FRONTLINE CANCER: Tracing the causes of breast cancer

Last year, more than 232,000 women were told they had invasive breast cancer — in which cancer cells have spread beyond the mammary glands — and another 64,000 were diagnosed with in situ breast cancer, in which the cancer is localized to the cells lining the breast ducts.

After cancers of the skin, breast cancer is the most common cancer among American women, accounting for almost a third of all newly diagnosed cases. It is also among the most deadly of cancers. Each year, approximately 40,000 women die from breast cancer. Only lung cancer kills more.

Who gets breast cancer? The obvious answer is women, though men are not immune. It’s 100 times less common in males, but more than 2,300 men will be diagnosed with the disease this year — and 430 will die. The majority of breast cancer cases involve women diagnosed after age 50. The median age of diagnosis is 61. They tend to be non-Hispanic white women, though African-American women have a higher incidence rate before age 40. Generally speaking, a woman living in the United States has a 12.3 percent lifetime risk (1 in 8) of being diagnosed with breast cancer, that’s up from 1 in 11 during the 1970s.

A lot of factors account for the increase in risk: Longer life expectancy, changes in reproductive patterns, menopausal hormone use, the rising prevalence of obesity and better detection rates through screenings.

What actually causes breast cancer is a tougher question. For insight, I turned to Ruth Patterson, Ph.D., a professor in the Department of Family & Preventive Medicine in the UC San Diego School of Medicine and leader of the Cancer Prevention Program at UC San Diego Moores Cancer Center. Here’s what Ruth had to say:

Among breast cancer survivors, there is a consistent belief that their own cancer was caused by stress, fate, family history or environmental factors, but research paints a more nuanced and often yet-to-be-explained picture.

Stress, personality and fate: There is no scientific evidence that a negative mental attitude can cause breast cancer, but chronic perceived stress may be something else. Some studies have found a link between chronic psychological stress and breast cancer. The evidence is strong in mouse studies, but less so in humans. As for fate or destiny, that is still beyond the ability of science to measure.

Family history or genetics: A large number of women identify these factors as the cause of their cancer, but in reality, just 5 to 10 percent of all breast cancers are clearly hereditary.

Environmental factors: Exposure to certain pesticides and the heavy metal cadmium are associated with increased breast cancer risk. At the moment, there is only a tenuous link between air pollution and breast cancer. Most scientists do not believe that environmental factors are a major cause of breast cancer.

Lifestyle factors: There is convincing evidence that low levels of physical activity, obesity, alcohol and cigarette smoking are risk factors for breast cancer and cancer recurrence. For example, physical inactivity is estimated to be responsible for approximately 10 percent of breast cancer mortality. Data regarding diet are conflicting, although fat intake may increase the risk of breast cancer.

Other factors: Age, taller height, higher socioeconomic status, high breast density (as evident in a mammogram), not bearing children, hormone replacement therapy and issues affecting hormonal status, such as a late natural menopause, have all been identified as potential risk factors for breast cancer.

Clearly there are factors and behaviors that exacerbate breast cancer risk and factors and behaviors that do not. Identifying them based upon sound science is an ongoing effort. One such effort is a study at Moores Cancer Center that involves assessing whether weight loss or metformin might reduce the risk of breast cancer mortality.

Metformin is a widely used oral antidiabetic drug that reduces glucose, LDL cholesterol and triglyceride levels. In some people, it also promotes weight loss. Emerging studies suggest that metformin can influence tumorigenesis (the formation of tumors) by reducing circulating levels of insulin in the system and by inducing energetic stress in cancer cells. The latter is caused by metformin inhibiting an enzyme that plays a key first step in the mitochondrial respiratory chain. Mitochondria are cells’ power plants. With this enzyme impaired, cancer cell energy levels, protein synthesis, growth and viability can be reduced.

Researchers are looking for breast cancer survivors interested in participating in a clinical trial investigating the effects of weight loss and metformin. If interested, contact Jessica Orotowski-Coleman at reachforhealth@ucsd.edu or (858) 822-3311.