Why is radiation used?
Who should receive radiation therapy?
How is radiation therapy delivered?
How soon after surgery should radiation start?
Radiation Reduces Mortality at 15 Years in Early Breast Cancer
According to a recent article published in the Lancet, radiation to the breast following surgery in early breast cancer not only reduces local recurrences, but also reduces mortality at 15 years following therapy.
Early breast cancer refers to cancer that is confined to the breast and/or axillary (under the arm) lymph nodes. Standard treatment for early breast cancer includes surgery to remove the cancer. Surgery may include breast-conserving therapy followed by radiation therapy, or a complete removal of the breast with or without radiation therapy.
Studies have indicated that radiation following surgery reduces the risk of a local or regional (locoregional) recurrence (cancer recurrences at or near the site of origin). However, long-term studies have been limited with regard to long-term survival that is associated with reductions in recurrences.
Researchers affiliated with the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) recently completed a large study to evaluate a possible association between mortality and locoregional recurrence rates in women with early breast cancer. Information included 42,000 women from 78 clinical trials that compared 24 different types of local treatments. Among these trials, however, only 10 trials that directly compared breast-conserving therapy with or without radiation therapy to mastectomy with or without radiation therapy resulted in a significant difference in locoregional recurrences and 15-year mortality.
- Approximately 75% of all locoregional recurrences occurred within the first 5 years following treatments.
- Radiation in patients treated with breast-conserving therapy reduced locoregional recurrences by 19%.
- 15-year mortality from breast cancer was reduced from nearly 36% to 30.5% in patients treated with radiation therapy following breast-conserving therapy compared to those not treated with radiation therapy.
- Radiation in patients treated with a mastectomy reduced locoregional recurrences by 17%.
- 15-year mortality from breast cancer was reduced from 60% to 54.7% in patients who received radiation therapy following a mastectomy compared to those treated with a mastectomy alone.
The researchers concluded that a reduction in the risk of locoregional recurrences with the use of radiation therapy significantly reduces the long-term risk of death caused by early breast cancer.
Reference: Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of Radiotherapy and of Differences in the Extent of Surgery for Early Breast Cancer on Local Recurrence and 15-Year Survival: an Overview of the Randomised Trials. Lancet. 2005; 366:2087-2106.
A shorter course and lower doses of radiation therapy to the breast results in equivalent outcomes among patients with early breast cancer who have undergone surgery compared to the standard longer course and higher doses.(1,2)
Early breast cancer is often treated with the surgical removal of the cancer followed by radiation therapy. Radiation therapy is used to kill cancer cells that may be remaining in the surrounding areas following surgery. Radiation therapy is associated with significant time commitments for patients and caregivers as well as side effects; in an effort to reduce these complications, lower doses and shorter courses of radiation therapy are being compared to standard radiation schedules.
Researchers from Canada recently conducted a clinical trial to compare the risk of cancer recurrences between two different radiation schedules among patients with early breast cancer. This trial included 1,234 women whose cancer had not spread to their lymph nodes. Participants had undergone the surgical removal of their cancer (lumpectomy) followed by either the standard radiation schedule or a shorter schedule with lower doses of radiation therapy. At 10 years recurrence rates were 6.7% for women treated with the standard radiation schedule compared with 6.2% for those treated with the shorter schedule.
The researchers concluded that for women with early breast cancer, a shorter radiation schedule with lower doses of radiation therapy provides equivalent results to that of the standard radiation schedule. In Canada the shorter course of radiation therapy has already been adopted as standard therapy, and it is thought that the United States will adopt the new radiation course soon.
What About Brachytherapy?
Alternative Approach to Breast Irradiation Shows Promise
According to a study presented at the annual meeting of the American Society for Therapeutic Radiology and Oncology, a one-week course of radiation therapy administered by balloon brachytherapy after lumpectomy for breast cancer has produced promising results. This approach requires much less time than standard radiation therapy.
