Lights off! Study: Cancer drugs best in dark _lowres

Photo provided by Tulane Public Relations -- Principal investigators and co-leaders of Tulane's Circadian Cancer Biology Group, Steven Hill (left) and David Blask (right), and team members Robert Dauchy and Shulin Xiang. Photograph by Paula Burch-Celentano

Sleeping with just a little bit of light in the room could render the popular breast cancer drug tamoxifen ineffective, according to a new study conducted by doctors at Tulane University School of Medicine. Conversely, sleeping in total darkness boosts the body’s production of melatonin, which by itself retards the growth of cancer cells and, in tandem with tamoxifen, can significantly reduce the size of tumors, the study shows.

The study, published this month in the journal Cancer Research, was led by Dr. Steven Hill, a member of Tulane’s Circadian Cancer Biology Group, which looks at the effects of the body’s 24-hour cycles on certain cancers. Other circadian rhythms include sleep and body temperature, Hill said.

Hill was joined by colleagues David Blask, Robert Dauchy and Shulin Xiang in producing the study, titled “Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer.”

In the 10-month study, Hill and his colleagues found that cancer cells, like humans, have a specific circadian rhythm. Disrupting that rhythm, even just a little bit, can affect the cancer’s metabolism and aggressiveness.

Hill and his group studied certain types of breast cancers, called estrogen receptor positive cancers, which affect 60 percent to 75 percent of breast cancer patients, according to the study. Those cancers are often treated with hormone-inhibiting drugs like tamoxifen.

The researchers transplanted human breast cancer tumors into three groups of rats and then exposed the rats to different cycles of light and darkness. The first group got 12 hours of light and 12 hours of complete darkness. The second group got 12 hours of light and 12 hours of darkness broken by a dim light, such as light coming under a door. The third group was the same as the second but received a hormone supplement in its drinking water.

The researchers found that tumors in rats exposed to the dim light at night grew more than twice as fast as tumors in rats that had 12 hours of total darkness, Hill said.

The key is melatonin, a natural body hormone produced in the part of the brain known as the pineal gland. Melatonin production goes up at night and down in the day. And when there is more melatonin, the cancer cells’ growth slows or even stops.

“I would say it puts the tumor to sleep,” Hill said.

The dim light the rats were exposed to at night was not bright enough to disrupt sleep or other circadian rhythms, but it did inhibit one thing: the production of melatonin, by as much as 95 to 98 percent, Hill said.

When the body doesn’t have a good period of melatonin production, cancer cells get more aggressive.

“They develop a hypermetabolism,” Hill said, meaning they grow unchecked throughout the night. In addition, the absence of melatonin made the tumors in the rats resistant to such drugs as tamoxifen, he said.

Tumors in the third group of rats — those with 12 hours of dim light exposure but a melatonin supplement — also showed far slower growth, very similar to the ones given 12 hours of complete darkness.

When melatonin was combined with tamoxifin, the tumors regressed, or got dramatically smaller, the study shows.

The Tulane study’s hypothesis is “interesting,” said Aditya Bardia, an oncologist at Massachusetts General Hospital’s Center for Breast Oncology. But she added a note of caution.

The conclusions are “not clinically validated or proven,” she wrote in an email. The strict light-dark cycle Hill and his colleagues subjected the rats to may be hard to replicate. “This is never so absolute in humans,” Bardia said.

The next step could be testing a small group of human tumors from actual breast cancer patients, Hill said. If the results from those tests are promising, the method could be ready for large-scale clinical trials, though those would still be some years away.

Hill is also seeing similar results in experiments on other types of cancers, such as prostate cancer, he said.

Hill advises cancer patients to sleep in complete darkness or with a mask on. And if they take tamoxifen, he suggests they take it in the late evening or just before they go to bed, so that it can benefit from the body’s natural production of melatonin.

“People with breast cancer need to try to get a minimum of eight hours of sleep in the dark,” he said. “And if you have insomnia, stay in the dark.”

Further, many common evening activities, such as reading on a phone or tablet computer, or watching TV, can have adverse effects even after the device is turned off.

“They emit blue and green wavelength lights that are the most potent at reducing melatonin synthesis. If one uses them prior to bedtime, studies have shown that can delay the nighttime rise of melatonin by 1 to 1½ hours,” he said.

Follow Faimon A. Roberts III on Twitter, @faimon.