Breast Cancer Research Articles

Research Progress in Brain Metastasis of Breast Cancer

Research Progress in Brain Metastasis of Breast Cancer

Computational Exploration of Naturally Occurring Flavonoids as TGF-β Inhibitors in Breast Cancer: Insights from Docking and Molecular Dynamics Simulations and In-vitro Cytotoxicity Study.

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-β) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-β inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation. This study explores naturally occurring flavonoids' interactions with TGF-β. Using molecular docking against the protein's crystal structure (PDB Id: 1PY5), Gossypin showed the highest docking score and underwent molecular dynamics simulation, revealing complex flexibility and explaining how flavonoids impede TGF-β signaling in breast cancer. ADMET predictions adhered to Lipinski's rule of Five. Insights into flavonoid-TGF-β binding offer a novel angle for breast cancer treatment. Flavonoids having a good docking score like gossypin, morin, luteolin and taxifolin shown potent cytotoxic effect on breast cancer cell line, MCF-7. Understanding these interactions could inspire flavonoid-based therapies targeting TGF-β to halt breast cancer growth. These findings pave the way for personalized, targeted breast cancer therapies, offering hope against this formidable disease.

Identifying SLC2A6 as the novel protective factor in breast cancer by TP53-related genes affecting M1 macrophage infiltration.

The high heterogeneity of breast cancer (BC) caused by pathogenic gene mutations poses a challenge to immunotherapy, but the underlying mechanism remains unknown. The difference in the infiltration of M1 macrophages induced by TP53 mutations has a significant impact on BC immunotherapy. The aim of this study was to develop a TP53-related M1 macrophage infiltration molecular typing risk signature in BC and evaluate the biological functions of the key gene to find new immunotherapy biomarkers. Weighted correlation network analysis (WGCNA) and negative matrix factorization (NMF) were used for distinguishing BC subtypes. The signature and the nomogram were both constructed and evaluated. Biological functions of the novel signature gene SLC2A6 were confirmed through in vitro and in vivo experiments. RNA-Sequencing and protein profiling were used for detecting the possible mechanism of SLC2A6. The results suggested that four BC subtypes were distinguished by TP53-related genes that affect M1 macrophage infiltration. The signature constructed by molecular typing characteristics could evaluate BC's clinical features and tumor microenvironment. The nomogram could accurately predict the prognosis. The signature gene SLC2A6 was found to have an abnormally low expression in tumor tissues. Overexpression of SLC2A6 could inhibit proliferation, promote mitochondrial damage, and result in apoptosis of tumor cells. The HSP70 family member protein HSPA6 could bind with SLC2A6 and increase with the increased expression of SLC2A6. In summary, the risk signature provides a reference for BC risk assessment, and the signature gene SLC2A6 could act as a tumor suppressor in BC.

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer

Abstract Background Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. Methods BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. Results miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. Conclusion This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

Multiwalled Carbon Nanotubes-Reprogrammed Macrophages Facilitate Breast Cancer Metastasis via NBR2/TBX1 Axis.

In recent years, carbon nanotubes have emerged as a widely used nanomaterial, but their human exposure has become a significant concern. In our former study, we reported that pulmonary exposure of multiwalled carbon nanotubes (MWCNTs) promoted tumor metastasis of breast cancer; macrophages were key effectors of MWCNTs and contributed to the metastasis-promoting procedure in breast cancer, but the underlying molecular mechanisms remain to be explored. As a follow-up study, we herein demonstrated that MWCNT exposure in breast cancer cells and macrophage coculture systems promoted metastasis of breast cancer cells both in vitro and in vivo; macrophages were skewed into M2 polarization by MWCNT exposure. LncRNA NBR2 was screened out to be significantly decreased in MWCNTs-stimulated macrophages through RNA-seq; depletion of NBR2 led to the acquisition of M2 phenotypes in macrophages by activating multiple M2-related pathways. Specifically, NBR2 was found to positively regulate the downstream gene TBX1 through H3k27ac activation. TBX1 silence rescued NBR2-induced impairment of M2 polarization in IL-4 & IL-13-stimulated macrophages. Moreover, NBR2 overexpression mitigated the enhancing effects of MWCNT-exposed macrophages on breast cancer metastasis. This study uncovered the molecular mechanisms underlying breast cancer metastasis induced by MWCNT exposure.

Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome

Background: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. Methods: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. Results: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. Conclusions: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer

Abstract Background Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. Results Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. Conclusions These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

Prediction of heart failure and all-cause mortality using cardiac ultrasomics in patients with breast cancer.