Early breast cancer refers to cancer that has not spread outside the breast or axillary (under the arm) lymph nodes. Treatment for early breast cancer may involve breast-conserving therapy (lumpectomy), in which only the area of cancer and a margin of healthy tissue are surgically removed, followed by radiation therapy. Standard radiation therapy involves five to seven weeks of treatment.
In an attempt to shorten treatment time, researchers are exploring balloon brachytherapy as an alternative way to deliver radiation therapy after lumpectomy. With this approach, a small balloon is inserted into the lumpectomy cavity (the space created when the tumor is removed). A catheter attached to the balloon is used to deliver radioactive “seeds” to the site. This approach limits exposure of healthy tissue to radiation and can to shorten treatment time to a week or less by delivering high doses of radiation.
Preliminary results from a study of women treated with balloon brachytherapy using the MammoSite® Radiation Therapy System were presented at the 2005 Annual Meeting of the American Society for Therapeutic Radiology and Oncology. The study evaluated 43 breast cancer patients who have been followed for a median of four years after treatment with MammoSite. Thus far, there have been no cancer recurrences among these women, and a majority has had a good cosmetic outcome. These women will be followed for a total of ten years in order to further assess treatment outcomes.
The lead author of the study stated, “This radiation technique is an excellent option for women with early breast tumors, especially those who are unable to have the standard six-week course of radiation, due to time constraints.” He notes that as many as 100,000 women per year in the U.S. could benefit from this approach.
Reference: American Society for Therapeutic Radiology and Oncology (ASTRO) Press Release. New One Week Radiation Treatment for Breast Cancer Patients Offers Promising Results. October 17, 2005.
Breast Brachytherapy Linked with More Complications and Higher Mastectomy Rate
Among women with early-stage breast cancer, use of brachytherapy to administer radiation therapy may result in more post-operative complications than conventional external beam radiation therapy, and may also increase the likelihood that a woman will later require a mastectomy. These results were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.
For women with early-stage breast cancer who are treated with breast-conserving surgery (lumpectomy), surgery is generally followed by radiation therapy in order to reduce the risk of cancer recurrence. Radiation therapy is often delivered to the whole breast from a machine outside the body (external beam radiation therapy). This treatment is commonly delivered on a daily basis for several weeks.
Breast brachytherapy is an alternative to traditional external beam radiation therapy for women who choose breast-conserving surgery. A specialized catheter that contains radioactive material is placed directly into the area of the breast where the cancer was removed. This is often done twice daily over a period of a week or so. Because this approach requires many fewer weeks of treatment than conventional external beam radiation therapy, it may be a much more convenient option for the patient. Information about the safety and efficacy of breast brachytherapy is somewhat limited, however, and clinical trials to address these issues are underway.
While awaiting the results of ongoing clinical trials, researchers at the MD Anderson Cancer Center conducted an analysis of Medicare claims data. The analysis included information about more than 130,000 female Medicare beneficiaries who were diagnosed with invasive breast cancer between 2000 and 2007. All of the women included in the analysis had been treated with breast-conserving surgery followed by either breast brachytherapy or whole-breast external beam radiation therapy.
- Use of brachytherapy increased over time. In 2000, less than 1% of the women had been treated with brachytherapy. By 2007, 13% of women were being treated with brachytherapy.
- Postoperative complications were more common in the brachytherapy group. Infectious complications, for example, developed in 16% of women treated with brachytherapy and 10% of women treated with external beam radiation therapy.
- By five years after treatment, 4% of women treated with brachytherapy had required additional treatment with a mastectomy, compared with 2.2% of women who had received external beam radiation therapy. The researchers note that the higher rate of mastectomy in the brachytherapy group could be due to breast cancer recurrence or breast complications.
These results raise the possibility that breast brachytherapy may be less effective and more apt to cause breast complications than whole-breast external beam radiation therapy. This was not a randomized trial, however, and the results should not be viewed as definitive. Ongoing trials of breast brachytherapy will provide more conclusive information about the risks and benefits of this approach.
