Breast cancer drug's effectiveness improved by sleeping in dark
Study finds link between tamoxifen resistant tumours and melatonin levels
Keeping a light on at night can suppress the body's production of a hormone called melatonin, possibly reducing the effectiveness of the breast-cancer drug tamoxifen, a study suggests.
“If you sleep with the lights on or the television on, that light can penetrate through your eyelid, hit your retina and have a negative effect on melatonin production, depending on the intensity of light,” said Steven Hill, professor of structural and cellular biology and chair for breast cancer research at the Tulane University school of medicine.
With his team at the Circadian Cancer Biology Group, Hill has been studying the link between melatonin levels, which peak at night in the dark, and drug-resistant breast cancer tumours.
“It’s one of the big problems for endocrine therapies or chemotherapies in any type of cancer you want to look at,” he explained.
Pathways of resistance
In the latest research, the team measured how melatonin levels changed the effectiveness of tamoxifen therapy in human breast cancer cells implanted in rats. They approached this by manipulating the undesirable pathways that support medication resistance and metastasis.
“You could look at it as power lines within the cell that control that cell’s growth and metabolism, its activity," Hill said. "And these pathways, some of them are protective and some of them are not protective.”
By shutting down the pathways that protect the cancer cells from medication, Hill said, there’s a better opportunity for tamoxifen to do its job, and that's what the team saw when higher levels of melatonin were present.
“There’s very clear pathways that are associated with tamoxifen resistance. But we recognize some of the pathways that melatonin shut down at night were the same pathways that were elevated in tamoxifen resistant tumours,” he said.
During the research, rats were exposed to varying degrees of light and darkness, simulating an average daily cycle. One phase included 12 hours of total darkness to simulate night. But the next phase’s night simulation had 12 hours of extremely low light, similar to having a hallway light filtering in under the door.
They found that the nighttime levels of melatonin alone slowed the growth of the tumours, but when tamoxifen was also administered ahead of the period of darkness, the tumours regressed even faster. Those results were the same when the animal subject was in complete darkness or getting melatonin as a supplement in dim light.
“When the cell is turned on and these protective mechanisms are turned on, the tumour is going to be very resistant to the chemotherapy, the endocrine therapy, to tamoxifen," Hill said.
"So what melatonin does is it shuts down, in these cancer cells, those protective pathways and lets the drug do its job.”
The researchers are looking at human clinical trials next.
Darkness recommended for everyone during sleep
Hill said the timing of when breast cancer patients take their medication may be something to consider.
“The FDA has no guidelines on when during the day you should take tamoxifen. So take your tamoxifen at night right before you go to bed, and I think our study suggests that melatonin will turn off a number of pathways that would prevent tamoxifen from working.”
Hill said that aside from breast cancer patients, everyone should be paying attention to light levels in their bedrooms. Being in the dark for eight hours — even if you’re not sleeping the whole time — is beneficial.