Radiation and breast cancer: a review of current evidence

Abstract

21AT = ataxia-telangiectasia; ATM = ataxia telangiectasia mutated; BBD = benign breast disease; DSB = double-strand break; EAR = excess absolute risk; ERR = excess relative risk; FFTP = first full-term pregnancy; HL = Hodgkin lymphoma; LSS = Life Span Study; NHEJ = non-homologous end joining.Available online http://breast-cancer-research.com/content/7/1/21 IntroductionThe mammary gland is very sensitive to radiationassociated carcinogenesis, especially after exposures at young ages. Many aspects of the association between radiation and breast cancer have been elucidated in the past decades. This review is intended to summarize widely recognized features of radiation-associated breast cancer and to add a more detailed overview of relevant recent findings, especially focusing on factors that modify the radiation-related risk. Epidemiology of breast cancerIn 2000, breast cancer was the most common malignant disease in women worldwide, with an estimated 1.05 million cases. Owing to high levels of screening in developed countries and the relatively favorable prognosis of early-stage disease, it is also the most prevalent malignancy in women, with almost 4 million women alive who have had breast cancer in the past 5 years [1]. In the USA, it is estimated that about 216,000 women will be diagnosed with breast cancer in 2004 and that 40,000 will die from the disease [2]. Male breast cancer is a rare disease, with an incidence about 1/100 of that for female breast cancer [2].Breast cancer is very rare before age 30 years, after which incidence rises steeply with advancing age up to about age 50 years. Thereafter, incidence still increases with age, but more slowly [3]. The strong dependence on age, as seen for many other adult-type cancers, is probably related to accumulating genetic damage that occurs during a human lifespan. The apparent change in slope of the age-incidence curve at about age 50 years is unique for breast cancer, and this is presumably related to hormonal changes associated with menopause, which is accompanied by a decrease in circulating estrogen levels AbstractThis paper summarizes current knowledge on ionizing radiation-associated breast cancer in the context of established breast cancer risk factors, the radiation dose-response relationship, and modifiers of dose response, taking into account epidemiological studies and animal experiments. Available epidemiological data support a linear dose-response relationship down to doses as low as about 100 mSv. However, the magnitude of risk per unit dose depends strongly on when radiation exposure occurs: exposure before the age of 20 years carries the greatest risk. Other characteristics that may influence the magnitude of dose-specific risk include attained age (that is, age at observation for risk), age at first full-term birth, parity, and possibly a history of benign breast disease, exposure to radiation while pregnant, and genetic factors.

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“…These risks must be outweighed by demonstrable benefit to patients (Hoffman et al, 1989; Boice et al, 1991; Brenner, 2004;Ronckers et al, 2005). Thoracic CT requires a radiation dose equivalent to 400 chest radiographs (8 vs 0.02 mSv), increasing the exposure to 20 mSv if the abdomen is included.…”

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“…The proliferating glandular breast tissue is assumed to be especially sensitive to radiation [92,93], and CTPA exposes maternal breasts to a much higher radiation dose than lung scintigraphy (Table IV). It has been estimated that exposure of the breasts of women aged 35 years old to 10 mSv increases the risk of breast cancer by approximately 14 % over the background rate for the general population [94].…”

Exposure to estrogen and ionizing radiation causes epigenetic dysregulation, activation of mitogen-activated protein kinase pathways, and genome instability in the mammary gland of ACI rats

“…To investigate the role of epigenetic changes in rat mammary gland tissues in response to E 2 exposure, IR, and the combined action of E 2 and IR, we first analyzed changes in the levels of global DNA methylation in rat mammary gland tissues of control and treated rats using a sensitive HpaII-based cytosine extension assay that measures and therapeutic irradiation. 5,[7][8][9] For instance, an elevated incidence of breast cancer has been reported in patients with scoliosis and tuberculosis, 7 women treated for benign breast disease, 10 and in cancer survivors who received radiation therapy. 5 The average dose of IR-exposure linked to breast carcinogenesis ranges between 0.2 and 20 Gy.…”

“…5,[7][8][9] For instance, an elevated incidence of breast cancer has been reported in patients with scoliosis and tuberculosis, 7 women treated for benign breast disease, 10 and in cancer survivors who received radiation therapy. 5 The average dose of IR-exposure linked to breast carcinogenesis ranges between 0.2 and 20 Gy. 5 Additionally, experimental in vitro and in vivo studies have also established that IR can alter the functioning of normal mammary gland epithelial cells and trigger their neoplastic transformation.…”

“…5 The average dose of IR-exposure linked to breast carcinogenesis ranges between 0.2 and 20 Gy. 5 Additionally, experimental in vitro and in vivo studies have also established that IR can alter the functioning of normal mammary gland epithelial cells and trigger their neoplastic transformation. 11,12 However, the exact nature of these radiation effects on the mammary gland needs to be further explored.…”