Radiation Therapy for Breast Cancer

This assignment examines the multifaceted aspects of radiation therapy in treating invasive breast cancer. It delves into both its positive contributions to patient care and potential drawbacks, including risks like lymphedema, second primary lung cancer, and myeloid neoplasms. The analysis also considers factors influencing treatment decisions, such as patient age, tumor characteristics, and advancements in radiotherapy techniques.

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Running head: RADIATION DOSIMETRY BIOLOGY AND PROTECTION
Radiation Dosimetry Biology and Protection
Name of student:
Name of university:
Author note:

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RADIATION DOSIMETRY BIOLOGY AND PROTECTION
Risk associated with radiation therapy in breast cancer patient
Introduction
Radiation therapy, together with chemotherapy and surgery, is one of the most
superior weapons of modern medicine that is being used for the treatment of cancer.
Radiation therapy is administered externally with the help of a high-energy X-ray beams, or
in an internal manner with the help of radioactive substances placed near the tumor being
treated When such therapy is considered for both palliative and curative purposes, literature
indicates that more than half of the total number of cancer patients need radiotherapy for at
least once during their care (Greenwalt et al., 2016). According to Agrawal (2014), radiation
therapy is considered as a pivotal component of comprehensive breast cancer treatment. Over
the past one decade, conservation treatment for breast cancer has been in focus, and the
application of post-mastectomy radiation has expanded rapidly, leading to increasing of the
number of patients receiving post-operative irradiation. Synchronized modifications in the
delivery of radiation therapy have been witnessed in the past; however, the technique has
been much debated for its harmful impact on the patient. A patient being exposed to ionising
radiation has been established to be a risk factor for several health complications. Research is
going on across the world to understand the exact negative impact that radiation therapy has
on breast cancer patients so that contemporary techniques can be developed and adopted
(Offersen et al.,2017).
The present paper is a literature review on the risks associated with radiation therapy
in breast cancer patient. It aims to analyse the existing literature on the concerned topic and
highlight the gaps in the literature. The purpose is to understand the direction of future

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research that would bring a drastic change in the delivery of radiation therapy for breast
cancer patients.
Literature review
Advancements in the screening and treatment of breast cancer have emerged from the
research domain putting in efforts to enable best possible patient outcomes. The survival rate
of breast cancer patients has increased solely due to such advancements, one of which is
radiation therapy. For particular at-risk groups of women undergoing mastectomy for tumour
removal, postmastectomy radiation therapy (PMRT) is known to reduce the risk of recurrence
at the locoregion and improve chances of survival. Evidence-based studies and population-
based studies point out to the fact that the use of radiation therapy is increasing with each
passing year (Jethwa et al., 2017). However, studies on the impact of the radiation on the
patient body post-therapy have thrown light on a number of risk factors associated with
radiation exposure and are to be discussed in here.
Agrawal (2014) highlighted the concerns raised about the risk of chronic and acute
side effects of radiation therapy in breast cancer survivors. As per the author, the most
noteworthy impact of radiation therapy includes reproductive dysfunction, cardiac toxicity,
skin changes, arm lymph oedema, pneumonitis (RP) and neuropathy. These are some of the
complications arising from adjuvant treatment. Cardiovascular toxicity that is chemotherapy-
induced include cardiomyopathy that might or might not be accompanied by endothelial
dysfunction, overt congestive heart failure (CHF) and arrhythmias. RT-induced
cardiovascular toxicity includes valvular disease, coronary artery disease (CAD), arrhythmias
and conduction disturbances, chronic pericardial disease, carotid artery stenosis and

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cardiomyopathy. Reproductive dysfunction after radiation therapy is subjected to the age of
the patient and the ovarian function when treatment is being done. Since the radiation cause
depletion of follicle pool in a dose-and drug-dependent manner, the ovarian damage is
evident. Apart from the negative impact of cancer therapy on ovarian function, much of the
substantiation from literature strongly indicates a negative effect on bone. Cancer treatment-
induced bone loss (CTIBL) is identified in a major proportion of patients becoming
permanently or temporarily amenorrheic after therapy. As per the author, radiation
pneumonitis in irradiated breast cancer patients is discussed in the literature for the last two
decades.
The findings of Agrawal (2014) is supported by Cheng et al., (2017) who reported
that radiotherapy of breast cancer involves incidental exposure of the heart to the harmful
impact of ionising radiation. As per the authors, the impact of the exposure on risk of heart
disease was uncertain. This uncertainty had been reported by a number of researchers
previously and Cheng et al. attempted to judge the truthfulness of this matter. The researchers
carried out a literature search with the help of MEDLINE and EMBASE databases with no
particular restrictions. Meta-analysis was done for this purpose that indicated that radiation
therapy had a strong association ith absolute risk increase of coronary heart disease (76.4 out
of 100000 person-years and cardiac death (125.5 out of 100000 person-years). The risk had
the tendency to increase within the first decade after radiation therapy for coronary heart
disease and from the second decade of radiation therapy for cardiac mortality. Risks for such
diseases were more in patients undergoing left-sided radiation therapy as compared to right-
sided. The study inferred that though contemporary radiation therapy might reduce the risk
rate, the chances of cardiotoxicity cannot be eliminated. The comparison of left-sided breast
and right-sided breast cancer treatment with radiation therapy dates back to early 2000s.

