PHILADELPHIA — The overexpression or underexpression of a newly identified set of genes related to lipid metabolism may help physicians identify whether or not a woman is at risk for hormone receptor-positive or hormone receptor-negative breast cancer and to subsequently tailor prevention strategies appropriately, according to data published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

Researchers 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.

They 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. They validated their results in a second group of women: 12 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.

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,” said Seema A. Khan, M.D., co-leader of the Breast Cancer Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.  “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.”

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 said.

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Read more about metabolism and TNBC in my book, Surviving Triple-Negative Breast Cancer.

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