Close to a quarter of women treated for breast cancer with the gold-standard therapy tamoxifen may stop taking the treatment after one year, even though the optimal duration of therapy is five years.

In a study scheduled for publication in the 1 March, 2007, issue of the US journal Cancer, researchers led by Thomas Barron of the Department of Pharmacology and Therapeutics at Trinity College Dublin and St James’s Hospital in Dublin, Ireland, reviewed a national database of 2,816 women aged 35 years and over who had started on tamoxifen for breast cancer. After 12 months they found 22% of the women had stopped using tamoxifen. At 24 months, 28% of the study cohort had come off tamoxifen and at 3.5 years, 35% had ceased treatment without starting on another therapy.

In clinical trials, discontinuation or non-persistence rates for tamoxifen are estimated at 16-32%, the authors noted. Previous studies in the clinical practice setting have reported significantly lower rates of non-persistence than observed by the Dublin team – 17% at the two-year stage and 31% at five years. However, these findings were drawn from self-reported data focusing on elderly patients, an inherently biased data collection method in a population accustomed to chronic medication, the researchers commented.

Mood swings and hot flushes triggering discontinuation

The most common reasons for discontinuing tamoxifen are the drug’s adverse effects, which include mood swings and hot flushes, although these are often successfully treated with antidepressant therapy. In the new study, age and a history of antidepressant use were identified as risk factors for coming off tamoxifen. Women between the ages of 35 and 44, or over 75 years old, were more likely to stop using tamoxifen, as were those reported to have used an antidepressant within one year of starting on tamoxifen.

The gold-standard status of tamoxifen – developed by AstraZeneca but now widely genericised – in the treatment of breast cancer is increasingly under challenge from the newer but more expensive aromatase inhibitors, including AZ’s own Arimidex (anastrozole). Scientists estimate, though, that tamoxifen prevents more than 40,000 recurrences of breast cancer worldwide each year. Anything less than five years of continual treatment, however, is associated with higher rates of recurrence and mortality, the researchers pointed out.

Their findings illustrate that treatment persistence with tamoxifen cannot be assured, while raising concerns about persistence with other oral hormonal therapies for breast cancer and with oral antineoplastics in general, the authors concluded. “This is of particular importance," they wrote, “as longer durations of adjuvant therapy may be recommended for breast cancer in the future and as cancer survivorship becomes a priority area in clinical practice and research.”