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RADIATION DOSIMETRY BIOLOGY AND PROTECTION
Giordano et al., (2005) had stated that patients with left-sided breast tumours are subjected to
a higher dose of radiation to the heart than patients with right-sided tumours.
Jagsi (2013) pointed out that radiation therapy is a crucial element of the
multidisciplinary management approach for invasive breast cancer. Radiation therapy not
only brings improvement in local control of tissue growth but also spares the patients from
the distress of recurrence. As per the authors, considerable progress is continuously being
moving toward the widespread benefits of the therapy. Nevertheless, the toxicity concerns of
therapy are to be brought into the limelight. The researchers highlighted that cardio-toxicity
impacts of radiotherapy for breast cancer. When a patient is exposed to high radiation dose,
exposure of the heart is a concern. Recent studies are noteworthy in raising concerns about
modern, conformal techniques. The left anterior descending coronary artery is incidentally
irradiated when high doses of radiation are give in tangential fields. Also, internal mammary
lymph node when treated can result in exposure of the right coronary vessels to the radiation
dose. While some studies have given the suggestion that cardiac risk magnitude has
decreased recently, it is striking that perfusion defects are found in patients undergoing
treatment with modern methods.
The similarity in findings is cited in the research of Darby et al., (2013) who carried
out a population-based case-control study of major coronary events in 2168 patient
undergoing radiation therapy after diagnosis of breast cancer. The coronary events included
coronary revascularisation, myocardial infarction and death from heart disease. The primary
result of the study was that exposure of the patient’s heart to radiation considerably leads to
an increase in the rate of ischemic heart disease. The sharp increase has a direct
proportionality with the dose of radiation and changes occur within a few years after first

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radiation exposure. It thereafter continues for as long as 20 years. Women who have
preexisting cardiac risk factors suffer more risk from radiotherapy when compared to other
women.
Research of Hong et al., (2017) however contradicted the studies of Agrawal, Darby
and Cheng while they researched on the health outcomes of breast cancer radiation therapy
based on the existing information that adjuvant radiation therapy (RT) for breat cancer leads
to substantive cardiac dose and cardiac risk. The researchers attempted to assess the mean
heart dose (MHD) of RT along with the estimated risk of cardiac toxicity in patients with
breast cancer in a community practice. Bivariate analyses and multivariable linear regression
tests were done with 1161 patients with left-sided breast cancer and receiving RT. The study
concluded that MHD was in varying degrees across the set of patients and the technique of
delivery influenced MHD in community settings. The overall risk of cardiac toxicity was
unassertive. The findings are in alignment with the studies of Hauqe et al., (2011) whose
research pointed out that radiation therapy had no direct association with cardiovascular
disease when follow up was done for 14 years. The study also brought into focus that tumor
laterality has the potential of modifying the association between radiation a cardiovascular
disease.
The rationale for decreased risk of heart disease due to radiation therapy can be
explained by the work of Giordano et al., (2005). The findings of the researchers had
concluded that a considerable progress has been made in treatment planning for radiation
therapy from the 1970s through late 2000s. The utilisation of large fraction sizes,
orthovoltage radiation and deep tangential fields or direct anterior internal mammary fields
for the treatment purpose techniques that were common in the early 2000s were a concern of

