Does progesterone protect from chemotherapy-induced peripheral neuropathy? A retrospective audit of breast cancer patients.

Abstract

e11552 Background: Paclitaxel is an integral component of chemotherapy for breast cancer but its benefit comes at the risk of peripheral neuropathy. There are experimental models of peripheral nerve injury in which progesterone is protective, possibly through remyelination and other mechanisms. Methods: We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel induced peripheral neuropathy, in a retrospective audit of breast cancer patients. Patients who had received paclitaxel chemotherapy for breast cancer were characterized as having CIPN or not by clinical history/examination. Results: 256 women treated with paclitaxel at our institution were assessed for CIPN. Of these 133(52%) were premenopausal and 123(48%) postmenopausal at diagnosis. 22(8.6%) had preexisting diabetes mellitus. Of the 133 premenopausal women 97(72.9%) developed chemotherapy induced amenorrhea (CIA). The incidence of CIPN was 23.1% in persistently premenopausal patients 47.4% in patients with CIA and 57.7% in postmenopausal patients. In patients with DM 81.8% had CIPN. In a multivariate logistic regression model, increasing age (continuous variable RR=1.04 95%CI 1.02-1.08 p=0.001) DM (RR=4.39 95% CI 1.42-13.38 p=0.01) and postmenopausal/CIA status (RR=2.48 95% CI 1.05-5.88 p=0.03) were risk factors for CIPN. Because patients developed CIA at variable times and circulating progesterone levels at the time of neurotoxin insult maybe variable in them such patients were excluded in the second model, which included only patients with continuing menses (n=36) and postmenopausal at diagnosis (n=123). In the latter model postmenopausal status (RR=3.5 95%CI 1.18-10.39 p=0.02) and DM (RR=6.8 95%CI 1.44-31.82 p=0.01) were associated with CIPN but increasing age (RR=1.03 95% CI 0.98-1.07 p=0.21) was not. Conclusions: These results suggest a neuroprotective effect of premenopausal status, possibly related to higher circulating levels of progesterone. We hypothesize that progesterone administration prior to taxane chemotherapy may protect against CIPN. This will be tested in a RCT.