Changes in p16INK4a (p16) expression, a biomarker of aging, in peripheral blood T-cells (PBTC) in patients receiving anthracycline (A) vs non-anthracycline (NoA) chemotherapy (CRx) for early-stage breast cancer (EBC).

Abstract

10060 Background: Age-related accumulation of senescent cells plays a causal role in some aspects of mammalian aging. We have shown that the total-body burden of senescent cells can be estimated by measuring the expression of the p16 tumor suppressor, a canonical effector of senescence, in human CD3+ PBTC (Liu et al, Aging Cell, 2009). Expression of p16 increases more than 10-fold over an adult human lifespan, and this rate of accumulation is accelerated by age-promoting exposures such as CRx or stem cell transplant (Sanoff et al, JNCI 2014; Wood et al, EbioMed 2016). Increased molecular age as evidenced by increased expression of p16 prior to CRx predicts a patient’s risk of CRx toxicity independently of chronological age (DeMaria et al, Cancer Discovery, 2017).This study investigates the impact of different types of CRx (A vs NoA) regimens on PBTC p16expression in pts with EBC. Methods: EBC pts who received neoAdj or Adj CRx had blood samples drawn for p16 assay prior to CRx initiation and again between 2 months and 1.5 years after the end of CRx. Expression of p16 mRNA in PBTC was determined using TaqMan real-time quantitative reverse transcription PCR. T-test compared p16change between A and NA groups. Results: 70 pts were evaluable. Pt. characteristics: median age 49 (range 32-76); 52 (74%) White, 14 (20%) black, 4 unknown; 39 (56%) ER or PR+ and HER2 neg, 18 (26%) triple negative, 13 (19%) HER-2 pos (all received trastuzumab). 53 pts (76%) had A (47 AC + taxane, 6 AC no taxane) and 17 (24%) NoA (all TC). Expression of p16 increased 2.0-fold in patients who received A-based CRx compared to 1.2-fold in NoA CRx (p = 0.04). There was no relationship of race, ER, PR or HER-2 status on change in p16expression. Conclusions: This study is ongoing and further results will be presented at the ASCO meeting. In this sample of EBC patients treated with A vs. NoA CRx regimens, A-based CRx is more strongly associated with increased biologic aging of T-cells compared to NoA CRx. These changes are equivalent of increased biologic aging of PBTC of 11 years (A) vs.6 years (NoA) and may have major consequences on the long-term survival of these pts.