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risk of heart disease. However, the mentioned techniques are now not in use as standard
practice. Another reason for decreased risk for heart disease can be attributed to the decreased
use of an en face photon or cobalt 60 fields for treating the internal mammary lymph nodes
and medial chest wall.
The impact of breast cancer radiotherapy on the risk of primary lung cancer has been well
discussed in the literature. Kaufman et al., (2008) studied the impact radiation therapy and
cigarette smoking has on the patient pertaining to second primary lung cancer. Prior studies
had indicated that women with breast cancer are at increased risk of suffering from
complciations from postmastectomy radiation therapy (PMRT) such as brachial plexopathy,
lymphedema, pneumonitis and cardiac complications in later stages of life. Further, radiation
was also found to be the cause of second primary cancer. The researchers had previously
conducted studies that indicated that secondary lung cancer in a patient with breast cancer
was more in frequency in the lung lying ipsilateral to the breast undergoing radiation in
comparison to the contralateral lung. The risk associated has a latency period of least ten
years. Further, smoking is a common risk factor for cancer in the lungs. Based on such
previous research the researchers undertook a study to evaluate the risk of lung cancer due to
PMRT among women who were smokers and non-smokers. A population-based nested case-
control study was conducted with women participants wherein patient cases had lung cancer
after ten years of diagnosis of breast cancer. Medical records underwent reviewing for
therapy for breast cancer, pathology, and history of smoking. Among the total number of
113-second primary lung cancer patients, women who were non-smokers and receiving
PMRT showed no higher risk of developing lung cancer when the comparison was done with
women who were non-smokers and were not given PMRT. The study inferred that smoking,
as well as PMRT, had a strong association with increased risk of lung cancer.

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The study of Taylor et al., (2017) further contributes to the topic of discussion, that is
a relationship between radiotherapy and lung cancer. The group of researchers estimated the
absolute risks of advanced and modern breast cancer radiotherapy that is for long-term. The
background of this study was the knowledge that radiotherapy can lead to second cancer of
lungs or heart diseases after a decade, as cited by Kaufman et al., (2008). Taylor and co-
researchers conducted their research in three parts. First, the researchers carried out a
systematic literature review of heart and lung doses in regimens for breast cancer published
between the years 2010 and 2015. Thereafter, a meta-analysis was done with patient data
wherein 40,781 women randomly assigned to breast cancer radiotherapy. Lastly, heart and
lung Excess Rate Ratio (ERR) in the trials were combined to be applied to present cardiac
mortality and lung cancer rates in data from a population with consideration of smoking and
non-smoking. Estimated absolute risks relevant to modern radiotherapy were identified as:
lung cancer, 0.3% for non-smokers and 4% for longterm smokers; and cardiac mortality,
0.3% for nonsmokers and 1% for smokers. It was therefore concluded that for patients who
are long-term smokers, risks of radiotherapy have the potential to outweigh the multiple
benefits of the therapy. For patients who do not smoke, the net impact of radiotherapy is more
powerful. It is implied that smoking cessation has the ability to reduce the arising risks of
radiotherapy in breast cancer patients.
The findings are consistent with the findings of the study by Grantzau and Overgaard
(2015). As radiotherapy has been long linked with increased second cancer risk at sites of
exposure, the researchers estimated the chances of suffering second-non-breast cancer after
the patient underwent radiotherapy for breast cancer. The study was a meta-analysis that with
the databases CINAHL and EMBASE. Primary endpoints were second cancers of
oesophagus, lung, thyroid as well as second sarcomas. After a span of five years of

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radiotherapy, there was a statistically significant relationship with second non-breast cancer
relative risk (RR), second lung cancer RR, oesophagus RR and second sarcomas RR. The risk
also was found to be increasing with the passage of time, and the highest was reported at
fifteen years of diagnosis of breast cancer for second oesophagus and lung cancer. There was
no statistically significant association between second thyroid cancer and radiotherapy. The
study proves that radiotherapy increases the chances of second non-breast cancer in organs
adjacent to the treatment fields considered for therapy previously.
In this context, the work of Tunio et al., (2017) is to be cited. The group of
researchers tried to answer the question that whether the thyroid gland is at risk in patients
suffering breast cancer and undergoing locoregional supraclavicular radiotherapy. They
presented the results of a pilot study. The aim of the study was the evaluation of the dose
distribution within the thyroid gland and its relation with hypothyroidism in patients with
breast cancer receiving supraclavicular radiation therapy. Forty patients having normal
thyroid function tests were randomly assigned into two groups; supraclavicularradiation
therapy and normal radiation therapy. From the study, it was indicated that risk of
hypothyroidism in breast cancer patients after supraclavicular radiation therapy is dependent
on the volume of the thyroid gland. Further, there is a chance of minimising the risk through
shielding the thyroid gland.
Zeidan et al., (2017) analysed the risk of myeloid neoplasms in older women after
undergoing radiotherapy with localised breast cancer. There has been an inconsistency in the
data present on the risk of myeloid neoplasms (MN) among patients who have survived
breast cancer after receiving radiotherapy. Surveillance, Epidemiology, and End Results
(SEER)±Medicare linked database was used by the researchers for studying older women

