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Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Aromatase inhibitors (AIs) are an important component of the adjuvant treatment of hormone receptor positive breast cancer (BC) but concerns regarding their cardiovascular safety remain. In this cross-sectional study nested in a breast cancer cohort, we investigated the association between AI exposure and early markers for cardiovascular disease in BC survivors.

Methods

The study population consisted of 569 women, who were 5–7 years (n = 277) or 10–12 years (n = 292) after BC diagnosis. All participants underwent carotid ultrasound, skin autofluorescence measurement and laboratory evaluation. To quantify AI exposure, we obtained the AI ratio by dividing the duration of AI use by the total duration of endocrine therapy (ET). Patients were classified according to their AI ratio into low (no ET or AI ratio < 0.40), intermediate (0.40 ≤ AI ratio ≤ 0.60) or high AI exposure (AI ratio > 0.60). The association between AI ratio and carotid intima media thickness (cIMT), advanced glycation end products (AGEs) and the presence of dyslipidemia was assessed using linear and logistic regression.

Results

Median age at study visit was 55.5 years (range 45.2–63.8). Forty percent (n = 231) of the study population had used AIs, of whom the majority sequentially with tamoxifen; median duration of AI use was 3.0 years. Mean cIMT and mean AGEs did not differ across AI exposure groups in univariable and multivariable analysis. The occurrence of dyslipidemia did not vary across AI exposure groups. Intermediate AI exposure was associated with more frequent occurrence of the combined endpoint (elevated cIMT, elevated AGEs and/or dyslipidemia). This association, however, was not present in the group with highest AI exposure.

Conclusion

AI exposure was not associated with cIMT, AGEs or the presence of dyslipidemia. These results do not prompt a change in current clinical practice, although further research is warranted to validate our findings over time and in different BC populations.

Trial registration number (clinicaltrials.gov): NCT02485626, June 30, 2015.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

AGEs:

Advanced glycation end products

AI(s):

Aromatase inhibitor(s)

AU:

Arbitrary units

BC:

Breast cancer

BMI:

Body mass index

CI:

Confidence interval

cIMT:

Carotid intima media thickness

CVD:

Cardiovascular disease

DCIS:

Ductal carcinoma in situ

ET:

Endocrine therapy

HDL:

High-density lipoprotein

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

ICD10:

International classification of diseases, 10th edition

IQR:

Interquartile range

LDL:

Low-density lipoprotein

NKI–AVL:

Netherlands Cancer Institute–Antoni van Leeuwenhoek

OR:

Odds ratio

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Acknowledgements

The authors would like to thank Sandra Fase and Andrea Meuleman for their help in data organization and collection.

Funding

Pink Ribbon/the Dutch Cancer Society (grant 2012.WO39.C143) supported the study financially.

Author information

Author notes

  1. Judy N. Jacobse, Lars C. Steggink, Michael Schaapveld and Gabe S. Sonke contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Annemiek van Ommen-Nijhof

  2. Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands

    Judy N. Jacobse

  3. Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Lars C. Steggink

  4. Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands

    Joop D. Lefrandt

  5. Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands

    Jourik A. Gietema

  6. Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Flora E. van Leeuwen & Michael Schaapveld

  7. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Gabe S. Sonke

  8. Department of Medical Oncology, University of Amsterdam, Amsterdam, The Netherlands

    Gabe S. Sonke

Authors
  1. Annemiek van Ommen-Nijhof
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Contributions

All authors contributed to the study conception and design. JJ and LS collected the data. AvO-N and MS prepared the data and performed the analyses. AvO-N wrote the first draft of the manuscript. All authors reviewed and revised the manuscript; all authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Annemiek van Ommen-Nijhof.

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Conflict of interest

Jourik Gietema reports institutional research support from Roche, Abbvie and Siemens. Gabe Sonke reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen and consultancy fees paid to the institution from Biovica and Seagen. Annemiek van Ommen-Nijhof, Lars Steggink, Judy Jacobse, Joop Lefrandt, Flora van Leeuwen and Michael Schaapveld report no competing interests.

Ethical approval

The institutional review board of the NKI-AVL approved the study and it is registered with ClinicalTrials.gov, identifier NCT02485626. The study was carried out according to the principles of the Declaration of Helsinki.

Consent to participate

All participants provided written informed consent prior to enrolment in the study.

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van Ommen-Nijhof, A., Jacobse, J.N., Steggink, L.C. et al. Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors. Breast Cancer Res Treat 196, 591–602 (2022). https://doi.org/10.1007/s10549-022-06714-0

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