It is commonly thought that chemotherapy results in higher response rates and more rapid responses than endocrine therapy, and is often used as the initial treatment for patients with hormone receptor-positive metastatic breast cancer with a poor prognosis, especially those with visceral metastases. A meta-analysis that included eight small randomized trials, all published prior to 1995, compared the response rates for chemotherapy alone with those of endocrine therapy alone . The pooled estimate of response rates showed an advantage for chemotherapy over endocrine therapy (relative risk 1.25, 95% CI 1.01 to 1.54), although the two largest trials had opposite findings [66,67]. No significant difference was seen in overall survival (hazard ratio, HR 0.94, 95% CI 0.79 to 1.12), and on subset analysis, there was no obvious trend to suggest an effect of age, menopausal status, or pattern of metastatic disease on the efficacy of either therapy. There was minimal and contrasting information on quality of life and toxicity.
A major limitation to these findings is that most patients in these trials had tumors of unknown hormone receptor status, since the predictive value of hormone receptor status on response to endocrine therapy was not yet appreciated. Nevertheless, chemotherapy remains the preferred modality for initial treatment of patients with rapidly progressive symptomatic disease or visceral crisis (end-organ dysfunction), given the higher likelihood of achieving a response with chemotherapy.
No survival benefit has been seen when chemotherapy and endocrine therapy were combined.
TIChemotherapy alone versus endocrine therapy alone for metastatic breast cancer.
AUWilcken N, Hornbuckle J, Ghersi D
SOCochrane Database Syst Rev. 2003;
BACKGROUND: Both chemotherapy and endocrine therapy can be used as treatments for metastatic breast cancer.
OBJECTIVES: To review the evidence and determine whether chemotherapy or endocrine therapy has the most beneficial effect on treatment outcomes (survival, response rate, toxicity and quality of life).
SEARCH STRATEGY: The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 16th September 2002 using the codes for "advanced breast cancer", "chemotherapy" and "endocrine therapy". Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library.
SELECTION CRITERIA: Randomised trials comparing the effects of chemotherapy alone with endocrine therapy alone on pre-specified endpoints in metastatic breast cancer.
DATA COLLECTION AND ANALYSIS: Data were collected from published trials. Hazard ratios were derived for survival analysis and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present.
MAIN RESULTS: The primary analysis of overall effect using hazard ratios derived from published survival curves involved six trials (692 women). There was no significant difference seen (HR=0.94, 95%CI 0.79-1.12, p=0.5). A test for heterogeneity was p=0.1. A pooled estimate of reported response rates in eight trials involving 817 women shows a significant advantage for chemotherapy over endocrine therapy with RR=1.25 (1.01-1.54, p=0.04). However the two largest trials showed trends in opposite directions, and a test for heterogeneity was p=0.0018. There was little information available on toxicity and quality of life. Six of the seven fully published trials commented on increased toxicity with chemotherapy, mentioning nausea, vomiting and alopecia. Three of the seven mentioned aspects of quality of life, with differing results. Only one trial formally measured quality of life, concluding that it was better with chemotherapy.
REVIEWER'S CONCLUSIONS: In women with metastatic breast cancer and where hormone receptors are present, a policy of treating first with endocrine therapy rather than chemotherapy is recommended except in the presence of rapidly progressive disease.
ADDepartment of Medical Oncology, Westmead Hospital, Westmead, NSW, Australia.XXX@XXXXXX.XXX
TICombination chemotherapy compared to tamoxifen as initial therapy for stage IV breast cancer in elderly women.
AUTaylor SG 4th, Gelman RS, Falkson G, Cummings FJ
SOAnn Intern Med. 1986;104(4):455.
In a randomized crossover study, 181 patients over the age of 65 with recurrent breast cancer received either tamoxifen or cyclophosphamide, methotrexate, and fluorouracil (CMF). After progression on tamoxifen, a hormone withdrawal period was required. Because of altered pharmacokinetics with aging, creatinine clearance was used in calculating the dose of CMF. Response rates were 45% on tamoxifen and 38% on CMF, with median durations of 10.4 and 7.9 months, respectively. Survival rates tended to favor tamoxifen as the initial treatment even in estrogen-receptor-negative patients. Additional disease control with hormone withdrawal occurred in 23% of patients, and this benefit was highly correlated with prior hormone response. We conclude that initiation of hormone therapy rather than CMF chemotherapy is justified in almost all situations in elderly patients, and combination chemotherapy, is safe and useful after hormone failure if modified on the basis of renal dysfunction.
TIA randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia.
SOJ Clin Oncol. 1986;4(2):186.
A prospective randomized clinical trial was performed in 339 postmenopausal patients with advanced breast cancer. Two single modality treatment sequences, doxorubicin plus cyclophosphamide (AC) followed on failure by tamoxifen (TAM), and TAM followed by AC, were compared with combined modality chemo-endocrine therapy (TAM plus AC). The response rate to initial TAM (22.1%) was inferior to that for AC (45.1%), and for TAM plus AC (51.3%). However, patients randomized to the sequence TAM followed by AC showed a 42.5% overall tumor response to sequential protocol therapy, similar to the 46.9% for those randomized to AC followed by TAM. Furthermore, survival in all three arms was almost identical. Adverse prognostic factors for survival were liver metastases, short disease-free interval, poor performance status, and prior adjuvant chemotherapy. In no subgroup was significantly better survival associated with initial cytotoxic therapy. Endocrine therapy followed on failure by cytotoxics is appropriate for postmenopausal patients with advanced breast cancer.