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Objective: The Exercise Program in Cancer and Cognition Study was a randomized controlled trial designed to determine whether 6 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 min 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‾ $\overline{X}$ = 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 2 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. [ABSTRACT FROM AUTHOR]

Background: The Society for Surgical Oncology's Choosing Wisely guidelines recommend against sentinel lymph node biopsy (SLNB) in favor of observation in this population. Recent analyses reveal that this has not been widely adopted. The purpose of this cost‐effectiveness analysis is to compare the costs and benefits associated with observation or SLNB in women >70 years old with hormone receptor–positive, clinically node‐negative, operable breast cancer. Methods: A decision tree with Markov modeling was created to compare treatment strategies using long‐term follow‐up data from clinical trials in this population. Costs were estimated from published literature and publicly available databases. Breast cancer–specific health‐state utilities were derived from the literature and expert opinion. One‐way, 2‐way, and probabilistic sensitivity analyses were conducted. A structural sensitivity analysis was performed to assess the effect of functional status and anxiety from nonevaluation of the axilla on cost‐effectiveness. Costs and benefits, measured in life‐years (LYs) and quality‐adjusted life‐years (QALYs), were tabulated across 10, 15, and 20 years and compared using incremental cost‐effectiveness ratios (ICERs). Results: SLNB is not cost‐effective from the payer or societal perspectives with ICERs of $138,374/LY and $131,900/LY, respectively. When QALYs were considered, SLNB provided fewer QALYs (SLNB, 10.33 QALYs; observation, 10.53 QALYs) at a higher cost (SLNB, $15,845; observation, $4020). Structural sensitivity analysis revealed that SLNB was cost‐effective in certain patients with significant anxiety related to axillary observation (ICER, $39,417/QALY). Conclusions: Routine SLNB in this population is not cost‐effective. The cost‐effectiveness of SLNB, however, is dependent on individual patient factors, including functional status as well as patient preference. [ABSTRACT FROM AUTHOR]

Background: Axillary pathologic complete response (pCR) confers higher overall and recurrence-free survival than residual axillary disease. Although breast pCR (ypT0) is associated with a pathologically negative axilla (ypN0) in human epidermal growth factor receptor 2-positive (HER2+) and triple-negative breast cancer (TNBC), how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes is incompletely understood. Methods: A single-institution cancer registry was retrospectively reviewed for patients receiving neoadjuvant chemotherapy (NAC) followed by surgery from 2010 to 2018. Fisher's exact tests compared proportion of breast and axillary pCR by tumor subtype (hormone receptor [HR]-positive /HER2–,HR+/HER2+,HR–/HER2+,HR–/HER2–). Logistic regression determined factors associated with ypN0. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results: The study enrolled 1348 patients. The median age was 54 years (interquartile range [IQR], 44–63 years), and 55% of the patients (n = 736) were postmenopausal. The tumor subtypes were HR+/HER2– (12%, n = 155), HR+/HER2+ (48%, n = 653), HR–/HER2+ (25%, n = 343), and TNBC (15%, n = 197). In the study, cT included T0 (1%, n = 18), T1 (20%, n = 272), T2 (53%, n = 713), T3 (17%, n = 230), and T4 (9%, n = 111), and cN included cN0 (51%, n = 687), cN1 (41%, n = 549), cN2 (5%, n = 61), and cN3 (3%, n = 43). Breast pCR and ypN0 occurred most in the HER2+ and TNBC subtypes. A negative association was found between ypN0 and age at diagnosis (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97–0.99; p < 0.001), cT4 stage (OR, 0.29; 95% CI, 0.09–0.91; p = 0.034), and HR+ subtypes (HR+/HER2–: OR, 0.54; 95% CI, 0.31–0.94; p = 0.028; HR+/HER2+: OR, 0.60; 95% CI, 0.39–0.93; p = 0.024). The HR–/HER2+ subtype was associated with ypN0 (OR, 1.70; 95% CI, 1.05–2.73; p = 0.030), and cN2/cN3 was negatively associated with ypN0 in HR+/HER2+ disease (OR, 0.26; 95% CI, 0.11–0.61; p = 0.002), HR–/HER2+ disease (OR, 0.42; 95% CI, 0.22–0.77; p = 0.005), and TNBC (OR, 0.11; 95% CI, 0.03–0.40; p = 0.001). Conclusion: Tumor subtype, clinical stage, and age at diagnosis may be important in consideration of de-escalation of axillary staging. [ABSTRACT FROM AUTHOR]

