Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy

Postmenopausal women with large primary oestrogen receptor-rich (>20 fmol/mg protein or 80 histoscore) breast cancers have been treated neoadjuvantly with either letrozole (2.5 or 10 mg daily n=12 in each case) or anastrozole (1 or 10mg daily n=12 and 11, respectively). Tumour was available for analysis before treatment (wedge biopsy) and 3 months later at definitive surgery (wide local excision or mastectomy). Clinical response to treatment was assessed by sequential measurements of tumour volume based on caliper assessment, ultrasound and mammography. Results showed that in these selected groups of patients a reduction in tumour volume with treatment was observed in 43 of 47 cases (91%). Pathological responses, i.e. clear decrease in tumour cellularity or increased fibrosis was evident in 32 cases (68%). Furthermore, there was a decrease with therapy in immunohistochemical staining for Ki67 in all tumours. Staining for progesterone receptor (PgR) was reduced in all 21 PgR-positive cancers treated with letrozole and in 16 of 17 positive cancers treated with anastrozole. These effects are at least as great as those seen in a non-randomised group of patients treated with tamoxifen over the same time period (additionally tamoxifen treatment was often associated with an increase in PgR staining). The results suggest that potent specific aromatase inhibitors will be valuable in treating hormone-dependent cancers.