Breast cancer chemotherapy/immunotherapy can be associated with treatment-limiting cardiotoxicity. Radiomics techniques applied to ultrasound, known as ultrasomics, can be used in cardio-oncology to leverage echocardiography for added prognostic value. To utilize ultrasomics features collected prior to antineoplastic therapy to enhance prediction of mortality and heart failure (HF) in patients with breast cancer. Patients were retrospectively recruited in a study at the West Virginia University Cancer Institute. The final inclusion criteria were met by a total of 134 patients identified for the study. Patients were imaged using echocardiography in the parasternal long axis prior to receiving chemotherapy. All-cause mortality and HF, developed during treatment, were the primary outcomes. 269 features were assessed, grouped into four major classes: demographics (n = 21), heart function (n = 7), antineoplastic medication (n = 17), and ultrasomics (n = 224). Data was split into an internal training (60%, n = 81) and testing (40%, n = 53) set. Ultrasomics features augmented classification of mortality (area under the curve (AUC) 0.89 vs. 0.65, P = 0.003), when compared to demographic variables. When developing a risk prediction score for each feature category, ultrasomics features were significantly associated with both mortality (P = 0.031, log-rank test) and HF (P = 0.002, log-rank test). Further, only ultrasomics features provided significant improvement over demographic variables when predicting mortality (C-Index: 0.78 vs. 0.65, P = 0.044) and HF (C-Index: 0.77 vs. 0.60, P = 0.017), respectively. With further investigation, a clinical decision support tool could be developed utilizing routinely obtained patient data alongside ultrasomics variables to augment treatment regimens.

Exploring Anticancer Properties of Medicinal Plants against Breast Cancer by Downregulating Human Epidermal Growth Factor Receptor 2.

Plants have a history of being employed in managing breast cancer. However, no scientific evidence supports the idea that these plants can effectively reduce the level of HER2 expression. In this study, extracts from 10 medicinal plants were evaluated for their anticancer properties against HER2-positive breast cancer cells through various methods, including the SRB assay, comet assay, annexin V-FITC dual staining, and immunoblotting. All extracts exerted antiproliferative activity against HER2-positive breast cancer cells. Furthermore, Terminalia chebula (T. chebula), Berberis aristata (B. aristata), and Mucuna pruriens (M. pruriens) reduced HER2 expression in tested cell lines. In addition, an increased Bax/Bcl-2 ratio was observed after the treatment. A comparative proteomics study showed modulation in the proteome profile of breast cancer cells after treatment with T. chebula, B. aristata, Punica granatum, M. pruriens, and Acorus calamus. Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex’s solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Plasma Circular RNAs as Biomarkers for Breast Cancer

Breast cancer (BC) is currently the most common neoplasm, the second leading cause of cancer death in women worldwide, and is a major health problem. The discovery of new biomarkers is crucial to improve our knowledge of breast cancer and strengthen our clinical approaches to diagnosis, prognosis, and follow-up. In recent decades, there has been increasing interest in circulating RNA (circRNA) as modulators of gene expression involved in tumor development and progression. The study of circulating circRNAs (ccircRNAs) in plasma may provide new non-invasive diagnostic, prognostic, and predictive biomarkers for BC. This review describes the latest findings on BC-associated ccircRNAs in plasma and their clinical utility. Several ccircRNAs in plasma have shown great potential as BC biomarkers, especially from a diagnostic point of view. Mechanistically, most of the reported BC-associated ccircRNAs are involved in the regulation of cell survival, proliferation, and invasion, mainly via MAPK/AKT signaling pathways. However, the study of circRNAs is a relatively new area of research, and a larger number of studies will be crucial to confirm their potential as plasma biomarkers and to understand their involvement in BC.

Lymph node metastasis prediction and biological pathway associations underlying DCE-MRI deep learning radiomics in invasive breast cancer

