omprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtype

Author(s):Show less -

Pavanelli, Ana Carolina ^{[1, 2]} ; Mangone, Flavia Rotea ^{[1, 2]} ; Yoganathan, Piriya ^[3] ; Bessa, Simone Aparecida ^{[1, 2]} ; Nonogaki, Suely ^[4] ; de Toledo Osorio, Cynthia A. B. ^[4] ; de Andrade, Victor Piana ^[4] ; Soares, Ibere Cauduro ^[5] ; de Mello, Evandro Sobrosa ^[5] ; Mulligan, Lois M. ^[3] ; Nagai, Maria Aparecida ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Discipline Oncol, BR-01246903 Sao Paulo - Brazil

^[2] Ctr Translat Res Oncol, Canc Inst Sao Paulo, Lab Mol Genet, BR-01246000 Sao Paulo - Brazil

^[3] Queens Univ Kingston, Canc Res Inst, Dept Pathol & Mol Med, 18 Stuart St, Kingston, ON K7L 3N6 - Canada

^[4] AC Camargo Canc Ctr, Dept Pathol Anat, BR-01509020 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Hosp Clin, Fac Med, Dept Pathol, Canc Inst Sao Paulo, HCFMUSP, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: Breast Cancer Research and Treatment; v. 192, n. 1, p. 43-52, FEB 2022.
• Web of Science Citations: 0

Abstract

Purpose Breast cancer (BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance. Methods Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays (TMAs) containing a cohort of 361 Luminal subtype BC. Results Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015). Conclusion Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC. (AU)

• FAPESP's process: 19/05252-4 - Characterization of new predictive biomarkers of response to endocrine therapy and HER2 inhibitors in breast cancer
• Grantee: Maria Aparecida Nagai
• Support Opportunities: Regular Research Grants