Late Complications Of Radiation Therapy For Breast Cancer: Evolution In Techniques And Risk Over Time
Zachary Brownlee1, Rashi Garg1, Matthew Listo1, Peter Zavitsanos1, David E. Wazer1,2, Kathryn E. Huber1
1Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine , Rhode Island Hospital and Brown University School of Medicine , , USA
Contributions: Conception and design: DE Wazer, KE Huber Administrative support: KE Huber Provision of study materials or patients: None Collection and assembly of data: None Data analysis and interpretation: None Manuscript writing: All authors Final approval of manuscript: All authors.
Correspondence to:
Abstract: Radiation therapy in combination with surgery, chemotherapy, and endocrine therapy as indicated, has led to excellent local and distant control of early stage breast cancers. With the majority of these patients surviving long term, mitigating the probability and severity of late toxicities is vital. Radiation to the breast, with or without additional fields for nodal coverage, has the potential to negatively impact long term cosmetic outcome of the treated breast as well as cause rare, but severe, complications due to incidental dosage to the heart, lungs and contralateral breast. The long-term clinical side-effects of breast radiation have been studied extensively. This review aims to discuss the risk of developing late complications following breast radiation and how modern techniques can be used to diminish these risks.
Keywords: Radiation breast cancer late toxicity
Treat Breast Cancer Protect The Heart
Future heart risks should not be the reason to abandon this important component of treatment. I dont think by any means it should make anyone forego radiation for breast cancer therapy, says Dr. Javid Moslehi, instructor in the department of medicine at Harvard Medical School, and co-director of the cardio-oncology program at Brigham and Womens Hospital.
The ultimate goal is to minimize the exposure to the heart as much as possible, Dr. Taghian says.
In the JAMA study, researchers found that having a woman lie on her stomach during radiation treatment reduced her exposure. Dr. Taghian uses a technique called the breath-hold with his patients. Holding a breath expands the lungs, which pushes the heart out of the radiations path. This technique can cut radiation exposure to different structures of the heart by 54% to 96%.
Protecting women from the side effects of radiation is not a one-size-fits-all approach. I dont think there is one method to fit all patients, he says. The bottom line is we have to try the optimal method for each patient to avoid exposing the heart.
Proton therapya relatively new radiation treatment that uses particles instead of traditional x-rayscan also lower a womans exposure, but very few centers currently offer this treatment. In the future, this will probably be the dominant way to spare the heart, Dr. Taghian says.
Allosteric Targeting Of Cxcr4 Receptor Reversed Paracrine Effect Induced By Irradiated Epithelial Cells
To investigate whether the observed effects depend on activation of the CXCR4 receptor, AMD3100, an allosteric inhibitor of CXCR4 receptor, was used. Addition of AMD3100 reversed the pro-metastasis associated effects of CMLE_IR such as relative cell growth 5A) , relative adhesion 5B) , migration and extravasation of breast cancer cells . Furthermore, AMD3100 treatment partially reversed CMLE_IR -induced morphological changes, as measured by factor shape 5E) .
Effect of an allosteric CXCR4 inhibitor on breast cancer cell growth and migration
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Nerve Damage Around The Treatment Area
Scaring from radiotherapy may cause nerve damage in the arm on the treated side. This can develop many years after your treatment. Symptoms include tingling, numbness, pain, and weakness. In some people, it may cause some loss of movement in the arm and shoulder.
Speak to your doctor if you notice any of these symptoms.
Newly Diagnosed Or Worried About A Symptom

In the days or weeks after a diagnosis of secondary breast cancer, you may feel distressed and find it hard to think clearly.
You can read our information for people newly diagnosed with secondary breast cancer, including where to find support.
If you havent been diagnosed but are worried about a symptom, find out more about the signs and symptoms of secondary breast cancer.
