Researchers at Northwestern University in Chicago confirmed thatrisk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer aid the development and implementation of distinct breast cancer prevention strategies.

According to study results published inCancer Prevention Research, overexpression or underexpression of a newly identified set of genes related to lipid metabolism may help physicians identify woman’s risk for developing hormone receptor-positive or hormone receptor-negative breast cancer. The results may help physicians tailor appropriate prevention strategies for their patients.

?Currently, three drugs can be used to prevent breast cancer in women who are at extremely high risk for the disease,? explained Seema A. Khan, M.D., co-leader of the Breast Cancer Program at the Robert H. Lurie Comprehensive Cancer Centerof Northwestern University in Chicago. ?However, these drugs prevent only breast cancers that are sensitive to hormones, commonly referred to as estrogen receptor-positive breast cancers. These drugs do not prevent breast cancers that are insensitive to hormones, or estrogen receptor-negative breast cancers.”

Preventing hormone-insensitive cancer
?We should not expose women at risk for hormone-insensitive breast cancer to the side effects of preventive medications that we know will not work for them,? Khan said. ?Moreover, if we knew who these women were, we could focus on them in terms of designing new studies to find a solution for preventing hormone-insensitive cancer.?

Gene expression
Khan and colleagues sought to find a way to identify women at risk for estrogen receptor-negative breast cancer by examining gene expression in the unaffected breasts of women who had a primary breast cancer of known estrogen-receptor status.

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Hormone receptor status of second cancer
They research team used this approach because prior research has indicated that if women who have had cancer in one breast subsequently develop a cancer in their second breast, the second cancer is likely to have hormone-receptor status that resembles the first cancer.

Using this logic, Khan and colleagues performed fine-needle aspiration on the unaffected breasts of 15 women with estrogen receptor-positive breast cancer and 15 women with estrogen receptor-negative breast cancer. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples.

They further validated the results in a second group of women including 12 women with estrogen receptor-positive disease, 12 with estrogen receptor-negative disease and 12 healthy controls. The cases in each set were matched by age, race and menopausal status.

Higher expression levels

The researchers identified 13 genes with significantly higher expression levels in samples from estrogen receptor-negative women. Eight of these genes were associated with lipid metabolism. ?This was interesting because obesity is a breast cancer risk factor for postmenopausal women, but obese women are generally thought to be at increased risk for hormone-sensitive cancer,? Khan noted. ?We were surprised to see that some of these genes that are associated with lipid metabolism, or the metabolism of fats, are actually more highly expressed in the unaffected breasts of women with estrogen receptor-negative breast cancer.?

Additional findings
The researchers also found significant overexpression of four of the genes associated with lipid metabolism ? DHRS2, HMGCS2, HPGD and ACSL3 ? in estrogen receptor-negative samples when compared with healthy women. In estrogen receptor-positive samples, two different lipid metabolism-associated genes ? UGT2B11 and APOD ? were underexpressed.

?It will be a few more steps before this information is practically useful, but we are hoping that it can take us to a place where we can obtain a breast sample from healthy women, see that they are at risk for a certain type of breast cancer and tailor the prevention strategy accordingly,? Khan observed.

For more information:
Wang J, Scholtens D, Holko M, Ivancic D, Lee O, Hu H,Chatterton RT, et al. Lipid Metabolism Genes in Contralateral Unaffected Breast and Estrogen Receptor Status of Breast Cancer. Cancer Prevention Research. Published OnlineFirst March 19, 2013; doi: 10.1158/1940-6207.CAPR-12-0304,

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