PHILADELPHIA — For rats bearing human breast tumors, exposure to dim light at night made the tumors resistant to the breast cancer drug tamoxifen, according to data published in Cancer Research, a journal of the American Association for Cancer Research. The negative effects of dim light exposure on tamoxifen treatment were overcome by giving rats a melatonin supplement during the night.
“Resistance to tamoxifen is a growing problem among patients with hormone receptor-positive breast cancer,” said Steven M. Hill, PhD, professor of structural and cellular biology and the Edmond and Lily Safra chair for breast cancer research at Tulane University School of Medicine in New Orleans. “Our data, although they were generated in rats, have potential implications for the large number of patients with breast cancer who are being treated with tamoxifen, because they suggest that nighttime exposure to light, even dim light, could cause their tumors to become resistant to the drug by suppressing melatonin production.
“Our study does not identify how much light exposure is needed to suppress nighttime melatonin production, and potentially drive tamoxifen resistance in humans, but we think that it could be as a little as the amount of light that comes in the bedroom window from a street light,” continued Hill, who is also director of the Tulane Center for Circadian Biology. “We are working toward conducting the studies that will answer this question.
“Although melatonin supplements are readily available over the counter at most drug and health-food stores, our research is not at a point where we can make a general recommendation that breast cancer patients taking tamoxifen should go out and buy melatonin,” Hill added. “Melatonin is produced by our bodies at a very specific time of day, exclusively during darkness at night, and taking melatonin supplements at the wrong time of day would potentially disrupt the circadian system, particularly the natural melatonin cycle, which may, in itself, paradoxically impair breast cancer responsiveness to tamoxifen.”
For the study, Hill and colleagues analyzed rats living in either normal light/dark conditions, with 12 hours of light followed by 12 hours of complete darkness, or conditions in which there were 12 hours of normal light followed by 12 hours of dim light. Melatonin levels in the blood of rats living in normal light/dark conditions rose during the dark period before decreasing again during the light period. In rats living in the dim night light conditions, melatonin levels remained low throughout the light/dark cycle.
Tumor growth in rats living in the dim night light conditions was 2.6-fold faster compared with tumor growth in rats living in normal light/dark conditions. In addition, tumors in rats living in dim night light conditions were completely resistant to tamoxifen, whereas tumors in rats living in normal light/dark conditions regressed significantly. If rats living in dim night light conditions were given a nighttime melatonin supplement, their tumors regressed.
“These data suggest that, in the not-too distant-future, it may be possible to combine melatonin and tamoxifen,” said Hill. “However, before this is done we would need to identify the optimal times of day to give the two because if the timing between the two is off, the advantage of giving them in combination may be lost. This brings up another important point: Our levels of melatonin are not determined by sleep, as many people think. It is actually the darkness that is important. During the night, if you sleep in a brightly lit room, your melatonin levels may be inhibited; however, if you are in the dark but cannot sleep, your melatonin levels will rise normally.”
The co-lead investigator of this study was David E. Blask, MD, PhD, professor in the Department of Structural and Cellular Biology at Tulane University School of Medicine. The study was supported by funds from the National Institutes of Health and the American Association for Laboratory Animal Science. Hill and Blask declare no conflicts of interest.