Tari A. King, MD

ABSTRACT The 21-gene Recurrence Score (RS) assay has been validated as both a prognostic and predictive tool in node-negative (pN0), estrogen receptor–positive (ER+), HER2-negative (HER2–) breast cancer. A large body of evidence supports the clinical utility of the RS in the node positive (pN+) population as well. Retrospective analyses of archived tissue from multiple clinical trials have found the RS to be prognostic in both endocrine therapy (ET)-treated and chemotherapy-treated patients with pN+ disease. Distribution of RS results in pN+ patients have also been consistent with those of pN0 populations. Data from the SWOG 8814 trial and large population-based registries further support the prognostic and potential predictive value of the RS. Specifically, patients with 1 to 3 positive nodes and RS less than 18 derived negligible benefit from adjuvant chemotherapy in these studies. In the prospective West German Study Group PlanB and ADAPT trials, pN+ patients with RS less than 11 and RS ≤25, respectively, who were treated with ET alone experienced excellent outcomes. Finally, 5-year results of the RxPONDER clinical trial randomizing patients with 1 to 3 positive nodes and RS ≤25 to ET alone vs ET plus chemotherapy confirmed an absence of chemotherapy benefit in postmenopausal patients. Clinical practice guidelines support use of the RS in the pN+, ER+/HER2– population, and many institutions have adopted the RS to guide clinical decision-making, resulting in a net reduction of adjuvant chemotherapy use. This review highlights the existing data supporting the prognostic and predictive ability of the RS in pN+ disease, current practice patterns related to RS use in this population, and emerging applications.

ABSTRACT Current guidelines for axillary surgery following systemic therapy do not differentiate between neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NAC). Without specific guidelines, many assume that axillary surgery after NET should mirror that after NAC; however, NET has traditionally been used for patients with biologically favorable disease, so alternative axillary surgery strategies may be appropriate. Unfortunately, clinical trials that have examined NET have not rigorously studied axillary management or outcomes. The limited observational data available reveal that axillary lymph node dissection (ALND) is less frequently performed for positive nodes following NET than NAC; ALND rates after NET are more like those of upfront surgery patients. Although outcomes of omitting ALND after NET in patients who remain node positive are unknown, hypothesis-generating work from the National Cancer Database suggests that most patients selected for NET have limited nodal burden, and the prognostic significance of residual nodal disease after NET may not carry the same implications as residual disease after NAC. As such, there is opportunity to define axillary surgery strategies after NET that differ from those used after NAC.