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Gene Profile May Help Identify Risk for Hormone-sensitive, Hormone-insensitive Breast Cancer

March 19, 2013
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  • Levels of 13 genes elevated in unaffected breasts of women with hormone receptor-negative breast cancer.
  • Eight of the genes were associated with lipid metabolism.
  • Ability to identify those at risk may help tailor prevention strategies.

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.

“Currently, three drugs can be used to prevent breast cancer in women who are at extremely high risk for the disease,” 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. “However, these drugs prevent only breast cancers that are sensitive to hormones, commonly referred to as estrogen receptor-positive breast cancers; they do not prevent breast cancers that are insensitive to hormones, or estrogen receptor-negative breast cancers.

“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.”

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.

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,” Khan said. “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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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit

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