Overview
The objective of radiation therapy to the breast is to kill cancer cells that could otherwise persist after therapy and cause breast cancer to relapse locally in the breast, surrounding chest wall, or axilla. Radiation therapy uses high energy x-rays to kill cancer cells that remain in the breast or surrounding lymph nodes after surgery. Radiation therapy is almost always utilized as part of the overall breast-conserving strategy because radiation decreases the risk of local cancer recurrence and improves survival. Radiation therapy is delivered to the breast and surrounding lymph nodes from a machine outside the body and is called external beam radiation therapy. Treatments are typically given daily over a 5-6 week period and additional concentrated radiation treatment, called a boost, may be given directly to a smaller area of the breast where the cancer was found.
Side effects from radiation therapy may include a swelling or heaviness in the breast, sunburn-like changes in the skin, and fatigue. Changes to the breast and skin usually go away in 6-12 months; however, in some women the breast may become smaller or firmer following radiation therapy. The size of the breast and the woman’s desire for breast reconstructive surgery are important considerations that should be addressed prior to receiving radiation treatment.
Ductal Carcinoma In Situ (DCIS)
Patients with DCIS treated with mastectomy do not need treatment with radiation therapy. Radiation therapy after a lumpectomy decreases the risk of cancer recurrence. In one clinical study, 818 women with DCIS and negative surgical margins were treated with breast radiation or no further therapy after a lumpectomy. Eight years following treatment, the recurrence of invasive cancer was 3.9% for patients treated with radiation therapy and 13.4% for patients not treated with radiation therapy.
Stage I Breast Cancer
Patients with node negative stage I breast cancers treated with breast-conserving surgery utilizing a lumpectomy are currently recommended to receive additional treatment with radiation therapy. This recommendation is based on 4 clinical studies that directly compared lumpectomy to lumpectomy plus radiation treatment. These studies found that patients treated with the combination of lumpectomy plus radiation had a superior clinical outcome. Other clinical studies have demonstrated that patients treated with lumpectomy without radiation are more likely to experience cancer recurrence than women treated with the combination of breast-conserving surgery and radiation.
Standard radiation therapy following a lumpectomy consists of a limited dose of radiation (50 Gy) to the entire affected breast. While this treatment leads to long-term outcomes similar to those from mastectomy, women under age 50 experience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. Researchers have theorized that an additional boost of radiation aimed only at the area from which the cancer was removed would reduce the rates of local recurrences, especially in younger patients.
The European Organization for Research and Treatment of Cancer conducted a clinical trial evaluating 5,318 women diagnosed with stage I or II breast cancer who had undergone a lumpectomy followed by the standard dose of radiation. Approximately half of the patients were given an additional small dose of radiation (16 Gy) to the area where the cancer had been located, while the other half received no additional treatment. Data indicated that the additional dose of radiation to the site of the removed cancer reduced the overall rate of a local recurrence by nearly 50%. Women 40 years old and younger exhibited the largest benefit, with local recurrences occurring in only 10.2% of patients receiving additional radiation, compared to 19.5% of those receiving standard treatment. Overall survival rates and the development of distant metastases were similar whether women received an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis (formation of scar tissue) were not affected by the additional radiation.
Patients with stage I node negative breast cancers treated with mastectomy do not typically require additional local treatment with radiation therapy. Some patients treated with mastectomy may however have an increased risk of local cancer recurrence. In these cases, the role of radiation therapy to prevent local cancer recurrence should be discussed with the treating oncologist. Node negative cancers at increased risk of local recurrence include cancers that involve the margin of resection.
Stage II-III Breast Cancer
Patients with node negative stage II breast cancers treated with breast-conserving surgery utilizing a lumpectomy are currently recommended to receive additional treatment with radiation therapy because radiation decreases the risk of local cancer recurrence and improves survival.
The role of radiation therapy following mastectomy in women with stage II or III breast cancer is somewhat controversial. An analysis of several clinical studies begun before 1985 found that radiation decreased the risk of local cancer recurrence by 67% and decreased the risk of dying from breast cancer by 6%, but did not improve survival. Survival was not improved because patients treated with radiation died for other reasons. These deaths resulted mainly from heart problems in older patients and could have been a late side effect from the radiation treatment. Because of these analyses, radiation therapy was not typically recommended for women with stage II or III breast cancer treated with mastectomy.
Standard radiation therapy following a lumpectomy consists of a limited dose of radiation (50 Gy) to the entire affected breast. While this treatment leads to long-term outcomes similar to those from mastectomy, women under age 50 experience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. Researchers have theorized that an additional boost of radiation aimed only at the area from which the cancer was removed would reduce the rates of local recurrences, especially in younger patients.