Background: Professional burnout represents a significant threat to the American healthcare system. Organizational and individual factors may increase healthcare providers' susceptibility or resistance to burnout. We hypothesized that during the COVID-19 pandemic, 1) higher levels of perceived organizational support (POS) are associated with lower risk for burnout and anxiety, and 2) anxiety mediates the association between POS and burnout. Methods: In this longitudinal prospective study, we surveyed healthcare providers employed full-time at a large, multihospital healthcare system monthly over 6 months (April to November 2020). Participants were randomized using a 1:1 allocation stratified by provider type, gender, and academic hospital status to receive one of two versions of the survey instrument formulated with different ordering of the measures to minimize response bias due to context effects. The exposure of interest was POS measured using the validated 8-item Survey of POS (SPOS) scale. Primary outcomes of interest were anxiety and risk for burnout as measured by the validated 10-item Burnout scale from the Professional Quality (Pro-QOL) instrument and 4-item Emotional Distress-Anxiety short form of the Patient Reported Outcome Measurement Information System (PROMIS) scale, respectively. Linear mixed models evaluated the associations between POS and both burnout and anxiety. A mediation analysis evaluated whether anxiety mediated the POS-burnout association. Results: Of the 538 participants recruited, 402 (75%) were included in the primary analysis. 55% of participants were physicians, 73% 25–44 years of age, 73% female, 83% White, and 44% had ≥1 dependent. Higher POS was significantly associated with a lower risk for burnout (-0.23; 95% CI -0.26, -0.21; p<0.001) and lower degree of anxiety (-0.07; 95% CI -0.09, -0.06; p = 0.010). Anxiety mediated the associated between POS and burnout (direct effect -0.17; 95% CI -0.21, -0.13; p<0.001; total effect -0.23; 95% CI -0.28, -0.19; p<0.001). Conclusion: During a health crisis, increasing the organizational support perceived by healthcare employees may reduce the risk for burnout through a reduction in anxiety. Improving the relationship between healthcare organizations and the individuals they employ may reduce detrimental effects of psychological distress among healthcare providers and ultimately improve patient care. [ABSTRACT FROM AUTHOR]

Objectives: Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors.Methods: Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded.Results: The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases.Conclusions: Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Early detection and timely intervention have potential to reduce late-stage lymphedema (LE) in patients with breast cancer undergoing axillary lymph node dissection (ALND). This study aims to determine if detection and early treatment of subclinical LE by using prospective monitoring with bioimpedance spectroscopy (BIS) can lead to reduced development of clinical LE. Methods and Results: Subclinical LE was prospectively detected using an L-Dex® U400 analyzer to measure BIS in 186 patients who underwent ALND between 2010 and 2013 through our LE monitoring program. Baseline measurements were obtained and at 3-6 month intervals for 5 years. Patients diagnosed with subclinical LE received short-term physical therapy, compression garments, and education about exercise, elevation, infection precautions, BMI, and hand usage. The control group had a preoperative baseline L-Dex® measurement, but had only clinical follow-ups with circumferential arm measurements. Mean age and BMI were 56 years and 28.3 kg/m2, respectively. The majority of the women underwent mastectomy (61%) and received chemotherapy (89%) and radiotherapy (77%). Thirty-three percent patients who had repeated L-Dex measurements were diagnosed with subclinical LE and received early intervention. Progression to clinical lymphedema occurred in 4.4% over an average of 20 months follow-up. In the control group, the incidence of clinical LE was 36.4%. Conclusion: Periodic monitoring of women at high risk for LE with BIS allows early detection and timely intervention for LE, which reduces the incidence of clinical LE from 36.4% to 4.4%. This may have implications for quality of life and health care costs. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response.Methods: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579.Findings: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred.Interpretation: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed.Funding: US National Cancer Institute (National Institutes of Health). [ABSTRACT FROM AUTHOR]

