Abstract 4231: Association between age of first full-term pregnancy and subsequent breast cancer risk

Abstract

Abstract Introduction Amongst the various risk factors for breast cancer (BC), age at first full-term pregnancy is still a complex problem. Early first full-term pregnancy (before 25 years of age) is believed to confer protection towards the development of BC after menopause compared to the risk in nulliparous women but is also correlated with a transient increase in the risk of developing BC soon after pregnancy. On the other hand, a late first pregnancy (after 35 years of age) is believed to increase the risk of developing breast cancer after menopause, equating or increasing the risk compared to nulliparous women. Material and Methods In our project, currently, we aim to do a pilot study with 4 fresh frozen normal samples of nulliparous and early-and late-parous women from Komen tissue bank (USA) and to create a mathematical model to determine how rates of both drivers and passengers mutations are affected by pregnancy and how the risk can be determined in parous and nulliparous women. We plan to measure low-frequency mutations from fresh frozen normal breast samples from patients with different reproductive stages using both Whole Genome Sequencing in this pilot group,and later on to expand the findings with Exome Sequencing on the remaining cohort of 55 normal samples. Results and Discussions We are currently in the process of analysing the data from the whole genome sequencing and whilst we do this, we are also collecting DNA from laser-capture microdissected epithelial and stromal cells, for the remaining samples. Bioinformatics tools are used to eliminate germline mutations from the stroma and to determine where the mutations are located within the genome, and how their frequency changes within the sample cohort. Conclusion While this study is aimed to understand the scientific basis of breast cancer and therefore it is not clinically applicable in the immediate future, understanding the cancer risk associated with age of pregnancy will provide future patients, in particular from at-risk categories, with an informed choice when deciding to plan a pregnancy and a surveillance programme could also be implemented to closely monitor any changes in the breast after a late pregnancy and improve early detection. Furthermore, we could hypothesise that in the long-term future, with the wider application of mammary ductoscopy, breast samples could be analysed in the clinic to calculate the mutation rate of the patient and identify individual risk. This risk stratification along with available predictors such as the ‘Gail model’ could be applied in breast cancer surveillance programmes. Note: This abstract was not presented at the meeting. Citation Format: Neha Tabassum. Association between age of first full-term pregnancy and subsequent breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4231.