Hormone Levels Predict Long-term Breast Cancer Risk

A study based on data from the Nurses' Health Study (NHS), one of the largest and longest-running observational studies of women's health, demonstrates that blood hormone levels predict breast cancer risk for postmenopausal women up to 20 years in advance.

“It's been well established that higher estrogen levels increase risk of postmenopausal breast cancer; however, most previous studies have less than 10 years of follow-up,” says study lead author Xuehong Zhang, MD, an epidemiologist at Brigham and Women's Hospital (BWH) and an instructor in medicine at Harvard Medical School in Boston, MA.

The prospective study undertaken by Zhang and colleagues and presented at the 11^th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held October 16–19, analyzed data from 796 women in the NHS who had postmenopausal breast cancer and had not received hormone therapy. Each patient was matched with 2 controls who were not diagnosed with breast cancer. Blood hormone tests were done once between 1989 and 1990 and a second time between 2000 and 2002.

“We found that women with hormones in the top 25% for estradiol, free estradiol, testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEAS) had a 50% to 107% higher risk of breast cancer compared with women in the lowest 25%,” Zhang says.

Notably, relative risks for developing breast cancer were similar at 1 to 10 years versus 11 to 20 years after blood collection, which Zhang says potentially could hold clinical implications.

“The next step is to better understand which subsets of hormones predict most of the risk and evaluate if the addition of hormone levels to current risk prediction models can substantially improve our ability to identify high-risk women who would benefit from enhanced screening or chemoprevention,” says Zhang. “If so, the current data suggest that hormone levels would not need to be measured in the clinic more than once every 10, or possibly 20, years.”

The study also shows that risk association is stronger in patients with hormone receptor (HR)–positive breast cancer. The investigators found that increased hormone levels, except for DHEAS, tracked closely with increased risk for HR-positive breast cancer. Elevated hormone levels were also associated with aggressive breast cancer—defined as recurrent or fatal cancer—though results were based on a relatively small number of patients.

Data on HR-negative cancers were inconclusive. “We did not have enough patients to fully understand risk for subtypes such as triple-negative, HER2-positive, and basal-like breast cancers,” acknowledges Zhang, who plans to work closely with colleagues at BWH's Channing Division of Network Medicine. That group has published other studies based on NHS data, including one that showed that high levels of multiple hormones simultaneously increase breast cancer risk.