Reference: Smith GL, Xu Y, Buchholz TA, Giordano SH, Smith BD. Partial breast brachytherapy is associated with inferior effectiveness and increased toxicity compared with whole breast irradiation in older patients. Presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. December 6-10, 2011. Abstract S2-
Boost Radiation for Early Breast Cancer Improves Local Control but Not Survival
According to results recently presented at the 2006 annual San Antonio Breast Cancer Symposium, boost radiation among women with Stage I or Stage II breast cancer reduces the risk of cancer recurrence within the breast but does not affect 10-year survival.
Breast-conserving surgery is generally followed by radiation therapy. In addition to receiving radiation therapy to the entire breast, women with early breast cancer often receive an additional boost of radiation to the area of the cancer.
To evaluate the benefits and side effects of boost radiation, researchers affiliated with the European Organisation for Research and Treatment of Cancer (EORTC) conducted a study among 5,318 women with early breast cancer.
After breast-conserving surgery, all patients received 50 Gy of radiation to the entire breast. Half the patients also received a 16 Gy radiation boost to the area of the cancer. The remaining patients received no further radiation therapy.
- Ten-year survival was 82% in both study groups (the group that received boost radiation and the group that did not receive boost radiation).
- The ten-year risk of cancer recurrence within the breast was 6.2% in patients who received boost radiation and 10.2% in patients who did not receive boost radiation.
- Young women (those under the age of 40) experienced the greatest reduction in recurrence risk following boost radiation.
- Severe fibrosis occurred in 4.4% of patients treated with boost radiation, compared with only 1.6% of patients who did not receive boost radiation.
The researchers concluded that the addition of boost radiation reduced the risk of cancer recurrence within the breast, particularly in younger patients, but did not improve 10-year survival.
Reference: Bartelink H, Horiot J, Poortmans P, et al. Impact of radiation dose on local control, fibrosis and survival after breast conserving treatment: 10-year results of the EORTC trial 22881-10882. Proceedings from the 2006 annual San Antonio Breast Cancer Symposium. Oral presentation December 14, 2006. Abstract #10.
Some Older Women with Early-Stage Breast Cancer May Be Receiving Radiation That Is Unlikely to Add Benefit
Up to two-thirds of older women with early-stage breast cancer may be receiving radiation therapy that may not provide additional benefit. These findings were recently released online by the journal Cancer.
The goal of radiation therapy in early breast cancer is to kill cancer cells that could otherwise remain after therapy and cause a recurrence. Studies have shown that patients with node-negative Stage I breast cancers who are treated with breast-conserving surgery (lumpectomy) and receive additional treatment with radiation therapy have improved outcomes. Patients who do not receive radiation after lumpectomy may be more likely to experience cancer recurrence. Based on recent findings, however, some researchers are questioning whether radiation is beneficial for all early breast cancer patients.
Findings suggest that women over age 70 who have Stage I estrogen-receptor positive breast cancer may not benefit from the addition of radiation therapy. According to a Phase III study, the Cancer and Leukemia Group B (CALGB) 9343 trial, these older patients might do just as well with lumpectomy and additional therapy with tamoxifen alone, rather than both tamoxifen and radiotherapy.
Researchers recently used data from the Surveillance, Epidemiology, and End Results (SEER) registry to assess the frequency of radiation therapy in addition to lumpectomy in older early-stage breast cancer patients. Researchers identified just over 40,000 women age 70 or older who underwent lumpectomy for early-stage breast cancer between 2000 and 2009. They assessed frequency radiation in addition to surgery among these women.
Among patients treated between 2000 and 2004, 69% received radiation in addition to lumpectomy, and 62% of those treated between 2005 and 2009 received additional radiation. Forms of radiation therapy included external beam, where radiation comes from a machine outside the body and is focused on the cancer, and implant radiation, where sources of radiation are put into or near the area that needs treatment. Use of implant radiation increased from just over 1% of patients between 2000 and 2004 to just over 6% between 2005 and 2009; the use of external radiation declined during this period. Radiotherapy in both forms was delivered less frequently over the course of the study.
