Genotypic and Phenotypic Predictors of Cancer Therapy Adherence and Symptom Trajectories in Women with Breast Cancer

Aromatase inhibitors (AI) such as anastrozole effectively prevent hormone receptor positive breast cancer (HR+BC) recurrence but suboptimal AI adherence is a problem linked to AI-related, highly-variable symptoms, which may have biological underpinnings. This dissertation study is an ancillary study of prospectively-collected data from parent observational studies. This study combined parent study data from postmenopausal women prescribed anastrozole for HR+BC with symptom data (N=360), adherence data (N=291), and banked biospecimens (N=122). This study identified distinct subgroups using group-based trajectory modeling (GBTM) based on self-reported symptom and anastrozole adherence trajectories over the first 18-months of therapy (Aim 1), identified combined symptom and adherence trajectories (Aim 2); and explored whether genotypic and phenotypic factors (e.g., demographic, clinical) were associated with trajectory group membership (Aim 3). Using neuropsychological symptom data (N=360) collected at pre-anastrozole, 6-, 12-, and 18-months post-initiation, we found five distinct trajectories of neuropsychological symptom burden (NSB)—low-stable, low-increasing, moderate-stable, high-stable, and high-increasing (Aim 1). Anastrozole adherence data (N=291) collected via electronic event monitoring (MEMS®) were measured continuously for 18 months. We used monthly calculations for GBTM and found five trajectories: very low, low, high/sharp decrease, high/slow decrease, and persistently high (Aim 1). Most women were adherent; however, within five months, anastrozole adherence was at or below 80% in more than one-third of the sample. The relationship between NSB and adherence trajectories were examined simultaneously using a dual GBTM in 291 women (Aim 2). After NSB trajectories were re-evaluated for the 291 sample, a dual trajectory analysis suggested a bidirectional relationship between NSB and anastrozole adherence. However, for most women, taking anastrozole does not result in increased neuropsychological symptom burden. Phenotypic risk factors (Aim 3) to predict trajectories with greater NSB (N=360), included younger age and baseline (pre-anastrozole) medication use, including anti-depressants, non-narcotic analgesics, narcotic analgesics, anti-anxiety, and no calcium/vitamin D use. Protective factors for women in the higher (better) adherence trajectories (N=291) included not using thyroid medications or antidepressants. Younger age predicted greater NSB in the dual GBTM. Genotypic factors for greater NSB were PGR rs471767 and ESR1 rs1884051. Genotypic factors for greater adherence were ESR1 rs985694 and PGR rs1942836