Molecular Subtypes of Breast Carcinoma in South Indian Women and their Correlation with Histomorphological and Clinical Features

Breast carcinoma is the commonest malignant tumour and the leading cause of carcinoma death in women worldwide with an incidence rate greater than 30 % of all cancers in urban Indian women. Though its detection is on the rise due to widespread screening programmes, there is no considerable fall in the mortality rate and survival. Breast cancers are heterogeneous in their morphology, clinical course and response to treatment. The conventional estrogen and progesterone receptors along with HER2/neu are notable for their differential expression among the subgroups. A crucial development in therapy has been the understanding that the presence of these markers correlates well with response to hormone therapy and chemotherapy. The determination of these receptors is regarded at present as the most powerful predictors in breast cancer management. The other important prognostic factors currently in use are the lymph node status, tumor size and grade. In spite of the numerous prognostic factors that have been identified, the clinical outcome continues to be hard to predict. Screening programmes and continuing advances in diagnostic and therapeutic techniques are allowing for the detection of smaller breast tumours magnifying the immediate need for newer prognostic markers. Normal breast ducts contain 3 types of epithelial cells. Luminal (glandular) cells, basal (myoepithelial) and stem cells. Basal cells typically express CK 5/6, CK 14 and CK 17 while luminal cells express CK 8 and 18. Cancers expressing basal cytokeratins 5 and 14 constitute a tumour subgroup that is typically hormone receptor negative, having a high grade and a high proliferative index. Basal like tumour markers are not routinely used in the standard histological diagnosis of breast cancers resulting in basal-like and non basal-like tumours being treated similarly. This could explain the poorer clinical outcome, higher recurrence rate, shorter disease free interval and different patterns of mortality over time. In patients without lymph node metastases, the prognostic significance of CK 5/6 is independent of tumour size, grade and hormone receptor status. CK 8/18 indicates the increasing degree of tumour