Risk factors for local recurrence after breast-conserving therapy for invasive carcinomas: a case-control study of histological factors and alterations in oncogene expression.

PURPOSE: Many studies have focused on histological risk factors for local recurrence (LR) after breast-conserving therapy (BCT). In addition to histological factors, we studied alterations in the expression of various proteins in relation to LR using a case-control approach. METHODS AND MATERIALS: Ninety-nine LR occurred in a patient cohort of 1,481 tumors treated with BCT. These patients were randomly matched, each with two controls. Matching was performed for age group (< or = 50 and > 50 years), pN stage, and follow-up time. Histology slides were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, CD31, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c-erbB2/neu, and p53. Statistical analyses were performed using conditional logistic regression. RESULTS: Sixty-six cases and 139 controls with invasive carcinoma remained for analysis. The following variables were significant risk factors for LR: young age (p = 0.006), high nuclear grade (p = 0.04), high mitotic count (p = 0.03), extensive DCIS around the tumor (p = 0.02) but not within the tumor, poorly differentiated type of DCIS (p = 0.03), > 20% ki-67 positive cells (p = 0.006), and PR negativity (p = 0.03). When the analysis was performed for patients < or = and > 50 years, these risk factors were found in the older patients, but not in the younger patients. CONCLUSION: High mitotic count and Ki-67 positivity are risk factors for LR. EDCIS surrounding the invasive tumor is a risk factor for LR, especially when of poorly differentiated type. Age is an important risk factor for LR independent of other risk factors, including alterations in oncogene expression.