Despite these improvements, extended letrozole did not significantly improve overall survival (OS). The 15-year OS rate was 74.0% in the letrozole arm and 72.3% in the placebo arm (HR, 0.92; 95% CI, 0.82-1.05; P = .21). Investigators did observe a trend toward fewer breast cancer deaths with letrozole, with a 15-year cumulative incidence of 5.0% vs 6.5% with placebo (HR, 0.78; 95% CI, 0.59-1.03; P = .08). Deaths from non-breast cancer or unknown causes were comparable between the arms, at 21.0% vs 21.2%, respectively (HR, 0.96; 95% CI, 0.84-1.11; P = .60).<\/p>\n
Among first DFS events, distant recurrence occurred in 5.1% of patients in the letrozole arm vs 7.0% in the placebo arm, and second primary cancers occurred in 14.4% vs 17.0%, respectively; these included second breast cancers (5.0% vs 6.0%) and non-breast primary cancers (9.4% vs 11.0%). Local recurrence (3.2% vs 3.6%) and death as a first event (12.6% vs 12.7%) were similar between groups.<\/p>\n
The DFS benefit was consistent across prespecified subgroups, with no significant treatment interactions by nodal status, prior tamoxifen use, bone mineral density (BMD) T-score, age, or type of surgery (P for interaction range, 0.21-0.98). In a multivariate analysis, treatment with letrozole remained independently associated with improved DFS (HR, 0.85; 95% CI, 0.77-0.94; P = .002).<\/p>\n
Regarding safety outcomes, extended letrozole did not significantly increase the risk of osteoporotic fractures or arterial thrombotic events. The 15-year cumulative incidence of osteoporotic fractures was 9.2% with letrozole vs 8.7% with placebo (HR, 1.08; 95% CI, 0.87-1.35; P = .47), and the incidence of arterial thrombotic events was 5.6% vs 5.5%, respectively (HR, 1.06; 95% CI, 0.80-1.41; P = .68).<\/p>\n
Between September 2006 and January 2010, the trial randomly assigned 3966 postmenopausal patients with estrogen receptor- or progesterone receptor-positive stage I, II, or IIIA invasive breast cancer who were disease free after 5 years of endocrine therapy, consisting of either 5 years of an AI or up to 3 years of tamoxifen followed by an AI to complete 5 years. Patients were randomly assigned to receive letrozole or placebo for 5 years, with stratification by pathologic nodal status, prior adjuvant tamoxifen, and lowest BMD T-score at the spine, hip, or femur (above \u20132.0 vs \u20132.0 or below). Follow-up was completed in August 2026, and 538 additional DFS events were recorded since the 10-year update.<\/p>\n
The primary end point was DFS, defined as local, regional, or distant recurrence; contralateral breast cancer; second non-breast primary cancer; or death from any cause as a first event. Secondary end points included OS, BCFI, distant recurrence, osteoporotic fractures, and arterial thrombotic events. Analyses followed the intent-to-treat principle, and the DFS analysis included 3906 patients (letrozole, n = 1952; placebo, n = 1954).<\/p>\n
Baseline patient, tumor, and prior treatment characteristics were balanced between the arms. Overall, 34% of patients were younger than 60 years, 57% had node-negative disease, 78% had HER2-negative disease (8% unknown), 25% had a lowest BMD T-score of \u20132.0 or below, 39% had received prior tamoxifen, and 61% had undergone breast-conserving surgery.<\/p>\n
Previously reported 10-year results from NSABP B-42 showed that extended letrozole significantly improved DFS, BCFI, and distant recurrence without a significant improvement in OS or a significant increase in osteoporotic fractures or arterial thrombotic events.2 The investigators concluded that the final 15-year results continue to support these findings, with extended letrozole producing a 15% reduction in DFS events, a 22% reduction in BCFI events, and a 28% reduction in distant recurrence.<\/p>\n
ReferencesMamounas EP, Bandos H, Geyer CE Jr, et al. Final analysis of NRG Oncology\/NSABP B-42, a randomized, double-blinded, placebo-controlled trial of extended letrozole in postmenopausal women with hormone-receptor positive breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA24.Mamounas EP, Bandos H, Rastogi P, et al. Ten-year update: NRG Oncology\/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial extended letrozole therapy in early-stage breast cancer J Natl Cancer Inst. 2023;115(11):1302-1309. doi: 10.1093\/jnci\/djad078 <\/p>\n","protected":false},"excerpt":{"rendered":"Despite these improvements, extended letrozole did not significantly improve overall survival (OS). The 15-year OS rate was 74.0%…\n","protected":false},"author":2,"featured_media":639152,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[134,111,139,69],"class_list":["post-639151","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-new-zealand","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/639151","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=639151"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/639151\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/639152"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=639151"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=639151"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=639151"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}