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Possible Side Effects Of External Beam Radiation
The main short-term side effects of external beam radiation therapy to the breast are:
- Swelling in the breast
- Skin changes in the treated area similar to a sunburn
Your health care team may advise you to avoid exposing the treated skin to the sun because it could make the skin changes worse. Most skin changes get better within a few months. Changes to the breast tissue usually go away in 6 to 12 months, but it can take longer.
External beam radiation therapy can also cause side effects later on:
Radiation Therapy For Breast Cancer May Have Long
HealthDay Reporter
WEDNESDAY, Sept. 22, 2021 — Younger women who undergo radiation for cancer in the left breast have a heightened risk of heart disease years later, a new study finds.
Among women who received radiation therapy for left-sided breast cancer, 10.5% developed coronary artery disease over the next 27 years, researchers found. That was close to double the rate among women who had radiation for tumors in the right breast.
Experts said the findings, published recently in the Journal of the American College of Cardiology: CardioOncology, are not unexpected.
Because of the heart’s anatomical position, the organ and its arteries are exposed to more radiation when a woman receives treatment for cancer in the left breast.
And previous studies have found that those women do have a higher long-term rate of coronary artery disease compared to women who receive treatment to the right breast.
But the new study focused on younger women, diagnosed before age 55, said researcher Gordon Watt, a postdoctoral fellow at Memorial Sloan Kettering Cancer Center in New York City.
Those women are likely to live for many years after their breast cancer treatment, so it’s important to understand what kinds of long-term follow-up they will need for their overall health, according to Watt.
He stressed that the point is not to deter women from receiving radiation therapy.
The study included 972 women who received radiation for stage 1 or stage 2 breast cancer between 1985 and 2008.
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If You Have Side Effects
Let your doctor or nurse know if you have side effects or are worried about anything.
When treatment ends you usually have regular appointments for about 5 years afterwards. You can talk to your doctor or nurse at these appointments. But you don’t have to wait for your next appointment if you get a new side effect or are worried about anything. You can bring the appointment forward.
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National Institute for Health and Care Excellence June 2018
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Treatment of primary breast cancerScottish Intercollegiate Guidelines Network, September 2013
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Postoperative radiotherapy for Breast Cancer: UK consensus statement
The Royal College of Radiologists, 2016
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Early Breast Cancer: ESMO Clinical Practice Guidelines 2019F Cardoso and others
How Is Radiation Therapy For Breast Cancer Performed
Most people lie on their back during the treatment though some breast treatments are performed while lying on your stomach . You place your arm above your head .
During the treatment, your treatment team:
- Positions and secures your body in the immobilization device. If you had a mastectomy, your provider might place a bolus on top of the treatment area to increase the radiation dose to the surface.
- Lines up the machine with the first treatment field. To protect themselves from radiation exposure, providers leave the room. Your provider can still hear and see you.
- Turns on the machine. You will hear a whirring noise, but you wont see the radiation beams. You must remain still. Depending on the radiation type and dose, treatment can take 30 seconds to several minutes.
- Returns to the room to position the machine to treat a different treatment field. Most people get treatment on two to five fields each day.
- Takes daily/weekly X-rays of the treatment field to make sure the radiation is hitting the correct area.
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Are There Any Risk Factors
Some people are more likely than others to develop radiation pneumonitis after radiation treatment. The biggest factor involves the size of the area receiving radiation treatment. The larger the area, the higher the risk of developing radiation pneumonitis. However, some newer, computer-assisted radiation techniques reduce this risk by delivering radiation more precisely.
Other things that can increase your risk include:
- receiving higher doses of radiation
- having poor lung function prior to treatment
In addition, taking chemotherapy drugs while receiving radiation therapy can also increase your risk. Chemotherapy drugs that may increase your risk include:
How Does Radiation Therapy Affect The Heart
Radiation therapy to the chest area often is part of the treatment for Hodgkin lymphoma and cancers of the lung, esophagus, or breast. Cardiotoxicity is a risk when a large volume of heart muscle is exposed to a high dose of radiation. Radiation dose is measured in Grays , and a heart dose of more than 30 35 Gy increases the risk of cardiotoxicity.
