A Randomized Clinical Trial Evaluating Tamoxifen in the Treatment of Patients with Node-Negative Breast Cancer Who Have Estrogen-Receptor–Positive Tumors

Abstract

We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen; P = 0.3). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent; P less than 0.00001). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation. The benefit was attained with a low incidence of clinically appreciable toxic effects. The magnitude of the improvement obtained does not preclude the need for future trials in which patients given tamoxifen could serve as the control group in an evaluation of potentially better therapies. Tamoxifen treatment is justified in patients who meet the eligibility criteria of the present study and who refuse to participate in those trials. Since patients with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not eligible for this study, no information is available to indicate that such patients should receive tamoxifen.

Delay to formalin fixation effect on breast biomarkers

“…The use of endocrine therapy for breast cancer treatment has been shown to have a dramatic impact on improving Delay to formalin fixation effect T Khoury et al disease-free survival and overall survival. 22 A negative result might suggest that the patient would benefit from cytotoxic chemotherapy alone or indicate that the patient requires no systemic therapy. Trastuzumab is given to patients who are found to have overexpression of HER2.…”

Tamoxifen reduces plasma homocysteine levels in healthy women

“…Hyperhomocysteinaemia is a risk factor not only for atherothrombotic diseases but also for venous thrombosis (Falc6n et al, 1994;den Heijer et al, 1996). Thus, the sporadic risk of venous thromboembolism observed in breast cancer patients treated with tamoxifen (Fisher et al, 1989;McDonald et al, 1995) could be ascribed to the drug inhibitory effect on plasma antithrombin III (Mannucci et al, 1996) or to its partial agonistic effects on other oestrogen-regulated target systems, possibly outweighing the protective effect due to the decrease in tHcy levels.…”

“…In light of the partial agonistic activity, which reflects the complex regulation of oestrogen signalling in the body (Pennisi, 1996), tamoxifen treatment has also been associated with a reduction in coronary heart disease (Rutqvist et al, 1993;McDonald et al, 1995), prevention of bone density loss (Love et al, 1992), sporadic excess of venous thromboembolism (Fisher et al, 1989;McDonald et al, 1995) and endometrial cancer (Rutqvist et al, 1987;Fisher et al, 1994) in adjuvant clinical trials.…”

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

“…Adjuvant therapy to reduce the risk of late recurrences appears to be beneficial in both breast and colorectal carcinoma (Fisher et al, 1989;Moertel et al, 1990). The detection of occult tumour cells in the peripheral blood of patients with solid tumours may be important in two different clinical situations.…”