Trial reportJournal of the National Cancer Institute2020
Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307.
Trial report in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 6 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for the Systemic Treatment of Patients with HR+/HER2- Early Breast Cancer 2025.Current oncology (Toronto, Ont.) · 2026Guideline
- Clinical and economic research of bone modifiers as adjuvant therapy for early breast cancer: A systematic literature review.Breast (Edinburgh, Scotland) · 2025Pooled it
- MASCC/ISOO Clinical Practice Statement: Adjuvant bone-modifying agents in primary breast cancer patients - prevention of medication-related osteonecrosis of the jaw.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Guideline
- Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis.The Cochrane database of systematic reviews · 2024Pooled it
- Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.Frontiers in oncology · 2022Pooled it
- Pooled it
- Trial
- A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer.Breast cancer research and treatment · 2024Trial
- Trial
- Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307).Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Trial
- The osteoporotic niche as a metabolic sanctuary for breast cancer dormancy and reactivation: A mechanistic perspective.iScience · 2026Review
- Bisphosphonates in breast cancer radiotherapy: associations with skeletal complications and treatment outcomes - a retrospective cohort study.Frontiers in oncology · 2026Article
- Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG.Journal of bone oncology · 2025Review
- Augmenting Insufficiently Accruing Oncology Clinical Trials Using Generative Models: Validation Study.Journal of medical Internet research · 2025Article
- Daily oral ibandronate with adjuvant endocrine therapy in postmenopausal women with estrogen receptor-positive breast cancer: editorial commentary.Annals of translational medicine · 2024Article
- Advancements in Understanding the Hide-and-Seek Strategy of Hibernating Breast Cancer Cells and Their Implications in Oncology from a Broader Perspective: A Comprehensive Overview.Current issues in molecular biology · 2024Review
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Clinical practice guidelines for full-cycle standardized management of bone health in breast cancer patients.Cancer innovation · 2024Article
- Article
- A narrative review: research progress of adjuvant intensive endocrine therapy for early breast cancer.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
Corrections and comments
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Authors and funding
23 authors at 18 institutions in 2 countries.
Funding
Abstract
backgroundAdjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer.
methodsPatients with stage I-III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided.
resultsA total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%).
conclusionsWe found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.