Tamoxifen is an estrogen-blocking medication typically used to treat breast cancer that has spread to other parts of the body. But new research conducted in rats suggests exposure to dim light at night - as little as that coming in a window from a street light - suppresses melatonin production, making tumors resistant to the drug.
The study, led by Prof. Steven M. Hill of Tulane University School of Medicine in New Orleans, LA, is published in Cancer Research, a journal of the American Association for Cancer Research.
"Our levels of melatonin are not determined by sleep, as many people think," explains Prof. Hill. "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."
He and his team note that disruption of circadian rhythms by night shift work or disturbed sleep could result in an increased risk of breast cancer and other diseases. For patients with hormone receptor-positive breast cancer, Prof. Hill adds that tamoxifen resistance "is a growing problem."
"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," he says.
Nighttime melatonin supplement resulted in regressed tumors
To conduct their study, the researchers observed rats with human breast tumors that were living in either normal light and dark conditions - which involved 12 hours of light and 12 hours of complete darkness - or alternative conditions - 12 hours of normal light and 12 hours of dim light.
- To treat breast cancer that has spread to other parts of the body
- To treat early breast cancer in women who have already been treated with surgery, radiation or chemotherapy
- To reduce risk of developing a more serious type of breast cancer in women who have had ductal carcinoma in situ
- To reduce risk of breast cancer in women at high risk for the disease.
The rats who were living under normal conditions had blood melatonin levels that rose during the dark period and fell again during the light period. However, the rats living in the alternative conditions had melatonin levels that remained low during the light/dark cycle.
Compared with the rats living in normal conditions, the rats living in the dim night light conditions had tumor growth that was 2.6-fold times faster.
Additionally, the team found that the rats living in the dim night light had tumors that were completely resistant to tamoxifen, while the rats living in normal conditions had tumors that significantly regressed.
However, the team also found that when given a nighttime melatonin supplement, the tumors of the rats living in dim night light conditions likewise regressed.
"These data suggest that, in the not-too-distant future, it may be possible to combine melatonin and tamoxifen," says Prof. 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."
He also notes that their study does not reveal how much light exposure is needed to decrease nighttime melatonin production, resulting in tamoxifen resistance in humans, "but we think that it could be as little as the amount of light that comes in the bedroom window from a street light."
Though melatonin supplements can be purchased over the counter, Prof. Hill cautions that their research is not yet at the point where he and his team can recommend that breast cancer patients on tamoxifen take melatonin:
"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."
The team is now conducting further studies to investigate how much light exposure suppresses nighttime melatonin production in humans to the point where it would make tumors tamoxifen-resistant.
Medical News Today recently reported on a study that suggested the gel form of tamoxifen is just as effective as the oral form, with fewer side effects.