Longer tamoxifen treatment drops risk of cancer recurrence, death

Prolonging treatment with adjuvant tamoxifen from 5 years to 10 years decreases risk of breast cancer recurrence (15% reduction over 5 years of therapy) as well as mortality (25% reduction at year 10) for women in the initial stages of breast cancer. Richard Gray, MD, MSc, of the University of Oxford, UK, presented this finding from results of the aTTom trial (Adjuvant Tamoxifen: To Offer More?) at the 2013 American Society of Clinical Oncology (ASCO) annual meeting in Chicago in early June.

Findings from the trial, which enrolled 6953 women, are consistent with those from the recently published ATLAS (Adjuvant Tamoxifen Longer Against Shorter) trial. For the pooled analysis of 17,477 patients in aTTom and ATLAS, there was a 9% reduced risk of death for patients taking tamoxifen for 10 years versus the 5-year treatment (RR 0.91, 95% CI [0.84, 0.97]; P = 0.008). The reduced mortality risk was sustained for the entire follow-up duration.

Regarding non-breast cancer risk of death, longer treatment with tamoxifen made little difference. However, there was slightly greater chance of endometrial cancer with increased tamoxifen treatment duration, though absolute hazard was just 0.5%. No further safety risks were noted.

Both the aTTom and ATLAS trials demonstrated that longer use of tamoxifen lowered recurrence risk after year 7. In addition, tamoxifen’s extended treatment effects in the aTTom trial may be even more significant than what’s being reported, because 60% of enrolled patients reportedly had unknown estrogen receptor (ER) status. (Approximately 15% of patients likely had ER-negative disease, and did not gain from tamoxifen use.)

Certain subsets of women may especially profit from extended tamoxifen treatment, such as those who experience amenorrhea after 5 years of adjuvant tamoxifen. For them, a switch to an aromatase inhibitor may be advisable until ovarian function is normalized. Once ovarian function returns, tamoxifen continuation may work well.

Women who stand to gain the most from prolonged tamoxifen treatment are those who are premenopausal after 5 years of tamoxifen, because of their higher disease risk.

Overall, potential extended treatment gains must be weighed against effect on quality of life, the age of a woman, and her fertility and family plans.

Another potential issue to consider is adherence, which (perhaps not surprisingly) begins to decline, especially after 4 years of treatment. Extended treatment beyond 5 years may pose additional adherence issues.