Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10851 comparing tamoxifen alone with modified radical mastectomy. Prospective randomized trial of tamoxifen vs surgery in elderly patients with breast cancer. Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial.
For treatment of early breast cancer in older women, little evidence is available from randomised trials. We conducted a randomised trial comparing modified radical mastectomy (MRM) with tamoxifen (TAM) as the sole initial therapy in 164 patients aged >/=70 years with operable breast cancer. 82 were treated by MRM and 82 with TAM. Survival curves were estimated using the Kaplan-Meier method: multivariate analyses were performed using the Cox's proportional hazards model. Endpoints included survival, time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. After a median follow-up of approximately 10 years, there was a significantly decreased time to progression in the TAM only group (logrank P<0.0001) and significantly shorter time to local progression within the TAM group (logrank P<0.0001). Overall survival of the two groups was similar. The results indicate that tamoxifen alone leads to an unacceptably high rate of local progression or relapse. Between 1982 and 1989, 200 patients aged 70 or over seen in one Breast Unit, who were considered to have a surgically resectable cancer of the breast were prospectively randomized to primary surgery or tamoxifen 20 mg per day. At a median follow-up of 6 years (range 3-11 years) and at the censoring date there were 61 first events in the tamoxifen group. Fifty three patients developed local relapse or progression of the cancer; three patients had simultaneous local progression or relapse and distant metastases. In addition a further five patients developed distant recurrence only. In the surgical arm there were 50 events. Thirty-six patients developed local recurrence only; eight had simultaneous local and distant recurrence. A further six patients developed distant metastases of which two subsequently developed local recurrence. There were 33 deaths in the tamoxifen group and 28 deaths in the surgical group of which 17 and 15, respectively were directly attributable to breast cancer. The disease-free interval did not differ between the two groups. Following treatment with tamoxifen, at the censoring date which was the date of last clinical examination or arbitrarily, the date of death, 39 patients had no evidence of relapse whereas in the surgical arm there were 50 patients who had no evidence of recurrence. Fifty-three patients in the tamoxifen arm had local relapse only and were available for crossover to surgery, 39 accepted surgery. Eight developed further local recurrence, 10 developed distant metastases and 21 remained free of disease. Thirty-six patients in the surgical group developed local relapse only and were available for crossover to tamoxifen. Thirty one accepted treatment with tamoxifen, 14 had progression of their local recurrence, seven developed distant metastases and 10 had no further recurrence. Thus in the tamoxifen group, 39 had no progression of their disease and a further 21 benefited from subsequent surgery: 60% in all. In the surgical group 50 had no recurrence of their disease and a further 10 benefited from subsequent tamoxifen therapy: 60% in all. To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen.
                Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease.
                Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation.
                The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.
Primary endocrine therapy should only be offered to women with oestrogen receptor (ER) positive tumours who are unfit for or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.