{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:33:16Z","timestamp":1791729196279,"version":"4.3.4"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Several researchers have claimed that classification of tumours on the basis of HER-2\/<jats:italic>neu<\/jats:italic> overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2\/<jats:italic>neu<\/jats:italic> positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1996 and 2002. 384 women with primary invasive breast cancer were compared with 566 screened women who were referred to the Unit and had not developed breast neoplasm by the time the data were analysed. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2\/<jats:italic>neu<\/jats:italic> protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to measure the risk heterogeneity between HER-2\/<jats:italic>neu<\/jats:italic>+ and HER-2\/<jats:italic>neu<\/jats:italic>-tumours. Separate analyses were performed for premenopausal and postmenopausal women and according to estrogen receptor status.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>In multivariate analysis without HER-2\/<jats:italic>neu<\/jats:italic> stratification, an increased breast cancer risk was associated with only <jats:italic>four<\/jats:italic> of the factors examined: use of oral contraceptives (OR = 4.40, 95%C.I: 1.46\u201313.28), use of HRT (OR = 7.34, 95%C.I: 2.03\u201326.53), an age at first full pregnancy more than 23 years (OR = 1.91, 95%C.I: 1.29\u20132.83) and body mass index more than 29 kg\/m<jats:sup>2<\/jats:sup> (OR = 3.13, 95%C.I: 2.02\u20134.84). Additionally, a history of abortion or miscarriage (OR = 0.56, 95%C.I: 0.38\u20130.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI &gt;29 kg\/m<jats:sup>2<\/jats:sup> revealed a relative connection that was stronger with positive than with negative HER-2\/<jats:italic>neu<\/jats:italic> tumours (ratio of OR's = 2.23, 95%C.I: 1.20\u20134.15, p = 0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy &gt;23 years and a BMI &gt;29 kg\/m<jats:sup>2<\/jats:sup> were associated with an increased risk in both HER-2\/<jats:italic>neu<\/jats:italic> groups, but the association was significantly stronger for the latter factor in the positive HER-2\/<jats:italic>neu<\/jats:italic> tumours (ratio of OR's = 2.46, 95%CI: 0.97\u20136.21).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our study did not confirm that the established or putative hormonal breast cancer risk factors differ regarding their relations with HER-2\/<jats:italic>neu<\/jats:italic>+ versus HER-2\/<jats:italic>neu<\/jats:italic>-breast tumours, with the exception of increased BMI. Further innovative studies with larger sample sizes are needed to examine how the status of these potentially modifiable breast cancer risk factors interacts with biological markers such as HER-2\/<jats:italic>neu<\/jats:italic> oncoprotein.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1472-6874-5-1","type":"journal-article","created":{"date-parts":[[2005,2,5]],"date-time":"2005-02-05T07:25:12Z","timestamp":1107588312000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Correlation of breast cancer risk factors with HER-2\/neu protein overexpression according to menopausal and estrogen receptor status"],"prefix":"10.1186","volume":"5","author":[{"given":"Nikos","family":"Tsakountakis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Sanidas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios","family":"Stathopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kafousi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nektaria","family":"Anogiannaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Georgoulias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris D","family":"Tsiftsis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"69_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/BF02106570","volume":"13","author":"R Callahan","year":"1989","unstructured":"Callahan R: Genetic alterations in primary breast cancer. 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