Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.

BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells. METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples. RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS. CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.

Comparison of methods for the isolation of human breast epithelial and myoepithelial cells.

Two lineages, epithelial, and myoepithelial cells are the main cell populations in the normal mammary gland and in breast cancer. Traditionally, cancer research has been performed using commercial cell lines, but primary cell cultures obtained from fresh breast tissue are a powerful tool to study more reliably new aspects of mammary gland biology, including normal and pathological conditions. Nevertheless, the methods described to date have some technical problems in terms of cell viability and yield, which hamper work with primary mammary cells. Therefore, there is a need to optimize technology for the proper isolation of epithelial and myoepithelial cells. For this reason, we compared four methods in an effort to improve the isolation and primary cell culture of different cell populations of human mammary epithelium. The samples were obtained from healthy tissue of patients who had undergone mammoplasty or mastectomy surgery. We based our approaches on previously described methods, and incorporated additional steps to ameliorate technical efficiency and increase cell survival. We determined cell growth and viability by phase-contrast images, growth curve analysis and cell yield, and identified cell-lineage specific markers by flow cytometry and immunofluorescence in 3D cell cultures. These techniques allowed us to better evaluate the functional capabilities of these two main mammary lineages, using CD227/K19 (epithelial cells) and CD10/K14 (myoepithelial cells) antigens. Our results show that slow digestion at low enzymatic concentration combined with the differential centrifugation technique is the method that best fits the main goal of the present study: protocol efficiency and cell survival yield. In summary, we propose some guidelines to establish primary mammary epithelial cell lines more efficiently and to provide us with a strong research instrument to better understand the role of different epithelial cell types in the origin of breast cancer.

Consenso de seguimiento de pacientes con cáncer de mama de la Sociedad Española de Senología y Patología Mamaria / Consensus document of the Spanish Society of Senology and Breast Disease on the follow-up of patients with breast cancer

A pesar del aumento en la prevalencia del cáncer de mama, el seguimiento de estas pacientes no está totalmente estandarizado. La Sociedad Española de Senología y Patología Mamaria propuso la elaboración de un documento de consenso sobre el seguimiento que debería proponerse a las pacientes afectas de lesiones de mama in situ e infiltrantes en estadios i-iii, tratadas con intención curativa, una vez finalizados los tratamientos iniciales. En su realización han colaborado profesionales de toda España de distintas especialidades y ámbitos de actuación. Fue presentado en el Primer Congreso Español de la Mama, que se celebró en octubre de 2013 en Madrid, para su refrendo por parte de la Sociedad, y se recogieron las aportaciones de los asistentes a la sala. El objetivo principal del seguimiento es la detección precoz de recurrencias locorregionales y a distancia, de nuevos primarios, y valorar los efectos secundarios de los tratamientos aplicados. Debe también cubrir las necesidades de soporte psicológico, así como la rehabilitación y reinserción sociolaboral posterior y la educación para la salud, corrigiendo hábitos de vida no saludables. No se han descrito diferencias significativas entre el seguimiento minimalista y el intensivo, respecto al índice de recurrencia, la supervivencia global y la calidad de vida. El tipo y los años de seguimiento deberían ser distintos para cada paciente según su riesgo de recidiva y la clasificación molecular de su lesión. Este consenso ha tenido el apoyo de otras sociedades científicas relacionadas con la enfermedad mamaria, asistentes al Primer Congreso Español de la Mama (AU)

Despite the increasing prevalence of breast cancer, there is no standardized protocol for the follow-up of breast cancer survivors. The Spanish Society of Senology and Breast Disease has supported a consensus document on the follow-up of breast cancer survivors, aimed at patients diagnosed with stage i to iii disease and with invasive and intraepithelial (in situ) lesions, and treated with curative intent, after completion of the initial treatment. Practitioners from all over Spain, with different specialities and areas of activity, participated in the drafting in the document. It was presented at the First Spanish Breast Congress (Primer Congreso Español de la Mama), which took place in October 2013, for the Society's approval. Input from the audience was considered. The main aim of follow-up is the early detection of local and distant recurrences, of new primaries, and evaluation of the adverse effects of the therapies applied. Follow-up should also include psychological support, education on healthy habits, rehabilitation, and social and work reintegration. No significant differences between minimalistic and intensive follow-up have been reported regarding recurrence, overall survival, and quality of life. The length, intervals, and intensity of follow-up should be tailored according to each patient's individual risk of relapse and molecular subtype. This consensus document has the support and endorsement of other scientific societies related to breast disease and present at the congress (AU)