Abstract PL1: Critical Decision Making in Radiation Therapy for Breast Cancer in 2015
Authors: Harris JR 
Published: May 2016

Abstract
In 2005, the EBCTCG meta-analysis demonstrated for the first time that RT after either breast-conserving surgery (BCS) or mastectomy not only reduced local-regional recurrence (LRR), but also improved long-term survival. At the time, they (erroneously) postulated that for every 4 LRR's avoid at 5 years, there was an additional survivor at 15 years. The EBCTCG subsequently adopted 'any first recurrence' as the primary endpoint for the effect of RT based on 1 – RT's established systemic effect in reducing both local and distant recurrence, 2 – that time to LRR is not strictly valid, and 3 – that the ratio between reduction in LRR and improvement in survival no longer held up. The new 'ratio' is that for every 1.5 first recurrences avoided at 10 years, there is an additional survivor at 20 years.
Over the last several decades, there has been a substantial reduction in local recurrence (LR) after BCS and RT. In series of patients treated in the 1970's, 5-year rate of LR was about 10% and in more recent series, it is about 2%. This decrease is attributable to 1 – improved mammographic evaluation, 2 – improved pathologic evaluation, and probably most importantly, 3 – the benefit seen with the addition of adjuvant systemic therapy. Also, over this time frame, risk factors for LR evolved with approximated subtype using ER, PR, HER2 status and either grade or Ki-67 now the main risk factor. 5-year LR is 6% for triple negative cancers and only about 1% for Luminal A cancers. Finally, hypofractionated breast irradiation has been established as at least equal to conventional fractionation.
Updated EBCTCG results show consistent proportional benefits for RT after either BCS or mastectomy although the absolute benefit is quite small in many subgroups. The addition of RT to BCS improves 15-year mortality by 8.5% in node-positive patients, but only 3.3% in node-negative patients.
Additionally, in the context of routine adjuvant systemic therapy, breast tangential irradiation (that treats much of the lower axilla) is sufficient to avoid regional recurrence if only 1 or 2 sentinel nodes are involved obviating the need for cALND. Also, there is evidence that internal mammary node and supraclavicular irradiation can improve 10-year disease-free survival in some patients treated with ALND.
Critical issues currently include:
1. Which patients can be spared RT after BCS? The CALGB has established hormonal therapy alone as a reasonable option in patients aged &gt; 70 years with largely low-grade, node-negative, ER+ breast cancer. Efforts are underway to identify additional ER+ patients who can be adequately managed by hormonal therapy alone. We are testing this approach in patients aged 50-75 with node-negative Luminal A cancers as determined by the Prosigna PAM-50 assay.
2. Which patients can be treated with hypofractionated RT? Available evidence is that it is nearly all patients getting breast tangents assuming adequate dose homogeneity.
3. In patients with 1 or 2 + SN's, should they receive high tangents (per Z-11) or full axillary and SC irradiation (per MA.20)? No easy answer, but one can use MD Anderson nomogram to estimate likelihood of + nSN's. If this is &lt; 25-30%, consider high tangents. If the primary is in the inner quadrant, it seems prudent to contour the IMN's for possible inclusion.
Citation Format: Harris JR. Critical Decision Making in Radiation Therapy for Breast Cancer in 2015. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PL1.