BACKGROUND:The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail. METHODS: In total, 444 consecutive invasive breast cancers that were documented in large-format histology slides and worked up with detailed radiologic-pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes. RESULTS: Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14-fold respectively 2.75-fold risk of cancer-related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)-positive cancers; estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) cancers; or basal-like cancers had a 2.18-fold, 2.33-fold, and 4.07-fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2-positive, and basal-like cancers were associated with significantly better long-term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple-negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant. CONCLUSIONS: Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal-like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters. Cancer 2013;119:1132-9. V C 2012 American Cancer Society.KEYWORDS: breast, breast cancer, multifocality, diffuse, molecular phenotypes, survival.
INTRODUCTIONBreast cancer mortality has decreased significantly in countries that have organized, population-based mammography screening 1 ; however, despite using the most recent diagnostic tools and modern therapeutic regimens, women are still dying from this disease. Therefore, exploring the prognostic information generated by radiologic, histologic, and molecular tumor characteristics is essential to facilitate individualized treatment and further decrease disease-specific mortality.Patient age, tumor size, histologic grade, and lymph node status still remain powerful prognostic indicators in patients with breast cancer.2,3 On the other hand, many second-generation prognostic parameters have emerged and have been introduced into routine practice, and the most prominent are estrogen receptor (ER), progesterone recepto...