Breast Cancer Cases Research Articles

Unlocking survival benefits: primary tumor resection in de novo stage IV breast cancer patients

ABSTRACT Background For patients with de novo stage IV breast cancer (BC), the conditions under which the primary tumor resection (PTR) may offer benefit remain unclear. Methods The SEER database provides treatment data for patients with de novo stage IV BC. We screened cases of metastatic BC diagnosed from 2010 to 2015, with primary endpoints of overall survival (OS) and cancer-specific survival (CSS). Results 9252 patients with stage IV de novo BC were enrolled. For OS, median survival time (MST) was 38 months with systematic treatment (ST) compared to 52 months with ST plus PTR (p < 0.001). For CSS, MST was 38 months for ST versus 54 months for ST plus PTR (p < 0.001). The results of the Cox proportional hazards regression analysis regarding PTR, for OS: bone metastasis (aHR 0.664, 95%CI 0.583–0.756, p < 0.001); liver-lung metastasis (aHR 0.528, 95%CI 0.327–0.853, p = 0.009). For CSS: bone metastasis (aHR 0.655, 95%CI 0.571–0.751, p < 0.001); liver-lung metastasis (aHR 0.549, 95%CI 0.336–0.889, p = 0.017). Kaplan-Meier analysis indicated that in patients with bone metastases and liver-lung metastases, PTR could improve survival outcomes. Conclusion Liver-lung metastases and bone metastases in patients with de novo stage IV BC could enhance both OS and CSS through PTR.

Abstract B022: Investigating how monocytes impair NK cell cytotoxicity in lung metastasis of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) accounts for 20% of breast cancer (BC) cases worldwide, yet due to its aggressive phenotype and lack of targeted therapies it has the worst prognosis amongst BC subtypes. Up to 40% of TNBC patients will relapse after treatment and develop distant metastasis. Metastasis is the complex process by which disseminated tumor cells (DTCs) leave the primary tumor and grow at distal sites. Since most metastases occur within 3 years of diagnosis, the rapid onset and lack of effective treatments in metastatic TNBC (mTNBC) means less than 20% of patients survive after 4 years. Even though it is the most “immune-activated” BC subtype, and immune checkpoint blockade (ICB) has shown clinical benefits in early TNBC, there is a clear need for novel immunotherapeutic approaches for patients with mTNBC. Natural killer (NK) cells are innate lymphocytes that function as the body’s first line defense against metastatic cancer cells. NK cells eliminate DTCs in the blood or at distal sites via NK cell cytotoxicity (NKCC) and this process is known to be impaired in successful metastasis. We hypothesized that other cells within the tumor microenvironment (TME) can inhibit NKCC at the earliest stages of metastatic outgrowth. We have used Cherry-niche, an in vivo labelling tool, to characterize how TME cells change in early and established lung micro-metastases by single-cell RNA sequencing (scRNA-seq) and flow cytometry. Our initial analyses showed that monocytes are highly enriched, not only in the entire metastatic lung, but specifically in the established niche surrounding DTCs. Although we detected a slight increase in total NK cells, there was a shift in maturation status with fewer mature NK cells (CD27-CD11b+) and more immature NK cells (CD27+/-CD11b-) in the metastatic lung. Furthermore, NK cells were largely absent from the metastatic niche and those that were present displayed a dysfunctional phenotype. CellChat and NicheNet analyses of our scRNA-seq data predicted that several receptor-ligand interactions, including the cytokine macrophage migration inhibitory factor (MIF), can mediate the crosstalk between NK cells and monocytes. Next, we developed an in vitro 3D co-culture system to study the effect of blood-derived monocytes on human NKCC against mTNBC cells. We found that monocytes can suppress NKCC against MDA-MB-231 cells and decrease the viability of mature NK cells. Furthermore, recombinant MIF was able to directly inhibit NKCC, whilst a selective MIF antagonist was able to rescue monocyte-induced impairment of NKCC. These data implicate MIF as a critical monocyte-derived factor in the suppression of NK cell function against mTNBC cells. Future work will aim to identify the exact mechanism by which MIF inhibits NKCC, whilst also evaluate the effect of monocyte depletion and MIF inhibition on metastatic outgrowth and NK cell activation/maturation in vivo. This study will reveal novel inter-cellular dynamics occurring in the metastatic lung, as well as immunotherapeutic targets that may restore NKCC in mTNBC. Citation Format: Christos Ermogenous, Luigi Ombrato, Gordon Beattie. Investigating how monocytes impair NK cell cytotoxicity in lung metastasis of triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B022.

