More Evidence for 10-Years of Tamoxifen in ER+ Breast Cancer

Richard G. Gray, MA, MSc

A British study has confirmed that 10 years of adjuvant tamoxifen substantially reduces late breast cancer recurrence and mortality among women with estrogen receptor-(ER) positive disease, supplying what investigators believe is the final piece of evidence supporting long-term use of the endocrine therapy.

The randomized, phase III aTTom study helps settle the question of whether 10 years of tamoxifen provides a benefit versus the more standard 5 years, said lead author Richard G. Gray, MA, MSc, discussing the findings at the American Society of Clinical Oncology (ASCO) Annual Meeting Sunday. The research was featured at a press conference and during the plenary session.

“There has been quite a remarkable improvement in the benefits of tamoxifen,” said Gray, a professor of Medical Statistics at the University of Oxford in the United Kingdom, during his presentation. “What is really impressive is the effect on breast cancer mortality.”

Gray said prior research has shown that 5 years of tamoxifen reduces breast cancer recurrence and mortality by approximately one-third over a 10- to 15-year period following diagnosis.

The benefits of longer treatment emerge later on, with reductions in recurrence starting to unfold after year 7 and reductions in mortality becoming evident after year 9, Gray indicated. He said the continued use of tamoxifen resulted in an additional 24% reduction in mortality after year 10.

“So, 10 years of tamoxifen compared to no tamoxifen reduces breast cancer mortality by a third in the first decade and a half in the second decade,” he said.

The results of the aTTom study mirror those of the international ATLAS trial, which Gray presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium in December. Together, the study results “provide proof beyond reasonable doubt” about the benefits of continuing tamoxifen treatment, Gray said.

In the aTTom trial, 6953 women with breast cancer who had been taking tamoxifen for 5 years were randomized to continue receiving tamoxifen for another 5 years or stop taking the drug. The trial was conducted from 1991 through 2005.

With follow-up of more than 10 years, there were 580 recurrences among women who had taken tamoxifen for 10 years, compared with 672 recurrences in the shorter-term treatment arm (P = .003).

Moreover, there were 392 breast cancer deaths after recurrence among participants who had taken the drug for a decade, compared with 443 deaths among those in the 5-year arm (P = .05).

When the results of the aTTom study and the ATLAS trial, which included 6846 women, are combined, the statistical significance of the benefits of longer tamoxifen administration are enhanced, with improvement in recurrence rates (P <.0001), breast cancer mortality (P = .002), and overall survival (P = .005), according to the aTTom abstract.

The disadvantages of taking tamoxifen for 10 years may include continuing menopausal symptoms such as night sweats and hot flashes, and rare adverse events such as an increased risk of endometrial cancer. In the aTTom trial, there were 102 cases and 37 (1.1%) deaths attributed to endometrial cancer in the 10-year tamoxifen arm, compared with 45 cases and 20 (0.6%) deaths in the 5-year group.

Gray said the benefits of longer treatment with tamoxifen outweigh the risks.

In the United States, the trial results likely will change the standard of care for women who are premenopausal at diagnosis to include 10 years of tamoxifen, said Sylvia Adams, MD, an associate professor at New York University School of Medicine who provided commentary on the study during the press conference. US women who are postmenopausal at diagnosis typically receive an aromatase inhibitor as adjuvant treatment but they may now consider incorporating extended tamoxifen into their treatment plan, Adams said.

In discussing the trial results at the plenary session, Ann H. Partridge, MD, MPH, director of the Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute in Boston, noted that late recurrence remains a major problem in hormone receptor-positive breast cancer. Longer-term use of tamoxifen presents opportunities for clinical benefits, but challenges will include getting patients to adhere to extended therapy and helping premenopausal younger women with breast cancer sort out the personal choices they may face with extended therapy, Partridge said.

Gray RG, Rea D, Handley K, et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 in 6,953 women with early breast cancer. J Clin Oncol. 2013;31 (suppl; abstr 5).

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