Single dose intraoperative radiotherapy (IORT) has gained popularity in the United States since the mid-2000s (1), with low complication and in-breast recurrence rates reported in the literature (1–3). Patients selected for IORT treatment are generally low risk individuals given their older age, smaller tumors, and high rates of estrogen receptor positivity (ER+) (1). The updated American Society for Radiation Oncology (ASTRO) consensus statement on partial breast irradiation delineates specific suitable characteristics (including 50 years of age or older with <2.5 cm screen detected invasive tumors of low or intermediate grade) for patients to be considered for low energy x-ray IORT treatment (3). In addition, it recommends low energy x-ray IORT should be offered as part of a prospective registry or trial.

Oncotype DX is a genomic assay which became available in the United States in 2004, with increasing use since it was first introduced (4). This assay informs risk of metastatic disease recurrence via recurrence score (RS) and thus can guide chemotherapy and antihormone therapy recommendations in select breast cancer patients. Current national guidelines including those from National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) support consideration for RS testing in select patients who have small ER+, HER2 negative breast cancers (5,6). RS testing can also be applied to patients with limited lymph node positive disease in select circumstances (4,7).

Based on current guidelines, there exists overlap between patients who may be candidates for IORT and those who may be considered for RS testing. In addition, RS is another way to assess the risk profile of patients currently being selected for IORT. However, data on RS testing in patients receiving IORT is lacking. Therefore the purpose of this study was to evaluate the pattern of RS testing and results, subsequent adjuvant chemotherapy recommendations, and antihormone therapy use in IORT patients treated at a single institution.

This is the largest study, to our knowledge, to evaluate RS testing utilization, results, and subsequent chemotherapy recommendations in IORT patients.

In the United States, between 10 and 39% of patients with breast cancer undergo risk stratification with RS testing (8,9). Rates of testing are highest for those individuals who are borderline candidates for adjuvant chemotherapy including younger women with intermediate grade tumors and limited lymph node involvement (8). Our study demonstrates a rate of RS testing of 24.3% with younger age and smaller tumor size associated with increased likelihood of testing.

Meta-analysis indicates that on a national level, low risk score occurs in 48.8% of tested patients; intermediate risk in 39.0%; and high risk in 12.2% (10). In prior studies of all breast cancer patients, high RS has been most closely associated with tumor grade and progesterone receptor status, although age, T stage, and lymphovascular invasion are also linked to increased RS (11,12). The IORT patients in our study have a better RS profile compared to the national trends, and are in keeping with those documented in a prior publication on IORT patients (13). Low risk (53%) and intermediate risk (44%) scores are more common in IORT patients, whereas high risk score (3%) is far less common. These results are in keeping with the patient and pathologic characteristics of the group and confirm that biologically low risk individuals are being offered IORT based on current guidelines.

Despite 24.3% (36/150) of IORT patients undergoing RS testing, adjuvant chemotherapy was added in only 2/36 tested individuals (5.5%) based on RS results. This is far below previous national data which indicates that adjuvant chemotherapy recommendation changes in 33% of patients after RS testing (10). Specifically, intermediate RS patients receive chemotherapy 12–80% of the time and high RS patients up to 95% of the time (14). High RS is associated with increased chemotherapy use (15). In our study, the rate of chemotherapy was 100% for high RS (one patient), but the rate of chemotherapy in intermediate risk patients was quite low (1/16, 6.3%). This is likely multifactorial and reflects the lower traditional clinical risk profile in the IORT patient population (1). Thus in general, RS testing is of limited clinical utility in terms of informing adjuvant chemotherapy for IORT patients with a similar profile to those in this study.

In terms of antihormonal treatment, the IORT patients in this study had a higher rate of medication compliance (85.5%) at the time of their last follow-up compared to national averages. Nationally antihormonal medication compliance is as low as 49% (16), with highest estimates indicating 67–78% compliance (17,18). At our institution, all multidisciplinary breast cancer providers stress antihormone medication compliance at each visit for all ER+ patients (IORT or otherwise). This focus and increased patient communication as to the importance of these medications may contribute to the observed high compliance rate.

Overall, our study documents RS testing frequency and results in IORT patients, assesses changes in adjuvant chemotherapy treatment based on RS, and evaluates antihormonal compliance in patients who receive IORT. Currently selected IORT patients who receive RS testing are most likely to have low or intermediate risk scores; high risk scores are rare. RS testing rarely results in adjuvant chemotherapy administration. This study confirms that biologically low risk patients are being selected for IORT and supports continued selective use of RS testing in IORT patients.