Decoding the elements for a cure

Winter 2014

Medical professionals have long known that the level of vitamin D in our body drops in the wintertime, especially if we live in a northern region. Vitamin D is important in the prevention of osteoporosis, lowering blood pressure in people with hypertension, and the prevention and treatment of depression, among other things. However, new research led by Lawson Health Research Institute’s Dr. Richard Kim has found that vitamin D deficiency can affect the body’s ability to metabolize an important drug used in breast cancer treatment.

It’s something that Canadians are all too familiar with – the dramatic effects of winter. The nights are longer, the days are shorter, the cold can be harsh and the weather can deter us from going outside. Considering that sunshine is essential to producing vitamin D in the body, it’s not uncommon to have a deficiency of this important vitamin if you live in a northern region, where skies are normally grey from October to March.

New research led by LHSC and Lawson Health Research Institute’s Dr. Kim, has found that this seasonal drop in vitamin D affects the body’s ability to metabolize an important drug called tamoxifen, which is used to treat and prevent the reoccurrence of estrogen receptor positive (ER+) breast cancer.

“During the winter months we noted that the blood level of the active form of tamoxifen, called endoxifen, is nearly 30 per cent lower than the level seen during summer, and therefore a significant number of our patients may not benefit as much from the drug during winter,” says Dr. Kim.

Dr. Kim is a leader in personalized medicine – which is a new way of practicing medicine using a patient’s genetic blueprint, as well as diet and environmental factors to tailor drugs and dosages specifically to the individual. At his personalized medicine clinic at LHSC, Dr. Kim and his team can identify women for whom tamoxifen will be effective by carrying out genotyping (form of DNA testing) to learn whether a woman is a poor, low, normal, or rapid metabolizer of the drug. Tamoxifen and endoxifen blood levels are measured using a state-of-the-art piece of equipment called a mass spectrometer.

According to Dr. Kim, it’s antiquated to think a drug affects each person the same way.

“Imagine that you are diagnosed with a major ailment, such as breast cancer,” explains Dr. Kim. “Your doctor prescribes medication to treat it. The hope is that this drug will help you. However, for some of our patients, and depending on the drug, those drugs or the prescribed dosages may not work well, or could cause unexpected side effects. The percentage of patients that experience this can be significant. When drugs are prescribed to fit an individual’s genetic profile, he or she can get timely access to better, safer treatments and avoid needlessly taking medications that are less likely to work, or cause significant side effects.”

In addition to the seasonal effect, Dr.Kim found there are other factors that affect tamoxifen’s efficiency.

Research shows that, due to their genetic makeup, nearly 10% of Canadian women are less likely to benefit from tamoxifen’s cancer fighting benefits because their livers do not produce enough of a certain enzyme that converts the drug into its active form. If these women unknowingly take the standard dose of tamoxifen for five years, the treatment may be suboptimal and possibly put them at a greater risk of their cancer coming back.

Also, there are many drug interactions, such as those caused by common antidepressants, which can markedly reduce the liver’s ability to generate the active form of the drug.

Armed with the knowledge and information gathered from the research, Dr. Kim and his team can help advise physicians in caring for their patients.

“These new clinical and genetic markers can help identify patients who will benefit from tamoxifen, as well as those patients at risk of suboptimal results. Now we can identify a woman who, in the past, would have been prescribed an ineffective treatment and look for other options, and if the test shows a woman is a normal metabolizer, it gives reassurance that she’ll really benefit from therapy.”

For those who metabolize the drug poorly, doctors may recommend switching to another type of hormonal therapy or to increase the tamoxifen dose in consultation with the patient’s oncologist, and see if the endoxifen levels reach the therapeutic range. Also, patients are now encouraged to consider vitamin D supplementation, especially over the winter months.

The discovery of the many factors affecting the efficacy of tamoxifen marks just one of many rays of hope for the future of personalized medicine.

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