The researchers concluded that while data from the CALGB trial indicated that radiation in addition to lumpectomy didn’t contribute to better outcomes for older women with early-stage breast cancer, many of these women continue to receive radiation. And while these researchers have observed a decrease in the amount of women receiving additional radiation, according to their findings, nearly two-thirds of older women continue to receive radiation that may not improve their outcomes over treatment with surgery and tamoxifen alone.
Risk of Heart Disease from Breast Cancer Radiation Declines
Although radiation exposure from breast cancer treatment is associated with a small risk of subsequent heart disease, the risk is lower than it was 20 years ago, according to the results of a study published early online in JAMA Internal Medicine.
Approximately 200,000 women are diagnosed with breast cancer every year in the United States alone. Treatment often involves radiation, used after surgery to kill any remaining cancer cells. This decreases the risk of local recurrence and improves survival. Like any treatment modality, however, radiation carries risks—including the increased risk of heart disease when radiation is used on the left breast, which is closer to the heart.
Because long-term breast cancer survival rates have improved dramatically in recent decades, researchers continue to look for ways to minimize long-term treatment-related complications. Researchers conducted an analysis to evaluate the risk of developing heart disease as a result of radiation treatment to the left breast—and found that the risk varies depending on the underlying risk of heart disease.
They report that the average risk of developing heart disease as a result of radiation exposure for breast cancer treatment is less than one percent. The risk increases for woman who already have a high underlying risk of developing heart disease—in these cases, the risk may be as high as 1 in 30. In contrast, women who already have a very low underlying risk of heart disease may face odds as low as 1 in 3000, which is a tiny risk.
The researchers note that the risk of developing radiation-induced heart disease is small enough that women should not skip radiation treatment as a result of this risk.
Women who have a high underlying risk of heart disease can reduce their risk of radiation-induced heart disease in the same way that anyone might reduce their risk—through healthy diet, exercise, and avoidance of tobacco. Researchers continue to investigate changes to radiation treatment that might reduce the risk of heart disease for high-risk patients in the future.
Brenner DJ, Shuryak I, Jozsef G, et al. Risk and risk reduction of major coronary events associated with contemporary breast radiotherapy. JAMA Internal Medicine. Published early online October 28, 2013. doi:10.1001/jamainternmed.2013.11790
Fatigue Persists in Some Patients Treated for Early Breast Cancer
According to an article recently published in the journal Cancer, fatigue is experienced by significantly more women treated for early breast cancer with chemotherapy and radiation than women who have not had cancer. This fatigue persists at six months following completion of therapy.
Early breast cancer is a highly curable disease with standard therapies. Because long-term survival is readily achieved, side effects from therapy, particularly those that persist, can significantly impact a patient’s quality of life.
Standard therapy for early breast cancer often includes chemotherapy and radiation therapy. Although side effects occurring during and immediately following treatment are well understood, those that persist long-term are still being identified.
Fatigue is a common side effect that is experienced by patients with cancer. Fatigue may be caused by the disease itself and may also be a side effect of therapy. Anemia, or low levels of red blood cells, is one known cause of fatigue; however, other causes are being evaluated in order to reduce or prevent fatigue.
Researchers from the Moffitt Cancer Center & Research Institute in Tampa, Florida, and the University of Kentucky recently conducted a clinical study to evaluate the presence of fatigue among patients with early breast cancer. This study included 221 women with Stages 0–II disease who were treated with either chemotherapy and radiation therapy or radiation therapy only. Fatigue levels were assessed at two, four, and six months after treatment was completed. Women who had not been diagnosed with cancer were also assessed for fatigue.
- There was more fatigue reported at all time measurements among breast cancer survivors than among women who had not been diagnosed with cancer.
- Differences in fatigue between breast cancer patients and women without cancer were attributed largely to treatment including both chemotherapy and radiation therapy.