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What Are The Long Term Side Effects Of Radiation For Breast Cancer
Long-term side effects can include:Breast changes: The breasts may shrink or become more dense after radiation. Brachial plexopathy: Radiation to the breast or chest wall can sometimes damage the nerves that run through the arm, wrist, and hand. Lymphedema: Lymphedema is swelling of the arm, hand, or chest.
Increased Secretion Of Cxcl12 And Mif By Irradiated Lung Epithelial Cells

The composition of CMLE and CMLE_IR was assessed to determine which cytokines were secreted by unirradiated versus irradiated lung epithelial cell. Semi-quantitative results from a cytokine array showed that CMLE_IR contained a total of 52 cytokines with a signal that exceeded that of CMLE condition . We selected the CXCL12 and MIF cytokines for further study because of a high fold change and a known role in breast cancer metastasis . CXCL12 and MIF, which had an 83.88-and 86.46-fold higher presence, respectively, in CMLE_IR compared to CMLE . Responding to fold changes rather than absolute change is intrinsically important in chemokine attraction and consequently regulation of metastasis . Quantitative ELISA data showed that irradiated lung epithelial cells had a secretion of CXCL12 and MIF that is 5.8-and 7.9-fold higher, respectively, than unirradiated lung epithelial cells 3B) . According to previous literature, both cytokines may affect metastasis through activation of the CXCR4 receptor on cancer cells . Western Blot analysis confirmed that cancer cell lines, that are known to have an invasive phenotype, have a higher expression of CXCR4 .
Increased secretion of CXCL12 and MIF by irradiated lung epithelial cells
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Know Your Heart Risks
Before having radiation for breast cancer, a woman should have a discussion with her oncologistas well as her cardiologist. Ask the oncologist what dose of radiation youll be getting, and how your heart will be protected during treatment. Talk to your cardiologist about your existing heart risks, and how to reduce them.
Its especially important to consider your heart if youre also having chemotherapy, which is well known for its cardiotoxicity. We cant avoid the heart risks with chemotherapy, but with radiation we could lower them using better technology and better understanding, Dr. Taghian says.
Though you may not be able to fully protect your heart from cancer treatment, there are other lifestyle-based heart disease risks you can control. In the JAMA research letter, women who were least likely to develop heart disease were those who were already at low risk based on their cholesterol, blood pressure, and C-reactive protein levels. Make sure the blood pressure is under control, youre not smoking, you have a healthy lifestyle, and you control your cholesterol, Dr. Moslehi advises.
About the Author
Why Is Exercise Important For Breast Cancer Patients
The excess energy also affects other processes such as inflammation and fat metabolism, which play a role in heart disease. If diet and exercise are important for prevention, they remain important for people who have breast cancer, Mehta said. Many people with cancer think they need to rest, she said.
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Radiation For Breast Cancer
Radiation therapy is treatment with high-energy rays that destroy cancer cells. Some women with breast cancer will need radiation, in addition to other treatments.
Depending on the breast cancer’s stage and other factors, radiation therapy can be used in several situations:
- After breast-conserving surgery, to help lower the chance that the cancer will come back in the same breast or nearby lymph nodes.
- After amastectomy, especially if the cancer was larger than 5 cm , if cancer is found in many lymph nodes, or if certain surgical margins, such as the skin or muscle, have cancer cells.
- If cancer has spread to other parts of the body, such as the bones, spinal cord, or brain.
Radiation For Breast Cancer Can Increase Heart Risks
- By Stephanie Watson, Executive Editor, Harvard Women’s Health Watch
When my mother was treated for breast cancer several years ago, she had just one objective in mind: to eradicate the cancer. For her, radiation therapy was the best way to do that.
Radiation, on its own or coupled with other treatments, has given many women like my mother the chance to survive their breast cancer. Yet years later, some of these women are encountering a residual side effect from their radiationheart disease.