Abstract C045: The extracellular matrix glycoprotein periostin supports chemotherapy resistance by modulating macrophage recruitment and phagocytosis in triple negative breast cancer

Abstract Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer cases and is notoriously aggressive, often developing resistance to standard chemotherapy thus leading to a high rate of metastatic relapse. Evidence suggests that this resistance is linked to changes in the extracellular matrix (ECM) composition, particularly an increase in periostin (POSTN) expression, which is also associated with poor prognosis in breast cancer. Our recent publication showed that the ECM alone can influence macrophage phenotypes. Furthermore, another study from our lab has demonstrated that POSTN mediates resistance to anti-angiogenic therapy by recruiting macrophages in pancreatic neuroendocrine tumors. Notably, POSTN deletion reduced monocyte/macrophage recruitment and enhanced cytotoxic CD8+ T-cell infiltration. Based on these findings, we hypothesized that paclitaxel (PTX), a widely used chemotherapeutic drug for the management of TNBC, may stimulate POSTN production by fibroblasts leading to the recruitment of pro-tumoral macrophages that facilitate tumor growth resulting into therapy resistance. In this study, we showed that PTX induces increased POSTN expression in mouse models of TNBC through immunohistochemistry, and in both 2D and 3D in vitro models via interactions between TNBC cell lines and mammary fibroblasts, as demonstrated by immunofluorescence. An in vitro migration assay confirmed that PTX-induced POSTN enhances the recruitment of human monocytes and macrophages, which display a mixed immunosuppressive and inflammatory phenotype, as revealed by flow cytometry. Not only did these recruited macrophages exhibit a reduced phagocytic capacity against labelled TNBC cells in an in vitro phagocytosis assay, but we also found that POSTN plays a crucial role in inducing SIRPα expression, that may diminish macrophage phagocytic potential. Increased sialylation and Siglec-1 expression are known to be linked to poor prognosis and polarization towards a more immunosuppressive macrophage phenotype in TNBC. Interestingly in our model, we observed that higher concentrations of recombinant human POSTN induce increased Siglec-1 expression on macrophages, a receptor that interacts with sialic acids in the tumor ECM. Further work using a decellularized tissue model that preserves only the ECM from patient-derived tumor biopsies pre- and post-chemo, aims to further explore the correlation between PTX-induced POSTN, ECM sialylation, and Siglec-1 expression on macrophages. Additionally, we have developed POSTN-knockout murine cancer cells and fibroblasts using CRISPR/Cas9, allowing us to investigate how POSTN influences macrophage phenotypes and chemotherapy responses in vivo. Understanding the mechanisms behind chemotherapy resistance in TNBC is crucial for developing effective treatments for this aggressive cancer subtype. By elucidating the intricate interplay between POSTN, macrophages, and chemotherapy response, we aim to identify new therapeutic strategies to improve outcomes for TNBC patients. Citation Format: Ludovica Tarantola, Ioanna Keklikoglou, Oliver M. Pearce. The extracellular matrix glycoprotein periostin supports chemotherapy resistance by modulating macrophage recruitment and phagocytosis in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C045.

