Local-regional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer

Abstract

594 Background: Triple negative (TN) basal-like breast cancers (Negative for ER,PR,HER2/neu) represent an aggressive phenotype, with unique clinical and pathologic features. The purpose of this study was to determine the prognostic significance of this classification with respect to local-regional relapse and distant metastasis in a cohort of conservatively managed breast cancer patients. Methods: A large data base of conservatively managed breast cancer patients with long term follow-up, in which all three immunhistochemical markers, ER,PR and HER2/neu were available was reviewed. Patients were classified as TN if they tested negative for all three markers. Of 442 patients in the data base with all three markers available, 100 were classified as TN. All clinical, pathologic, outcomes and molecular marker data were entered into a computerized database. Results: As of September 2005, with a median follow-up of 7 years, of the 442 patients in the study there have been 50 in-breast relapses, 10 nodal relapses, 68 distant relapses and 62 deaths. Compared with the other subtypes, the TN cohort had a poorer overall survival (67% vs 75%, p = .096), poorer distant metastasis-free rate (61% vs 75%, p = .002), poorer cause-specific survival (67% vs 78%, p = .03), and poorer nodal relapse-free rate (93% vs 99%, p = .021). In a multivariate Cox regression analysis, TN subtype was an independent predictor of distant metastasis (HR=2.6, CI 1.53–4.35, p = .004) and cause- specific survival (HR= 2.36, CI 1.28–4.38, p= .006). There was no significant difference in local (in-breast) control between the TN and other subtypes. BRCA testing was performed on 85 patients in this cohort, of whom 8 had deleterious mutations in BRCA1 and 6 had deleterious mutations in BRCA2. Of 8 BRCA1 mutant patients 7 were classified as TN, while only 1 of 6 BRCA2 patients were TN (p < .001). Conclusions: Patients classified as TN have a poor prognosis with respect to overall, disease free and cause specific survival. However there was no evidence that these patients are at higher risk for local relapse following conservative surgery and radiation. BRCA1 mutant patients develop predominantly TN tumors. No significant financial relationships to disclose.