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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.)