Association of Stein-Leventhal Syndrome with the incidence of postmenopausal breast carcinoma in a large prospective study of women in Iowa

A recent article by Anderson et al.1 published in Cancer reported the results from a cohort study including 472 women with a history of Stein-Leventhal syndrome (SLS). No association emerged between SLS and risk of breast carcinoma (14 cases overall). SLS is characterized by menstrual irregularities, infertility, a high level of androgens, and obesity, which are clinical and hormonal conditions associated with the risk of breast carcinoma. Other studies have shown inconsistent data regarding the association between SLS and the risk of breast carcinoma.2, 3 Thus, it is also important to examine further the issue in consideration of the recent hypothesis of an association between SLS and insulin resistance and hyperinsulinemia4 (i.e., possible risk factors for breast carcinoma). Therefore, we analyzed data from a large case-control study on breast carcinoma conducted between June 1991 and February 1994 in six Italian areas: the provinces of Pordenone and Gorizia, the urban areas of Milan and Genoa, the province of Forlì in northern Italy, the province of Latina near Rome in central Italy, and the urban area of Naples in southern Italy. Study methods have been described previously.5, 6 The cases studied were 2569 women (median age 55 years; range, 23-74 years) with incident (i.e., diagnosed within 1 year before the interview), histologically confirmed breast carcinoma who were admitted to the major teaching and general hospitals in the areas under surveillance. The controls were 2588 women (median age, 56 years; range, 20-74 years) who were admitted for acute conditions (22% for traumas, 33% for other orthopedic disorders, 16% for acute surgical conditions, 18% for eye disorders, and 12% for other diseases). The structured questionnaire included information on personal characteristics and habits, education and other socioeconomic factors, general lifestyle, habits such as smoking, alcohol, and coffee consumption, a food frequency section, and menstrual and reproductive history. A past history of 23 selected medical conditions or procedures also was elicited7; among these, information was collected on history of SLS Table 1. In this data set women with breast carcinoma were significantly more educated, reported fewer full term pregnancies, and were more often premenopausal than control subjects.4 Body mass index was associated inversely with breast carcinoma risk in premenopausal women, but was directly associated in postmenopausal women.6 To allow for the possible confounding or modifying effect of these factors in the computation of the odds ratio (OR) of breast carcinoma in women with SLS, we have included in the regression equations, in addition to design variables (i.e., study area and age in quinquennia), years of education (< 7, 7-11, and ≥ 12 years), parity (0, 1, 2, 3, and ≥ 4 births), quintile of body mass index, and, when appropriate, menopausal status. The distribution of cases and controls according to history of SLS and menopausal status is shown in Table 1. A total of 14 cases (0.5%) and 16 controls (0.6%) reported a history of SLS. The OR of breast carcinoma in women with a history of SLS was 0.8 (95% confidence interval [CI] 0.4-1.7) when the whole series was considered, and 1.0 (95% CI, 0.4-2.8) and 0.8 (95% CI, 0.3-2.4), respectively, when the analysis was conducted in strata of premenopausal and postmenopausal status. The main limitation of this data set is that the diagnosis of SLS was self-reported. However, interviewers were instructed to check information in clinical records and whenever inconsistencies emerged, to reinterview the cases and controls. Despite this limitation, these data confirm the lack of an association between SLS and the risk of breast carcinoma. A more consistent association between SLS (as a cause of high unopposed estrogen levels before menopause) and risk of endometrial carcinoma has been reported.8 Therefore, hormonal factors may act on breast carcinogenesis in a different and more complex manner. Fabio Parazzini M.D.*, Carlo La Vecchia M.D. , Silvia Franceschi M.D. , Renato Talamini Sc.D.?, Eva Negri M.D.?, Pier Giorgio Crosignani Sc.D.**