Updated National Comprehensive Cancer Network (NCCN) guidelines for the management of invasive breast cancer (version 1.2017) recommend that maximal disease stage guide radiation therapy. An overview of the guideline as it relates to radiation therapy was provided by Kilian E. Salerno, MD, at the NCCN 22nd Annual Conference held in Orlando, FL.
Define the Target
Dr Salerno, Director of Breast Radiation and Soft Tissue/Melanoma Radiation, Roswell Park Cancer Institute, Buffalo, NY, addressed the appropriate choices for radiotherapy (whole breast irradiation, partial breast irradiation, radiation to the chest wall, and regional nodal irradiation [RNI]) for various patient subgroups. “When we’re treating, we really want to define what the target is,” she said.
The clinical trials that have informed the NCCN guidelines are the EBCTCG meta-analysis, as well as the MA.20 and EORTC 22922 trials, the latter 2 having assessed the efficacy of RNI.
The EBCTCG meta-analysis of 22 randomized clinical trials found reductions in 10-year locoregional recurrence and overall recurrence and 20-year breast cancer mortality with radiation therapy after mastectomy and axillary surgery in women with 1 to 3 positive nodes. The absolute benefit on disease-free survival with radiation therapy was 5.6% at 10 years and 7.9% at 20 years. No benefit was found in patients with node-negative disease.
The NCCN guidelines state that hypofractionation is the preferred method of delivering radiation therapy. Hypofractionation employs a shorter treatment course using larger doses per fraction. It achieves local control and breast cosmesis that is at least equivalent to that achieved with conventional fractionation, said Dr Salerno. “I really hope that we move away from this concept of standard fractionation being conventional because I would argue for breast radiation, hypofractionation is standard as well.”
The recommendation is to deliver a total of 40 to 42 Gy in daily fractions for whole breast radiotherapy, or 34 to 38.5 Gy given in twice-daily fractions for accelerated partial breast irradiation (APBI).
Following breast-conserving therapy, the NCCN guidelines include radiation therapy to the whole breast, preferably with hypofractionation, with or without a boost. The use of radiation therapy should be guided by maximal disease stage at diagnosis (before chemotherapy) and also by pathology results after chemotherapy is completed.
For patients with node-negative invasive breast cancer, whole breast irradiation with or without boost to the tumor bed is recommended. RNI should be considered in patients with 1 to 3 positive nodes and central/medial tumors or tumors >2 cm with other high-risk features (ie, young age or extensive lymphovascular invasion).
Following mastectomy, evidence is strong that radiation therapy reduces the risk of locoregional recurrence and breast cancer–specific mortality. Use of radiation in this setting should be based on the patient’s risk that considers life expectancy, age, comorbidities, tumor features, response to neoadjuvant chemotherapy, and biologic subtype.
“Preliminary studies of APBI suggest that rates of local control in selected patients with early-stage breast cancer may be comparable to those treated with standard whole breast radiation therapy,” according to the updated guideline. The NCCN guidelines for suitability of APBI accepts the updated American Society for Radiation Oncology criteria:
- ≥50 years of age with invasive ductal carcinoma in situ (DCIS) measuring ≤2 cm (T1 disease) with negative margin widths ≥2 mm, no lymphovascular invasion, estrogen receptor (ER)-positive status, and negative for the BRCA mutation
- Low/intermediate nuclear grade, screen-detected DCIS measuring ≤2.5 cm with negative margin widths ≥3 mm.
Omission of Radiation
Omitting radiation altogether is acceptable in selected patients at low risk of recurrence. These are as defined by women aged ≥70 years with clinical stage I, ER-positive/progesterone receptor–positive, clinically node-negative disease with negative surgical margins who will receive adjuvant endocrine therapy.
Two new categories for omission of radiation are patients with homozygous ATM mutation and those with Li-Fraumeni syndrome.
RNI: Consider Individual Risk
The decision to use RNI should be based on an assessment of individual risk for recurrence using nomograms or recurrence scores, said Dr Salerno. RNI was found to improve locoregional disease-free survival, distant disease-free survival, and breast cancer mortality, but not overall survival, with 10-year median follow-up in women who underwent breast-conserving surgery in the MA.20 and EORTC22922 studies.
In general, RNI is recommended for patients with ≥4 positive nodes or locally advanced disease. It should be strongly considered for patients with 1 to 3 positive nodes, according to the NCCN, and may also be considered for node-negative patients at high risk for recurrence.
EBCTCG (Early Breast Cancer Trialists’ Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127-2135.
Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-316.
Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373:317-327.
Correa C, Harris EE, Leonardi MC, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol. 2017;7:73-79.