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Hormonal Treatment Duration in Elderly Patients: An Open Question

Centro di Riferimento Oncologico, Aviano, Italy
Oncology Institute of Southern Switzerland, Lugano, Switzerland, and European Institute of Oncology, Milan, Italy
The Cancer Council Australia and University of Sydney, Sydney, Australia

To the Editor:

In the June 15, 2003, issue of the Journal of Clinical Oncology, Sacco et al [1] reported the results of a randomized trial comparing 2 versus 5 years of adjuvant tamoxifen in the treatment of early breast cancer patients ages 50 years or older (with an age limit of 70 years). Their results confirm those of the last overview [2] that longer therapy duration is associated with a better treatment outcome, at least for patients with estrogen receptor (ER)–positive tumors. In fact, although there was no statistically significant difference in disease-free survival (DFS) and overall survival between the 5-year and the 2-year durations in the overall group, the ER-positive cohort had a statistically significant prolongation of DFS with 5-year tamoxifen. No difference in overall survival was observed (hazard ratio, 0.98; 95% CI, 0.72 to 1.32) after a median follow-up of 52 months postrandomization (78 months after surgery) even in ER-positive patients.

In their discussion, the authors noted, "tamoxifen prolongation of treatment was also associated with a doubled risk of thromboembolic events, and that the excess risk was almost entirely counterbalanced by the benefit derived from the protection against contralateral breast cancer." Although this tradeoff may be appropriate for younger postmenopausal patients, we suggest that it is time to re-evaluate the duration of endocrine treatment in elderly patients (those more than 70 years old). We are seeing more of these patients in our clinics, but they are substantially underrepresented in the clinical trials from which treatment policies are derived. In this older subset of patients, the impact of protection from a contralateral breast cancer has far less importance than the risk of a thromboembolic event. In our International Breast Cancer Study Group Trial IV [3] we found that only 1 year of tamoxifen plus low-dose prednisone adjuvant treatment influenced survival at 21 years' median follow-up in an elderly population of patients (ages 66 to 80 years) with node-positive breast cancer. The study started in 1978, at which time only 45% of the patients had a hormonal receptor assay, and of these, 33% were positive and 12% were negative.

Given that we have no data on the morbidity of longer periods of treatment in patients more than 70 years old, the issue of the duration of hormonal treatment in elderly patients remains an open question.

Ragaz et al [4] calculated that the relative risk of mortality for thromboembolic events among tamoxifen users was 1.5 at the age of 50, but it dramatically increased to 17.5 at the age of 80. The recent data of an adjuvant trial with the new class of aromatase inhibitor [5] showed a significantly lower incidence of deep venous thrombosis with anastrozole, but it is too early to draw conclusions on mortality and disease control. There are few if any data on the optimal duration of aromatase inhibitors. The issue of which is the best hormonal treatment will be answered in the next few years

We suggest that a randomized trial for elderly women with endocrine responsive disease is needed to address the question of duration of hormonal therapy in order to identify the optimal duration for this ever-increasing group.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Sacco M, Valentini M, Belfiglio M, et al: Randomized trial of 2 versus 5 years of adjuvant tamoxifen for women aged 50 years or older with early breast cancer: Italian Interdisciplinary Group for Cancer Evaluation study of adjuvant treatment in breast cancer: J Clin Oncol 21:2276-2281, 2003[Abstract/Free Full Text]

2. Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: An overview of the randomized trials. Lancet 351:1451-1467, 1998[CrossRef][Medline]

3. Crivellari D, Price K, Gelber RD, et al: Adjuvant endocrine therapy compared with no systemic therapy for elderly women (age 66-80) with early breast cancer: 21-year results of International Breast Cancer Study Group Trial IV. J Clin Oncol 21:4517-4523, 2003[Abstract/Free Full Text]

4. Ragaz J, Coldman A: Survival impact of adjuvant tamoxifen on competing causes of mortality in breast cancer survivors, with analysis of mortality from contralateral breast cancer, cardiovascular events, endometrial cancer and thromboembolic episodes. J Clin Oncol 16:2018-2024, 1998[Abstract]

5. The ATAC Trialists Group: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomised trial. Lancet 359:2131-2139, 2002[CrossRef][Medline]

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