Background: Background:A plethora of studies have failed to define a group of patients that can forgo radiation to complete BCS without a significant increase in recurrence rate. This has resulted in overtreatment with radiation of an estimated 85% of patients with favorable breast cancers. RFA added to standard BCS (eRFA) may not only reduce the need for re-excision for close or focally positive margins but may obviate the need for whole breast irradiation in favorable breast cancer patients. Methods: In an IRB-approved risk-adjusted protocol, 267 T0-2, No breast cancer patients from 7 different sites were screened for a Phase II multicenter protocol of BCS followed by cavitary RFA (eRFA) without adjuvant radiation and followed for margins, recurrence, breast pain, cosmesis and QOL. Results: 242 patients were accrued to the study with a median follow-up of 36 months. Re-excision for positive margins was < 5%. The in breast recurrence rate was 2.5%. In this risk adjusted model XRT was added when SLNB was positive. 20% of cohort received XRT. Breast pain @ 6 months was 19% with RFA+XRT Versus 1.7% with RFA alone(p < 0.05). Cosmesis was good or excellent in > 90% of patients. QOL did not change after eRFA. Conclusions: eRFA may be a new paradigm for treating favorable patients that desire lumpectomy who either cannot or do not want radiation. A majority of the patients avoided re-excision, WBI and/or mastectomy. Treatment in lieu of XRT is safe and effective and may increase definitive treatment compliance for patients as it is complete at the time of surgery. Clinical trial information: 01153035.