Regional Nodal Irradiation in Early-Stage Breast Cancer

Amanda Breakey, Mercer University College of Pharmacy

According to the National Cancer Institute, radiation therapy following breast-conserving surgery greatly reduces the risk of local breast cancer recurrence and moderately reduces the risk of death from breast cancer.1 In a meta-analysis of multiple randomized phase III trials, the American Society for Radiation Oncology (ASTRO) stated that results conclusively demonstrated that survival after breast-conserving surgery followed by whole-breast radiation therapy is equivalent to mastectomy for the treatment of stages I and II invasive breast cancer. While whole-breast irradiation therapy has been the standard of care for over 20 years according to ASTRO, there is little evidence on the use of regional nodal irradiation following breast-conserving surgery.2

Title: Regional Nodal Irradiation in Early-Stage Breast Cancer3
Design Randomized controlled; N= 1,832
Objective Examine whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes in women with breast cancer following breast-conserving surgery.
Study Groups Whole-breast irradiation plus regional nodal irradiation (nodal-irradiation group; n= 916) and whole-breast irradiation alone (control group; n= 916)
Methods Before randomization, patients were stratified according to the following:

–       Number of axillary nodes that were removed (< 10 or ≥ 10),

–       Number of positive axillary nodes (0, 1 to 3, or > 3)

–       Type of chemotherapy (anthracycline-containing, other, or none)

–       Hormonal therapy (yes or no)

–       Treatment center

Following stratification and with the use of a centralized minimization procedure, patients were randomly assigned to one of the two study groups.

Duration 2000- 2007
Primary Outcome Measure Overall survival
Baseline Characteristics There was no significant difference between the groups at baseline. Baseline median age was 53 in control group and 54 in nodal-irradiation group. Most patients (99%) had tumors that were categorized as either T1 (measuring ≤2 cm) or T2 (measuring >2 cm but ≤5 cm), had one to three positive axillary nodes (85%), and had ER-positive disease (75%). Most of the patients received combination chemotherapy (91%) with an anthracycline (86%) or with a taxane (26%), along with endocrine therapy (76%).
Event WBI

(n= 916)


(n= 916)

No. of patients with event, (%)
Death 168 (18.3) 155 (16.9)
Breast cancer 113 (12.3) 93 (10.2)
Other cancer 26 (2.8) 32 (3.5)
Cardiovascular cause 11 (11.2) 11 (1.2)
Other cause 12 (1.3) 8 (0.9)
Unknown 6 (0.7) 11 (1.2)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events:

Adverse Event WBI (n= 927) WBI + RNI (n= 893)
           No. of patients with event (%)
Fatigue 13 (1.4) 16 (1.8)
Pain 5 (0.5) 7 (0.8)
Radiation dermatitis 23 (2.5) 45 (5.0)
Cardiac 2 (0.2) 8 (0.9)
Lymphedema 4 (0.4) 10 (1.1)
Neuropathy 1 (0.1) 6   (0.7)
Pneumonitis or fibrosis 1 (0.1) 0   (0)
Joint 2 (0.2) 0   (0)
Skin 2 (0.2) 11 (1.2)
Subcutaneous tissue 0 (0) 3   (0.3)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence.

The addition of regional nodal irradiation to whole-breast irradiation demonstrated a reduction in breast cancer recurrence in patients with node-positive or high-risk node-negative disease. However, regional nodal irradiation did not increase the rate of overall survival among these patients. The study was conducted from 2000-2007; and many of the newer evidence based standards of care in place today were not known or utilized during the time of this trial. The study suggests that clinical decisions should be tailored to fit the needs of individual patients.


  1. National Cancer Institute. Radiation Therapy after Breast-Conserving Surgery Improves Survival 2011. Accessed August 05. 2015.
  2. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88(3):553-64.
  3. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015;373(4):307-16. Accessed August 04, 2015.

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