Abstract 5237: Sex-dependent association of circulating sex steroids, pituitary hormones and treatment-free survival in patients with chronic lymphocytic leukemia

Abstract

Abstract Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in the western world, and is not considered a hormone-regulated cancer but sex is a known risk factor with a significant male/female ratio (2:1) in its incidence with male patients more frequently developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic effect on CLL progression. However, a detailed evaluation of sex steroids and pituitary hormones in CLL patients is still lacking. In 156 CLL patients, we quantitatively profiled 15 circulating sex steroids (androgens, estrogens and progesterone) by sensitive and specific mass spectrometry and two pituitary hormones (luteinizing hormone (LH) and follicular secreting hormone (FSH)) by immunoassay. Data were analyzed separately by sex and in relation to treatment-free survival (TFS). Univariate and multivariate analyses of TFS were performed using Cox's proportional hazard model with hormone levels as continuous variables. Median age of CLL patients was 59.8 and 62.9 years for men and postmenopausal women, respectively. Common CLL prognostic markers had very similar frequencies between male and female cases. Median TFS was shorter for male patients than for women (80.7 vs. 135.0 months, P=0.033). Circulating profiles of hormones in CLL patients were significantly different from those of healthy donors whereas male cases had higher steroid levels than female patients. In male CLL cases, sex steroid levels were not significantly associated with TFS; however, higher LH levels were associated with shorter TFS in multivariate analyses with an adjusted hazard ratio (HRadj) of 2.11 (P = 0.004). In female CLL cases, high levels of potent androgens testosterone, dihydrotestosterone (DHT) and the sum of methoxy estrogens were significantly associated with improved TFS with HRadj values of 0.24 (P =0.007), 0.54 (P=0.023) and 0.31 (P =0.034), respectively. This study is the first to establish a link between outcome of CLL patients and circulating sex steroid and pituitary hormones, revealing a sex-specific hormonal imbalance associated with disease progression. This work was supported by a Canadian Institutes of Health Research grant to CG. EPA holds scholarships from Université Laval foundation - Leadership and sustainable development award and CHU de Québec foundation - Fernand Labrie excellence award. Citation Format: Eric P. Allain, Karin Venzl, Patrick Caron, Véronique Turcotte, David Simonyan, Michaela Gruber, Trang Le, Éric Lévesque, Chantal Guillemette, Katrina Vanura. Sex-dependent association of circulating sex steroids, pituitary hormones and treatment-free survival in patients with chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5237.