Study shows neither improves survival outcomes in early-stage, ER-positive breast cancers

Neither sentinel lymph node biopsy (SLNB) nor radiotherapy was associated with improved five-year locoregional recurrence-free survival (LRFS) or disease-free survival (DFS) in older women with estrogen receptor (ER)-positive, clinically node-negative breast cancer, according to a study published in JAMA Network Open.

These results lend support to the continued de-implementation of both SLNB and RT according to the Choosing Wisely and National Comprehensive Cancer Network guidelines.

“Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published,” wrote senior author Priscilla F. McAuliffe, MD, PhD, of the UPMC Hillman Cancer Center, Magee-Women’s Research Institute, and the University of Pittsburgh School of Medicine, and colleagues.

“As the population in the United States ages, the incidence of cancers in older patients is estimated to increase, and these cancers are expected to account for nearly 70% of all cases diagnosed by 2030. A critical risk factor for the development of breast cancer is age, with most of those diagnosed being older than 65 years and nearly 20% being older than 75 years. Few guidelines exist for the clinical treatment of older patients with breast cancer because of their lack of representation in randomized clinical trials. Most breast cancer randomized clinical trials exclude women who are older, have existing comorbidities, and/or are cognitively impaired. Oncologists often make treatment decisions with uncertainty in this age group,” they wrote.

Further, management and treatment of breast cancer in older women can pose challenges, including the tendency for older patients to experience adverse treatment effects that can negatively affect their daily functioning.

“Older populations can be subjected to both overtreatment and undertreatment; because they are more likely to have comorbidities and functional limitations, physicians are less likely to treat cancers aggressively, leading to increased risk for locoregional recurrence and decreased overall survival. Conversely, overtreatment of a cancer that ultimately will not lead to death subjects these patients to unnecessary tests and procedures,” explained McAuliffe and colleagues.

The Choosing Wisely guideline was established by the American Board of Internal Medicine Foundation and recommends against the routine use of SLNB for axillary staging in patients older than 70 years with early-stage, hormone receptor-positive clinically node-negative breast cancer. The guideline was adopted by the Society of Surgical Oncology, but adherence remains low, and conclusive evidence supporting definitive omission of SLNB is lacking.

Further, the current guideline from the National Comprehensive Cancer Network (NCCN) recommends the deimplementation of radiotherapy in this group of patients, based on strong evidence from the Cancer and Leukemia Group B 9343 study, which showed that adjuvant tamoxifen citrate monotherapy, without radiotherapy, was a viable treatment strategy in this specific patient population.

Thus, McAuliffe and colleagues conducted this study, using data from an integrated cancer registry and EHR from a single healthcare system in Pennsylvania, to identify 3,361 women, ages 70 years or older (median age: 77.0 years), who had been diagnosed with early-stage, ER-positive, ERBB2-negative, clinically node-negative breast cancer treated at 15 hospitals. They further limited cases to those from 2010-2014, including 2,109 patients who were followed for a median of 4.1 years.

In all, 65.3% had undergone SLNB, while 54.4% received adjuvant radiotherapy. McAuliffe and fellow researchers document a steady increase of SLNB rates, 1.0% per year, despite the 2016 adoption of the Choosing Wisely guideline. Conversely, radiotherapy rates decreased slightly, by 3.4% per year.

They found no association between SLNB and either LRFS (HR: 1.26; 95% CI: 0.37-4.30; P=0.71) or DFS (HR: 1.92; 95% CI: 0.86-4.32; P=0.11) in propensity score-matched cohorts. Further, radiotherapy was not associated with LRFS (HR: 0.33; 95% CI: 0.09-1.24; P=0.10) or DFS (HR: 0.99; 95% CI: 0.46-21.0; P=0.97).

Upon subgroup analysis, stratification by tumor grade or comorbidity was not associated with either LRFS or DFS. In comparisons of patients treated with SLNB and those who didn’t, the absolute rates of recurrence were low (3.5% and 4.5%, respectively), as they were in patients who received radiotherapy and those who did not (2.7% and 5.5%).

“Despite limited follow-up time and wide CIs in the survival analysis, the results of this study suggest the following: (1) SLNB can safely be omitted, in accordance with the Choosing Wisely guideline recommendation, in older patients with ER-positive, clinically node-negative breast cancer; (2) RT can safely be omitted, in accordance with results of the CALBG 9343 trial and NCCN guideline, in older patients with ER-positive, clinically node-negative breast cancer on the basis of LRFS and DFS; (3) rates of RT and SLNB remain high, suggesting that additional studies are needed to investigate why this is the case; and (4) in accordance with the CALGB 9343 trial, low rates of locoregional recurrence with or without RT and low rates of pathological node positivity after SLNB were found, adding further support for the omission of both interventions,” concluded McAuliffe et al.

Study limitations include effects on propensity score matching or multivariate analyses due to lack of data on predicted life expectancy, ECOG performance status, socioeconomic status, or performance status and limited follow-up.

  1. The deimplementation of both sentinel lymph node biopsy (SLNB) and radiotherapy should be strongly considered in older patients with estrogen receptor–positive, clinically node-negative breast cancer, suggested results from a recent study.

  2. SLNB and radiotherapy were not associated with improved five-year locoregional recurrence-free survival or disease-free survival in older women with estrogen receptor-positive, clinical node-negative breast cancers.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

This study was funded, in part, by UPMC Health Services Division and the Shear Family Foundation.

McAuliffe reported no disclosures.

Cat ID: 22

Topic ID: 78,22,282,494,730,22,935,191,691,192,925,481