Abstract Background The relationship between the biological pathways related to deep learning radiomics (DLR) and lymph node metastasis (LNM) of breast cancer is still poorly understood. This study explored the value of DLR based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in LNM of invasive breast cancer. It also analyzed the biological significance of DLR phenotype based on genomics. Methods Two cohorts from the Cancer Imaging Archive project were used, one as the training cohort (TCGA-Breast, n = 88) and one as the validation cohort (Breast-MRI-NACT Pilot, n = 57). Radiomics and deep learning features were extracted from preoperative DCE-MRI. After dual selection by principal components analysis (PCA) and relief methods, radiomics and deep learning models for predicting LNM were constructed by the random forest (RF) method. A post-fusion strategy was used to construct the DLR nomograms (DLRNs) for predicting LNM. The performance of the models was evaluated using the receiver operating characteristic (ROC) curve and Delong test. In the training cohort, transcriptome data were downloaded from the UCSC Xena online database, and biological pathways related to the DLR phenotypes were identified. Finally, hub genes were identified to obtain DLR gene expression (RadDeepGene) scores. Results DLRNs were based on area under curve (AUC) evaluation (training cohort, AUC = 0.98; validation cohort, AUC = 0.87), which were higher than single radiomics models or GoogLeNet models. The Delong test (radiomics model, P = 0.04; GoogLeNet model, P = 0.01) also validated the above results in the training cohorts, but they were not statistically significant in the validation cohort. The GoogLeNet phenotypes were related to multiple classical tumor signaling pathways, characterizing the biological significance of immune response, signal transduction, and cell death. In all, 20 genes related to GoogLeNet phenotypes were identified, and the RadDeepGene score represented a high risk of LNM (odd ratio = 164.00, P < 0.001). Conclusions DLRNs combining radiomics and deep learning features of DCE-MRI images improved the preoperative prediction of LNM in breast cancer, and the potential biological characteristics of DLRN were identified through genomics.

Adenocarcinoma originating in the anterior mediastinum diagnosed by endobronchial ultrasound-guided transbronchial cryobiopsy: a case report

Abstract Background Endobronchial ultrasound-guided transbronchial cryobiopsy (EBUS-cryobiopsy) is advantageous for collecting larger specimens with minimal crushing; however, it has not been widely used for mediastinal tumors. Case presentation A 73-year-old woman with a history of left breast cancer underwent surgery followed by radiotherapy. Computed tomography showed a mass in the anterior mediastinum that was in extensive contact with the sternum on the ventral side and partly with the trachea on the dorsal side. Two computed tomography-guided needle biopsies (CTNBs) were performed on the mass; however, a definitive diagnosis was not made because of severe crush artifacts. Subsequently, we performed EBUS-cryobiopsy and safely obtained sufficient specimen volume with minimal crushing. The histopathological diagnosis was adenocarcinoma, with immunobiological features distinct from those of previous breast cancers. Her overall diagnosis was a rare tumor originating in the anterior mediastinum. Conclusions EBUS-cryobiopsy can be safely performed in narrow areas surrounded by major blood vessels, and the obtained specimens may be superior to CTNBs for histopathological diagnosis.

A novel immune‑related lncRNA as a prognostic biomarker in HER2+ breast cancer

A novel immune‑related lncRNA as a prognostic biomarker in HER2⁺ breast cancer

Ocular metastases profile in a tertiary hospital in São Paulo, Brazil

Abstract Objective Ocular metastases are the most common intraocular tumours in adults. Data regarding the occurrence of these tumours in the Brazilian population is scarce. We aimed to investigate the profile of ocular metastases of patients referred to tertiary hospital service in São Paulo, Brazil. Design Retrospective study. Participants Patients referred to the Ocular Oncology service of the Federal University of São Paulo with initial diagnostic hypothesis of ocular metastasis. Methods Data was retrospectively collected from medical records from June 2017 to June 2023. Age, sex, primary tumour site, previous knowledge of the systemic diagnosis, laterality, initial visual acuity (VA), local or systemic treatment and mean follow-up period were obtained. Results A total of 37 cases were referred to the ocular oncology division due to a suspected ocular metastasis, 15 (40.5%) were confirmed. Mean age at diagnosis was 53.47 ± 16.01 years old, the majority (86.7%) of patients already knew the systemic diagnosis. Breast cancer (66.7%) was the most common primary site, followed by Lung cancer (26.7%). Both eyes were affected in 66.67% of the cases, all patients had metastases at the choroid (100.0%), and the mean initial VA was 1.37 ± 1.04 logMAR. Chemotherapy was the main systemic treatment modality (73.3%), and most patients had no ocular treatment (53.3%). The mortality rate along the follow-up period was 30.0%. Conclusions Considering the number of new patients absorbed by the Ocular Oncology service over the study period, the frequency of ocular metastases was relatively low. The patients’ characteristics was comparable to data published in the international literature.

A single-arm pilot of MyInspiration: a novel digital resource to support spiritual needs of patients undergoing cancer-directed surgery.

