Obesity Type Influences Breast Cancer Risk

Abdominal fat associated with ER-/PR- cancer, but not ER+/PR+

Where fat accumulates on a woman's body may influence the type of breast cancer she is susceptible to, a Chinese case-control study found.

Obese women with large amounts of visceral fat, as measured by waist-to-hip ratio, had a significantly greater risk for estrogen and progesterone receptor negative (ER-/PR-) breast cancer compared with women with less visceral fat (odds ratio 1.64; 95% CI 1.23-2.18; P=0.05). However, visceral fat was not significantly associated with ER+/PR+ cancer, according to the report by Zhigang Yu, MD, PhD, of Shandong University in China, and colleagues.

Obese women with higher amounts of subcutaneous fat, as measured by body-mass index (BMI), were at significantly greater risk for ER+/PR+ breast cancer (OR 1.68; 95% CI 1.27-2.22; P=0.001) but not ER-/PR- cancer, compared with women with BMIs in the normal range, Yu and colleague wrote online in The Oncologist.

"A possible reason is that subcutaneous fat is involved in estrogen production, which may promote ER+ breast cancer," Yu said in a statement. "Visceral fat is more closely related to insulin resistance and may be more likely to promote ER- breast cancer."

"The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes," the research team wrote, "supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens."

The results also imply that tamoxifen, which is approved for breast cancer prevention in high-risk women but is not effective against ER- cancer, may not be effective in women with excessive abdominal fat, the study authors said.

"Different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor-negative breast cancer, stricter weight-control measures may be advised in these individuals."

Decisions about using medications for breast cancer prevention are mainly based on risk-assessment tools such as the Gail Model and the National Cancer Institute Breast Cancer Risk Assessment Tool, Yu and colleagues said. "However, none of these tools can distinguish between ER+ and ER- breast cancer risk, and other risk-assessment factors are therefore needed."

The case-control study included 1,316 women ages 25 to 70 newly diagnosed with breast cancer at 21 hospitals in northern and eastern China. Women with recurrent or metastatic breast cancer, other concurrent malignancies, or a prior history of cancer were not included. The control group was comprised of randomly selected healthy outpatients who visited the hospitals for a regular physical exam. The investigators used logistic regression analysis to assess relationships between body size-related factors and breast cancer risk according to receptor status.

Obesity is a well-known risk factor for female breast cancer, and the study results confirmed this: For example, women weighing more than 62 kg had a 21% increased risk of ER+/PR+ breast cancer (OR 1.21; 95% CI 1.02–1.45) and a 34% increased risk of ER-/PR- breast cancer (OR 1.34; 95% CI 1.03–1.73), compared with women who weighed less than 62.0 kg, the study found.

Yu et al noted that an important limitation of the study was that it included only body-size measurements taken at the time of breast cancer diagnosis and did not include potentially relevant factors such as weight gain over time or use of hormone-replacement therapy.

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