Study Finds Adjuvant Anastrozole Reduces Recurrence Risk vs Tamoxifen in Postmenopausal Women With Ductal Carcinoma in Situ
In a phase III trial (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-35) reported in The Lancet, Margolese et al found that adjuvant anastrozole significantly improved the breast cancer–free interval vs tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ who had received lumpectomy plus whole-breast irradiation. The benefit was seen mainly in patients younger than age 60.
Study Details
In this double-blind trial, 3,104 patients from 333 sites in the United States, Canada, and Mexico were randomized between January 2003 and June 2006 to receive daily anastrozole at 1 mg (n = 1,552) or tamoxifen at 20 mg (n = 1,552) for 5 years. Randomization was stratified by age < 60 vs ≥ 60 years. The primary outcome was breast cancer–free interval was defined as time from randomization to any breast cancer event, consisting of local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ, on intention-to-treat analysis.
The anastrozole and tamoxifen groups were generally balanced for age (47% in both < 60 years), race/ethnicity (88% and 87% white), tumor evident on mammogram (98% and 96%), comedo necrosis (43% and 47%), palpable tumor (8% and 9%), tumor size (≥ 1 cm in 25% and 24%, unknown for 41% and 40%), and body mass index (< 25.0 kg/m2 for 24% and 26%).
Recurrence Rates
Median follow-up was 9.0 years, with a total of 212 breast cancer–free interval events observed. Events occurred in 90 patients in the anastrozole group vs 122 in the tamoxifen group (hazard ratio [HR] = 0.73, P = .0234). A significant time-by-treatment interaction was observed (P = .0410), with event curves diverging after the first 60 months.
A significant interaction was also observed between treatment and age group (P = .0379). Among women aged < 60 years, events occurred in 34 anastrozole vs 63 tamoxifen patients (HR = 0.53, P = .0026); among those aged ≥ 60 years, events occurred in 56 vs 59 (HR = 0.95, P = .78). Five-year breast cancer–free interval rates were 96.3% in both groups, and estimated 10-year rates were 93.1% vs 89.1%.
Among all events, invasive disease occurred in 43 vs 69 patients (HR = 0.62, P = .0123), and ductal carcinoma in situ occurred in 47 vs 53 patients (HR = 0.88, P = .52). Ipsilateral recurrence was observed in 46 vs 55 patients (HR = 0.83, P = .34), including invasive disease in 17 vs 22 patients (HR = 0.39, P = .39) and ductal carcinoma in situ in 29 vs 33 patients (HR = 0.87, P = .59). Contralateral disease was observed in 39 vs 60 patients (HR = 0.64, P = .0322), including invasive disease in 21 vs 40 patients (HR = 0.52, P = .0148) and ductal carcinoma in situ in 18 vs 20 patients (HR = 0.90, P = .73). Disease at a distant site was observed in 4 vs 7 patients (HR = 0.57, P = .37).
A total of 186 deaths were observed, including 98 in the anastrozole group vs 88 in the tamoxifen group (HR = 1.11, P = .48). Estimated overall survival was 97.9% vs 98.0% at 5 years and 92.5% vs 92.1% at 10 years. No interaction between treatment and age group was observed (P = .38). Death due to breast cancer occurred in five vs eight patients.
Adverse Events
Second primary cancers occurred in 107 patients in the anastrozole group vs 102 in the tamoxifen group (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 0.78–1.37), with a nonsignificantly greater incidence of uterine cancer in the tamoxifen group (8 vs 17 cases, RR = 0.47, 95% CI = 0.18–1.15). Fracture was nonsignificantly more common with anastrozole (69 vs 50 patients, RR = 1.38, 95% CI = 0.95–2.03).
Other adverse events did not markedly differ between the groups, except for a higher incidence of thrombosis or embolism in the tamoxifen group (0.8% vs 2.7%); there were 17 grade 4 events in tamoxifen patients and 3 grade 4 events and 1 grade 5 event in anastrozole patients. Overall, the rates of arthralgia and myalgia of any grade were somewhat increased in the anastrozole group (grade ≥ 3 arthralgia in 5% vs 4%, myalgia in 2% vs 1%).
The investigators concluded: “Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer–free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ.”
The study was funded by the National Cancer Institute and AstraZeneca Pharmaceuticals LP.
Richard G Margolese, MD, of the Jewish General Hospital, McGill University, Montreal, Canada, is the corresponding author of The Lancet article.
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