This study aimed to assess the feasibility, acceptability, and satisfaction associated with the MyInspiration intervention, a digital spiritual support tool for patients undergoing cancer surgery. Additionally, we evaluated changes in spiritual well-being and the ability to find meaning in their experience with cancer before and after the intervention. This was a prospective, single-arm pilot study. Feasibility and acceptability were assessed by ratio of participants who completed all assessments among individuals who hadsigned consent forms. Satisfaction was assessed with 5 Likert-style questions around user experience. Patient spiritual well-being and finding meaning in their experience with cancer were measured at baseline and post-intervention. Forty patients were enrolled, the majority of whom were female (80.0%) and diagnosed with breast cancer (52.5%), with an average age of 54.4years (SD = 13.7, range 29.0-82.0). Regarding feasibility and acceptability, 76.9% of patients who consented to participate completed the full study protocol. In assessing satisfaction, 59% of patients were satisfied with the overall experience of MyInspiration. There was no difference in spiritual well-being pre-/post-intervention. There was a difference in pre (M = 1.95, SD = .95) and post (M = 2.23, SD = .86) scores relative to "finding meaning in the cancer experience" with a mean difference of 0.28 (p = 0.008). MyInspiration was feasible and acceptable to patients, and the majority were satisfied with the tool. The intervention was associated with changes in patients' ability to find meaning within their cancer experience. Arandomized control trial is needed to evaluate the efficacy of the tool in a broader population of patients with cancer.

Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer.

Our study provides a strong basis for understanding the mechanisms by which proteasome inhibitors exert anticancer effects. We find open chromatin regions that change during proteasome inhibition, are typically accessible in non-basal breast cancers.

Exploring the potential of machine learning in gynecological care: a review.

Gynecological health remains a critical aspect of women's overall well-being, with profound implications for maternal and reproductive outcomes. This comprehensive review synthesizes the current state of knowledge on four pivotal aspects of gynecological health: preterm birth, breast cancer and cervical cancer and infertility treatment. Machine learning (ML) has emerged as a transformative technology with the potential to revolutionize gynecology and women's healthcare. The subsets of AI, namely, machine learning (ML) and deep learning (DL) methods, have aided in detecting complex patterns from huge datasets and using such patterns in making predictions. This paper investigates how machine learning (ML) algorithms are employed in the field of gynecology to tackle crucial issues pertaining to women's health. This paper also investigates the integration of ultrasound technology with artificial intelligence (AI) during the initial, intermediate, and final stages of pregnancy. Additionally, it delves into the diverse applications of AI throughout each trimester.This review paper provides an overview of machine learning (ML) models, introduces natural language processing (NLP) concepts, including ChatGPT, and discusses the clinical applications of artificial intelligence (AI) in gynecology. Additionally, the paper outlines the challenges in utilizing machine learning within the field of gynecology.

PheSeq, a Bayesian deep learning model to enhance and interpret the gene-disease association studies

AbstractDespite the abundance of genotype-phenotype association studies, the resulting association outcomes often lack robustness and interpretations. To address these challenges, we introduce PheSeq, a Bayesian deep learning model that enhances and interprets association studies through the integration and perception of phenotype descriptions. By implementing the PheSeq model in three case studies on Alzheimer’s disease, breast cancer, and lung cancer, we identify 1024 priority genes for Alzheimer’s disease and 818 and 566 genes for breast cancer and lung cancer, respectively. Benefiting from data fusion, these findings represent moderate positive rates, high recall rates, and interpretation in gene-disease association studies.

Examining the communication work of women whohave tested BRCA-positive: "I feel this responsibility to letpeopleknow".

Inheriting a pathogenic variant in the BRCA1 or BRCA2 gene considerably increases a woman's risk levels for developing breast and ovarian cancer. In addition to serious physical health implications, women with a BRCA pathogenic variant may face psychosocial challenges, including those related to navigating the often demanding process of communicating about topics regarding BRCA with family and other social network members. Based on in-depth interviews with 24 women who tested BRCA-positive, we found that-consistent with the conceptualization of communication work articulated by Donovan-Kicken etal. (2012) as an extension of the theory of illness trajectories (Corbin & Strauss, 1988)-the labor of communicating about BRCA genetic risk entails (a) duties, (b) challenges, (c) strategies, and (d) shared work. Within each category, our results illuminate particular characteristics of communication work for women who have tested BRCA-positive, which are commonly tied to the profound health consequences that a pathogenic variant may have for them and, potentially, for their genetic relatives. Our findings offer useful theoretical implications regarding communication work in this context. Furthermore, our results yield valuable practical insight for genetic counselors and other health care professionals regarding the struggles that can accompany communication work for women who have tested BRCA-positive as well as the strategies that participants reported using to manage or avoid these challenges.