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An Analysis of Primary Hormonal Therapy without Surgery for Elderly Patients with Operable Breast Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: A meta-analysis of existing data on the primary management of operable breast cancer in elderly women demonstrates that when the approach is hormonal (tamoxifen) rather than surgery, local recurrence is higher. Overall survival, however, was not different.
Source: Hind D, et al. Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review. Br J Cancer. 2007;96:1025-1029.
The standard of care for early-stage breast cancer in women of all ages has been well established to include surgery with or without adjuvant radiation, chemotherapy, or hormonal therapy. In this country, primary endocrine therapy is not typically considered an option. However, in the UK there is a growing trend towards treating women over 70 years of age with primary endocrine therapy. Over 40 percent of women over the age of 70 in the UK, with breast cancer, are being treated with primary endocrine therapy. The justification advanced is that surgery for breast cancer, especially when it includes axillary node dissection, is associated with a high morbidity and negative impact on overall quality of life, whereas the natural history of breast cancer in older women is often indolent.1 However, the duration of local disease control has been demonstrated to be shorter than with surgery, and it is not unusual that surgical intervention is ultimately required.2
This study was designed to compare the overall survival (OS) and progression free survival (PFS) of surgery with or without endocrine therapy to endocrine therapy alone. The Cochrane Breast Cancer Group Specialized Register served as the database for seven eligible randomized controlled trials included in this meta-analysis. Six of these trials had published outcome data. Three of the trials were surgery vs primary endocrine therapy, and three were surgery plus endocrine therapy vs primary endocrine therapy; only one of these studies reported estrogen receptor status of the tumors. Tamoxifen was used as the endocrine therapy in all of the trials. When surgery alone was compared to primary endocrine therapy, there was no significant difference in the OS (HR 0.98, 95% CI 0.74-1.30, P = 0.9), but there was a significant difference in the PFS (HR 0.55, 95%CI 0.39-0.77, P = 0.0006). Similar results were seen in the surgery with endocrine therapy group vs primary endocrine therapy, with no significant difference in OS (HR 0.86. 95%CI 0.73-1.00, P = 0.06), but a significant difference in the PFS (HR 0.65, 95% CI 0.5300.81, P = 0.0001). This study demonstrates that although surgery (with or without endocrine therapy) may have comparable overall survival to primary endocrine therapy, primary endocrine therapy does not provide the same level of local control of breast cancer. Further trials addressing the hormone receptor status and using other forms of endocrine therapy such as aromatase inhibitors are needed to evaluate the appropriateness of primary endocrine therapy in older women.
The results of this meta-analysis will come as a surprise to few U.S. oncologists. It makes sense that primary endocrine therapy would be less effective at local control than surgery and also that overall survival may be no different. When it comes to patient management, U. S. surgeons and oncologists are often very conservative. One needs only to remember how long it took (nearly a century) to adopt the modified rather than radical mastectomy as the primary surgical approach for resectable breast cancer. Once again, it is a matter of local control, and this time, the meta-analysis would seem to favor the more aggressive, surgical approach.
Yet, optimal therapy for elderly patients with small, hormone receptor positive cancers remains to be defined. Like so many issues in geriatric medicine, patient heterogeneity presents problems when it comes to generalizing "standard" approaches. Women at the age of 70 may be very healthy, and for them optimal primary breast cancer therapy should probably be no different than younger patients. However, for those with substantial comorbidity, survival may be more a function of other factors and minor differences in the success of primary breast cancer management of lesser importance. For these patients, the risks of surgery, albeit typically minimal, may be exaggerated and the local control provided by tamoxifen or other hormonal approach may be an excellent choice. One thing that geriatricians emphasize in examining issues relevant to older patients is that patients should be examined in the context of functional status and not chronological age. The study that needs to be done (not included in the current meta-analysis) would be an assessment of primary hormonal therapy vs surgery in those post menopausal patients with 2 or more comorbidities associated with limitation in one or more of the activities of daily living. My guess is that hormonal therapy might come out on top in that trial.
1. Preece PE, et al. Br Med J. (Clin Res Ed). 1982;284:869-870.
2. Gaskell DJ, et al. Br J Surg. 1992;79:1317-1320.