ArticlesPrevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women
Introduction
The idea of interfering with the initiation and promotion ofbreast cancer by means of pharmaceutical compounds (chemoprevention) arose about a decade ago. There are many experimental and epidemiological data to support the use of tamoxifen as a chemopreventive. This drug has both oestrogenic and antioestrogenic properties.1, 2 These properties, including reduction of circulating insulin-like growth factor 1, inhibition of angiogenesis, and induction of apoptosis, help explain the otherwise unexpected response to tamoxifen seen in oestrogen-receptor-negative, postmenopausal women.3 Women with breast cancer have a 2–3-fold increased risk of contralateral breast cancer. In the randomised trials with adjuvant tamoxifen of breast cancer, the incidence of contralateral breast cancer decreased by around one-third.3, 4, 5, 6, 7, 8, 9, 10 This result, and the good safety profile in cancer patients based on large numbers of women with long follow-up, put tamoxifen among the front runners for evaluation as a chemopreventive in breast cancer.
However, side-effects of tamoxifen include an increased occurrence of endometrial cancer.8, 9. In view of this potential adverse event, we undertook a randomised trial in women who had had a hysterectomy. Such women have a reduced risk of breast cancer when there has been an associated bilateral oophorectomy.10
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Participants and inclusion and exclusion criteria
The Italian Tamoxifen Prevention Study includes healthy women aged 35–70 who had had a total hysterectomy for reasons other than neoplasm. Women were recruited via national advertising and also from direct contact with gynaecologists throughout Italy (with a minority of cases recruited from abroad). Women with severe concurrent illness or history of cardiac disease were excluded from randomisation. Endometriosis and suspected or certain previous deep-vein thrombosis were also exclusion
Results
The study involves 55 participating centres, of which 51 were in Italy, three in South America (Brazil two, Argentina one), and one in Greece. Most patients (5230, 96·7%) were recruited in Italian centres.
5408 women were randomised (figure 1), with a median age of 51 years (table 1). 3837 women are still on treatment. The overall median time on study intervention is 30·5 months. 1422 women dropped out of the study, and 149 have completed 5 years of treatment. For deaths, cancer diagnosis, and
Discussion
The principal investigators were concerned about the large numbers of women withdrawing from the study, the unexpected finding with hypertriglyceridaemia, the findings about vascular events, and the number of well women complaining about the side-effects of tamoxifen. In agreement with the data-monitoring committee, we ended recruitment in June, 1997. The study investigators were informed during the 6-monthly meeting (held on July 11, 1997), of the decision to end recruitment to the trial
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