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A point mutation in the estrogen receptor alpha gene, <jats:italic>ESR1<\/jats:italic>, referred to as A908G or K303R, was originally identified in breast hyperplasias and was reported to be hypersensitive to estrogen. We recently detected this mutation at a low frequency of 6% in invasive breast tumors of the Carolina Breast Cancer Study (CBCS).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>In this report, we evaluated risk factors for invasive breast cancer classified according to the presence or absence of the <jats:italic>ESR1<\/jats:italic> A908G mutation in the CBCS, a population-based case-control study of breast cancer among younger and older white and African-American women in North Carolina. Of the 653 breast tumors evaluated, 37 were <jats:italic>ESR1<\/jats:italic> A908G mutation-positive and 616 were mutation-negative.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p><jats:italic>ESR1<\/jats:italic> A908G mutation-positive breast cancer was significantly associated with a first-degree family history of breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to 6.28), whereas mutation-negative breast cancer was not. Comparison of the two case subgroups supported this finding (OR = 2.65, 95% CI = 1.15 to 6.09). There was also the suggestion that longer duration of oral contraceptive (OC) use (OR = 3.73, 95% CI = 1.16 to 12.03; <jats:italic>P<\/jats:italic><jats:sub>trend<\/jats:sub> = 0.02 for use of more than 10 years) and recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; <jats:italic>P<\/jats:italic><jats:sub>trend<\/jats:sub> = 0.10 for use within 10 years) were associated with <jats:italic>ESR1<\/jats:italic> A908G mutation-positive breast cancer; however, ORs for comparison of the two case subgroups were not statistically significant. Hormone replacement therapy use was inversely correlated with mutation-negative breast cancer, but the effect on mutation-positive cancer was unclear due to the small number of postmenopausal cases whose tumors carried the mutation. Mutation-negative breast cancer was associated with several reproductive factors, including younger age at menarche (OR = 1.46, 95% CI = 1.09 to 1.94) and greater total estimated years of ovarian function (OR = 1.82, 95% CI = 1.21 to 2.74).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>These preliminary results suggest that OCs may interact with the <jats:italic>ESR1<\/jats:italic> A908G mutant receptor to drive the development of some breast tumors.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr1731","type":"journal-article","created":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T18:13:31Z","timestamp":1181153611000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation"],"prefix":"10.1186","volume":"9","author":[{"given":"Kathleen","family":"Conway","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloise","family":"Parrish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon N","family":"Edmiston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn","family":"Tolbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiu-Kit","family":"Tse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Moorman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Newman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C","family":"Millikan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,6,6]]},"reference":[{"key":"1696_CR1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/oxfordjournals.epirev.a036102","volume":"15","author":"MC Pike","year":"1993","unstructured":"Pike MC, Spicer DV, Dahmoush L, Press MF: Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. 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