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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
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