Serrano Davide, Johansson Harriet, Bertelsen Bjørn-Erik, Gandini Sara, Mellgren Gunnar, Thomas Parijatham, Crew Katherine D, Kumar Nagi B, Macis Debora, Aristarco Valentina, Guerrieri-Gonzaga Aliana, Lazzeroni Matteo, D'Amico Mauro, Buttiron-Webber Tania, Briata Irene Maria, Spinaci Stefano, Galimberti Viviana, Vornik Lana A, Villar-Sanchez Eduardo, Brown Powel H, Heckman-Stoddard Brandy M, Szabo Eva, Bonanni Bernardo, DeCensi Andrea
Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, Italy.
Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
J Natl Cancer Inst. 2024 Dec 1;116(12):1979-1982. doi: 10.1093/jnci/djae183.
The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a presurgical study of alternative exemestane schedules. Postmenopausal women candidates for breast surgery for estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg once daily (QD), 25 mg 3 times/week (TIW), or 25 mg per week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in nonmalignant tissue. Estradiol was nearly suppressed in all groups in the nonmalignant tissue (QD vs TIW P = .364 and QD vs QW P = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in nonmalignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy. Trial Registration: Clinical Trials.gov NCT02598557 and EudraCT 2015-005063-1.
该药物在靶组织中的活性有助于确定促进癌症预防治疗的最小有效剂量。在此，我们展示了来自一项关于依西美坦替代给药方案的术前研究中乳腺组织内的依西美坦和性激素浓度。因雌激素受体阳性乳腺癌而准备接受乳腺手术的绝经后女性被随机分配，在手术前4 - 6周每天一次服用25毫克依西美坦（QD）、每周三次服用25毫克（TIW）或每周一次服用25毫克（QW）。使用QTRAP 6500 +液相色谱 - 串联质谱系统从匀浆冷冻组织中分析药物和性激素。仅在QD组的非恶性组织中检测到较高浓度的组织药物浓度。在非恶性组织中，所有组的雌二醇几乎都受到抑制（QD组与TIW组比较，P = 0.364；QD组与QW组比较，P = 0.693）。相比之下，在癌组织中观察到剂量反应趋势。基于非恶性组织中雌二醇的抑制情况，应探索更低剂量的依西美坦给药方案用于乳腺癌预防治疗。试验注册：ClinicalTrials.gov NCT02598557和EudraCT 2015 - 005063 - 1。
