The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort

Lasse Refsgaard; Marie Louise Holm Milo; Emma Skarsø Buhl; Jesper Møller Jensen; Else Maae; Martin Berg; Ingelise Jensen; Mette Holck Nielsen; Ebbe Laugaard Lorenzen; Lise Bech Jellesmark Thorsen; Stine Sofia Korreman; Birgitte Vrou Offersen

doi:10.1016/j.radonc.2024.110705

The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort

Lasse Refsgaard^*, Marie Louise Holm Milo, Emma Skarsø Buhl, Jesper Møller Jensen, Else Maae, Martin Berg, Ingelise Jensen, Mette Holck Nielsen, Ebbe Laugaard Lorenzen, Lise Bech Jellesmark Thorsen, Stine Sofia Korreman, Birgitte Vrou Offersen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy. Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008–2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose–response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival. Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16–17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01–1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01–1.56). Conclusion: AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.

Original language	English
Article number	110705
Journal	Radiotherapy and Oncology
Volume	204
ISSN	0167-8140
DOIs	https://doi.org/10.1016/j.radonc.2024.110705
Publication status	Published - Mar 2025

Keywords

Agatston score
Breast cancer
Cardiac toxicity
Coronary artery calcification
Coronary artery disease
Dose-response relationship
Mean heart dose
Radiotherapy
Survival analysis

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10.1016/j.radonc.2024.110705

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Refsgaard, L., Holm Milo, M. L., Buhl, E. S., Jensen, J. M., Maae, E., Berg, M., Jensen, I., Nielsen, M. H., Lorenzen, E. L., Thorsen, L. B. J., Korreman, S. S., & Offersen, B. V. (2025). The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort. Radiotherapy and Oncology, 204, Article 110705. https://doi.org/10.1016/j.radonc.2024.110705

@article{de70e2ce4d1c4d6fbe0d237ddf319c5e,

title = "The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort",

abstract = "Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy. Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008–2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose–response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival. Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16–17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01–1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01–1.56). Conclusion: AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.",

keywords = "Agatston score, Breast cancer, Cardiac toxicity, Coronary artery calcification, Coronary artery disease, Dose-response relationship, Mean heart dose, Radiotherapy, Survival analysis",

author = "Lasse Refsgaard and {Holm Milo}, {Marie Louise} and Buhl, {Emma Skars{\o}} and Jensen, {Jesper M{\o}ller} and Else Maae and Martin Berg and Ingelise Jensen and Nielsen, {Mette Holck} and Lorenzen, {Ebbe Laugaard} and Thorsen, {Lise Bech Jellesmark} and Korreman, {Stine Sofia} and Offersen, {Birgitte Vrou}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2025",

month = mar,

doi = "10.1016/j.radonc.2024.110705",

language = "English",

volume = "204",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Refsgaard, L, Holm Milo, ML, Buhl, ES, Jensen, JM, Maae, E, Berg, M, Jensen, I, Nielsen, MH, Lorenzen, EL, Thorsen, LBJ , Korreman, SS & Offersen, BV 2025, 'The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort', Radiotherapy and Oncology, vol. 204, 110705. https://doi.org/10.1016/j.radonc.2024.110705

The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort. / Refsgaard, Lasse; Holm Milo, Marie Louise; Buhl, Emma Skarsø et al.
In: Radiotherapy and Oncology, Vol. 204, 110705, 03.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort

AU - Refsgaard, Lasse

AU - Holm Milo, Marie Louise

AU - Buhl, Emma Skarsø

AU - Jensen, Jesper Møller

AU - Maae, Else

AU - Berg, Martin

AU - Jensen, Ingelise

AU - Nielsen, Mette Holck

AU - Lorenzen, Ebbe Laugaard

AU - Thorsen, Lise Bech Jellesmark

AU - Korreman, Stine Sofia

AU - Offersen, Birgitte Vrou

PY - 2025/3

Y1 - 2025/3

N2 - Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy. Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008–2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose–response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival. Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16–17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01–1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01–1.56). Conclusion: AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.

AB - Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy. Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008–2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose–response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival. Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16–17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01–1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01–1.56). Conclusion: AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.

KW - Agatston score

KW - Breast cancer

KW - Cardiac toxicity

KW - Coronary artery calcification

KW - Coronary artery disease

KW - Dose-response relationship

KW - Mean heart dose

KW - Radiotherapy

KW - Survival analysis

UR - http://www.scopus.com/inward/record.url?scp=85214306106&partnerID=8YFLogxK

U2 - 10.1016/j.radonc.2024.110705

DO - 10.1016/j.radonc.2024.110705

M3 - Journal article

C2 - 39725067

AN - SCOPUS:85214306106

SN - 0167-8140

VL - 204

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

M1 - 110705

ER -

The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort

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Keywords

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