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RADIATION DOSIMETRY BIOLOGY AND PROTECTION
with breast cancer diagnosis and surgery. Radiation therapy was ascertained, and a new
diagnosis of MN was recorded with the SEER registry. Out of the total 60426 patients, 316
women were found to be diagnosed with MN. The results had consistency with multiple
sensitivity analyses. The data suggested that radiation therapy increases chances of MN
among older cancer survivors. However, the risk is relatively small.
On assessing the risk factors for breast cancer recurrence after intraoperative radiation
therapy (IORT), Sperk et al., (2017) had commented that lymphangioinvasion, young age,
triple negative tumours, medial tumour localization and the resection status were confirmed
as risk factors after IORT. Positive lymph nodes without lymphangioinvasion and size of the
tumor were not noteworthy risk factors. High-risk factors were a combination of positive
lymph nodes and lymphangioinvasion as well as triple negative tumors. Eldredge-Hindyet al.,
(2014) identified that breast IORT has a discreet toxicity profile that is marked by several
changes in the body such as seroma formation, liponecrosis, fibrotic changes and
calcifications. Studies have however indicated that skin toxicities lie dryness,
hyperpigmentation, skin erythema and pruritus is mild and less frequent in patients with
IORT. The researchers also noted that patients of breast cancer are undergoing radiation
therapy experience complications apart from infection. This condition is marked by the
deposit of brown fluid in the tumor bed with mild, overlying skin erythema. Fat necrosis
commonly occurs in the body after one month of surgery in older women who have high
amount of fat tissue in their breasts. Additionally, other studies document toxicity findings of
radiation therapy. There is a certain heterogeneity in the reported rate of different toxicities in
the literature. The dissimilarity is due to differences in IORT dose and techniques, nonuiform
systems for toxicity scoring and varying follow-up length. Further, recall bias is also reported
in retrospective series.

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Kaidar-Person et al., (2015) criticised previous literature that showed that
significantly fewer ipsilateral breast tumor recurrences are linked with the inclusion of whole-
breast radiotherapy in the treatment plan with adjuvant endocrine therapy after surgery for
breast cancer. The researchers recommended that as treatment with neither radiation therapy
or endocrine therapy would lead to a detectable survival advantage, patients are to be aware
of the high burden of complications arising from both the treatment. The complications that
the therapies entail are to be analysed thoroughly for understanding the benefits and
challenges. The study of Norman et al., (2010) contradicts the findings of studies highlighting
the link between radiation therapy and impact on lymph by stating that that radiation therapy
does not increase the risk of lymphedema. Though the study suggested the presence of other
therapies as an influencing factor for risk due to radiation therapy, there is a need for more
research into this matter for clarifying the arising doubts since different studies have
considered different definitions for lymphedema.
Conclusion
Radiation therapy is being widely used across settings as the best possible treatment
option for breast cancer. It provides a considerable reduction in regional and local recurrence
rates for breast cancers in both early stage and locally advanced stage and contributes to
progress in overall survival. A rich pool of data has attempted to assess the relationship
between radiation exposures and subsequent health issues. Although the population differ in
radiation quality, dose and timing, consistent findings from case studies have indicated that
risks associated with such therapy are of much importance. Despite the fact that therapeutic
radiation has multiple benefits, the arising complications such as cardiac diseases and lung
cancer cannot be ignored. Though some controversies are evident from the above literature

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review regarding the detrimental impact of radiation therapy, the majority of the literature
evidence point out towards the risks associated with the therapy. Increased knowledge of
radiation-related influences has an imperative role in assisting the treatment approach for
patients with breast cancer and improving follow-up care. The long-term hazards and health
complications in the general population are to be monitored in a direct manner for
understanding the extent of the negative impact. The relationship between radiotherapy and
health risk has much clinical relevance when it comes to individual screening, modification
of risk factor and prevention of diseases. There is an immediate need of advancing our
knowledge on the appropriate techniques for patient selection and application of radiation so
that therapeutic approach is far more safer. Efforts are to be given continually for reduction of
the burden of radiation therapy. Further research based on the gaps of existing literature
would surely define optimal management for breast cancer patients after radiation therapy.

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