rol importante en el tratamiento, y muchos esfuerzos están destinándose a buscar otras combinaciones de quimioterapia y nuevas drogas, mientras que las actuales guías no especifican un tratamiento para este tipo de cánceres. En el presente documento se hace una revisión sobre las características epidemiológicas y clínicas, los posibles factores pronósticos y sobre algunas estrategias terapéuticas contra el CMTN.

Triple negative breast cancer (CMTN, Spanish acronym) is a malignant neoplasm characterized by the absence of expression of estrogen, progesterone and HER2 receptors. Recent studies have shown that CMTN is a heterogeneous group including different neoplasm with different prognosis. However, because genetic profiles are not a standard practice in conventional diagnosis of breast cancer, it is hard to properly identify this breast cancer subtype. CMTN is characterized by its high-incidence epidemiological patterns in African-American and Latin people, and lower incidence in Caucasian people, and constitutes a public health issue due to its high morbidity and mortality. Due to the absence of therapeutic targets, chemotherapy has a key role in treatment, and many efforts are being deployed to seek other combinations of chemotherapy and new drugs, while the current guides do not specify treatment for this type of cancer. This document reviews the epidemiological and clinical characteristics, the potential prognosis factors and some therapeutic strategies against CMTN.