Radiotherapy significantly ameliorates the prognosis and decreases the incidence rate of life loss in breast cancer patients and has been an indispensable element in the systematic treatment of the disease. Regardless of the use of radiotherapy, luminal A breast cancer has the most favorable clinical outcomes after ionizing irradiation compared to that in HER2-positive cancer and TNBC. Differences in outcomes between these subtypes of the disease are mainly determined by differential radioresistivity, aggressiveness, and malignance of the subtypes. X-rays eliminate tumor cells through increased cell cycle arrest, which concomitantly induces an unavoidable severe side effect in normal stem cells in the adjacent tissues. The intensification of radioresistance in HER2-positive breast cancer is ascribed to multiple molecular mechanisms; in contrast, several drugs or compounds sensitize the cells to radiation and increase irradiation efficacy in luminal cancer and TNBC via specific pathways.


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  1. Irrespective of the selection of radiotherapy paradigm, luminal A breast cancer has an overall favorable prognosis relative to HER2-positive and TNBC subtypes partially due to individual radiosensitivity of these subtypes.
  2. Ionizing irradiation induces ablation of the tumor mainly through increasing the cell cycle arrest to promote apoptosis and senescence; however, ionizing radiation induces serious adverse effects in the normal stem cells in the adjacent tissues.
  3. HER2-positive breast cancer has high radioresistance that is correlated to the transactivation of the NF-κB-mediated HER2 promoter inducing HER2 overexpression, β-catenin expression during EMT and the Fak-mediated pathway.
  4. Medications or compounds reinforce radiosensitivity in luminal breast cancer and TNBC largely due to an increase in the ROS level and modulation of DNA double-strand break- and/or apoptosis-related proteins, such as 8-OHdG, γH2AX, and p53.

Abbreviation list

BCS, breast-conservation surgery; ESBC, early-stage breast cancer; LR, local recurrence; DM, distant metastasis; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple negative breast cancer; CWBI, conventional whole-breast irradiation; APBI, accelerated partial-breast irradiation; HWBI, hypofractionated whole-breast irradiation; DCIS, ductal carcinoma in situ; LRR, locoregional recurrence; IBTR, ipsilateral breast tumor relapse; DFS, disease-free survival; OS, overall survival; DDSB, DNA double-strand breakage; NHEJ, non-homologous end joining; HR, homologous recombination repair pathway; H3K9, histone 3 lysine-9; pO2, partial pressure of oxygen; EGFR, epidermal growth factor receptor; HDACis, histone deacetylase inhibitors; Trx, thioredoxin; ROS, reactive oxygen species; H4R, histamine 4 receptor; CXCR 4, chemokine receptor 4.

Ethics statement

This article does not contain any studies with human participants or animals performed by any of the authors.


The authors report no conflicts of interest in this work.

Lin He,1 Yang Lv,2 Yuhua Song,1 Biyuan Zhang3
1Breast Center B Ward, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Department of Oncology, The PLA Navy Anqing Hospital, Anqing, Anhui Province, People’s Republic of China; 3Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China


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Source: Cancer Management and Research.
Originally published June 28, 2019.

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