Abstract C011: The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause

Abstract Background: Reproductive factors and sex hormones are tightly linked to systemic immunity. However, no studies have examined whether reproductive factors and exogenous hormone use modulate the immune microenvironment of breast tissue. Methods: We prospectively evaluated the associations of reproductive factors (age at menarche, parity, age at first birth, age at menopause, and menopausal status) and exogenous hormone use (oral contraceptives, and menopausal hormone therapy (MHT)) with breast tumor and normal-adjacent tissue immune cell markers among 935 breast cancer cases in the Nurses’ Health Studies. We deconvoluted immune cell abundance using CIBERSORTx and derived gene expression signatures of markers for immune checkpoint (PD1, PDL1, and CTLA4), co-regulatory signal and antigen presentation (MHC class I/ II and T cell receptor) and mammary cytokine signaling (IFN gamma, IL2, IL4, IL12, IL13, TGF beta). Linear regression was used with adjustment for potential confounders. Results: Majority of participants had estrogen receptor (ER)-positive breast cancer (81%) and were post-menopausal at diagnosis (72%). Compared to tumors from pre-menopausal women, tumors from post-menopausal women had higher signature scores for tumor pro-inflammatory cytokine signaling (IFN gamma, IL2, IL4, IL12, IL13, TGF beta) and antigen presentation (FDR≤0.05). Several of the inflammatory cytokine signatures showed modest inverse relations with signatures of immune checkpoint markers (ρ=-0.3 to -0.4). Women who reported current use of estrogen only MHT had higher expression of CTLA4 in ER-positive breast tumors. For normal-adjacent tissues of ER-positive tumors, parity was associated with higher CD8+ T cell abundance, higher PDL1 expression and lower cytokine signaling in normal-adjacent tissues at p≤0.05; while breastfeeding was associated with lower abundance of CD8+ T cell and higher expression of cytokine signaling in normal-adjacent tissues of ER-negative tumors (p≤0.05). None of the associations in normal-adjacent tissues met FDR significance. The associations between other reproductive factors and immune cell profiles were in general weak. Conclusions: Our study suggests pre-diagnostic reproductive factors may influence breast tumor immune profiles. Future studies are needed to validate these results. Citation Format: Cheng Peng, Yuxi Liu, Yujing Heng, Clara Bodelon, Daniel Stover, Wendy Y. Chen, Michelle D. Holmes, A. Heather Eliassen, Peter Kraft, Rulla M. Tamimi. The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C011.

Comprehensive characterization of invasive mammary carcinoma with lobular features: integrating morphology and E-cadherin immunohistochemistry patterns.

Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports. A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): (1) ductal/membranous, (2) lobular/loss, (3) lobular/aberrant, (4) mixed, (5) ductal/loss or aberrant, and (6) lobular/membranous. In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, 4 (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 25.9% (15/58) of cases in group 3, characterized by aberrant E-cadherin patterns, were initially diagnosed as ILC, highlighting a significant diagnostic discrepancy. In group 6, where membranous E-cadherin pattern was present with lobular morphology, only 3.4% (2/58) were diagnosed as ILC in the original reports, indicating diagnostic challenges in morphology and immunohistochemistry discordance. Similarly, in group 5, which had ductal morphology with loss or aberrant E-cadherin expression, the initial diagnosis rate of IBC-NST was 33.3% (9/27), reflecting the complexities in interpreting discordant cases. In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.

Biogenic synthesis of silver nanoparticles from Hylocereus undatus peel waste: exploring EGFR inhibition for targeted therapy of cervical and breast carcinomas

Abstract Background Cancer is one of the leading causes of death worldwide, with breast and cervical cancers being the most common among women. Over 100,000 new cases of breast cancer and 510,000 new cases of cervical cancer are diagnosed annually. This study aimed to develop and evaluate an eco-friendly, low-cost method to synthesize silver nanoparticles using Hylocereus undatus (dragon fruit) peel extract for their anticancer activity. Results Silver nanoparticles loaded with Hylocereus undatus fruit peel extract were successfully developed by a green synthesis technique and were optimized by UV–vis spectroscopy. The nanoparticles had an average size of 71.66 nm, a polydispersity index of 0.3754, and a zeta potential of − 38.52, with a spherical shape and 79.5% silver content. Their maximum absorbance was at 448 nm. Further, in vitro anticancer activity via MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was evaluated and the synthesized nanoparticles displayed IC50 values at 23.51 µg/ml and 23.66 µg/ml against Hela and MDA MB 231 cell lines, respectively. Cytocompatibility studies showed high cell viability (≥ 95%) in L929 mouse fibroblast cells, indicating low toxicity. In silico analyses, including network pharmacology and molecular docking, identified kaempferol and quercetin as key anticancer compounds, with epidermal growth factor receptor (EGFR) (PDB ID: IM17) being the most significant protein target. Docking studies performed by using the Glide module of Schrodinger’s software displayed that kaempferol and quercetin had higher binding affinities for EGFR as compared to the standard drug erlotinib, with MET 769 being a crucial binding site. Conclusion Thus, the outcomes suggest that synthesized silver nanoparticles loaded with Hylocereus undatus fruit peel extract could be a potential and promising drug carrier aiding in cancer treatment.

Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.

Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk. We used data from a nested case-control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects). The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00-5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13-4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93-4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05-1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75-1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol. Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.

Assessing the correlation between Gamma passing rate and clinical dosimetric variations in breast cancer IMRT plans with multi-leaf collimator errors: perspectives from the ArcCHECK QA system.

This study aimed to comprehensively investigate the influence of multi-leaf collimator (MLC) position errors on both the clinical absolute dose distribution and Gamma passing rate (%GP) in intensity-modulated radiation therapy (IMRT) plans for breast cancer. Additionally, the correlation between %GP and the clinical absolute dose relative difference (%DE) caused by MLC position errors was analysed. Ten IMRT plans for breast cancer were randomly selected. Systematic and random MLC position errors were introduced into DICOM files representing the investigated treatment plans by modifying the plan files and adjusting the MLC positions. Systematic errors were categorized as MLC opening errors, closing errors, and shift errors. The %DE in the tumour planning target volume (PTV) and organs at risk (OARs) caused by MLC errors were statistically analyzed using dose-volume histogram (DVH) analysis. The ArcCHECK quality assurance (QA) system was used to detect the %GP differences between baseline plans and plans with MLC errors. The correlation between %GP and %DE was obtained using linear regression methods. The results of this study indicate that MLC opening and closing errors have a significant impact on %DE and %GP in IMRT plans for breast cancer. Opening and closing errors can be detected at a gamma level of 3%/2mm, if error values are greater than or equal to 0.5mm, and %GP can predict DVH dosimetric changes caused by MLC opening and closing errors. It is concluded that DVH-based verification of IMRT plans can serve as an adjunct method to Gamma analysis to improve QA accuracy for breast cancer cases. Additionally, it is concluded that greater attention should be given to MLC leaf opening and closing errors in clinical practice.

Associations of radiotherapy receipt with lung cancer risk by histological subtype among breast cancer survivors in the United States.

Radiotherapy for breast cancer has been associated with an increased risk of secondary malignancies, including primary lung cancer. Whether this association varies by histological subtype of lung cancer remains unknown. Based on the data from 12 Surveillance, Epidemiology, and End Results registries, we examined the association between radiotherapy receipt and the risk of subtype-specific subsequent primary lung cancer (SPLC) among female first primary breast cancer cases diagnosed between ages 20 and 84 from 1992 to 2020. More than half (53%) of the 550,007 breast cancer survivors identified had undergone radiotherapy as part of their initial breast cancer treatment. Over an average follow-up of 9.7 years, 8014 survivors developed SPLCs. For small-cell carcinoma, the standardized incidence ratio (SIR) compared with the general population was higher for survivors who received radiotherapy (SIR = 1.15, 95% confidence interval [CI] = 1.06-1.25) but similar for those who did not receive radiotherapy (SIR = 1.00, 95% CI = 0.91-1.09), with the difference in SIRs being statistically significant (p = .003). Similar associations were found for squamous cell carcinoma (SIRyes = 1.16, 95% CI = 1.08-1.24 vs. SIRno/unknown = 1.06, 95% CI = 0.98-1.15; p = .07). The increased risks were confined to ipsilateral SPLC, with the greatest SIRs for small-cell carcinoma occurring 5-10 years since breast cancer diagnosis (SIR = 1.83, 95% CI = 1.53-2.19) and for squamous cell carcinoma with a latency of 10 years or more (SIR = 1.64, 95% CI = 1.42-1.88). In contrast, the risk of developing adenocarcinoma did not vary by radiotherapy receipt (SIRyes = 1.23, 95% CI = 1.18-1.28 vs. SIRno/unknown = 1.17, 95% CI = 1.12-1.22; p = .18), indicating additional risk factors in play. The findings suggest a distinct carcinogenic pathway of radiation-induced lung cancer across histological subtypes and may inform risk-stratified surveillance guidelines for SPLC.

