{'fraction_non_alphanumeric': 0.027088897367417018, 'fraction_numerical': 0.017932086989698587, 'mean_word_length': 5.069444444444445, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Tamoxifen and estrogen replacement therapy as agents of disease prevention.

In the August 15, 1990, issue of the Journal, Love et al (7) provide important information on the effects of tamoxifen on blood cholesterol. In an accompanying article, Prentice (2) correctly suggests that a major determinant of tamoxifen's ultimate value as a breast cancer preventive agent will be its effect on coronary heart disease, and estimates a 40% reduction based on the cholesterol results. Prentice noted, however, that the data relating cholesterol to the risk of coronary heart disease in women are relatively sparse, making this estimate imprecise. Moreover, cholesterol changes may be only one aspect of the effect of tamoxifen on the risk of coronary heart disease. At the recent NIH Consensus Development Conference on Early Stage Breast Cancer, Stewart (3) presented an update of the Scottish adjuvant tamoxifen trials, with follow-up ranging from 5 to 11 years. In these studies, tamoxifen was administered at a dose of 20 mg/d for at least 5 years. Among postmenopausal women, there were 18 deaths due to acute myocardial infarction in the 267 control patients compared with 5 such deaths in the 266 tamoxifen-treated patients. Because this is an approximately 70% reduction in the number of deaths due to acute myocardial infarction (with wide confidence intervals), confirmation of these results is clearly needed. Estrogen replacement therapy is also proposed as a disease prevention agent and has been estimated from epidemiological studies to provide a 48% reduction in the risk of coronary heart disease (4). Table 1 shows our current estimates of the effects of long-term use of tamoxifen and estrogen replacement therapy on mortality from relevant conditions. In constructing this table, we have, whenever possible, attempted to limit our consideration to studies employing tamoxifen for at least 5 years, as the effects may well differ with short-term use. Since tamoxifen appears to preserve bone (5), we have assumed that the effect of tamoxifen on mortality due to osteoporotic fractures is equivalent to that in users of estrogen replacement therapy. Although one trial that used 40 mg of tamoxifen per day suggested an increased incidence of endometrial cancer (6), other studies using 20 mg per day have not (3). The effect of tamoxifen on the subsequent incidence of breast cancer is conservatively estimated to be a 50% reduction: the two current, long-term adjuvant tamoxifen trials show approximate reductions of 57% (National Surgical Adjuvant Breast and Bowel Project, ref. 7) and 56% (Scottish trials,