The European Organization for Research and Treatment of Cancer conducted a clinical trial evaluating 5,318 women diagnosed with stage I or II breast cancer who had undergone a lumpectomy followed by the standard dose of radiation. Approximately half of the patients were given an additional small dose of radiation (16 Gy) to the area where the cancer had been located, while the other half received no additional treatment. Data indicated that the additional dose of radiation to the site of the removed cancer reduced the overall rate of a local recurrence by nearly 50%. Women 40 years old and younger exhibited the largest benefit, with local recurrences occurring in only 10.2% of patients receiving additional radiation, compared to 19.5% of those receiving standard treatment. Overall survival rates and the development of distant metastases were similar whether women received an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis (formation of scar tissue) were not affected by the additional radiation.
In late 1997, the results of two clinical studies evaluating treatment with mastectomy followed by chemotherapy with or without radiation in premenopausal women with stage II-III breast cancer were reported in the New England Journal of Medicine. In both studies, women treated with radiation following mastectomy and chemotherapy lived longer and were less likely to develop a recurrence of cancer. Radiation therapy decreased the risk of dying from cancer by approximately 33%. The probability of surviving 10 years from treatment was increased from 54% to 64% and 45% to 54% in the two studies, respectively. No significant long-term side effects of radiation therapy were reported. Current evidence increasingly supports the use of radiation following surgery and chemotherapy in women with stage II or III breast cancer. Certain groups of women known to be at high risk of local breast cancer recurrence should strongly consider radiation therapy. These include:
- Cancer greater than 5 centimeters in greatest dimension
- 4 or more involved axillary lymph nodes
- Cancer involving the margin of resection
What is the Optimal Sequence of Radiation in Stage I-III Breast Cancer?
The timing or sequence of radiation therapy may be important. A large clinical study has addressed the question of whether radiation therapy should be given before or after chemotherapy following breast-conserving surgery. Following breast-conserving surgery, half the patients were treated with chemotherapy followed by radiation and half were treated with radiation followed by chemotherapy. The patients treated with chemotherapy followed by radiation were more likely to be alive 5 years from treatment than patients treated with radiation followed by chemotherapy. Patients treated with chemotherapy survived longer because they were less likely to experience systemic (metastatic) recurrence of their cancer. Patients treated with radiation first, however, were less likely to experience a local recurrence of their cancer.
It is much easier to treat local recurrence of cancer than systemic recurrence of cancer and this may explain why patients treated with chemotherapy followed by radiation had improved survival compared to patients treated with radiation followed by chemotherapy. An additional explanation is that delivering radiation therapy before chemotherapy treatment of systemic disease may adversely affect the doctor’s ability to deliver the chemotherapy treatment. Although the sequence of treatments is undergoing continued evaluation, the current data suggest that standard treatment of breast cancer outside the context of a clinical study should include definitive surgery first, followed by systemic chemotherapy and lastly, radiation. Hormone therapy can begin during or following radiation therapy. One notable exception to this sequence is patients with locally advanced breast cancer. In these patients, administration of chemotherapy prior to surgery (neoadjuvant) may allow for greater breast conversation.
Stage IV or Recurrent Breast Cancer
Radiation therapy also plays an important role in women with stage IV or recurrent breast cancer. Chemotherapy and hormonal treatment are the mainstay for women who have stage IV breast cancer at the time of diagnosis. Local control of breast cancer eradication has less impact on a patient’s outcome because the major cause of treatment failure is systemic cancer recurrence. Therefore, radiation therapy to the involved breast has not typically been recommended for women receiving systemic chemo-hormonal therapy for metastatic breast cancer.
More recent aggressive chemotherapy treatment of stage IV breast cancer has been reported to produce long-term survival without cancer recurrence in 15-20% of women. Since these women are not experiencing a systemic cancer recurrence, prevention of cancer recurrence in the breast or lymph nodes is of greater importance. The results of a clinical study in which women with stage IV breast cancer achieving a complete remission to chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant and local radiation to the breast was recently reported and raises the question of whether radiation may be beneficial in women with stage IV breast cancer in complete remission.
In this study, the patients in complete remission treated with radiation therapy had a lower relapse rate and were more likely to be alive without evidence of cancer recurrence than women not treated with radiation therapy. The chance of relapse was 36% in patients not treated with radiation, compared to 19% in patients treated with radiation. Thirty-one percent of patients treated with radiation were alive without evidence of cancer recurrence at 4 years following treatment, compared to 21% of patients who were not treated with radiation. Patients treated with radiation were also more likely to live longer, with 30% alive 4 years following treatment, compared to only 16% of patients not treated with radiation.
While this clinical study was not designed to evaluate the role of radiation therapy in patients achieving a complete remission to chemotherapy, consolidative treatment with radiation therapy after chemotherapy-induced clinical remissions in women with stage IV breast cancer appears to reduce the risk of cancer recurrence and may improve a patient’s chance of overall survival. Future clinical studies will need to be designed to evaluate the role of radiation in patients with stage IV breast cancer in a more formal manner.
Radiation for Palliation
Radiation therapy also plays an important role in providing symptomatic relief from advanced breast cancer. Patients developing metastatic cancer to the bone, skin, selected lymph nodes, and other sites can achieve a complete remission when treated with radiation to the site of cancer recurrence. Radiation can relieve symptoms from cancer and prevent fractures of bones when used early.
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