Abstract A010: AIB1 genotypes impact prognosis in endocrine-treated breast cancer patients – data from a population-based cohort

Abstract

Abstract Background and purpose: The response to exogenous hormones differs between individuals. Part of the interindividual drug response can be attributed to genetic variation in the host. Previously it has been shown that the estrogen receptor (ER) coactivator amplified in breast cancer-1 (AIB1) genotype plays a role in response to oral contraceptives. Certain AIB1 genotypes have also been associated with breast cancer risk. Since others have shown that tumor AIB1 protein levels may predict response to different types of endocrine treatments, we aimed to investigate the prognostic impact of three functional single nucleotide polymorphisms (SNPs) in the AIB1 gene in patients with ER+ breast cancer. Method and materials: The study comprises 503 patients with a first invasive primary ER-positive breast cancer from the BCBlood cohort. Patients were included October 2002 to October 2008 in Lund, Sweden and followed until June 2019. DNA was extracted from blood. Clinicopathological factors, treatments and breast cancer events were obtained from preoperative questionnaires, patient charts and registry data. The AIB1 SNPs (rs6094752, rs2230782, rs2076546) were analyzed at the Region Skåne Competence Center of Skåne University Hospital in Malmö, Sweden. The software and equipment in the MassARRAY® platform (Sequenom, inc.) with the reagents included in the iPLEX™ genotyping kit were used to perform analyses according to the manufacturer’s instructions. Haplotypes were constructed based on crosstabulation and diplotypes were assembled from haplotypes. Univariable survival analyses were conducted with Kaplan-Meier and Log-rank tests and multivariable Cox regression was used to obtain adjusted hazard ratios (HR) with 95% confidence intervals. Results: In terms of adjuvant endocrine treatment, 127 used no endocrine treatment, 170 received Tamoxifen (TAM), 63 received an aromatase inhibitor (AI), and 143 received sequential treatment with TAM>AI or AI>TAM. During follow-up, 123 patients had breast cancer events. Four haplotypes were found: CGA (77.0%), CCA (12.2%), CGG (7.4%), TGA (3.3%). The common diplotype CGA_CGA (59.9%) was not associated with breast cancer events in TAM-treated patients (Log-rank P=0.54). Conversely, in non TAM-treated patients (± AIs), CGA_CGA was associated with less than half the risk for breast cancer events (HR 0.48 (95% CI 0.26-0.87), adjusted for age, BMI, tumor characteristics and adjuvant treatments. In all patients, there was a significant interaction (Pinteraction=0.023) between TAM and CGA_CGA with a 2-fold risk for breast cancer events in TAM-treated CGA_CGA carriers compared with other patients. Conclusion: The results suggest that AIB1 genotypes have differential prognostic impact depending on type of endocrine treatment in breast cancer patients. The study lends further support that host factors yield important information that can be used to refine selection of adjuvant treatment. If confirmed in a randomized trial of endocrine treatments, AIB1 genotype may be used to better tailor endocrine therapy to each patient. Citation Format: Louise Ebbesen, Alexandra Wiberg, Christopher Godina, Helga Tryggvadottir, Karolin Isaksson, Helena Jernstrom. AIB1 genotypes impact prognosis in endocrine-treated breast cancer patients – data from a population-based cohort [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A010.