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Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: a literature-based meta-analysis of randomized trials

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Abstract

Background

Endocrine therapy with aromatase inhibitors (AIs) is the cornerstone of adjuvant systemic treatment for postmenopausal patients with hormone receptor-positive breast cancer. It has become clear that hormone receptor-positive breast cancer carries a consistent risk of relapse up to 15 years after diagnosis. Extended duration of adjuvant AIs therapy after completing initial standard adjuvant AIs-containing therapy may prevent late recurrence and death. We performed a meta-analysis to assess the real impact of the extended adjuvant therapy with AIs.

Methods

A literature-based meta-analysis of the randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, Embase, Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. The endpoints were disease-free survival (DFS), overall survival (OS), local recurrence, distant recurrence, contralateral breast cancer, non-breast cancer-related death, and toxicity.

Results

Eight trials comprising 15,966 patients met the inclusion criteria. The pooled analysis revealed a significant improvement in DFS (RR = 0.79; 95% CI 0.68–0.91), distant recurrence (RR = 0.75; 95% CI 0.58–0.96), and contralateral breast cancer (RR = 0.53; 95% CI 0.40–0.70) in the extended AIs group. While there was not significant improvement in OS (RR = 1.00, 95% CI 0.99–1.01), non-breast cancer-related death (RR = 1.16, 95% CI 0.96–1.41), and local recurrence (RR = 0.82; 95% CI 0.64–1.06), the subgroup analysis showed that the patient with tumor size > 2 cm (HR = 0.74, RD = − 0.31, P = 0.05 vs. HR = 0.85, RD = − 0.16, P = 0.20), node positive status (HR = 0.77, RD = − 0.27, P = < 0.0001 vs. HR = 0.89, RD = −0.12, P = 0.19) and previous chemotherapy use (HR = 0.75, RD = − 0.29, P = 0.003 vs. HR = 0.91, RD = −0.10, P = 0.44) would get a greater DFS benefit with extended AIs. Longer treatment with AIs was associated with an increased risk ratio of bone pain (RR = 1.26, RD = 0.04, P = 0.003), bone fractures (RR = 1.59, RD = 0.02, P = 0.002), osteoporosis (RR = 1.53, RD = 0.07, P = 0.005), myalgia (RR = 1.26, RD = 0.04, P = 0.02), and treatment discontinuation for adverse events (RR = 1.51, RD = 0.06, P = 0.0009).

Conclusion

After initial standard AIs-containing adjuvant therapy, extended AIs therapy could further bring a DFS benefit for postmenopausal patients with early breast cancer, especially in the patients with high-risk characteristics.

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Availability of data and materials

All data and materials used in this research are freely available in PubMed, Embase, and Cochrane Library. References have been provided.

Abbreviations

RCTs:

Randomized controlled trials

ASCO:

American Society of Clinical Oncology

SABCS:

San Antonio Breast Cancer

RR:

Risk ratio

HR:

Hazard ratio

RD:

Risk difference

CI:

Confidence intervals

ER:

Estrogen receptor

PR:

Progesterone receptor

N±:

Node positive or negative

DFS:

Disease-free survival

OS:

Overall survival

LR:

Local recurrence

DR:

Distant recurrence

CBC:

Contralateral breast cancer

NBCD:

Non-breast cancer-related death

TAM:

Tamoxifen

ANA:

Anastozole

LET:

Letrozole

AIs:

Aromatase inhibitors

OFS:

Ovarian function suppression

AG:

Aminoglutethimide

COMB:

Combination

mo:

Month

plac:

Placebo

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Acknowledgements

We thank Luping chen for her support and guidance throughout the project.

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Not applicable.

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Authors and Affiliations

  1. Department of Oncological Surgery, Shaoxing Second Hospital, Shaoxing, China

    Xiaoying Qian, Zhian Li, GuoDong Ruan & Wu Ding

  2. Department of Surgery, Shaoxing Keqiao Women & Children’s Hospital, Shaoxing, China

    Chuanjian Tu

Authors
  1. Xiaoying Qian
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  2. Zhian Li
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  3. GuoDong Ruan
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  4. Chuanjian Tu
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  5. Wu Ding
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Contributions

W Ding designed the study and developed the analysis plan. W Ding and X.Y. Qian analyzed the data and performed meta-analysis. Z.A. Li and X.Y. Qian assessed the risk of bias. X.Y. Qian contributed in writing of the article. C.J. Tu and G.D. Ruanuan revised the manuscript and polished the language.

Corresponding author

Correspondence to Wu Ding.

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The authors declare that they have no competing interests.

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This article does not contain any studies with human participants or animals performed by any of the authors. Ethical approval was not applicable for this systematic review and meta-analysis.

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Informed consent was obtained from all individual participants included in the study.

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Qian, X., Li, Z., Ruan, G. et al. Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: a literature-based meta-analysis of randomized trials. Breast Cancer Res Treat 179, 275–285 (2020). https://doi.org/10.1007/s10549-019-05464-w

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