ArticlesNeoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial
Introduction
For premenopausal women with oestrogen receptor (ER)-positive or progesterone receptor (PgR)-positive breast cancer, treatment options include ablative surgery, radiotherapy, or cytotoxic chemotherapy. Endocrine treatments include the ER antagonist tamoxifen, and luteinising hormone releasing hormone (LHRH) agonists such as goserelin, which offer the potential for reversible ovarian ablation. Goserelin has shown efficacy for the treatment of premenopausal breast cancer, with equivalent disease-free survival to cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy in those patients with ER-positive disease.1 Although extended goserelin treatment is associated with a known reduction in bone mineral density,2 it offers a more favourable safety profile than does cytotoxic chemotherapy.3 The combination of tamoxifen plus goserelin has shown improved progression-free survival compared with goserelin alone;4 however, a report5 suggested that the combination of tamoxifen with goserelin was not better than either drug alone (although patients also received concomitant cytotoxic chemotherapy). Present guidelines suggest that tamoxifen alone or with ovarian function suppression are standard treatment options for premenopausal women with ER-positive breast cancer.6
Based on the efficacy shown in postmenopausal women with early breast cancer,7, 8, 9 aromatase inhibitors in combination with ovarian suppression are now being assessed for the treatment of premenopausal women with early-stage breast cancer.
Early clinical data in premenopausal women have suggested that the combination of anastrozole and goserelin results in a greater reduction in mean oestradiol concentrations than does the combination of tamoxifen plus goserelin,10 and data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12)11 have shown that 3-year adjuvant therapy with anastrozole plus goserelin is associated with similar disease-free survival to that associated with adjuvant tamoxifen plus goserelin therapy.11
The period before surgery offers an important treatment window to downstage breast tumours, which might allow for breast-conserving surgery rather than mastectomy.12 This window provides the potential for an improved cosmetic outcome together with a reduction of surgical morbidity.13, 14 Aromatase inhibitors have shown to be effective and well tolerated neoadjuvant treatments in postmenopausal women with early breast cancer.15 Therefore, the role of aromatase inhibitors plus goserelin for premenopausal breast cancer is of interest.
In this Study of Tamoxifen or Arimidex, combined with Goserelin acetate, to compare Efficacy and safety (STAGE), we aimed to compare anastrozole plus goserelin versus tamoxifen plus goserelin in the neoadjuvant setting (24 weeks of presurgical therapy) in premenopausal Japanese women with ER-positive early breast cancer.
Section snippets
Study design and patients
This phase 3, double-blind, randomised, parallel-group, multicentre study compared the efficacy and safety of anastrozole with that of tamoxifen in the neoadjuvant setting in premenopausal women with operable breast cancer receiving concomitant goserelin treatment.
We enrolled premenopausal women aged 20 years or older with ER-positive and HER2-negative breast cancer (ER-positive defined by ≥10% nuclear staining by immunohistochemistry; HER2-positive defined by immunohistochemistry 3 positivity
Results
Between Oct 2, 2007, and May 29, 2009, at 27 centres in Japan, 197 patients were randomly assigned to receive anastrozole plus goserelin (anastrozole group, n=98) or tamoxifen plus goserelin (tamoxifen group, n=99; figure). 185 patients completed the 24-week neoadjuvant treatment period and received breast surgery (figure).
Patient demographics and baseline characteristics were generally well balanced between the treatment groups (table 1). The number of patients with tumour grade 3 was higher
Discussion
During 24 weeks of neoadjuvant treatment, a greater proportion of premenopausal women with ER-positive, HER2-negative breast cancer who received anastrozole plus goserelin showed a tumour response benefit than did those who received tamoxifen plus goserelin. Further, a higher proportion of patients in the anastrozole group than in the tamoxifen group received breast-conserving surgery. These data suggest that anastrozole plus goserelin is an effective neoadjuvant treatment option in this
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