P16INK4aexpression after chemotherapy in older women with early-stage breast cancer.

Abstract

9002 Background: Breast cancer (BC) is a disease of aging. In healthy humans, p16INK4a expression increases markedly in peripheral blood T-lymphocytes with chronologic age and exposure to mutagens such as tobacco. The expression of p16INK4a increases exponentially with age, with an average 10-fold increase between ages 20 and 80 years old (Liu et al, Aging Cell, 2010). To determine the effects of BC therapy on a molecular marker of aging, we measured T-cell expression of p16INK4a in older women undergoing therapy for early stage BC. Methods: Pts ≥65 yrs with Stage I-III BC had p16INK4a expression measured in peripheral blood T-cells isolated by magnetic bead sorting on the same day as phlebotomy. Expression of p16INK4a was determined at least 3 months after the completion of BC therapy by TaqMan qRT-PCR. Expression of p16INK4a was measured in replicate and normalized to a housekeeping control gene (18S ribosomal RNA). Expression analysis was determined by investigators blinded to clinical data. Results: 73 of 200 planned patients have had T-cell expression of p16INK4a assessed. Mean/median age range (years) for all pts was 73/71 and (65-93). All pts had surgery, 42 (58%, mean age 74), had no chemotherapy (CRx) and 31 (42%, mean age 71) had CRx. Of the 31 with CRx 19 (61%) had anthracyclines, 24 (77%) cyclophosphamide, and 20 (65%) breast irradiation. Expression of p16INK4a was not correlated with endocrine therapy use or radiotherapy. Expression was increased in patients treated with CRx (Table). Conclusions: In the oldest patients, CRx use was associated with increased expression of p16INK4a, a molecular marker of aging. In patients over the age of 65, CRx use is associated with a more than one decade increase in a marker of molecular age. Accrual continues and expanded data will include toxicity assessment based on pre-treatment p16INK4a. Supported by the Breast Cancer Research Foundation, New York, NY; the Burroughs Wellcome Fund; and the National Institute of Aging (AG024379). Age group No. of pts. No CRx vs. CRx Log2 [p16INK4a] (SEM) No CRx vs. CRx P value All (age adjusted) 42 / 31 7.52 (0.15) / 8.12 (0.14) 0.009 Age 65-74 25 / 23 7.89 (0.18) / 8.23 (0.17) 0.23 Age ≥ 75 17 / 8 8.23 (0.23) / 9.22 (0.30) 0.03