Blood hormone tests predicted a woman’s risk for developing postmenopausal breast cancer for up to 20 years, according to data from the Nurses’ Health Study presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research.
“We found that a single hormone level was associated with breast cancer risk for at least 16 to 20 years among postmenopausal women not using postmenopausal hormones,” said Xuehong Zhang, M.D., an epidemiologist at Brigham and Women’s Hospital and an instructor in medicine at Harvard Medical School in Boston, Mass. “We, and others, are now evaluating 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. 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.”
Zhang and colleagues analyzed 796 patients with postmenopausal breast cancer who had not received hormone therapy. They conducted blood hormone tests at two time points: between 1989 and 1990, and between 2000 and 2002. They then matched each patient with two controls who were not diagnosed with breast cancer.
Women with hormone levels in the highest 25 percent for estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) had a 50 percent to 107 percent greater chance for developing breast cancer compared with women in the lowest 25 percent. Relative risks for developing breast cancer were similar at one to 10 years versus 11 to 20 years (also 16 to 20 years) after blood collection.
Zhang and colleagues also investigated whether these higher hormone levels were more closely linked to hormone receptor- (HR) positive breast cancers and if they predicted risk regardless of tumor aggressiveness.
In the first case, they found that elevated levels of estradiol increased a woman’s risk for HR-positive breast cancer. In general, increased hormone levels, except for DHEAS, tracked closely with increased risk for HR-positive breast cancer. Data on HR-negative cancers were inconclusive.
Elevated hormone levels were also associated with aggressive breast cancer, which the study defined as recurrent or fatal cancer. “The relationship was comparable or possibly stronger for recurrent and fatal breast cancer than it was for overall breast cancer risk, although these results were based on relatively small numbers of participants,” said Zhang.
Researchers also confirmed the protective effect of sex hormone-binding globulin (SHBG), which seems to negate the cancer-causing effects of certain hormones. Women in the highest 25 percent of SHBG levels had a 30 percent lower risk for breast cancer compared with women in the lowest 25 percent for SHBG levels.
Zhang noted that the study had low case numbers for several cancer subgroups, including HER2-positive, triple-negative and basal-like breast cancers. More research is necessary to determine the relationship between elevated hormone levels and these important breast cancer subtypes.
B105 Postmenopausal plasma sex hormone levels and subsequent risk of breast cancer over 20 years of follow-up. Xuehong Zhang1, Shelley S. Tworoger1, A. Heather Eliassen1, Susan E. Hankinson2. 1Brigham and Women’s Hospital and Harvard Medical School, Boston, 2University of Massachusetts, Amherst.
Background: Although plasma estrogen and androgen levels are significantly positively associated with risk of postmenopausal breast cancer, it is unknown how long a single blood hormone measure can predict subsequent breast cancer risk as most prior studies have included less than 10 years of follow-up. If including hormone levels into current breast cancer risk prediction models improves discriminative ability, evaluating how the hormone/breast cancer association varies by years since blood collection can help determine the most relevant time period for hormone measures. In addition, whether the associations vary by tumor hormone receptor status is unclear.
Methods: We conducted a prospective nested case-control analysis within the Nurses’ Health Study cohort. Blood samples were collected in 1989-1990 and then in 2000-2002. Among eligible postmenopausal women not using postmenopausal hormones (PMH) at blood collection, 796 cases were diagnosed through June, 2010. Two control subjects (n=1,583) were matched to cases on age and time of blood collection. We used unconditional logistic regression analyses to estimate the relative risks (RRs, 95%CIs) by controlling for breast cancer risk factors.
Results: The intra-class correlation coefficients for the two blood measures collected 10 years apart were 0.69 for estradiol, 0.71 for testosterone, 0.54 for dehydroepiandrosterone sulfate (DHEAS), and 0.74 for sex hormone-binding globulin (SHBG). Overall, women in the top 25% of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS (compared to the lowest 25% of levels) were at a 50-107% higher risk of breast cancer (all p-trends<0.004). Relative risks were similar when comparing cases diagnosed 1-10 vs. 11-20 years (and 16-20 years) after blood collection (all p-values for interaction by follow-up period>0.15). For example, comparing the highest with lowest (reference) quartile of hormones measured 10 year or less before breast cancer diagnosis, the multivariable RRs (95%CIs) for overall breast cancer were 2.0 (1.4-2.7; p-trend<0.001) for estradiol, 1.4 (1.1-1.9; p-trend=0.001) for testosterone, and 0.63 (0.47-0.85; p-trend=0.006) for SHBG. The comparable RRs (95%CIs) for blood samples collected 11-20 years before diagnosis were 2.0 (1.3-3.1; p-trend=0.002) for estradiol, 1.6 (1.0-2.4; p-trend=0.11) for testosterone, and 0.68 (0.44-1.04; p-trend=0.04) for SHBG. Importantly, with the exception of DHEAS, the associations varied significantly by hormone receptor status of the tumor. For example, the multivariable RRs (95%CIs) comparing the highest vs. lowest quartile were 2.8 (2.0-4.0; p-trend<0.001) for ER+/PR+ tumors (n=347) vs. 1.1 (0.6-2.1; p-trend=0.98) for ER-/PR- tumors (n=80) for estradiol (p-heterogeneity<0.01), 1.8 (1.3-2.5; p-trend<0.001) vs. 0.6 (0.3-1.2; p-trend=0.35) for testosterone (p-heterogeneity<0.01), and 0.46 (0.31-0.67; p-trend=0.01) vs. 1.07 (0.56-2.06; p-trend=0.67) for SHBG (p-heterogeneity=0.01).
Conclusions: A single blood sex hormone measurement in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 20 years.