IMPORTANCE Based on randomized evidence expert guidelines in 2011 endorsed shorter hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients. without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. EXPOSURES PHA 408 Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks HGF of treatment). MAIN OUTCOMES AND MEASURES Use of hypofractionated and conventional WBI total and radiotherapy-related health care expenditures and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment age comorbid disease prior chemotherapy axillary lymph node involvement intensity-modulated radiotherapy practice setting and other contextual variables. RESULTS Hypofractionated WBI increased from 10.6%(95%CI 8.8%-12.5%) in 2008 to 34.5%(95%CI 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95%CI PHA 408 6 in 2008 to 21.2%(95%CI 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures PHA 408 in the 1 year after diagnosis were $28 747 for hypofractionated and $31 641 for conventional WBI in the hypofractionation-endorsed cohort (difference $2894; 95%CI $1610-$4234; < .001) and $64 273 for hypofractionated and $72 860 for conventional WBI in the hypofractionation-permitted cohort (difference $8587; 95%CI $5316-$12 017; < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBI in either cohort. CONCLUSIONS AND RELEVANCE Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However only 34.5%of patients with hypofractionation-endorsed and 21.2%with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013. Breast cancer accounts for the largest portion of national PHA 408 expenditures on cancer care estimated to reach $158 billion in 2020.1 Breast conservation therapy is the most common treatment for early-stage breast cancer.2 Whole breast irradiation (WBI) recommended for most women after breast conserving surgery reduces local recurrence and improves overall survival.3 Conventional WBI comprising 5 to 7 weeks of daily radiation fractions (ie treatments) has been the mainstay of treatment in the United States. Hypofractionated WBI is a shorter duration treatment alternative to conventional WBI comprising fewer but higher-dose fractions generally delivered over 3 weeks. In 2010 2010 the Ontario Clinical Oncology Group published updated findings from a randomized trial with 12-year median follow-up showing that a 3-week hypofractionated WBI schedule yielded similar cancer control and breast cosmetic outcomes to a 5-week conventional WBI schedule.4 5 These findings reinforced the body of evidence supporting shorter radiation treatment schedules from 3 prior randomized trials (the United Kingdom’s Standardisation of Breast PHA 408 Radiotherapy (START)-A and START-B and the Royal Marsden Hospital/Gloucester Oncology Center trials).6-9 In 2011 American Society for Radiation Oncology practice guidelines endorsed hypofractionated WBI as “equally effective for in-breast tumor control and comparable in long-term side effects” with conventional WBI for patients with early-stage breast cancer who satisfied 4 criteria: age 50 years or older pathologic stage T1 or T2N0 no prior chemotherapy and radiation dose heterogeneity higher or lower than 7% of prescription dose. The guidelines10 also permitted hypofractionated WBI for other patients with early-stage breast cancer stating that “this guideline should not be interpreted to prohibit or oppose the use of hypofractionated WBI for patients not meeting all the criteria ” particularly among women younger than 50 years old in whom “the available data did appear to support the equivalence of conventional and hypofractionated WBI.” In 2013 the Choosing Wisely initiative aimed at reducing low-value health care encouraged physicians and patients undergoing breast conservation therapy to discuss the duration of WBI a.