Kilian E. Salerno, MD
Updated guidelines for the management of invasive breast cancer, issued by the National Comprehensive Cancer Network (NCCN), define indications for radiation therapy, the use of biomarkers and multigene assays in clinical decision making, and new concepts in endocrine therapy in early-stage and advanced-stage estrogen receptor (ER)-positive breast cancer.
An overview of the updates added to version 1.2017 of the NCCN guidelines1 was presented at the 2017 NCCN Annual Conference.
Suitability Requirements for Radiation Targets
“When we’re treating, we really want to define what the target is,” said Kilian E. Salerno, MD, associate professor of oncology and director of breast radiation and soft tissue/melanoma radiation, Roswell Park Cancer Institute, and clinical associate professor, Department of Radiation Oncology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo. Treatment targets for radiation in breast cancer include wholebreast irradiation, partial-breast irradiation (PBI), radiation to the chest wall, and regional nodal irradiation (RNI).
A meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) informed the need for radiation therapy following surgery in the updated guidelines, showing that radiation therapy reduced the incidence of locoregional recurrence, overall recurrence, and breast cancer mortality in patients with ≥4 positive nodes.2
Similar effects were seen in patients with fewer positive nodes.
In women treated with whole-breast irradiation, an appropriate margin under the latest NCCN guidelines is 2 mm in women with ductal carcinoma in situ (DCIS) and “no tumor on ink” for women with stage I-II invasive carcinoma. The preferred method of delivering radiation therapy, according to the NCCN, is hypofractionation, which employs a shorter treatment course that uses larger doses per fraction. Hypofractionation achieves local control and breast cosmesis that is at least equivalent to that achieved with conventional fractionation, said Salerno.
“I hope that we move away from this concept of standard fractionation being conventional because I would argue that for breast radiation, hypofractionation is standard as well,” Salerno said. 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 PBI (APBI).
The NCCN guidelines for suitability of APBI accept the updated American Society for Radiation Oncology criteria,3
which stipulate that patients ≥50 years with invasive DCIS measuring ≤2 cm (T1 disease) with negative margin widths of ≥2 mm, no lymphovascular invasion, ER-positive status, and negative for the BRCA
mutation, and patients with a low or intermediate nuclear grade screen-detected DCIS measuring ≤2.5 cm with negative margin widths of ≥3 mm are both eligible for APBI.
Omission of radiation is acceptable in selected women at a lower risk of recurrence, as defined by women ≥70 years with clinical stage I, ER-/progesterone receptor-positive, clinically node-negative disease with negative surgical margins who would receive adjuvant endocrine therapy.
Whether or not to treat with RNI is based on assessment of an individual’s risk for recurrence using nomograms or recurrence scores, said Salerno. RNI was found to improve locoregional disease-free survival (DFS), distant DFS, and breast cancer mortality, with 10 years’ median follow-up in women who underwent breast conservation surgery in the MA.204
studies. Both studies looked at higher-risk patients and reduced the rate of regional and distant recurrences. However, an improvement was not seen in overall survival.
In general, RNI is recommended for patients with ≥4 positive nodes or locally advanced disease, should be strongly considered for patients with 1 to 3 positive nodes, and may be considered for node-negative patients at high risk of recurrence (Table).
Table. Locoregional Treatment by Surgical Axillary Staging After Mastectomy
Incorporating Multigene Assays
The latest version of the NCCN breast cancer guidelines incorporate the use of genomic expression profiling to assist in adjuvant treatment decision making in women with hormone receptor (HR)-positive, HER2-negative breast cancer. Lee S. Schwartzberg, MD, povided a summary of the state of biomarkers and multigene assays in breast cancer.