Triple-negative breast cancer, which is often associated with aggressive presentation, seems moderately related to body mass index and exercise status – factors that could be modified to reduce a woman’s risk of developing the disease.
The associations were "modest in magnitude and not statistically significant," lead author Amanda I. Phipps, Ph.D., and associates wrote in the March issue of Cancer Epidemiology, Biomarkers, and Prevention. Only weight increase between age 35 and 50 years was significantly related with the tumor (hazard ratio [HR] 1.69 for a gain of more than 6 kg, compared with a gain of less than 2.5 kg).
"However, given the potentially modifiable nature of these exposures, the results suggest that there may be ways postmenopausal women can impact their risks of both estrogen receptor-positive and triple-negative breast cancer," the authors said (Canc. Epidem. Biom. Prev. 2011;20:1-10 [doi: 10.1158/1055-9965.EPI-10-0974]).
Neither hormone receptors nor HER2 are overexpressed in women with the triple-negative subtype. When compared with estrogen receptor–positive breast cancer, triple-negative cancers are more likely to present with high tumor grade, elevated Ki-67 and p53 expression, and a poorer prognosis. Triple-negative tumors also are more likely to occur in black women and BRCA1 carriers, and to be diagnosed at younger ages.
Dr. Phipps of the Fred Hutchinson Cancer Research Center, Seattle, and her coauthors extracted their data from the Women’s Health Initiative. From the total cohort of 162,000 women, their final analysis consisted of 3,116 cases with complete tumor marker data, of which 307 (10%) were triple-negative and 2,610 (84%) were ER-positive. The rest were ER-negative, PR-negative, and HER2-positive (154 cases); ER-negative, PR-positive, and HER2-negative (31 cases); or ER-negative, PR-positive, and HER2-positive (14 cases).
Triple-negative tumors were associated with body mass index, with the highest association (HR 1.35) occurring between the highest quartile (BMI 31 kg/m2 or more) and the lowest quartile (less than 23.75 kg/m2). There was a similar association of BMI and ER-positive tumors compared with estrogen receptor-negative tumors (HR 1.39).
Waist-hip ratio was not significantly associated with any of the cancer subtypes, but waist and hip circumferences were nonsignificantly associated with the risk of ER-positive tumors. For triple-negative tumors, there were modest but nonsignificant associations between waist circumference (HR 0.66) and hip circumference (HR 0.88).
Women with increased BMI at age 50 (highest vs. lowest quartile) were most at risk for triple-negative breast cancer at age 50 (HR 1.93), but, again, this was not a significant finding.
The authors also found a modest but, again, not significant inverse association between the triple-negative subtype and physical activity. The association between the highest tertile of exercise (strenuous vs. none; HR 0.77) was not significant. "For both subtypes, there was some suggestion that these modest associations were limited to moderate to low-intensity activity," the authors noted.
"Despite substantial molecular and clinical differences between triple-negative and ER-positive breast cancers, these subtypes of disease appear similar in their associations with baseline BMI and recreational physical activity," the authors wrote. The finding of a modest positive association between waist circumference and ER-positive tumors is in line with prior studies, probably because excess abdominal fat influences hormone levels.
"On the contrary, triple-negative breast cancers are hormone-receptor negative by definition, yet we observed a similar positive association between BMI and breast cancer risk for both subtypes, suggesting that nonhormonal factors may also play a role in mediating associations with this aspect of body size."
There may be some biologic plausibility to this theory, they said. "In particular, obesity is associated with increased inflammation and with increased levels of insulin and insulin-like growth factors, which may impact breast cancer risk."
The results of the study point out a possible benefit to lifestyle modifications, especially in light of the more aggressive nature of triple-negative breast cancers, the authors said: "The risk of triple-negative breast cancer was reduced, albeit not to the extent of statistical significance, among women who were physically active and among women with lower BMI.
"These factors were similarly associated with the lower risk of ER-positive breast cancer, suggesting that the protective effects of these exposures are not breast cancer-subtype-specific and that there may be lifestyle modifications that postmenopausal women can make to reduce their risk of triple-negative and ER-positive breast cancer."
The authors disclosed no financial conflicts. The National Heart, Lung, and Blood Institute sponsored the Women’s Health Initiative; the National Cancer Institute sponsored the subanalysis.