Examining the link between p16, an aging biomarker, and a clinically meaningful functional outcome in older adults with early breast cancer.

Abstract

12122 Background: Chemotherapy is thought to accelerate aging by disrupting fundamental processes of aging such as cellular senescence. Senescence is a state of terminal cell cycle arrest that is linked to increased inflammation, tissue damage, and impaired regeneration. In older adults with early breast cancer, treatment with neo/adjuvant chemotherapy is associated with persistent increases in circulating p16 INK4a (p16) expression, an established biomarker of senescence. However, it remains unknown whether higher levels of p16 correlate with clinically meaningful aging outcomes, such as physical function, in older adults with early breast cancer. Methods: We analyzed a prospective cohort of 501 adults age >65 with stage I-III breast cancer receiving neo/adjuvant chemotherapy. We assessed physical function using the timed up and go test (TUG), at two time points: pre-chemotherapy (T1) and post-chemotherapy (T2). The TUG score was measured as the time (in seconds) a participant takes to stand up from a standard armchair, walk 3 meters, turn around, walk back to the chair, and sit down. We collected blood at T1 and quantified p16 expression levels in circulating CD3+ T lymphocytes. Expression of p16 was determined using TaqMan quantitative reverse-transcription polymerase chain reaction. We calculated the Spearman correlations to examine the relationship between blood p16 levels at T1 with TUG score at T1, at T2, and change in individual TUG score from T1 to T2. Results: The median age of participants was 70 years (range 65-86). The majority (64.4%) had stage II/III disease and 58.1% received an anthracycline. Baseline TUG scores were available for 467 participants and baseline p16 data were available for 317 participants. The mean baseline p16 level was 10.2 log 2 p16 units (SD = 0.9). Mean TUG scores were 11.4 sec (SD = 4.6) at T1 and 11.5 sec (SD = 5.3) at T2. The mean change in TUG score from T1 to T2 was 0.3 (SD = 4.2). There was no significant correlation observed between p16 and TUG score at T1 (r = 0.11, p = 0.05), T2 (r = 0.06, p = 0.36), or the change in TUG score from T1 to T2 (r = 0, p = 0.99). Conclusions: In this cohort of older adults with early breast cancer treated with neo/adjuvant chemotherapy, we did not find a correlation between pretreatment p16 and physical function as measured by TUG. Future studies are needed to understand the role of biological aging markers in improving precision risk assessment of treatment toxicity in older adults with cancer. Clinical trial information: NCT01472094 .