Journal of Steroid Biochemistry & Molecular Biology 86 (2003) 107–109 Rapid communication Is there a benefit by the sequence anastrozole–formestane for postmenopausal metastatic breast cancer women? Paolo Carlini a,∗ , Gianluigi Ferretti a , Serena Di Cosimo a , Elvira Colella a , Riccardo Tonachella a , Adriana Romiti b , Silverio Tomao b , Antonio Frassoldati c , Paola Papaldo a , Alessandra Fabi a , Enzo Maria Ruggeri a , Francesco Cognetti a a Department of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi 53, Rome, Italy b Department of Experimental Medicine and Pathology, University of “La Sapienza”, Rome, Italy c Division of Medical Oncology, University of Modena, Modena, Italy Received 15 January 2003; accepted 17 April 2003 Abstract To explore the different sequence interactions between reversible non-steroidal (anastrozole, ANZ and letrozole, LTZ) and non-reversible steroidal aromatase inhibitors (formestane, FOR and exemestane, EXE), we evaluated the clinical benefit (CB) in postmenopausal breast cancer patients, who had previously received anastrozole and subsequently formestane. In 19 out of 21 patients (90.5%), a clinical benefit response was achieved by anastrozole, with a median duration of 12 months. Out of the 21 women progressing on anastrozole, 12 achieved stable disease (SD) ≥ 6 months by formestane only. The overall clinical benefit was 66.5%. The median duration of clinical benefit was 11 months with a time to progression of 6.5 months. The median duration of clinical benefit in our series is similar to that reported in two phase II trials with the sequence aminogluthetimide → formestane and aminogluthetimide → exemestane as third-line hormonal therapy, suggesting a non-cross-resistance between the two classes of inhibitors. © 2003 Elsevier Ltd. All rights reserved. Keywords: Postmenopausal metastatic breast cancer (PMBC); Anastrozole; Formestane 1. Introduction Anastrozole (ANZ), letrozole (LTZ), and exemestane (EXE) are effective first-line treatment for patients with endocrine responsive metastatic breast cancer [1]. Patients treated with a first-line aromatase inhibitor are likely to ac- quire drug-resistance and the most appropriate second-line endocrine therapy has not been established so far. Tamoxifen may be an effective second-line therapy in advanced breast cancer refractory to ANZ [2]. In a study by Harper-Wynne and Coombes [3], 9 out of 12 postmenopausal metastatic breast cancer (PMBC) women, previously showing a clin- ical benefit (CB) by formestane (FOR), achieved further stable disease (SD) by ANZ. It has been suggested that FOR markedly inhibits the aromatase activity even though pre-treatment with ANZ produces an increase of this activity [4]. ∗ Corresponding author. Tel.: +39-06-52666919; fax: +39-06-52665637. E-mail address: pcarlini@iol.it (P. Carlini). 2. Patients and methods To explore the different sequence interactions between re- versible non-steroidal (ANZ and LTZ) and non-reversible steroidal aromatase inhibitors (FOR and EXE), we evalu- ated the clinical benefit (CB = CR + PR + SD ≥ 6 months), according to the British Breast Group recommendations [5], in PMBC patients who had previously received ANZ 1 mg per day and subsequently, FOR 250 mg biweekly from 1996 to 2000. The patients received FOR if they showed PD af- ter at least 12 weeks or more since they started receiving ANZ. The median age of the 21 patients identified at the time of FOR initiation was 64 years. Nineteen out of 21 pa- tients received FOR after ANZ, with no other concomitant treatment. The remaining two patients received FOR and first-line chemotherapy after ANZ. Eighteen patients had previously received adjuvant therapy (6 on tamoxifen and chemotherapy, 10 only on tamoxifen, 2 only on chemother- apy) and 9 patients received first-line chemotherapy before ANZ. 0960-0760/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0960-0760(03)00249-8