Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis

Spring, Laura M.; Gupta, Arjun; Reynolds, Kerry L.; Gadd, Michele A.; Ellisen, Leif W.; Isakoff, Steven J.; Moy, Beverly; Bardia, Aditya

doi:10.1001/jamaoncol.2016.1897

Cited by 396Breast Cancer Treatment StudiesEstrogen and related hormone effectsAdvanced Breast Cancer Therapies

Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis

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Spring, Laura M., Gupta, Arjun, Reynolds, Kerry L., Gadd, Michele A., Ellisen, Leif W., Isakoff, Steven J., Moy, Beverly, Bardia, Aditya·2016·JAMA Oncology

DOI 10.1001/jamaoncol.2016.1897PMC PMC5738656

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Abstract

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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Myelosuppression risk is elevated in older people.
“Primary prophylaxis with granulocyte colony-stimulating factors is advisable for patients receiving chemotherapy in view of the higher risk of myelosuppression in older individuals [[84], [85], [86]].”
From Adapting care for older cancer patients during the COVID-19 pandemic: Recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group (2020) · cites this paper as [86]

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[61]Ma CX Gao F Northfelt D A phase II trial of neoadjuvant palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with anastrozole for clinical stage 2 or 3 estrogen receptor positive HER2 negative (ER+HER2−) breast cancer (BC) Presented at: San Antonio Breast Cancer Symposium December 11, 2015 San Antonio, TX Abstract S6-05

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Abstract P5-13-02: Neoadjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer: Comprehensive systematic review and meta-analysis
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Self-citation
Comparative Efficacy of Neoadjuvant Endocrine Therapy, Neoadjuvant Chemotherapy, and Neoadjuvant Chemo‐Endocrine Therapy in Estrogen Receptor–Positive Breast Cancer Patients: A Meta‐Analysis
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Abstract PO4-17-06: Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery
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Abstract P4-11-26: Efficacy of neoadjuvant endocrine therapy versus chemotherapy in ER+ HER2-negative breast cancer: a single-center matched-cohort study. Preliminary results
Kovalenko, E. I., Титова, Т. А., Жуликов, Я. А., Fedko, V. A., Khoroshilov, M. V., Petrovskiy, A., & Артамонова, Е. В. (2025) · Clinical Cancer Research · doi:10.1158/1557-3265.sabcs24-p4-11-26
Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer
Kim, H. J., Noh, W. C., Lee, E. S., Jung, Y. S., Kim, L. S., Han, W., Nam, S. J., Gong, G. Y., Kim, H. J., & Ahn, S. H. (2020) · Breast Cancer Research · doi:10.1186/s13058-020-01288-5 · Cited by 63 · see citing works

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: Spring, Laura M.
Gupta, Arjun
Reynolds, Kerry L.
Ellisen, Leif W.
Isakoff, Steven J.
Moy, Beverly
Bardia, Aditya
Venue: JAMA Oncology
Publisher: American Medical Association (AMA)
Published: 2016-11-01
Volume: 2
Issue: 11
Pages: 1477
ISSN: 2374-2437 (ISSN-L)
DOI: 10.1001/jamaoncol.2016.1897
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 › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis

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