Enhancing Lung and Breast Cancer Screening with Advanced AI and Image Processing Techniques

This research investigates the application of CNNs for diagnostics improvements in lung and breast cancers based on AI image classification approaches. Using the datasets with 15,000 images describing lung cancer and 10,000 images describing cases of breast cancer, the models showed high performance: 90% for lung cancer and 99% for breast cancer classification. The descriptive analysis pointed out different features in imaging, such as dense tissue structure and irregular cell patterns; the models successfully identified these. The findings underlined the vital role that AI could play in assisting radiologists by delivering preliminary analysis, triaging high-risk cases, and leading to early cancer detection. Essential challenges were highlighted: ethical considerations concerning patients' privacy and AI algorithms' transparency. The limitation of the dataset diversity resulted in the conclusion that only broader data can ensure good generalization in various clinical settings. They recommended integrating the AI tool with clinical workflow and also called for training radiologists for effectiveness. Future research directions include real-time imaging and patient data integration for comprehensive diagnostic support and multi-modal approaches that combine imaging with genomics for more precise predictions. This leads to a more personalized cancer diagnosis and treatment plan, thus ultimately improving the results of the patients. This research, therefore, underlines the transformative capabilities of AI and image processing in modernizing cancer screening and diagnostics toward more accurate and efficient healthcare practices.

Triple Negative Breast Cancer: Experience of the Obstetrics and Gynecology Department 2 Over A Period of 3 Years about 105 Cases at the Hassan II University Hospital in Fes

Introduction: Breast cancer is the second leading cause of death worldwide and the leading cancer in women. It is both the most common and the leading cause of death in women from cancer, thus posing a real public health problem. It presents tumor heterogeneity on the histological and molecular levels, explaining the diversity of presentations, responses to treatments, and prognosis. Triple-negative breast cancer is defined by the absence of expression of hormone receptors: estrogen receptors (ER), progesterone receptors (PR) and by the absence of overexpression or amplification of genes encoding HER2 receptors (Human epidermal growth factor receptor 2) and representing only a minority of breast cancers (10-20%). The therapeutic choices for this type of breast cancer are limited because patients do not benefit from hormonal therapy or targeted therapies, which poses a real problem in therapeutic management. Our objective is to describe the epidemiological, clinical, anatomo-pathological characteristics, as well as the evolutionary profile after adequate management of triple-negative breast cancer through the analysis of a series of cases of triple-negative breast cancer collected at the gynecology-obstetrics department 2 at the Hassan II University Hospital in Fez. Method: This is a retrospective study of a series of triple negative breast cancer cases collected in the gynecology-obstetrics department II at the Hassan II University Hospital in Fez during the period between January 2020 and December 2023. Inclusion criteria: Histologically confirmed triple negative infiltrating breast cancer treated in the gynecology-obstetrics department 2 of the Hassan II University Hospital in Fez. IHC = ER = 0% RP = 0% HER2 negative Exclusion criteria: male sex and presence of distant metastases. Results: On the epidemio-clinical level: a peak in frequency between 31 and 42 years old, and 45.7% of patients still in genital activity. On the anatomo-pathological level: ...

Gestational breast cancer: distinctive molecular and clinico-epidemiological features

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6–15% of BC cases in women aged 20–44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012–03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012–03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.

