Abstract 2271: bcl-2 expression in HER2-positive breast carcinoma subtypes

Abstract Background: HER2-positive breast cancers comprise 20-30% of all breast cancers; amplification of HER2 confers a poorer prognosis. While treatment with anti-HER2 targeted therapies has dramatically improved outcomes in this group, a significant subset of patients develops resistance, highlighting the need for novel therapeutic options. In addition, like triple negative breast carcinomas, HER2-positive invasive carcinomas also consist of different intrinsic subtypes with different responses to therapy and different overall prognosis. Finally, recent reports suggest that bcl-2 expression contributes to resistance to anti-HER2 therapies. In this study, we evaluated expression of bcl-2 in HER2-positive breast tumors and correlated the expression of bcl-2 with HER2 subtype, patient demographics and histologic and molecular characteristics. Design: The study population consisted of 114 patients with HER2-positive invasive breast carcinoma treated with surgical excision or mastectomy at Northwestern Memorial Hospital (2009-14) (mean age 53, range 18-80). Electronic medical records were reviewed for patient demographics. Pathologic tumor characteristics (histologic type, size, grade, lymph node status) and tumor marker profile (ER, PR, p53 and Ki-67) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of bcl-2 (Dako, clone 124). Results: Overall, these HER2-pos breast carcinomas were almost exclusively of ductal histologic type (101/114, 88.6%). Almost ¾ of the cases were poorly differentiated, grade 3 carcinomas (83/114, 73%), while the other 31 were grade 2 tumors. No grade 1 tumors were seen. bcl-2 was expressed in 64/114 (56%) of the HER2-pos carcinomas. No association of the bcl-2 expression with age, race, tumor size, lymph node status, p53 expression, or Ki-67 proliferation index was seen. Of interest, this sample of HER2-pos carcinomas was almost equally balanced between ER-neg/HER2-pos (HER2 subtype) and ER-pos/HER2-pos (Luminal B subtype), 54 vs 60 cases respectively. bcl-2 was differentially expressed in these two HER2-pos tumor subtypes: only 9/54 (14%) of the HER2 subtype expressed bcl-2 compared to 55/64 (85.9%) of the Luminal B subtype (p<0.0001). Conclusions: 1. bcl-2 is expressed in just over half of the HER2-pos carcinomas. 2. bcl-2 expression is far more common in Luminal B compared to the HER2-pos subtype of breast carcinomas. 3. bcl-2 expression does not appear to have a differential expression between age or racial groups and does not correlate with tumor size or lymph node status. Our findings add to the understanding of the molecular mechanisms that drive the different subtypes of HER2-pos breast carcinomas and raise the possibility that bcl-2 targeted therapies may lead to novel therapeutic approaches for the management of subgroups of patients with HER2-pos breast tumors. Citation Format: Kalliopi P. Siziopikou, Alexandra Larson, Luis Z. Blanco, Virginia Kaklamani. bcl-2 expression in HER2-positive breast carcinoma subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2271.