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Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis
Open accessAbstract
IMPORTANCE: Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. OBJECTIVE: To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. DATA SOURCES: Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. STUDY SELECTION: Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion. DATA EXTRACTION AND SYNTHESIS: Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. RESULTS: The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). CONCLUSIONS AND RELEVANCE: Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.
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Metadata
- Authors
- Spring, L. M., Gupta, A., Reynolds, K. L., Gadd, M. A., Ellisen, L. W., Isakoff, S. J., Moy, B., & Bardia, A.
- Affiliations
- Harvard University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Bardia, Aditya
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-11-01
- Volume
- 2
- Issue
- 11
- Pages
- 1477
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC5738656
- OpenAlex
- W2467606258
- Cited by
- 396
- References
- 60
- Citations by year
- 2026: 28 · 2025: 52 · 2024: 48 · 2023: 36 · 2022: 48 · 2021: 56 · 2020: 63 · 2019: 26 · 2018: 13 · 2017: 18 · 2016: 8
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001102)
- National Cancer Institute (K12CA087723, T32CA071345)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Keywords
- neoadjuvant endocrine therapy, estrogen receptor-positive breast cancer, aromatase inhibitors, breast-conserving surgery, clinical response rate, combination chemotherapy, treatment toxicity, randomized controlled trials meta-analysis
- MeSH terms
- Breast Neoplasms, Female, Humans, Receptors, Estrogen, Randomized Controlled Trials as Topic, Treatment Outcome, Chemotherapy, Adjuvant, Antineoplastic Agents, Hormonal, Neoadjuvant Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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