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Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause

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Abstract

Purpose

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer.

Methods

We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6 months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare).

Results

In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11 years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (− 18.1% ± 4.7% vs. − 20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9 cm2 ± 2.7 cm2 vs. 11.8 cm2 ± 2.0 cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89 cm ± 0.15 cm vs. 0.83 cm ± 0.16 cm, p = 0.06) although not statistically significant.

Conclusion

In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

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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.

Author information

Author notes

  1. Billy Lin and Alexis LeVee have contributed equally as first authors.

Authors and Affiliations

  1. Division of Cardiology, University of California Riverside, Riverside, CA, USA

    Billy Lin

  2. Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Billy Lin, Alexis LeVee, Louie Cao & Reva Basho

  3. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Alexis LeVee

  4. Ellison Institute of Technology, Los Angeles, CA, USA

    Reva Basho

  5. Department of Cardiology, University of Arizona School of Medicine, Phoenix, AZ, USA

    Balaji Tamarappoo

  6. Barbra Streisand Women’s Heart Center, Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA

    Janet Wei

  7. Mayo Clinic Women’s Health and Division of General Internal Medicine, Jacksonville, FL, USA

    Chrisandra Shufelt

Authors
  1. Billy Lin
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  2. Alexis LeVee
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Contributions

Conceptualization: [BL, AL, BT, JW, CS]; Methodology: [BL, AL, BT, JW, CS]; Formal analysis and investigation: [BL, AL, LC]; Writing—original draft preparation: [BL]; Writing—review and editing: [BL, AL, LC, RB, BT, JW, CS].

Corresponding author

Correspondence to Chrisandra Shufelt.

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The authors have not disclosed any competing interests.

Ethical approval

The Cedars-Sinai Medical Center Institutional Review Board approved this retrospective study protocol with a waiver for individual written consent.

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Lin, B., LeVee, A., Cao, L. et al. Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07344-4

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