Breast conservation without axillary dissection: the role of axillary radiotherapy

Abstract

Breast cancer is a heterogeneous disease. Many women who are given adjuvant cytotoxic chemotherapy for breast cancer receive no benefit from this treatment because established micrometastases are resistant to the chemotherapy. Integrated analysis of genetic alterations that i) disregulate the cell division process, resulting in faster cell proliferation, ii) affect physiologically cell death mechanisms that cause slower rates of cell loss and iii) enhance drug resistance, may be useful for defining the biology of response of breast carcinoma to adjuvant treatment. Immunohistochemistry with antibodies recognizing ER, PgR, Ki-67, HER-2/neu, ~53, bcl-2, encoded products was performed on 156 primary high risk breast carcinoma (Premenopausal patients: T> 1 cm, G2-3, NO1, any ER/PgR status; Postmenopausal: T> 1 cm, G2-3, NO-l, ER-/PgR-) who received four cycles of adjuvant HD EC (Epirubicin 120 mg/m’ iv. on day 1, Cyclophosphamide 600 mg/m2 i.v. on day 1) with or without Lonidamine between March 1991 and December 1993. Graphical correspondence analysis of multivariate relationship showed that a p53-, bcl-2+, HER-Uneu-phenotype with nuclear grade 2 and low Ki-67 score characterizes most lobular carcinomas (ILC) while ductal carcinomas (IDC) were frequently identified by a bc12-, p53+, HER-2/ neu-phenotype with nuclear grade 3 and high Ki-67 score. Separate multivatiate analysis (Cox model) demonstrated an independent prognostic role of ~53, nodal status and Ki-67 score in predicting short-term (36 months) disease-free-survival in the IDC group whereas only bcl-2 emerged as significant predictive parameter in the ILC group. Multiparametric analysis conducted on several biopathological parameters might be useful for distinguishing different biological behaviours of breast carcinoma in the adjuvant setting. Our findings suggest that bcl-2 and ~53 may play an important role in ILC and IDC respectively.