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Personalizing the Management of Breast Cancer

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At the 28th Annual San Antonio Breast Cancer Symposium, a special mini-symposium has highlighted an exciting field of breast cancer research that individual genetic differences, including some almost undetectable changes in single bases that make up the DNA chain, can help to determine if a woman will get cancer, and if she will respond to treatment.

Christine Ambrosone, PhD, from Roswell Park Cancer Institute, spoke about the effects of genetic variability on breast cancer risk and prognosis.

Dr. Ambrosone pointed out that, "Although we can identify risk factors for many diseases, they do not completely explain the variability that we see in cancer."

"For example, although cigarette smoking is a powerful risk for lung cancer, only about 10% of long-term smokers actually develop this disease."

"This stems in part from heterogeneity within "at-risk" populations, which may be easy to detect (e.g., how individuals metabolize drugs) or may be almost undetectable, down to the level of changes in single DNA nucleotides (SNPs)."

"A long and complex pathway traces initial environmental exposure to the formation of DNA damage to the development of invasive cancer, and every step is subject to individual variability."

As an example, Dr. Ambrosone discussed the role of oxidative stress in both the origin and the treatment of breast cancer.

Oxidative stress has been implicated in many diseases, and many people have at least considered taking large doses of antioxidant vitamins (vitamin C, vitamin E, etc.) to protect against these diseases.

Dr. Ambrosone has identified SNPs associated with chemicals involved in oxidative stress, and used them to answer questions of interest to clinicians and patients alike: Can breast cancer risk be reduced by the consumption of fruits, vegetables, and specific supplemental antioxidants?

Can response to cancer therapy be predicted by variation in SNPs related to oxidative stress?

Alison Dunning, PhD, from Strangeways Research Laboratory in Cambridge, UK, is also using SNPs, this time to find out why first-degree relatives of breast cancer patients are twice as likely to develop breast cancer as members of the general population.

She and her colleagues are studying populations in East Anglia, where 98% of the population is of north-western European ancestry.

After some promising early work, her group has now embarked on a project that will use SNPs to examine the whole genome scan, with the hope of catching all cancer susceptibility genes, both common alleles with moderate effects, and rarer ones with large effects.

SNPs are also being used in this field of pharmacogenomics to see how genetic variability affects how people respond to chemotherapy drugs.

David Flockhart, MD, PhD, from Indiana School of Medicine, is looking at the variability of response to tamoxifen in breast cancer patients.

He has found that small polymorphisms in a particular enzyme that is involved in the metabolism of tamoxifen will reduce its effectiveness, leading to faster recurrence and an increased rate of breast cancer progression.