Estrogen receptor positive (ER+) breast cancer is the most common subtype of breast cancer and is an age-related disease. The peak incidence of diagnosis occurs around age 70, even though these post-menopausal patients have low circulating levels of estradiol (E2). Despite the hormone sensitivity of age-related tumors, we have a limited understanding of the interplay between systemic and local hormones, chronic inflammation, and immune changes that contribute to the growth and development of these tumors. Here, we show that aged F344 rats treated with the dimethylbenz(a)anthracene / medroxyprogestrone acetate (DMBA/MPA) carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment promotes tumor initiation and impacts growth. Single-nuclei RNA-seq (snRNA-seq) of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with an estrone (E1)-predominant estrogen disposition in the systemic circulation, tumors in older patients increase HSD17B7 expression to convert E1 to E2 in the tumor microenvironment (TME) and have local E2 levels similar to pre-menopausal patients. Concurrently, trackable increases in several chemokines, defined most notably by CCL2, promote a chronically inflamed but immune dysfunctional TME. This unique milieu in the aged TME, characterized by high local E2 and chemokine-enriched chronic inflammation, promotes both accumulation of tumor-associated macrophages (TAMs), which serve as signaling hubs, as well as polarization of TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Pharmacologic targeting of estrogen signaling (either by HSD17B7 inhibition or with fulvestrant) and chemokine inflammation both decrease local E2 and prevent macrophage polarization. Overall, these findings suggest that chronic inflammation and hormonal disposition are critical contributors to the age-related nature of ER+ breast cancer development and growth and offer potential therapeutic insight to treat these patients., Translational Summary: We uncover the unique underpinnings establishing how the systemic host environment contributes to the aged breast tumor microenvironment, characterized by high local estradiol and chronic inflammation with immune dysregulation, and show that targeting avenues of estrogen conversion and chronic inflammation work to restore anti-tumor immunity.

Purpose: Explore factors influencing pain management among female breast cancer survivors aged 65+ years with moderate to severe pain based on a score of 4 or greater on the 0-10 numeric rating scale., Design: Qualitative descriptive study., Methods: We interviewed 21 purposefully sampled women aged 65+ years who experienced moderate to severe pain. Researchers coded interview transcripts for factors affecting study participants' pain management experiences., Results: Pain management facilitators included patient-centered interactions with care teams and reliance on psychosocial assets. Challenges included ineffective care team interactions and participants' negative perceptions of opioid analgesia. Other factors included pain attributed to cancer treatment, pain management plan adherence, and psychosocial influencers., Conclusions: With regard to this sample, patient-centered communication and pain management education help female breast cancer survivors aged 65+ years manage their pain. Mitigation of opioid stigma and undermanaged painful comorbid conditions could further optimize pain management. Further research on the effects of breast cancer treatment, level of adherence to pain management recommendations, and psychosocial influences on pain management is needed., Clinical Implications: Providing contact information for care team members during and after clinic hours facilitates open communication, including timely reporting of new and undertreated pain. Collaborating with the patient and care team on a clear pain management plan and establishing parameters for when to notify the care team empower patients to optimize management of their pain. Verifying patients' understanding of prescribed analgesia and management of side effects and providing education as needed may reduce negative perceptions of opioid analgesia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Background: Malignant phyllodes tumors (MPT) are rare fibroepithelial breast cancers with no known effective systemic therapy; metastatic progression portends a dismal prognosis. We sought to describe the genomic landscape of MPTs through genomic profiling and immunotherapeutic biomarker analysis., Materials and Methods: Cases of sequenced MPT were identified from a Clinical Laboratory Improvement Amendments-certified, College of American Pathologists-accredited laboratory (Foundation Medicine). All cases underwent genomic profiling using adaptor ligation-based, next-generation sequencing assay of 324 genes. Tumor agnostic immunotherapy biomarkers, microsatellite instability, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression were evaluated. Fisher's Exact Tests and analysis of variance were used to test for differences between groups and for continuous variables as appropriate., Results: Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent and 41 (30.4%) were metastatic. Median age was 54 years (range 14-86). The median TMB was 2.5 mut/Mb and 3 were TMB-high (≥10 mut/Mb). 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥1). Most commonly altered genes included TERT-promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%). Several tumors harboring genomic alterations with US Food and Drug Administration-approved indications in other tumor types were found including NF1, PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations., Conclusions: In the largest genomic evaluation of MPT to date, multiple clinically actionable mutations were found. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment., (© The Author(s) 2024. Published by Oxford University Press.)