Thousands of Canadian breast cancer patients who take tamoxifen for years in the hope of fending off a recurrence may be doing it for naught: Because of their genetic makeup, the drug is doing little or nothing to help them.
A test that could tell which patients are less likely to benefit from the drug is not widely available in Canada. The test is being done in the United States, but it is expensive, and requires women to send blood samples or cheek swabs to the U.S. labs that perform it.
The test is looking for a variation in the gene that controls the activity of the CYP2D6 enzyme that might make the tamoxifen less effective in combatting cancer.
Some women are balking at the $500 cost for the test, while others are forging ahead, even though medical oncologists disagree on whether to recommend it to patients.
The Canadian Association of Provincial Cancer Agencies hasn't taken a position because it says the scientific evidence isn't reliable enough.
However, its executive director, Heather Logan, said women have a right to information about the test, and patients should discuss it with their clinicians.
Ellen Warner, director of Pynk, the breast cancer program for younger women at Toronto's Sunnybrook Health Sciences Centre, said her "gut feeling" is that all women on tamoxifen should be tested. So far, about a dozen women have sent their blood to the Mayo Clinic for testing.
Some physicians are also using Toronto-based pharmacy.ca, which sends patients' cheek swabs to a U.S. teaching hospital, providing results in two weeks.
An estimated 22,700 women will be diagnosed with breast cancer in Canada this year. Many of them will be given tamoxifen: 206,490 prescriptions of the generic drug were filled last year, costing $4.8-million, according to IMS Health, a private health-information and consulting-services company.
Dianne Theoret-Major, 47, was diagnosed with breast cancer earlier this year, and tested in June for the genetic variation that affects the activity of enzyme CYP2D6.
"I didn't care about the cost," said Ms. Theoret-Major, who lives in Halton Hills, northwest of Toronto. "... I have two kids, aged 13 and 12. It's a real worry to me and I wanted to do everything I could so I was still in their life. I did not want to turn around in six months to find out I should be on another drug."
As it turned out, she was able to stay on tamoxifen. Her medical oncologist, Sandy Sehdev, believes all women on tamoxifen or who are going to be on it should be tested.
"What would I do for my mom or wife," asked Dr. Sehdev, who practices medicine at William Osler Health Centre in Brampton. "I would only recommend to my patients what I would recommend to my family."
Typically, patients with estrogen-receptor-positive breast cancer who are premenopausal are prescribed tamoxifen, now a generic drug, for five years. Studies show it reduces cancer recurrence by 50 per cent.
The enzyme CYP2D6, known as 2D6, converts tamoxifen into a substance called endoxifen, which is what exerts the cancer-fighting effect. Variations in the gene that controls 2D6 mean that up to 7 per cent of people on tamoxifen have an inactive enzyme.
Those 7 per cent are low metabolizers, meaning they produce little or no 2D6 and may not be able adequately to convert tamoxifen to endoxifen. The metabolization levels are also important, some researchers say, when a patient is on antidepressants, which can interfere with tamoxifen's effectiveness.
Some oncologists suggest that how a woman feels on tamoxifen can be a sign: if she is having hot flashes, the drug is working. If not, the opposite may be true.
"If you feel good on tamoxifen, the good news is you feel great," said Dr. Warner, a medical oncologist. "The bad news is that it's probably not working."
Those who are found to be low metabolizers are usually switched to aromatase inhibitors, a class of drugs that are far more costly than tamoxifen. As well, since most patients on tamoxifen are premenopausal, they would also have to take an ovary-suppressing medication.
Karen Gelmon, co-chair of the National Cancer Institute of Canada clinical trials group breast site committee, calls studies on the genetic variation intriguing but not definitive, and said the data are "too shaky" to make a decision.
"When we have good scientific evidence," said Dr. Gelmon, a medical oncologist, in a telephone interview from Vancouver, B.C., "we will rush to put it into guidelines."
Likewise, Pamela Goodwin, director of Marvelle Koffler Breast Centre at Mount Sinai hospital and head of the medical oncology breast program at Princess Margaret Hospital, both in Toronto, believes routine testing is premature because she doesn't think there is enough evidence to warrant it, adding that she and others continue to discuss studies' results.
"We would be the first to do something if we thought it was clear that it impacted the outcomes," Dr. Goodwin said. "... It's one of these ones where I don't know if we're going to reach a point whether there will ever be enough evidence. But we're going to stay on top of it."
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