Purpose To examine the effects of melatonin supplementation on sleep, mood, and hot flashes in postmenopausal breast cancer survivors. Methods In a randomized, double-blind, placebo-controlled study, 95 postmenopausal women with a prior history of stage 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 3 mg oral melatonin (n=48) or placebo daily (n=47) for 4 months. Sleep, mood, and hot flashes were assessed at baseline and four months via self-administered questionnaire using the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiologic Studies – Depression (CES-D), and the North Central Cancer Treatment Group (NCCTG) hot flash diary, respectively. Results Eighty-six women (91%) completed the study and provided pre and post questionnaires. At baseline, 52% of participants reported poor sleep in the month prior to enrollment. Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. For example, the mean change in PSQI score was −0.1 in the placebo group compared to −1.9 in the melatonin group (p<0.001). There were no significant differences in measures of depression or hot flashes. Conclusions Sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment. This is the first randomized placebo-controlled study among breast cancer survivors to demonstrate that melatonin was associated with an improvement in subjective sleep quality, without any significant adverse effects.

We examined compliance with and the effects of melatonin supplementation on breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3 ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo-controlled study, postmenopausal women with a prior history of stage 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned to either 3 mg oral melatonin (n=48) or placebo daily for 4 months. Plasma samples were collected at baseline and after completion of the intervention. The primary endpoints were compliance and change in estradiol and IGF-1/IGFBP-3 levels. 95 women were randomized (48 to melatonin and 47 to placebo). 86 women (91%) completed the study and provided pre and post intervention bloods. Melatonin was well-tolerated without any grade 3/4 toxicity and compliance was high (89.5%). Overall, among postmenopausal women with a prior history of breast cancer, a 4 month course of 3 mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3 levels. Compliance was comparable between the two groups. Short-term melatonin treatment did not influence estradiol and IGF-1/IGBBP-3 levels. Effects of longer courses of melatonin and among premenopausal women are unknown. The particularly low baseline estradiol levels in our study population may have hindered the ability to detect any further estradiol lowering effects of melatonin.

Background: Night shift work has been classified by the International Agency for Research and Cancer and the World Health Organization as a probable carcinogen, presumably due to its effect on the melatonin pathway. Extensive laboratory and some human data also support that melatonin may influence breast cancer risk, although the mechanism is not clear. Both pharmacologic and physiologic doses of melatonin inhibit the growth of malignant cells of the breast in vitro and in animal models. Study Design: 95 postmenopausal women with a prior history of Stage 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were recruited to a double-blind randomized trial of 4 months of 3 mg melatonin daily compared to placebo. Endpoints included changes in breast cancer biomarkers, sleep, hot flashes, and mood. Results: 5 subjects on melatonin and 4 on placebo withdrew from the study or did not complete the 4 month assessment leaving 86 women (43 on placebo and 43 on melatonin) with evaluable data. Melatonin was well-tolerated without any grade 3/4 toxicity. At baseline, there was no statistical difference between the two arms for any of the endpoints or standard demographic characteristics. Mean age was 59 years (range 38-71) with mean 8 years since diagnosis. At 4 months, there were no statistically significant differences between the two groups for the biomarker endpoints (estradiol, IGF-1, IGFBP-3, or IGF-1/IGFBP-3 ratios), depressive symptoms, or hot flashes. However, subjects taking melatonin had significantly improved sleep quality, sleep duration, and total sleep scores compared with subjects taking placebo. Conclusions: Among postmenopausal women with a prior history of breast cancer, a 4 month course of 3 mg melatonin daily did not influence IGF-1, IGFBP-3 or estradiol levels. Effects of longer courses of melatonin and among premenopausal women are unknown. However, melatonin was effective in improving sleep quality among breast cancer survivors without any significant adverse effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-431.