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July 12, 2023Journal of Cardiovascular Development and DiseaseOpen Access

Early Development of Atherosclerotic Plaques in the Coronary Arteries after Radiotherapy for Breast Cancer (BACCARAT Study)

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Key result

Coronary radiation dose linked to ~2.3-fold higher odds of 2-year plaque progression per Gy.

OR 2.32 per 1 Gy to LMCA
95% CI 1.08-4.97
P=0.03
n=101

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Why the study?

Radiotherapy for breast cancer can increase coronary artery disease risk years later, prompting evaluation of early plaque development and associations with cardiac radiation exposure.

Is cardiac radiation dose during breast cancer radiotherapy associated with the early development of calcified and non-calcified coronary atherosclerotic plaques over 2 years?

Key Points

To assess the development of overall, calcified, and non-calcified coronary atherosclerotic plaques over two years after breast cancer radiotherapy and evaluate associations with cardiac radiation exposure.
Prospective study of 101 patients with left- or right-sided breast cancer treated with radiotherapy without chemotherapy (NCT02605512).
Coronary CT angiography was performed before radiotherapy and at 2-year follow-up to evaluate changes in plaque count across the coronary network.
Mean radiation doses were measured for the heart, left ventricle, and coronary arteries, with dose associations evaluated using logistic regression models.
Atherosclerotic plaques were present in 37% (37/101) of patients at baseline and increased to 42% (42/101) at 2 years post-radiotherapy, with 7 patients demonstrating overall plaque development.
The risk of overall plaque development was significantly associated with mean radiation dose to the left main coronary artery (OR at 1 Gy = 2.32, 95% CI 1.08–4.97, p = 0.03) and circumflex coronary artery (OR at 1 Gy = 2.27, 95% CI 1.09–4.74, p = 0.03).
Among the 7 patients with new plaque development, 5 developed calcified plaques and 4 developed non-calcified plaques, all occurring in patients with left-sided breast cancer.

Study Design

Type

Cohort (n=101)

Blinding

Radiologist blinded to time of scanning (baseline/follow-up) and laterality of radiotherapy

Multicenter

No

Structured PICO

Is cardiac radiation dose during breast cancer radiotherapy associated with the early development of calcified and non-calcified coronary atherosclerotic plaques over 2 years?

P

Population

101 female patients (mean age 58 years) with left- or right-sided breast cancer treated with adjuvant 3D conformal radiotherapy without chemotherapy, free of prior severe cardiovascular disease, followed for 2 years.

E

Exposure

Adjuvant three-dimensional conformal radiation therapy (3D-CRT) after breast-conserving surgery or mastectomy (50 Gy in 25 daily fractions of 2 Gy over 5 weeks, or 47 Gy in 20 daily fractions of 2.35 Gy over 5 weeks, with optional 12-12.5 Gy tumor site boost), quantified by volume-weighted mean radiation doses (Dmean in Gy) to the heart, left ventricle, and coronary arteries (LMCA, LAD, CX, RCA).

O

Outcome

Development of overall coronary atherosclerotic plaques (defined as an increase of at least 1 in the number of coronary segments containing any plaque between baseline before RT and 2 years after RT), assessed by contrast-enhanced coronary CT angiography blinded to scan timing and RT laterality.surrogate

Main Result

Odds Ratio: 2.32 (95% CI 1.08–4.97)

p-value: p=0.03

Coronary CT angiography demonstrates that radiation dose to the left main and circumflex coronary arteries during breast cancer radiotherapy is associated with early development of both calcified and non-calcified coronary plaques within 2 years.

Limitations

Small sample size (101 patients) and small number of patients with the event of interest (7 patients)
Inability to perform multivariable analyses due to the very limited number of events
Did not evaluate the impact of radiotherapy and radiation dose on the degree of coronary stenosis
Statin or cholesterol-lowering drug initiation after radiotherapy was not collected or analyzed
Small sample size (n=101) and small number of plaque development events (n=7)
Multivariable analysis adjusting for cardiovascular risk factors (such as diabetes) could not be performed due to the limited number of events
Impact of radiotherapy and radiation dose on the degree of coronary stenosis was not evaluated
Information on statins or other cholesterol-lowering drugs initiated after radiotherapy was not collected

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Answers are grounded in this paper and cite their sources.

Implication

Coronary dose sparing may warrant consideration in breast radiotherapy; extends prior CAD risk data to early plaque changes but remains hypothesis-generating.

Abstract

Background—Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods—The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results—At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion—Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512.

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Cite This Study

Honaryar et al. (2023) conducted a cohort in Unilateral breast cancer treated with radiotherapy without chemotherapy (n=101). Cardiac radiation exposure during adjuvant 3D conformal breast cancer radiotherapy (specifically mean dose to the left main coronary artery) was evaluated on Overall coronary atherosclerotic plaque development (increase in the number of coronary segments containing any plaque by at least 1 on coronary CT angiography at 2 years) (OR 2.32 per 1 Gy to LMCA, 95% CI 1.08-4.97, p=0.03). Radiation dose to the left main (OR 2.32 per 1 Gy, p=0.03) and circumflex (OR 2.27 per 1 Gy, p=0.03) arteries was associated with 2-year coronary plaque development after breast radiotherapy.

synapsesocial.com/papers/6a87185f713eb98b40ca26ee https://doi.org/10.3390/jcdd10070299

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