Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

Abstract

<b><i>Introduction:</i></b> The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). <b><i>Methods:</i></b> Four treatment plans were created (3D-CRT and IMRT –/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. <b><i>Results:</i></b> The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, <i>p</i> = 0.002), contralateral BC (49 vs. 31%, <i>p</i> = 0.002) and ischaemic heart disease (41 vs. 27%, <i>p</i> = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, <i>p</i> = 0.002) and ERR for secondary lung cancer (75 vs. 58%, <i>p</i> = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. <b><i>Conclusion:</i></b> Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.

Current Cardioprotective Strategies for the Prevention of Radiation-Induced Cardiotoxicity in Left-Sided Breast Cancer Patients

“…Intensity Modulated RT (IMRT) represents an advanced form of 3D-Conformal RT that alters the intensity of multiple photon beams and delivers them from diverse directions, creating highly conformal dose distributions [33,79]. With regard to the literature, IMRT achieves the administration of lower doses to a greater proportion of cardiac tissue, thus resulting in an improved sparing of the OARs, dose uniformity, and the coverage of the target volume in comparison to3D-CRT [80].Studies have illustrated that the irradiation of the internal mammary chain (IMC) in left-sided BC patients increases the cardiac dose [81].…”

“…Studies have shown that VMAT is beneficial for left-sided BC patients by administering lower doses to healthy tissues, including the heart and coronary arteries, and avoiding the induced cardiac dysfunction [36]. In 2021,Zhang et al enrolled 30 patients undergoing RT after a mastectomy [81].Compared to IMRT, VMAT treatment plans resulted in better target volume coverage and reduced heart tissue exposure to radiation.…”

Incidence of Nonkeratinocyte Skin Cancer After Breast Cancer Radiation Therapy

“…[8][9][10] The role of radiation therapy in subsequent cancer development has been studied for a range of primary cancers, including those of the prostate and rectum, 11 head and neck, 12 and breast. 13 Much of the literature focuses on secondary lung cancer or cardiovascular disease risk after breast cancer radiation therapy. 13,14 Yet less is known about the long-term overall risk of subsequent nonkeratinocyte skin cancers after breast cancer radiation therapy or other treatments.…”

“…The role of radiation therapy in subsequent cancer development has been studied for a range of primary cancers, including those of the prostate and rectum, head and neck, and breast . Much of the literature focuses on secondary lung cancer or cardiovascular disease risk after breast cancer radiation therapy .…”

“… 13 Much of the literature focuses on secondary lung cancer or cardiovascular disease risk after breast cancer radiation therapy. 13 , 14 Yet less is known about the long-term overall risk of subsequent nonkeratinocyte skin cancers after breast cancer radiation therapy or other treatments. In a study published in 2004 using data from 1973 to 1999, researchers found a positive association between radiation therapy for breast cancer and cutaneous melanoma.…”