Abstract P4-04-03: PIK3CA mutations in breast tumor specimens in a cohort (n=791) of a multicentric study and associations to known prognostic factors and survival data

Abstract

Abstract Introduction: The PI3K/AKT/mTOR signalling pathway plays an important role in cellular processes like proliferation, apoptosis, survival and adhesion of tumor cells. It is one oft the most deregulated pathways in cancer. In up to 30% of breast cancers, dysregulation of this pathway is reported, resulting from mutations in the PIK3CA gene that encodes the catalytic subunit (p110a). Hotspots of mutations, comprising 86 % of all observed PIK3CA-mutations, were described in exon 9 (helical domain, E542K, G > A; E545K, G > A) and exon 20 (kinase domain, H1047R, A > G). Prevalence and the prognostic impact of the PIK3CA mutations as well as the predictive value with regard to endocrine therapy are controversially discussed. In this study we describe the prevalence of the three most frequent PIK3CA mutations in a consecutive cohort of breast cancer patients and its association to tumor characteristics, to known prognostic factors and survival data. Methods: The cohort consists of 1,047 patients who were newly diagnosed for non-metastatic breast cancer in one of 6 German breast centres from 2009 to 2011 and who were registered within the prospective PiA-study (Prognostic assessment in routine Application, NCT 01592825). DNA of 806 fresh frozen tumors were available for analyzation by qPCR (exon 9: C 763 and C760; exon 20: C 775). Associations between the PIK3CA mutation status and clinical, pathological parameters were evaluated using binary logistic regression model. Survival probabilities were estimated by Kaplan-Meier-method, Log-Rank-Test and Breslow-Test. Recurrence free interval (RFI) was defined according to STEEP criteria. Results: Mutation status for the three most common PIK3CA mutations was available for 791 tumors. The mutation rate was 29.2%. Only two tumors harbored two mutations (C 765, C 763). Tumors with a PIK3CA mutation were significantly more frequent in HR positive tumors (32%; p=0,001), in HER2 negative tumors (31%, p=0,010) and in tumors with low or intermediate histological grade (39%; 32% resp., each p<0,001). In triple negative tumors, PIK3CA mutations were found in 13%. There was no significant association to age, menopausal status, tumor size, nodal status and uPA/PAI-1 status. Tumors with a PIK3CA mutation showed a slightly better recurrence-free interval (93.6%, CI 93.2-94.01 vs. 90.3%, CI 89.9-90.7). We found a prognostic impact on RFI after 5 ys F/U in patients with HR-negative tumors (93% vs 71%) and those with TNBC (100% vs. 70%). Conclusion: PIK3CA mutations occur frequently in breast cancer tumors. We found a prognostic impact only in patients with HR-negative and TNBC tumors. This data adds important information to the heterogeneous results of other previously published patient cohorts. In summary in our study, tumors that harbour a mutation of the PIK3CA-gene, were associated to prognostically more favorable factors and a better recurrence-free intervall. Citation Format: Reinhardt K, Thomssen C, Volker H, Tilmann L, Christoph U, Susanne P, Jutta J, Joerg B, Edith W, Karl-Friedrich B, Eva Johanna K, Martina V. PIK3CA mutations in breast tumor specimens in a cohort (n=791) of a multicentric study and associations to known prognostic factors and survival data [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 P4-04-03.