Breast cancer risk reduced in younger women with higher body fat

Contrary to the body of evidence that has been accrued over the years showing that obesity increases the risk of developing breast cancer in postmenopausal women, a new study from investigators at the University of North Carolina Lineberger Comprehensive Cancer Center found the opposite to be true for premenopausal women—higher body fat was linked to lower breast cancer risk. Findings from the new study—published recently in JAMA Oncology, in an article entitled “Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women”—underscores the need to better understand breast cancer risk factors in younger women before menopause.

"The drivers of breast cancer risk can be different for young women compared to older women, so we need to do a better job of understanding what contributes specifically to breast cancer risk in younger women so we can make appropriate recommendations for them," explained senior study investigator Hazel Nichols, Ph.D., assistant professor in the UNC Gillings School of Global Public Health. "This study is not a reason to try to gain weight to prevent breast cancer. Heavier women have a lower overall risk of breast cancer before menopause, but there are a lot of other benefits to managing a healthy weight that should be considered. What it does do is help us to try to understand what contributes to breast cancer risk in younger women."

Since breast cancer is less common in younger women, researchers pooled data from 19 different studies to investigate breast cancer risk for a group of 758,592 women who were younger than 55 years. Breast cancer is most common in older women, with a median age of diagnosis at 62 in the United States. Obesity has been linked to higher risk for breast cancer in women after menopause, which occurs, on average, at age 51 in the United States.

"Studies often have smaller numbers of premenopausal breast cancers since breast cancer is less common at younger ages, and the evidence was not as strong as for postmenopausal breast cancer," Dr. Nichols noted.

In the current study, the researcher's analysis linked a higher body mass index, or BMI, to lower breast cancer risk for younger women across this age group, even for women within a normal weight range.

"We saw a trend where, as BMI went up, cancer risk went down," Dr. Nichols remarked. "There was no threshold at which having a higher BMI was linked to lower cancer risk."

The largest reductions in risk were for BMI between the ages of 18 and 24, with a 23% lower breast cancer risk linked to each five-unit increase in BMI during this period. At ages 25 to 34, each five-unit increase in BMI was linked to 15% lower risk. There was a 13% lower risk for BMI at ages 35 to 44, and a 12% lower risk for BMI at ages 45 to 54 years.

Moreover, the researchers saw the association for estrogen- or progesterone-receptor-positive breast cancer, but they did not see a consistent relationship for BMI and triple-negative breast cancer or hormone-receptor-negative breast cancer.

The research team hypothesized that multiple factors could be contributing to the link between higher BMI and lower breast cancer risk in younger women, such as differences in hormones, including estrogen, growth factors, or breast density. Estrogen can be a driver of breast cancer, but there are diverse levels and sources of estrogen before and after menopause. Before menopause onset, the primary source of estrogen comes from the ovaries, and estrogen produced by fatty tissue may help to downregulate the amount of estrogen produced by the ovaries.

"The amount of estrogen produced by your ovaries is driven by feedback loops in your body," Dr. Nichols stated. "The small amount of estrogen produced by fat tissue before menopause may help tell the ovaries that they can produce less estrogen and also regulate other hormones or growth factors." After menopause, women with higher adipose tissue typically have higher estrogen levels.

The researchers were intrigued and encouraged by their findings. They are continuing their studies, hoping to better understand the complex relations ship between age, weight, and cancer risk.

“Although breast cancer is more common at older ages, it's actually the most common type of cancer diagnosed among reproductive-aged women,” Dr. Nichols concluded. “Understanding risk factors that may operate differently before menopause is critical to reducing breast cancer risk in young women, but these factors are hard to study in traditional settings where there are fewer young women in cancer research.”

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