NE Oncology Issue – February 2014
Rea DW, et al. ECC 2013:1860
Tamoxifen given for five years after surgery for estrogen receptor (ER)-positive early breast cancer reduces recurrence and breast cancer mortality and is more effective than treatment for shorter durations. However, it is uncertain what advantage there may be to extending tamoxifen treatment to 10 years. At ECC 2013, Rea and colleagues presented the overall and subgroup findings of the aTTom study.1
- A total of 6,953 women with ER+ (n = 2,755) or ER-untested (n = 4,198) invasive breast cancer from 176 U.K. centres, who were relapse-free after five years of prior adjuvant tamoxifen, were randomized to stop tamoxifen or continue to year 10.
- Annual follow-up recorded compliance, recurrence, mortality, and hospital admissions.
- Allocation to continue tamoxifen to year 10 reduced breast cancer recurrence compared with that after just five years of tamoxifen (10 vs. 5 years of tamoxifen: 614/3,470 vs. 711/3,486; rate ratio (RR) = 0.86 [95% CI: 0.77–0.96], p = 0.006). (Figure 1)
- This reduction in breast cancer recurrence was time dependent, based on the number of years from the start of treatment (10 vs. 5 years of tamoxifen): (Figure 2)
- Years 5–6: RR = 1.11 (95% CI: 0.89–1.37);
- Years 7–9: RR = 0.85 (95% CI: 0.71–1.02);
- Years 10–14: RR = 0.72 (95% CI: 0.59–0.87);
- Years 15+: RR = 0.83 (95% CI: 0.56–1.24).
- Overall, longer treatment trended towards reduced breast cancer mortality, but was not significant (10 vs. 5 years of tamoxifen: 426 vs. 466 breast cancer deaths; RR = 0.91 [95% CI: 0.80–1.04], p = 0.2). (Figure 3)
- Compared with breast cancer mortality in the 5-year tamoxifen group, a reduction in breast cancer mortality with 10 years of tamoxifen was only observed at 10–14 years from the start of treatment (RR = 0.78 [95% CI: 0.64–0.95]). (Figure 3)
- All-cause mortality was not significantly different between the 10-year and 5-year groups (944 vs. 995 deaths; RR = 0.95 [95% CI: 0.87–1.04], p = 0.2).
- In the 10-year tamoxifen group, there were more endometrial cancers (102 vs. 47, p <0.0001), but there was no difference in the number of endometrial cancer deaths between the two groups (10 vs. 5 years of tamoxifen: 31 vs. 23, p = 0.27).
- aTTom confirms the recently reported findings of the complementary ATLAS study2 — continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in breast cancer recurrence.
- Continuing tamoxifen beyond 5 years also reduces breast cancer mortality: while there is no effect in years 5–9, there is a 22% reduction after year 10.
- Endometrial cancer risk is increased with longer tamoxifen, but the observed increase in endometrial cancer deaths is numerically small and statistically non-significant.
- The magnitude of the benefit of continuing tamoxifen beyond 5 years makes this an appropriate option for almost all women with ER-positive early breast cancer.
References: 1. Rea DW, Gray RG, Bowden SJ, et al. Overall and subgroup findings of the aTTom trial: A randomised comparison of continuing adjuvant tamoxifen to 10 years compared to stopping after 5 years in 6953 women with ER positive or ER untested early breast cancer. ECC 2013:1860. 2. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013;381:805–16.
Carolyn Owen, MD
Dr. Carolyn Owen completed postgraduate training in internal medicine and hematology at the University of Ottawa and the University of British Columbia, respectively, followed by a research fellowship in molecular genetics at Barts and the London School of Medicine and Dentistry in London, UK. Her research focused on familial myelodysplasia and acute myeloid leukemia. She is currently an Assistant Professor at the Foothills Medical Centre & Tom Baker Cancer Centre, and her clinical interests are low-grade lymphoma and chronic lymphocytic leukemia. She is also the local principal investigator in Calgary for several clinical trials in these areas.
Douglas A. Stewart, BMSc, MD, FRCPC
Dr. Douglas A. Stewart is currently a professor in the Departments of Oncology and Medicine, and Chief of the Division of Hematology and Hematological Malignancies at the University of Calgary. Since July 1994, he has been practising medical oncology at the Tom Baker Cancer Centre in Calgary, where he is a member of the Breast Cancer and Hematology Tumour Groups, Leader of the Hematology/Blood and Marrow Transplant Program, and Provincial Leader of the Hematology Tumour Team for the Alberta Health Services Cancer Care Program. His research interests focus on clinical trials involving hematological malignancies and hematopoietic stem cell transplantation. Dr. Stewart has authored over 80 peer-reviewed manuscripts and over 120 abstracts.
Richard R. Furman, MD
Dr. Furman is a member of the Lymphoma/Myeloma Service in the Division of Hematology/ Oncology at the New York Weill Cornell Medical Center. He is head of the chronic lymphocytic leukemia (CLL) and Waldenstrom’s macroglobulinemia (WM) program at Weill Medical College, and focuses on identifying new and promising therapies for patients with CLL and WM. Along with collaborators at Columbia Presbyterian, Johns Hopkins, Roswell Park Cancer Institute, and Ohio State University, Dr. Furman has initiated the Waldenstrom’s Research Consortium in order to enhance treatment and understanding of WM.