Headlines

As reported by The Hartford Courant, February 6, 2005.

Breast Cancer Mystery Frustrates Scientists

Electric Light Just Latest of Many Suspects

By William Hathaway

Richard Stevens wants to shed some light on the murky origins of breast cancer.

The University of Connecticut cancer epidemiologist says there still is no scientific consensus about why the incidence of the disease is so much higher in the developed world.

The literature on breast cancer is littered with discredited theories about environmental and lifestyle factors that may contribute to the onset of the disease.

"We knew more about the cause of breast cancer 20 years ago than we do today," Stevens said. "What we do know is that it must have something to do with industrialized society."

Only a few theories have withstood scientific scrutiny, and no single factor explains a great percentage of breast cancer cases.

But that hasn't stopped people from looking for new explanations.

Now, Stevens and a few other researchers are focusing on a little-known suspect - electric light.

Their theory that artificial light can cause breast cancer is simple. Prolonged periods of exposure to artificial light disrupt the body's circadian rhythms - the inner biological clocks honed over thousands of years of evolution to regulate behaviors such as sleep and wakefulness. The disruption affects levels of hormones such as melatonin and the workings of cellular machinery, which can trigger the onset of cancer, Stevens theorizes.

"Mankind has only been exposed to these light sources for 150 years or so," Stevens said.

So far, the theory is based largely on suggestive, but inconclusive, observational studies. For instance, night-shift workers such as nurses tend to be more prone to develop breast cancer than day-shift workers, and blind women are less likely to have breast cancer than women with sight.

In a recent study, Stevens and scientists at Yale University School of Medicine identified a possible genetic mechanism that could help explain how artificial light could trigger breast cancer. Pre-menopausal women with a variation of a "clock gene," which helps govern the regulation of the body's response to night and day, tend to have a higher risk of cancer.

"I'm not saying this is a cause, but that the evidence shows it is worth investigating," Stevens is quick to caution.

The fact that the origins of breast cancer still are being debated - and that new theories are emerging more than three decades after the United States declared a war on cancer - illustrates just how stealthy breast cancer is.

Scientists estimate that about nine out of 10 breast cancer cases are triggered by environmental and lifestyle factors rather than inherited risk. Smoking has long been identified as a cause of lung cancer, and a virus, human papillomavirus, causes cervical cancer.

But with breast cancer, researchers are not sure what lifestyle or environmental causes women should worry about.

Some widely circulated theories have little data to support them and have been largely rejected by the scientific community. Antiperspirants and wire bras fall into this category, according to the National Cancer Institute. In 2003, the institute convened 100 breast cancer experts who concluded there is no evidence that miscarriages or abortions increase the risk of breast cancer.

Yet epidemiologists such as Stevens say other risk factors must exist and they urge that more studies be conducted.

"We absolutely need studies," said Deborah Winn, chief of the clinical and genetic epidemiology research branch of the National Cancer Institute. "If we have those answers, we might have the potential to improve prevention."

While the number of deaths from breast cancer has declined over the years, the incidence of the disease has increased slowly over the decades in the developed world, most studies show. And when a woman from a low-risk country moves to a high-risk country, her risk of breast cancer increases as well.

That's why suspicion centered on factors such as diet or pollutants such as pesticides.

Scientists believed for years that high levels of dietary fat accounted for differences in the rates of breast cancer in the developed and undeveloped worlds. But fat has largely been exonerated in breast cancer, Stevens said. A recent study in the Journal of the American Medical Association showed that even a diet heavy on fruits and vegetables did not protect women from the disease. And while pesticides can cause cells in laboratory dishes to turn cancerous, they have never been conclusively linked in large-scale studies to clusters of breast cancer cases.

There are plenty of oddities in the breast cancer epidemiology studies. Obesity is a risk factor for women - but only after menopause. Prior to menopause, obese women tend to get breast cancer less often than thinner peers.

Science, however, does say with great certainty that at least one factor plays a crucial role in the development of breast cancer: the female hormone estrogen, said Dr. Melinda Irwin, assistant professor in the department of epidemiology and public health at the Yale University School of Medicine.

For instance, Irwin notes that girls who get their first periods early in life and women who enter menopause late in life - in both cases, increasing their exposure to estrogen - are clearly at greater risk of breast cancer than their peers. Women who give birth to children before the age of 30 have a lower risk of breast cancer than women who give birth after 30 and women who never become mothers at all. Women who take hormone replacement therapy are also at higher risk.

Irwin has also done research that suggests that exercise, which can lower estrogen levels, offers women some protection against the development of breast cancer.

But Stevens and others believe other elements of modern lifestyle and environment must play a role in increasing the risk of breast cancer.

In the mid-1980s, Stevens investigated connections between cancer and the use of electric power. The work helped set off a controversial debate over whether there was a link between electric power lines and the development of cancer. It got him thinking about the potential role of electric lighting.

For most of human history, people slept or rested during dark hours - and produced the hormone melatonin. Melatonin levels regulate circadian rhythms and may, some studies suggest, affect estrogen levels as well. Artificial light tends to disrupt those rhythms, with reduced levels of melatonin believed to lead to an increase in estrogen production.

The light theory of breast cancer has received a boost in recent years with the discovery of clock genes, a group of about eight genes that help regulate circadian rhythms. It turns out that clock genes play an important role in the activation of genes governing cell cycle regulation and apoptosis, or cell suicide. Malfunctions in these processes have been linked to the development of cancer.

But for now, the light theory is firmly on the fringe of scientific consensus.

Many scientists believe that the search for environmental and lifestyle triggers for breast cancer will not turn up one major villain, but many different culprits that account for small percentages of breast cancer cases.

"I think we will be hard-pressed to find a single etiology to breast cancer. A woman's body is so complex and exposed to so many different things," said Dr. Kristen A. Zarfos, assistant professor of surgery and medical director of the University of Connecticut Health Center Women's Specialty Health Program.

"It might be a combination of small effects of a lot of things we know about," Stevens conceded. "But if not, then what is it? It is frustrating that major drivers have just not emerged for breast cancer as they have for other major cancers."