AS716 - Feasibility of RNA sequencing using archival tumor specimens collected in WHI LILAC

Investigator Names and Contact Information

Aditi Hazra (ahazra@hsph.harvard.edu)

Introduction/Intent

Breast cancer is the most common site of cancer among women worldwide (with an estimated 2.3 million new cases worldwide). Knowledge of the relationship between etiologic drivers of breast carcinogenesis, such as germline genetic variants and lifestyle risk factors (e.g. body mass index, hormone therapy use, co-morbidities), tumor features (nuclear grade) and breast tissue gene expression are critical to improve our understanding of the underlying biological mechanisms that result in diagnosis with aggressive breast cancer, which is more prevalent among women of color. However, these relations have not been systematically studied in a racially diverse and inclusive breast cancer population with extensive epidemiologic covariate data. We propose pilot aims to evaluate the feasibility of using archival, formalin-fixed paraffin embedded (FFPE) tissue from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study for bulk RNA sequencing. Pilot data will inform the feasibility of conducting a larger transcriptome study to identify gene signatures associated with stage and subtype-specific prognosis and outcomes using the WHI LILAC tissue specimens and breast cancer covariate data. The deliverable from this feasibility study will be quality control data (including FastQC report and PCA for the technical replicates and similarity of gene expression profiles). The results of the pilot study (n=12 samples) may catalyze future validation and consortium analyses (e.g., with Southern Community Cohort, Carolina Breast Cancer Study, and/or the AMBER consortium) to better understand gene signatures associated with stage and subtype-specific prognosis and inform precision treatment.

Specific Aims

Pilot Aim 1. Develop collaborations with WHI LILAC investigators, including senior cancer epidemiologists, oncologists to identify and acquire 12 breast tumor blocks with sufficient tumor cells for sequencing, in replicate.

Pilot Aim 2. Evaluate quality control data including FFPE specimen quality, RNA integrity, and library preparation for sequencing (n=12 breast cancer blocks and unstained slides, including 6 stage I or II cases and 6 stage III or IV cases; if possible including representative estrogen receptor positive and negative samples). The pilot data will inform the feasibility of conducting a larger transcriptome study using the WHI LILAC tissue specimens and breast cancer covariate data (AS607). The overarching goal of the future study is identify stage and subtype-specific gene signatures associated with breast cancer prognosis and outcomes in an inclusive study population.