Breast irradiation in women with early stage invasive breast cancer following breast conservation surgery. Provincial Breast Disease Site Group.

GUIDELINE QUESTIONS: 1) Should breast irradiation be given to women with early stage invasive breast cancer (stage I and II) following breast conservation surgery (lumpectomy with clear resection margins and axillary dissection)? 2) Is there an optimal schedule for breast irradiation? 3) What is a reasonable interval between definitive surgery and the start of breast irradiation? 4) Are there patients who can be spared breast irradiation after lumpectomy?

OBJECTIVE: To make recommendations about the use of breast irradiation in women with early stage invasive breast cancer following breast conservation surgery.

OUTCOMES: Local control is the primary endpoint of interest. Survival, quality of life (addressed through the adverse effects of radiotherapy) and cosmesis are also considered.

PERSPECTIVE (VALUES): Evidence was selected and reviewed by 6 members of the Breast Disease Site Group (Breast DSG) of the Ontario Cancer Treatment Practice Guidelines Initiative. Earlier drafts of the evidence-based recommendation were reviewed, discussed and approved by the Breast DSG, which comprises medical oncologists, radiation oncologists, surgeons, epidemiologists, pathologists and a medical sociologist. There was no participation by a community representative in the development of this guideline.

QUALITY OF EVIDENCE: There are 5 randomized controlled trials (RCTs) and 1 meta-analysis comparing breast irradiation with no breast irradiation following breast conservation surgery; 6 randomized trials comparing breast conservation surgery plus breast irradiation with mastectomy are also included, as well as several retrospective studies.

BENEFITS: All of the 5 RCTs showed a significant decrease in local recurrence rates among patients receiving radiotherapy. In the 4 trials with a median follow-up of 5 years or longer, the relative risk reduction with breast irradiation ranged from 69% to 88%. The absolute differences ranged from 16% (p < 0.001) to 25% (p < 0.001). Despite the effect on local recurrence, no difference in survival was detected in any of the 5 trials. Most of the patients with local recurrence in these trials underwent mastectomy.

HARMS: Major adverse effects of breast irradiation occur very infrequently.

PRACTICE GUIDELINE: Women with early stage invasive breast cancer (stage I and II) who have undergone breast conservation surgery should be offered postoperative breast irradiation. The optimal fractionation schedule for breast irradiation has not been established, and the role of boost irradiation is unclear. Outside of a clinical trial, 2 commonly used fractionation schedules are suggested: 50 Gy in 25 fractions to the whole breast, or 40 Gy in 16 fractions to the whole breast with a local boost to the primary site of 12.5 Gy in 5 fractions. Shorter schedules (e.g., 40 or 44 Gy in 16 fractions) have also been used routinely in some centres. The enrollment of patients in ongoing clinical trials is encouraged. Women who have undergone breast conservation surgery should receive local breast irradiation as soon as possible after wound healing. A safe interval between surgery and the start of radiotherapy is unknown, but it is reasonable to start breast irradiation within 12 weeks after definitive surgery. For women who are candidates for chemotherapy, the optimal sequencing of chemotherapy and breast irradiation is unknown. It is reasonable to start radiotherapy after the completion of chemotherapy, or concurrently if anthracycline-containing regimens are not used. For further information, please refer to Ontario Cancer Treatment Practice Guidelines Initiative's practice guideline "Surgical Management of Early Stage Invasive Breast Cancer (stage I and II)."