RESUMEN
The presence or absence of estrogen and progesterone steroid hormone receptor expression (ER, PR) is an essential feature of invasive breast cancer and determines prognosis and endocrine treatment decisions. Among the four ER/PR receptor phenotypes, the ER-/PR+ is infrequent, and its clinical relevance has been controversially discussed. Thus, we investigated its clinical significance and gene expression pattern in large datasets. In a retrospective clinical study of 15,747 breast cancer patients, we determined the ER/PR subtype survival probabilities using Kaplan-Meier and Cox regression analyses. From The Cancer Genome Atlas (TCGA) breast cancer dataset, PAM50 expression signature and pathway analyses were performed to test for distinct molecular features. In our cohort, the ER-/PR+ phenotype has been observed at a frequency of 4.1 % and was associated with an improved 10-year survival for stage I cancers compared to the ER+/PR+ reference subtype (median; 95 % CI 88.1 %; 83-93 vs. 84.3 %; 82-86 %, P = 0.024) as was confirmed by multivariate analysis over the entire follow-up (HR 0.59, 95 % CI 0.38-0.92, P = 0.021). This association lacked significance when including all stages. ER-/PR+ patients treated with antihormonal agents (34.5 %) had shorter survival compared to their non-treated counterparts (Log-rank P = 0.0001). PAM50 signatures suggest a distinct configuration for the ER-/PR+ phenotype. This specific phenotype has been further separated by a set of 59 uniquely expressed genes. Our study supports the notion of the existence of an ER-/PR+ phenotype with clinical and molecular features distinct from the large group of ER+/PR+ patients.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Perfilación de la Expresión Génica , Fenotipo , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Transcriptoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Treatment decisions in breast cancer depend on TNM classification and the assessment of additional variables with have an impact on survival. We examined whether histological subtyping breast cancer as either ductal or lobular is related to disease outcome. PATIENTS AND METHODS: We examined a large data base of 14198 breast cancer patients. RESULTS: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. However, the data further showed that invasive lobular carcinomas have a higher probability of being oestrogen receptor (ER)- and progesterone receptor (PR)-positive and a lower probability of being c-erbB2-positive. They also showed a higher average age at the time of diagnosis in comparison with invasive ductal carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p = 0.031). The multivariable Cox regression analysis showed that ER, PR, nodal status, grade and tumour size predicted disease outcome with statistical significance, while the histological subtype (invasive ductal or lobular) was not a significant predictor of disease outcome. CONCLUSION: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. On the other hand our data gives some indication that lobular and ductal breast cancer appear to be different biological entities.