Antitumour and biological effects of letrozole and GnRH analogue as primary therapy in premenopausal women with ER and PgR positive locally advanced operable breast cancer

Preoperative endocrine therapy is effective in postmenopausal patients with breast cancers expressing oestrogen receptor. We investigated the activity of primary therapy with letrozole in combination with GnRH analogue in premenopausal women with T2-T4 N0-N2 breast cancer, whose tumours expressed oestrogen and progesterone receptors. We measured the expression of molecular factors involved in responsiveness to endocrine agents including ER alpha, EGFR, HER2, MAP kinases ( and phosphorylated forms) ER-beta I, both at initial biopsy and at the time of surgery. Thirty-five patients were included and 32 patients were evaluable for response. Sixteen patients (50%, 95% CI 32-68%) obtained a partial response, 16 patients were stable. One patient showed pathological complete response (3%, 95% CI 0-16%). Response was significantly associated with younger age (P < 0.05) and a longer duration of treatment (P < 0.05). Treatment significantly decreased ER alpha-p-Ser 118 and upregulated ER-beta 1, independently of response. No or negligible overexpression of EGFR was observed at baseline or after treatment in this population. Preoperative letrozole and GnRH analogue are effective in premenopausal women. A biological response in terms of downregulation of phosphorylated ERa was observed in all patients. Future investigations might focus on treatments of longer duration