P16(INK4a)expression after chemotherapy in older women with early-stage breast cancer.

Abstract 9002 Background: Breast cancer (BC) is a disease of aging. In healthy humans, p16(INK4a) expression increases markedly in peripheral blood T-lymphocytes with chronologic age and exposure to mutagens such as tobacco. The expression of p16(INK4a) 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 p16(INK4a) in older women undergoing therapy for early stage BC. Pts ≥65 yrs with Stage I-III BC had p16(INK4a) expression measured in peripheral blood T-cells isolated by magnetic bead sorting on the same day as phlebotomy. Expression of p16(INK4a) was determined at least 3 months after the completion of BC therapy by TaqMan qRT-PCR. Expression of p16(INK4a) was measured in replicate and normalized to a housekeeping control gene (18S ribosomal RNA). Expression analysis was determined by investigators blinded to clinical data. 73 of 200 planned patients have had T-cell expression of p16(INK4a) 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 p16(INK4a) was not correlated with endocrine therapy use or radiotherapy. Expression was increased in patients treated with CRx (Table). In the oldest patients, CRx use was associated with increased expression of p16(INK4a), 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 p16(INK4a). Supported by the Breast Cancer Research Foundation, New York, NY; the Burroughs Wellcome Fund; and the National Institute of Aging (AG024379). [Table: see text].