Evolution in the risk of adverse events of adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer

Abstract

Background

Adjuvant endocrine therapy is a gold standard in early-stage, hormone receptor positive breast cancer. In postmenopausal women, aromatase inhibitors (AIs) are associated with improved outcome compared to tamoxifen monotherapy. Differences in the toxicity profiles of these drugs are described; however, little is known about whether the risk of adverse events changes over time.

Methods

Sequential reports of large, randomized, adjuvant endocrine therapy trials comparing AIs to tamoxifen were reviewed. Data on pre-specified adverse events were extracted including cardiovascular events, bone fractures, cerebrovascular disease, endometrial cancer, secondary malignancies excluding breast cancer, venous thrombosis and death without recurrence. Odds ratios (ORs) were calculated for each adverse event at each time over the course of follow-up. The change in the ORs for adverse events over time was evaluated using weighted linear regression.

Results

Analysis included 21 reports of 7 trials comprising 30,039 patients and reporting outcomes between 28 and 128 months of follow-up. Compared to tamoxifen, AIs use was associated with a significant reduction in the magnitude of increased odds of bone fracture over time (β = − 0.63, p = 0.013). There was a non-significant decrease in the magnitude of reduced odds of secondary malignancies over time (β = 0.448, p = 0.094). The differences in other toxicity profiles between AIs and tamoxifen did not change significantly over time.

Conclusions

The increased risk of bone fractures associated with adjuvant AIs falls over time and after discontinuation of treatment. Differences in other toxicities between AIs and tamoxifen do not change significantly over time including a persistently elevated risk of cardiovascular events.

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Abbreviations

DFS:

Disease free survival

OS:

Overall survival

AI:

Aromatase inhibitors

RCT:

Randomized controlled trial

OR:

Odds ratio

CI:

Confidence interval

NNH:

Number needed to harm

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Funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors

Contributions

Conceived and designed the work: DR EA HG; Acquisition of data: DR HG; Analysis and interpretation of data: DR RY AM AD RS EA HG Wrote the manuscript with input from all authors: DR HG; All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hadar Goldvaser.

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Conflict of interest

Dr. Yerushalmi reports personal fees from: Roche (Consulting, Invited speaker), Pfizer (Consulting), Novartis (Consulting), Teva (Invited speaker), Medison (Invited speaker), MSD (Invited speaker), Astra-Zeneca (Invited speaker) and Novartis (Invited speaker), all outside the submitted work. Dr. Moore reports honorarium fees from MSD and Roche, all outside the submitted work. Dr. Amir reports personal fees from Genentech/Roche (Expert Testimony), personal fees from Apobiologix (Consulting), personal fees from Myriad Genetics (Consulting), personal fees from Agendia (Consulting), personal fees from Sandoz (Consulting), all outside the submitted work. Dr. Goldvaser reports personal fees from: Roche (honorarium), Pfizer (honorarium), Novartis (honorarium and consulting) all outside the submitted work. The other authors have no conflicts of interest to declare.

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Reinhorn, D., Yerushalmi, R., Moore, A. et al. Evolution in the risk of adverse events of adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer. Breast Cancer Res Treat 182, 259–266 (2020). https://doi.org/10.1007/s10549-020-05715-1

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Keywords

  • Breast cancer
  • Adjuvant
  • Tamoxifen
  • Aromatase inhibitors
  • Toxicity
  • Adverse events