GnRH analogues and ovarian ablation: their integration in the adjuvant strategy

Ovarian ablation, either by surgery or radiation, has been clearly shown to be an effective adjuvant therapy for pre-menopausal women following breast cancer surgery. The 1995 Oxford Overview confirmed this effect in trials of ovarian ablation compared to no other systemic adjuvant therapy. In trials of chemotherapy plus ovarian ablation compared to the same chemotherapy alone, however, the addition of ovarian ablation, although tending to add benefit, did not achieve a statistically significant positive effect. Data exist from a variety of randomized trials of adjuvant chemotherapy suggesting that pre-menopausal women who become amenorrhoeic after chemotherapy achieve a better outcome than those who continue to menstruate. These data are not consistent among all trials, however. There are few trials that compare ovarian ablation directly to chemotherapy, but those few that exist, as well as indirect comparisons, suggest that the effects of ovarian ablation, particularly in estrogen-receptor-positive women, are similar in magnitude to those of chemotherapy. Several large trials comparing chemotherapy to the LH-RH analogue Zoladex (goserelin) and studying the addition of Zoladex to adjuvant chemotherapy will be available by 1999 or 2000 and will provide considerable additional information on this matter.