Based on the CALGB 9343 study, patients age ≥ 70 with pT1N0 ER/PR + HER2- breast cancer treated with lumpectomy and endocrine therapy have been considered candidates for omission of radiotherapy. This NCDB retrospective analysis of 11,891 patients was conducted to determine whether recurrence score (RS) test (Oncotype Dx) is predictive of who may benefit from radiation following breast conservation therapy. Patients were stratified based on their RS where: low risk=1-10, intermediate risk=11-25, high risk=26-99. The study found an overall survival benefit with the use of radiotherapy in patients with RS≥ 11, but not in patients with RS< 11. Among older women with hormone receptor positive breast cancer and high and intermediate scores, there was a survival benefit with the addition of radiation. The authors recommend assessment of RS in this older subset of patients and adjuvant radiation should be considered when RS ≥ 11. Future prospective studies should evaluate the use of RS to determine benefit of radiation.

Reference (Pub-Med Link): Chevli, N., Haque, W., Tran, K. T., et al. (2022). 21-Gene recurrence score predictive for prognostic benefit of radiotherapy in patients age ≥ 70 with T1N0 ER/PR + HER2- breast cancer treated with breast conserving surgery and endocrine therapy. Radiotherapy and Oncology, 174, 37–43. https://doi.org/10.1016/j.radonc.2022.06.013

Key Institution: USA (NCDB analysis)
Keywords: Cancer Biology, Breast

Long-term (five-year) follow-up of TARGIT-A, a prospective phase III randomized trial of 1153 patients ≥ age 45 with invasive ductal carcinoma of the breast no larger than 3.5cm status post breast-conservation surgery randomized to delayed intraoperative radiation therapy (IORT) delivered as second operative procedure via reopening of lumpectomy site vs external beam radiation therapy (EBRT). Primary outcome: Noninferiority margin of 2.5% local recurrence (LR) rate at 5 years. 581 patients were randomized to IORT, 572 to EBRT. Delayed IORT was not non-inferior to EBRT. The 5-year LR rate was 3.96% for IORT vs 1.05% for EBRT (statistically significant). At long-term follow-up at median 9 years, the following measures were not statistically significantly different between groups: LR-free survival, mastectomy-free survival, distant disease-free survival, overall survival. Conclusion: patients treated with delayed IORT after lumpectomy had a higher rate of local recurrence compared to patients treated with EBRT, though no difference in mastectomy-free survival, distant disease-free survival, or overall survival.  

(Open Access)

Reference (PubMed Link): Vaidya JS, Bulsara M, Saunders C, et al. Effect of delayed targeted intraoperative radiotherapy vs whole-breast radiotherapy on local recurrence and survival: Long-term results from the targit-a randomized clinical trial in early breast cancer. JAMA Oncol 2020;6:e200249.

Key Institution: Multi-Institution (TARGIT-A trial)
Keywords: Breast cancer, intraoperative radiotherapy, whole breast irradiation

This trial was a randomized phase 3 non-inferiority trial which compared standard hypofractionated (40 Gy in 15 fx) to two ultra-hypofractionated regimens (26 Gy and 27 Gy in 5 weekly fx). Over 4000 patients were included and were T1-T3, N0-2, M0, any hormone and HER2 status allowed, after both breast conserving surgery and mastectomy.  No nodal coverage was allowed but 10 Gy or 16 Gy boost was allowed in 2 Gy fractions (25% received boost across all arms). Ipsilateral breast recurrence at5 years was found to be noninferior in both 26 and 27 Gy groups, and clinician as well as patient and photographic assessments of breast cosmesis were noninferior in the26 Gy group. There was also no difference in distant relapse or mortality between arms at 5 years. Of note very low risk patients (aged ≥65 years, pT1, grade 1 or 2, estrogen receptor [ER] positive, HER2 negative, pN0, M0) were excluded part way through the trial to increase the event rate. Overall, this trial showed very favorable results for the 26 Gy in 5 fx group with a moderate follow up in a favorable group of patients

(Open Access)

Reference (PubMed Link): Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.

Key Institution: Multi-Institutional
Keywords: Hypofractionated, breast cancer

This paper reports on a randomized controlled trial of women >40 years old with DCIS or N0 breast cancer treated with lumpectomy and randomized to external beam APBI (38.5Gy/10fx BID) or whole breast RT (WBI)(45.4/16fx or 50Gy/25fx). Primary outcomes were ipsilateral breast tumor recurrence (IBTR). 2135 women enrolled with median follow-up of 8.6 years. 8-year cumulative rates of IBTR were 3.0% with APBI and 2.8% with WBI, not significantly different. Acute >grade 2 toxicity occurred in 28% in APBI and 45% in WBI (p<0.0001). Late >grade 2 toxicity was 32% in APBI and 13% in WBI (p<0.0001). Adverse cosmesis was more common after APBI at 3 years (absolute difference 11.3%), 5 years (16.5%) and 7 years (17.7%). Overall, APBI had non-inferior IBTR compared to WBI. Although there was less acute toxicity with APBI, there was increased late toxicity as well as adverse cosmesis (potentially related to the BID fractionation schedule). 

Reference (PubMed Link): Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (rapid): A randomised controlled trial. Lancet 2019;394:2165-2172.

Key Institution: Multi-Institution (Canada, Australia, NZ)
Keywords: Breast cancer, APBI, whole breast irradiation