The researchers concluded: “Findings suggest that fatigue is a greater problem for breast cancer survivors in the 6 months after completion of chemotherapy than for women with no cancer history. Future research should include longer-term follow-up to determine the persistence of fatigue in this population of survivors.”
Women with breast cancer who have completed therapy and are experiencing fatigue may wish to speak with their healthcare provider about reducing this side effect.
Reference: Jacobsen P, Donovan K, Small B, et al. Fatigue after treatment for early stage breast cancer. Cancer. 2007;110:1851 – 1859.
 Palta M, Palta P, Bhavsar NA, et al. The Use of Adjuvant Radiotherapy in Elderly Patients with Early-Stage Breast Cancer: Changes in Practice Patterns after Publication of Cancer and Leukemia Group B 9343. Cancer [early online publication]. December 8, 2014.
 Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343. Journal of Clinical Oncology. 2013 Jul 1;31(19):2382-7. doi: 10.1200/JCO.2012.45.2615.
Radiation Therapy for Early Stage Node Positive Breast Cancer
More Extensive Radiation Therapy May Provide Benefit in Early Breast Cancer.
The addition of regional lymph node irradiation (radiation therapy to lymph nodes around the breast) may improve outcomes for some women with early breast cancer. These results were published at the 2011 annual meeting of the American Society of Clinical Oncology.
Treatment of early breast cancer often involves breast-conserving surgery, whole-breast radiation therapy, and (when appropriate) systemic therapies such as chemotherapy and hormonal therapy. When the cancer has high-risk features, such as a large tumor size or more than three positive axillary (under-the-arm) lymph nodes, treatment may also involve radiation to the lymph nodes around the breast (regional nodal irradiation). For women with only a few positive axillary lymph nodes, however, it’s been uncertain whether this more extensive radiation provides a benefit.
To evaluate regional nodal irradiation, researchers conducted a study among 1,832 women with node-positive or high-risk node-negative breast cancer. In addition to breast-conserving surgery and other standard breast cancer treatments, women were assigned to receive either whole-breast radiation therapy or whole-breast radiation therapy plus regional nodal irradiation.
- Regional nodal irradiation reduced the risk of cancer recurrence. At five years, the risk of developing a recurrence in or near the breast was 3.2% among women treated with whole-breast radiation therapy plus regional nodal irradiation, compared with 5.5% among women treated with whole-breast radiation therapy alone.
- Regional nodal irradiation also reduced the risk of cancer recurrence at other sites in the body. Risk at five-years was 7.6% among women treated with whole-breast radiation therapy plus regional nodal irradiation, compared with 13% among women treated with whole-breast radiation therapy alone.
- Regional nodal irradiation increased the risk of side effects such as lymphedema (swelling caused by a build-up of lymph fluid) and pneumonitis (inflammation of the lungs).
In a prepared statement, the lead author of the study noted “These results are potentially practice-changing. They will encourage physicians to offer all women with node-positive disease the option of receiving regional nodal irradiation. Adding regional nodal irradiation improved disease-free survival, lowered the risk of recurrences, and there was a positive trend toward improved overall survival, while not greatly increasing toxicities.”
Reference: Whelan TJ, Olivotto I, Ackerman I et al. NCIG-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA1003.
Women diagnosed with early breast cancer may wish to speak with their radiation oncologist regarding their individual risks and benefits of different radiation schedules.
- Whelan TJ, et al. Long-term results of a randomized trial of accelerated hypofractionated whole breast irradiation following breast conserving surgery in women with node-negative breast cancer. Proceedings from the 2008 annual meeting of the American Society of Therapeutic Radiation Oncology. Plenary Session. Abstract #60.
- Dewar JA, Haviland JS, Agrawal RK et al. Hypofractionation for early breast cancer: First results of the UK standardization of breast radiotherapy (START) trials. Proceedings of the 43rd Annual Meeting of the American Society of Clinical Oncology. Chicago, IL. June 1-5, 2007. Abstract #LBA518.
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