Anatomic Pathology / EGFR and CK5/6 and Breast Cancer Metastases

Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non–basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer. Breast cancer is one of the most common malignant tumors in women, and it comprises a remarkably heterogeneous group of diseases. Management of breast cancer depends on clinical and pathologic features of the tumor, including patient age, tumor size, histologic type and grade, lymph node stage, and lymphovascular invasion. In addition, molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) have been proven to provide therapeutic, predictive, and prognostic value.1,2 Triple-negative (TN) breast carcinoma is a clinical subtype of breast cancer characterized by lack of expression of ER, PR, and HER2 protein. It represents approximately 10% to 17% of all breast carcinomas and is more prevalent among young African, African American, and Latino women.3,4 As compared with other subtypes of breast carcinomas, TN tumors have an onset at a younger age (<50 years) with a higher grade and higher rate of axillary node positivity.2,4,5-7 They typically demonstrate a unique molecular profile, aggressive behavior, and distinct patterns of metastasis.1 The metastases tend to be more aggressive and visceral with hepatic, central nervous system, and lung being common sites. TN carcinomas lack molecular targets commonly used in targeted therapy, making them very difficult to treat, and they have worse relapse-free and overall survival.5 Developing a novel treatment strategy to treat TN tumors is crucial for improving the prognosis of patients with these tumors. TN breast carcinomas can be further divided into 2 subtypes: basal-like and non–basal-like, although not all basalUpon completion of this activity you will be able to: • list the immunohistochemical stains that can be applied to identify basal-like triple-negative breast carcinomas. • describe association of epidermal growth factor receptor and CK5/6 expression with development of metastatic disease in basal-like triplenegative breast carcinoma. • define an independent risk factor for metastatic disease in basal-like triple-negative breast carcinoma. • provide a potential candidate for therapeutic target for treatment of basal-like triple-negative breast carcinomas. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit TM per article. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 847. Exam is located at www.ascp.org/ajcpcme.