Skipping tam doses increases risk of death

SAN FRANCISCO—Breast cancer patients who skip 30% of their tamoxifen doses increase their risk of death from breast cancer by 16%, Scottish researchers reported at the first annual ASCO Breast Cancer Symposium (abstract 130). Ten percent of women in this study were in that category of compliance.

"While an occasional missed tablet is not a great worry, once you take tamoxifen less than 70% of the time, your survival significantly decreases," said lead investigator Alastair M. Thompson, MD, professor of surgical oncology, University of Dundee, Scotland. "Problems associated with adhering to therapy may become increasingly important as more women are taking aromatase inhibitors (AIs) in place of tamoxifen, because AIs do not stay in the body as long and therefore missing doses may be more worrisome."

The researchers reviewed the records of 2,080 women treated for breast cancer between 1993 and 2002. Most (79%) were prescribed tamoxifen as an adjuvant treatment after surgery. They used clinical and cancer registry records to determine the stage of cancer for each patient and pharmacy records to determine the proportion of tamoxifen prescriptions that had been filled.

Dr. Thompson explained that although the current recommended duration for adjuvant tamoxifen therapy is 5 years, the median time women in the study took tamoxifen was 2.42 years, in part because at study initiation there was not yet consensus on the optimal duration for adjuvant tamoxifen.

Median adherence to tamoxifen was 92%. Only 49% of the women in this study took tamoxifen for 5 years, and 19% discontinued tamoxifen after 2 years or less.

Duration of tamoxifen use was associated with improved breast cancer survival, and time off tamoxifen was associated with increased risk of death from breast cancer.

An unexpected finding was that higher socioeconomic class women were least likely to have been given tamoxifen. Dr. Thompson told Oncology NEWS International that the reason for this is unknown. He speculated that it might reflect the fact that during 1993-2002, the medical center also offered laparoscopic oophorectomy as an adjuvant option, and that women of higher socioeconomic class might have preferred that approach.

Did you take your pill today?

One of the study's strong points is that assessment of compliance was based on prescription refills, not just on asking patients whether they had taken their medication, said Julie R. Gralow, MD, who moderated a press briefing on this research.

"Studies like this point out just how noncompliant our patients are," said Dr. Gralow, associate professor of medical oncology, University of Washington School of Medicine. "The result was a 16% increase in risk of death. We should be asking each of our patients every time we see them, 'Are you taking your pills every day?' and if not, why not? We also need to tell patients what to do if they miss a dose—do you try to make it up, or do you just wait until the next dose is due?"

Adherence matters

Ann H. Partridge, MD, MPH, assistant professor of medicine, Harvard Medical School, has also studied tamoxifen adherence in women with primary breast cancer. Dr. Partridge found similar problems with adherence in US patients: 23% missed taking tamoxifen on more than one-fifth of days studied (J Clin Oncol 21:602-606, 2003).

"Dr. Thompson's study provides more evidence that some women do not take their hormonal therapy for breast cancer as directed and, most important, that adherence matters," Dr. Partridge said. "This study raises this important but often overlooked issue in oncology. For women with breast cancer, tamoxifen is one of the most effective drugs. But it can only work to reduce risk and save lives if women are taking it."