Oophorectomy and Gonadotropin Releasing Hormone Analogue

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The sporadic use of adjuvant oophorectomy after breast cancer surgery in younger women was continued by surgeons for many years in the hope of preventing recurrence. Randomized trials looking at its value date back 50 years.37 Unfortunately, these early trials suffer from the lack of hormone responsiveness of most breast cancers in premenopausal women and they predate our ability to predict responsiveness with hormone receptor measurements. The EBCTCG conducted overview meta-analyses of adjuvant oophorectomy in 1985, 1990, and 1995. The most recent overview encompassed 12 trials randomizing 2,100 women to surgical or radiation oophorectomy versus no castration.38 In women under the age of 50 years, oophorectomy resulted in an 18 percent relative decrease in recurrence, an 18 percent relative decrease in death, and, at 15 years after surgery, an absolute decrease of 6.3 percent in death from any cause, compared with women not getting the procedure (p < .001).38 The relative benefit was the same in node-negative and node-positive patients.38 These results are very similar to the chemotherapy meta-analysis results. Furthermore, in a Scottish trial, adjuvant CMF was compared with oophorectomy in premenopausal women with node-positive disease.39 There was no difference seen in the overall result. In women with receptor-positive tumors, the trend was the superiority of castration; in receptor-negative disease CMF appeared better.

In the United States, adjuvant surgical castration is rarely done these days, with tamox-ifen the preferred adjuvant hormonal approach in younger women (if any hormonal approach is used). The introduction of gonadotropin-releasing hormone (GnRH) analog has the potential to change this practice. These drugs, when given by slow-release depot injection, continually stimulate the pituitary, eventually depleting it of FSH and LH. This results in the cessation of ovarian function, achieving a biochemical oophorectomy.7 The GnRH analog, goserelin (Zoladex) and leuprolide (Lupron) have antitumor activity comparable with oophorectomy and with tamoxifen against overt hormone-responsive metastatic disease in premenopausal women.40 Furthermore, their action on the ovary is reversible. Currently, the European "ZEBRA" study is comparing adjuvant goserelin with chemotherapy in pre-menopausal women. Despite its proven efficacy as adjuvant therapy in younger women, oophorectomy is unlikely to be widely accepted in the United States.

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