Results from the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) study “will have a follow-on effect of being able to guide physicians about the advantages of longer than 5 years of therapy for the premenopausal woman,” said V. Craig Jordan, OBE, PhD, DSc, Scientific Director at the Lombardi Comprehensive Cancer Center, Georgetown University, in Washington, DC, in an interview with The ASCO Post. ATLAS found that extending tamoxifen therapy from 5 to 10 years for women with estrogen receptor (ER)-positive breast cancer further reduced recurrence and mortality. 

Tamoxifen Forever?

If tamoxifen therapy for 10 years is better than 5 years, would lifelong tamoxifen be even better still? Dr. Jordan said that when he came from the United Kingdom to the United States in the 1980s to pursue research at the University of Wisconsin Comprehensive Cancer Center, “my battle cry, I have to embarrassingly say, was ‘tamoxifen forever,’ because there was no real reason why you should stop it.” Tamoxifen was a relatively new drug then, having become available for the treatment of metastatic breast cancer at the end of 1977, he noted. “We didn’t think in terms of 5 years. We thought in terms of keeping patients on tamoxifen, to see what would actually happen with this safe drug,” he added. 

Dr. Jordan no longer advocates “tamoxifen forever.” His research found that “very low concentrations of physiological estrogen” can destroy breast cancer cells after years of antihormonal treatment. This finding was supported by results from the Women’s Health Initiative study that postmenopausal hysterectomized women who took estrogen replacement therapy had a decreased incidence of breast cancer. 

“The estrogen has gone in there and killed off estrogen-deprived cells in the breasts in women in their 60s,” he said. “So you have this long-term beneficial effect. I would put money on there being the same effects from estrogen in a women’s body after long-term tamoxifen has set up and controlled these cells. When the woman’s own estrogen comes back, it kills off the cells, and that’s what causes the decreases in the mortalities.”

While the recommendation for tamoxifen use has not yet been extended to 10 years, Dr. Jordan said, “Let’s say it gets from 10 years to 15 years” and “you’re in your 30s and develop ER-positive breast cancer. You now go on and take tamoxifen until your early 50s. Then you stop and continue to get all the benefits through the postmenopausal years.” Given the results of the ATLAS study, “a woman in her 30s or 40s should not be considering 5 years of tamoxifen as chemoprevention, but maybe 10 years, and then stopping and seeing the added benefit of that in her postmenopausal years,” Dr. Jordan said. ■