High body fat in younger women is associated with a lower risk of premenopausal breast cancer, according to new data from a large-scale study co-led by the University of North Carolina Lineberger Comprehensive Cancer Center.
The findings from the study, “Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women,” were published in JAMA Oncology.
Breast cancer is the most common type of invasive cancer in women and the second leading cause of death after lung cancer. The disease affects mostly older women between 50 and 75 and is relatively rare in women under 25.
“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,” Hazel Nichols, PhD, assistant professor at UNC Gillings School of Global Public Health, said in a press release.
Increasing age is considered one of the biggest risk factors for this type of cancer. With every 10 years after menopause, the risk of developing breast cancer multiplies twofold. In addition to aging, late menopause and high body fat also contribute to an increase in the probability of developing breast cancer. In fact, women who reach menopause late, after the age of 55, have twice the risk of developing breast cancer, while obesity is considered a high-risk factor for the disease in older postmenopausal women.
However, other studies suggested the relationship between body fat and increased susceptibility toward developing breast cancer could be the opposite in younger premenopausal women.
To investigate the association of body mass index (BMI) with premenopausal breast cancer risk at different ages, researchers pooled individual data from 19 prospective cohort studies involving 758,592 women under 55, including 13,082 cases of breast cancer.
Researchers found that higher BMI was correlated with lower breast cancer risk, especially in women between 18 and 24, who had a 23 percent lower risk per five-unit increase in BMI. This effect was much lower in older women between 45 and 54, who had only a 12 percent lower risk. This observation also was true for women with a normal body weight.
“We saw a trend where, as BMI went up, cancer risk went down,” Nichols said. “There was no threshold at which having a higher BMI was linked to lower cancer risk.”
Investigators also saw that these inverse associations were stronger for estrogen- or progesterone-receptor positive breast cancer in women from all age groups, but failed to find a consistent relationship between BMI and triple negative or hormone-receptor negative breast cancer.
Multiple factors could contribute to the link between higher BMI and lower breast cancer risk in younger women, such as differences in hormone levels, growth factors, or breast density, Nichols said.
Estrogen levels, in particular, could play a major role in this association.
Before menopause, the primary source of estrogen is the ovaries. But the fatty tissue also produces small amounts of estrogen, which signals the ovaries to produce less of this hormone. Because estrogen is thought to fuel the growth of breast cancer cells, lower amounts of estrogen will also mean lower breast cancer risk.
“The amount of estrogen produced by your ovaries is driven by feedback loops in your body,” Nichols said. “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.”
However, after menopause, women with more fatty tissue also produce more estrogen.
“After menopause, the ovaries are no longer the primary source of estrogen,” she said. “Instead, most estrogens come from adipose, or fat, tissue,” she said. “Women who have more adipose tissue after menopause usually have higher levels of estrogen which can contribute to higher breast cancer risk. In young women, estrogen is one factor that contributes, but it’s not the whole story.”
The group will now focus on analyzing the role of other risk factors that increase breast cancer susceptibility at younger ages, including pregnancy, and take a closer look at how risk patterns shift with weight changes in early to mid-adulthood.
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