Tamoxifen Alone vs Adjuvant Tamoxifen for Operable Breast Cancer in the Elderly
Abstract & Commentary
Synopsis: Breast cancer is the most common malignancy in women and is very common in older patient populations. Women older than age 70 comprise 15-20% of patients. Some of these older patients may not be able to tolerate or do not desire the standard surgical procedures of either lumpectomy or mastectomy. In addition, as these patients will be an increasing proportion of the overall breast cancer population, it is important to define which aspects of treatment are most critical to overall outcome. This is helpful to the individual patients and their families so they can make an informed choice. It is also critically important to physicians and health care planners. Two randomized trials showed no difference in survival between elderly patients treated with tamoxifen alone or surgery alone. One study showed that locoregional control was better in the surgery group, but the differences were not statistically significant. Another trial reported a high rate of local relapse after surgery.
Source: Mustacchi G, et al. Ann Oncol. 2003;14: 414-420.
This paper presents the long-term results of the Italian Trial, GRETA, after analysis of local responses, distant metastases incidence and dates, and causes of death. This was a randomized, multicenter phase III study that compared the efficacy of tamoxifen alone vs surgery followed by adjuvant tamoxifen in women older than 70. Eligibility required histologic evidence of invasive breast cancer that was potentially operable. Patients were randomized to tamoxifen alone (160 mg loading dose day 1, followed by 20 mg daily) for 5 years or surgery followed by tamoxifen 20 mg/d for 5 years. The extent of surgery was not prescribed and radiation therapy was not part of the study. Between March 1987 and June 1992, 474 women older than 70 with operable breast cancer were recruited. The median age of the patients was 76 years, and the majority of the tumors were T1 (55.2%), with 60.3% of patients N0.
In the tamoxifen-alone group, there was 41.6% response rate (CR+PR). At a median follow-up of 80 months, 11.2% of patients in the surgical arm and 45.2% in the tamoxifen-alone arm had a local progression. No difference in breast cancer deaths was found between the 2 groups of treatment. Deaths from other causes were highly significant. Fifty percent of patients without recurrence died from cardiovascular disease. This has been seen in trials of lymphoma and prostate cancer in elderly patients.1,2
The role of tamoxifen in the adjuvant treatment of postmenopausal women is well established.3 The current study demonstrated that local therapy did not influence survival, as there was no difference between the 2 arms. However the high rate of local progression in the tamoxifen-alone group indicates that minimal surgery followed by adjuvant tamoxifen is the most appropriate treatment in older patients with operable breast cancer. Tamoxifen alone is an alternative as sole first-line treatment only in frail patients unfit for surgery or refusal. The loading dose used in the surgery arm of the trial may have led to the longer distant metastases-free survival in favor of the tamoxifen-alone group.
Comment by Stuart M. Lichtman, MD, FACP
This study adds more information to the treatment algorithm of breast cancer in elderly patients. It also confirms earlier data that in clinical trials in elderly patients, overall survival is often influenced by other factors, particularly comorbidity. If one is looking at overall survival and is not concerned about locoregional recurrence, tamoxifen alone, in an estrogen receptor positive tumor, may be an appropriate alternative. In an attempt to define breast cancer therapy in elderly women, it has been shown that radiation therapy may be withheld without a significant effect on survival.4 This again indicates that local therapy does not significantly influence overall survival. This study has some limitations. It does not address the issue of adjuvant radiation therapy. It also did not specify the type of surgery the patients were to receive or the need for axillary dissection. It is also not possible to know whether the use of aromatase inhibitors would give the same results. Patients should be made aware of their treatment options and what role each modality plays in local recurrence, systemic recurrence, and overall survival.
Dr. Lichtman is Associate Professor of Medicine, NYU School of Medicine, Division of Oncology; Don Monti Division of Medical Oncology North Shore University Hospital, Manhasset, NY.
References
1. Newschaffer CJ, et al. J Natl Cancer Inst. 2000;92: 613-621.
2. Vose JM, et al. J Clin Oncol. 1988;6:1838-1844.
3. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451-1467.
4. Hughes KS, et al. Proc Annu Meet Am Soc Clin Oncol. 2001;20:93(abstract).
Women older than age 70 comprise 15-20% of breast cancer patients. Some of these older patients may not be able to tolerate or do not desire the standard surgical procedures of either lumpectomy or mastectomy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content