A new research letter published in JAMA Internal Medicineestimates that the increased lifetime risk for a heart attack or other major heart event in women whove had breast cancer radiation is between 0.5% and 3.5%. The risk is highest among women who get radiation to the left breastunderstandable, since thats where the heart is located.
The heart effects of radiation begin emerging as soon as five years after treatment, according to a large European study out earlier this year in The New England Journal of Medicine. That study also found that, for every 1 gray of radiation , a womans heart risk rises by 7.4%. Even small doses of radiation can cause trouble, says Dr. Alphonse Taghian, professor of radiation oncology at Harvard Medical School and chief of breast radiation oncology at Massachusetts General Hospital.
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Who Is More Likely To Get Lung Cancer After Radiation
You’re more likely to get lung cancer after radiation therapy if you’re a long-term smoker who kept smoking after cancer treatment. In one study, the risk of dying from lung cancer after radiation treatment for breast cancer was 4% for long-term smokers compared to 0.3% in nonsmokers.
Like radiation therapy, smoking also damages DNA. That’s why smokers are already at high risk for many types of cancer.
The dose of radiation you get and the area that’s exposed to radiation could affect your chance of getting lung cancer in the future. In general, your odds of lung cancer go up if you get higher doses of radiation and they’re delivered closer to your lungs.
When Should I Call The Doctor
You should call your healthcare provider if you experience:
- Severe skin or breast inflammation.
- Signs of infection, such as fever, chills or weeping skin wounds.
A note from Cleveland Clinic
Radiation therapy can lower the risk of cancer recurrence and cancer spread. The treatment affects everyone differently. Most side effects go away in a few months after treatments end. Some problems last longer. You should tell your healthcare provider about any problems you have while getting treatment. Your provider may change the therapy slightly to minimize issues while still effectively treating the cancer.
Last reviewed by a Cleveland Clinic medical professional on 03/19/2021.
References
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This Consequence Can Affect The Breast And Other Parts Of The Body
Rony Kampalath, MD, is board-certified in diagnostic radiology and previously worked as a primary care physician. He is an assistant professor at the University of California at Irvine Medical Center, where he also practices. Within the practice of radiology, he specializes in abdominal imaging.
In breast cancer treatment, radiation fibrosisscar tissue that forms as a result of damage caused by radiation therapycan occur in the breast and chest wall. It can also strike the lungs and bones. It often begins with inflammation during radiation therapy and is most common in the first two years post-treatment, though it can occur up to 10 years after therapy is completed.
Fibrosis is a potentially painful, life-long condition, as the tissue changes may be permanent. However, you have a lot of options for treating it, including medications, physical therapy, and more.
This article explains what you need to know about radiation induced breast fibrosis, including its causes, symptoms, and treatment options.
Fat Necrosis Versus Local Recurrence

The use of MR imaging has some advantages in the differential diagnosis of fat necrosis and a recurred lesion. MR imaging with fat suppression can suggest the possibility of fat necrosis. On contrast-enhanced MR imaging, no enhancement, early enhancement and spiculated enhancement for a cystic lesion containing fat-fluid level can suggest the possibility of fat necrosis. The use of three-dimensional fat-suppressed dynamic MR imaging also appears to be efficacious for the specific detection of malignancies .
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What Should I Expect After Radiation Therapy For Breast Cancer
You may notice fatigue as well as skin changes while undergoing radiation therapy. Your skin may become irritated, tender and swollen . People with fair skin may develop a red sunburn appearance. People with dark skin may notice darkening of the skin. This condition can also cause dry, itchy, flaky skin. Your skin may peel as you get close to finishing treatments . This skin irritation is temporary. Your provider can prescribe creams or medications to ease discomfort, if needed.
Skin discoloration can persist after treatment ends. Some people with fair skin have a slight pink or tan appearance for several years. You may also see tiny blood vessels in the radiated area. These vessels look like thin red lines or threads. These are not cause for concern.