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McGuire in the studies conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The historical information reported here reflect the memories of Drs. Richard J. Santen and Laurence L. Demers and comprehensive documentation provided in the literature references cited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The project of development of aromatase inhibitors began with the mis-assumption that the regimen of aminoglutethimide and hydrocortisone represented a \u201cmedical adrenalectomy\u201d and primarily represented the blockade of adrenal steroidogenesis. Later studies demonstrated that aminoglutethimide blocked the aromatase enzyme by 95\u201398%. A key research step involved isotopic kinetic studies in post-menopausal women using\n                      <jats:sup>3<\/jats:sup>\n                      H-androstenedione and\n                      <jats:sup>14<\/jats:sup>\n                      C estrone to precisely measure aromatase under equilibrium conditions. Dr. William L. McGuire provided major advice to the investigators, suggested enlistment of key collaborators, provided laboratory assistance in measuring ER levels, and facilitated funding for the studies. Observational studies involved 147 patients treated with the AG\/HC regimen and the results demonstrated efficacy of the regimen. Later, randomized controlled trials demonstrated the equivalence of this regimen to surgical adrenalectomy and tamoxifen. In order eliminate the need for HC, three selective inhibitors of aromatase were developed and shown to induce remissions statistically significantly greater than achieved with the anti-estrogen, tamoxifen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These studies provided definitive evidence of the superiority of aromatase inhibitors over tamoxifen in postmenopausal women with hormone responsive breast cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10549-026-08059-4","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T07:17:12Z","timestamp":1787210232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["History of the early development of aromatase inhibitors for treatment of breast cancer"],"prefix":"10.1007","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-5192","authenticated-orcid":false,"given":"R. 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