Abstract P1-09-12: TP53 expression in relation to clinical and etiologic factors in breast cancer subtypes

Abstract

Abstract TP53 is a well-known tumor suppressor gene and mutations in TP53 are the most frequent genomic event in most cancers including breast cancer. Recent studies have shown that the frequency, spectrum, timing, and clinical implications of TP53 mutations varied in different molecular subtypes of breast cancer. For example, the frequency of TP53 mutations is the highest in basal-like subtype and lowest in luminal A tumors. However, the evaluation of TP53 protein expression, as a surrogate for TP53 mutations, in large studies in the context of tumor subtypes is limited. In addition, the etiologic relevance of TP53 expression is yet to be investigated. The goal of this study is to evaluate the association of clinical and breast cancer risk factors with TP53 expression, measured using immunohistochemistry (IHC), in breast cancer molecular subtypes. The analysis included 7,226 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China. Subtypes were defined as Luminal A: ER+ and PR+, HER2–, and low grade (grades 1 or 2); luminal B/HER2–: ER+ and/or PR+, HER2–, and high grade (grade 3); luminal B/HER2+: ER+ and/or PR+, HER2+ (regardless of grade); HER2-enriched: ER–, PR–, and HER2+; Triple-negative (TN): ER–, PR–, and HER2–. As expected, positive TP53 staining showed the lowest frequency in the luminal A (46%) and highest in the TN (61%) and HER2-enriched (63%) subtypes (P-value <0.001). Overall and particularly in luminal A patients, positive TP53 staining was associated with higher frequencies of aggressive tumor features such as higher grade, larger tumor size, higher proliferative index, and EGFR expression. Compared with TP53– patients, TP53+ patients were more likely to have younger ages at onset and increased parity, but these associations were largely driven by the luminal A subtype [OR (95% CI) vs nulliparity = 2.67 (1.59, 4.51); 2.63 (1.52, 4.55); 3.68 (2.01, 6.72) for 1, 2, and ≥3 children, respectively (P-trend = 0.006)]. Luminal A/TP53+ patients were also more likely to have breastfed [OR (95% CI) ever vs never = 1.38 (1.03, 1.85)] than luminal A/TP53– patients. These findings suggest that TP53 IHC staining might be used to further refine the classification of luminal A breast cancer into subgroups with distinct clinical and etiologic relevance. Citation Format: Yang XR, Abubakar M, Guo C, Koka H, Sung H, Guida J, Deng J, Zhou B, Hu N, Lu N. TP53 expression in relation to clinical and etiologic factors in breast cancer subtypes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-12.