Ovarian suppression

Initially achieved by surgical oophorectomy (9), this represents not only the first endocrine treatment option developed empirically at a time its mechanism of action was poorly understood, but also the first systemic treatment strategy for any cancer form. Subsequently replaced by ovarian irradiation (10), today ovarian suppression in general may be achieved through "medical oophorectomy" with so-called LH-RH analogues; see detailed description of compounds in (11). Interestingly, while specific LH-RH receptors have been identified in breast cancer (12), there is no direct evidence for a mechanistic role of LH-RH receptors in tumors during therapy with LH-RH analogues. While studies in meta-static disease have not revealed any difference in response rate between medical oophorectomy and surgical oophorectomy/irradiation (13), it should be recognized that this evidence is based on a limited number of studies involving a small number of patients.

Several issues remain unaddressed; while surgical and radiological ablation are irreversible, it is not clear for what duration LH-RH analogues should be administered either in the adjuvant setting or to long-term responders with metastatic disease. As continuous ovarian suppression is a requisite for many subsequent treatment options (including aromatase inhibitors), patients with metastatic disease responding to treatment with an LH-RH analogue may be candidates for subsequent surgical or radiological ablation, as subsequent second-line therapy with aromatase inhibitors requires suppression of ovarian function.

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