Still Waiting After 110 Years: The Optimal Use of Ovarian Ablation As Adjuvant Therapy for Breast Cancer

摘要: Although Schinzinger first suggested that oophorectomy might be used to treat breast cancer in 1889, it is Sir George Beatson who associated with its establishment as an effective therapeutic modality based on his seminal 1896 Lancet publication describing successful treatment of young women advanced bilateral oophorectomy. Studies surgical were followed by those assessing ovarian irradiation, leading ultimately the 1948 launch at Christie Hospital (Manchester, United Kingdom) randomized trial ablation (OA) using irradiation versus no OA for premenopausal operable cancer. By 1960s, many considered adjuvant cancer, but interest subsided demonstration efficacy chemotherapy and belief failed alter survival women. This view was challenged serial reports Early Breast Cancer Trialists’ Collaborative Group showing or suppression (OS) offered unequivocal benefit compared therapy under 50 years age. In addition, suppressive ablative effects recognized, which raised possibility benefits mediated part indirect ovary estrogen deprivation. These observations led a generation trials OA/OS surgery, radiotherapy, luteinizing hormone–releasing hormone agonists addition chemotherapy. this issue, Ejlertsen et al report long-term outcome patients treated such trial, Danish Cooperative (DBCG) Trial 89B. study randomly assigned 762 steroid receptor–positive early deemed high risk recurrence (axillary nodal involvement tumor size 5 cm) receive pelvic form nine courses cyclophosphamide, methotrexate, fluorouracil (CMF) intravenously every 3 weeks. Both therapies well tolerated, there apparent difference overall after median follow-up time 10.5 358 events (hazard ratio 1.11; 95% CI, 0.88 1.42). The unique strengths include maturity, exclusion known receptor–negative are unlikely from endocrine therapy, focus essentially node-positive population recurrence, uniform approach therapy. Potential limitations use regimen some consider substandard era taxanes anthracyclines, failure incorporate tamoxifen, elements statistical design power. DBCG 89B investigators noninferiority test hypothesis not inferior Active-control often when choice placebo-controlled unethical. However, type challenging because need define acceptable margin inferiority reduce introducing potentially suboptimal into clinical practice while maintaining reasonable sample size. predefined 750 chosen permitted detection 25% relative decrease disease-free clinically unacceptable twosided testing 5% 20%. observed unadjusted hazard estimate 0.99 (95% 0.81 1.22; P .95) rejects null inequality supports alternative equality. upper boundaries CIs do rule out possible 22% greater 42% CMF, raises question whether adequately powered address meaningful way. Nonetheless, conclusion radiationinduced CMF have similar effect receptor-positive likely correct. joins four other published studies comparing goserelin, leuprolide variations shown results hormone-responsive disease. only exclusively induce excluded disease (although enrolled subjects had unknown receptor status), thereby limiting inclusion expected gain nothing derive A tragedy all these trials, concurrent tested OA/OS, they tamoxifen prevailing JOURNAL OF CLINICAL ONCOLOGY E D I T O R L VOLUME 24 NUMBER 31 NOVEMBER 1 2006