Effects of aerobic exercise on neurocognitive function in postmenopausal women receiving endocrine therapy for breast cancer: The Exercise Program in Cancer and Cognition randomized controlled trial.

Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling. Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017). Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.

Use of natural language understanding to facilitate surgical de-escalation of axillary staging in patients with breast cancer.

Natural language understanding (NLU) may be particularly well-equipped for enhanced data capture from the electronic health record (EHR) given its examination of both content- and context-driven extraction. We developed and applied a NLU model to examine rates of pathological node positivity (pN+) and rates of lymphedema to determine if omission of routine axillary staging could be extended to younger patients with ER+/cN0 disease. We found that rates of pN+ and arm lymphedema were similar between patients 55-69yo and ≥70yo, with rates of lymphedema exceeding rates of pN+ for clinical stage T1c and smaller disease. Data from our NLU model suggest that omission of SLNB might be extended beyond Choosing Wisely recommendations, limited to those over 70 years old, to all postmenopausal women with early-stage ER+/cN0 disease. These data support the recently-reported SOUND trial results and provide additional granularity to facilitate surgical de-escalation.

Use of Natural Language Understanding to Facilitate Surgical De-Escalation of Axillary Staging in Patients With Breast Cancer.

PURPOSE: Natural language understanding (NLU) may be particularly well equipped for enhanced data capture from the electronic health record given its examination of both content-driven and context-driven extraction. METHODS: We developed and applied a NLU model to examine rates of pathological node positivity (pN+) and rates of lymphedema to determine whether omission of routine axillary staging could be extended to younger patients with estrogen receptor-positive (ER+)/cN0 disease. RESULTS: We found that rates of pN+ and arm lymphedema were similar between patients age 55-69 years and ≥70 years, with rates of lymphedema exceeding rates of pN+ for clinical stage T1c and smaller disease. CONCLUSION: Data from our NLU model suggest that omission of sentinel lymph node biopsy might be extended beyond Choosing Wisely recommendations, limited to those older than 70 years and to all postmenopausal women with early-stage ER+/cN0 disease. These data support the recently reported SOUND trial results and provide additional granularity to facilitate surgical de-escalation.

Electronic Health Record-Based Nudge Intervention and Axillary Surgery in Older Women With Breast Cancer: A Nonrandomized Controlled Trial.

Importance: Choosing Wisely recommendations advocate against routine use of axillary staging in older women with early-stage, clinically node-negative (cN0), hormone receptor-positive (HR+), and HER2-negative breast cancer. However, rates of sentinel lymph node biopsy (SLNB) in this population remain persistently high. Objective: To evaluate whether an electronic health record (EHR)-based nudge intervention targeting surgeons in their first outpatient visit with patients meeting Choosing Wisely criteria decreases rates of SLNB. Design, Setting, and Participants: This nonrandomized controlled trial was a hybrid type 1 effectiveness-implementation study with subsequent postintervention semistructured interviews and lasted from October 2021 to October 2023. Data came from EHRs at 8 outpatient clinics within an integrated health care system; participants included 7 breast surgical oncologists. Data were collected for female patients meeting Choosing Wisely criteria for omission of SLNB (aged ≥70 years with cT1 and cT2, cN0, HR+/HER2- breast cancer). The study included a 12-month preintervention control period; baseline surveys assessing perceived acceptability, appropriateness, and feasibility of the designed intervention; and a 12-month intervention period. Intervention: A column nudge was embedded into the surgeon's schedule in the EHR identifying patients meeting Choosing Wisely criteria for potential SLNB omission. Main Outcomes and Measures: The primary outcome was rate of SLNB following nudge deployment into the EHR. Results: Similar baseline demographic and tumor characteristics were observed before (control period, n = 194) and after (intervention period, n = 193) nudge deployment. Patients in both the control and intervention period had a median (IQR) age of 75 (72-79) years. Compared with the control period, unadjusted rates of SLNB decreased by 23.1 percentage points (46.9% SLNB rate prenudge to 23.8% after; 95% CI, -32.9 to -13.8) in the intervention period. An interrupted time series model showed a reduction in the rate of SLNB following nudge deployment (adjusted odds ratio, 0.26; 95% CI, 0.07 to 0.90; P = .03). The participating surgeons scored the intervention highly on acceptability, appropriateness, and feasibility. Dominant themes from semistructured interviews indicated that the intervention helped remind the surgeons of potential Choosing Wisely applicability without the need for additional clicks or actions on the day of the patient visit, which facilitated use. Conclusions and Relevance: This study showed that a nudge intervention in the EHR significantly decreased low-value axillary surgery in older women with early-stage, cN0, HR+/HER2- breast cancer. This user-friendly and easily implementable EHR-based intervention could be a beneficial approach for decreasing low-value care in other practice settings or patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT06006910.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.