A case of inflammatory breast cancer following augmentation with silicone injections

A case of inflammatory breast cancer following augmentation with silicone injections

Evaluating Outcomes for Women with Metastatic Breast Cancer: Palliative Care Consultations, Hospital Charges, and Length of Stay

Introduction: Women with late-stage metastatic breast cancer are at an increased risk of pain and distress from symptoms and often struggle with associated emotional and financial burden of their disease. Palliative care is known to alleviate symptom burden in patients with end-stage, terminal diseases but is often underutilized in both inpatient and outpatient settings. The current study aims to investigate the prevalence of palliative care consultation on inpatients with metastatic breast cancer and examine the association between palliative care consultation and length of hospital stay and total hospital charges. Methods: Patients diagnosed with metastatic breast cancer between 1998–2017 were abstracted from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Database (NIS). The primary outcome was the presence of a palliative care consultation (PCC) during the inpatient stay. Secondary outcomes were hospital length of stay and total hospital charges. Multivariable logistic regression was used to examine factors associated with the presence of a PCC. The relationship between PCC and hospital length of stay and total hospital charges were investigated using linear regression. Results: 513,509 cases of metastatic breast cancer were identified, 5.7% had a documented in-hospital palliative care encounter. Of those who received PCC, total hospital charges were about USD 5452 less than those who did not receive consultation. Women who received PCC had higher odds of a longer hospital stay. Predictors of PCC were older age, non-White race, and residing in a lower-income ZIP code. Conclusions: Palliative care remains to be an underutilized resource among patients with end-stage metastatic breast cancer.

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

BackgroundMenopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.MethodsData from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.ResultsMHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).ConclusionsOur study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.

Current status and challenges in HER2 IHC assessment: scoring survey results in Japan.

This study aimed to assess the concordance of human epidermal growth factor receptor 2 (HER2) expression scoring by immunohistochemistry (IHC) among practicing pathologists in Japan, given the challenging nature of scoring and the critical role of HER2 status in breast cancer management. Whole slide images (WSI) from 20 invasive breast cancer cases (1 representative WSI per case) selected to represent a diverse IHC scores and staining patterns were used in an online survey involving seven reference pathologists who established consensus HER2 IHC scores (0 to 3 +) decided by majority interpretation. Participating pathologists nationwide scored the same 20 WSI cases online using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guidelines. Deidentified case metadata were registered in the uPath system. A total of 144 participating pathologists responded. The scoring results of the participating pathologists most commonly agreed with the consensus IHC score, followed by a ± 1 point deviation and no survey responses with > 1 point deviation. The mean percentage of agreement with the consensus score for all 20 cases was 63.4%. In cases where the reference pathologists' scores were discordant, the participating pathologists also showed a lower concordance rate. This study highlighted the current status of HER2 expression scoring by IHC for breast cancer among pathologists in Japan. These findings underscore the challenges in HER2 IHC scoring cases and emphasize the need for improved standardization and training, especially in the evolving landscape of HER2-targeted therapies.

The role of adjuvant endocrine treatment in ER+, PR−, HER2− early breast cancer: a retrospective study of real-world data

Purpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET. Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively. Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000). Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68–2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37–3.68, p = 0.799). 65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with aggressive clinicopathological features and more tend to have distant metastasis rather than nodal involvement or local relapse. ER+/PR-/HER2- early BC did not seem to benefit from adjuvant ET.

Breast cancer incidence and mortality, by age, stage and molecular subtypes, by race/ethnicity in Canada.

Breast cancer (BC) characteristics and outcomes in Canada related to race/ethnicity are not currently documented. Age-specific and age-standardized BC incidence and mortality rates, age distribution of cases, proportions of stage, and molecular subtypes were calculated for women aged 20+, by race/ethnicity, using 2006 and 2011 Canadian Census Health and Environment Cohort databases of linked census, cancer, and death data. In 47105 BC cases, age-specific incidence rates were higher in Filipina (rate ratio (RR) = 1.27, 95%CI, 1.11-1.46) and multiethnicity (RR = 1.57, 95% CI, 1.18-2.08) compared to White women aged 40-49; and Filipina (RR = 1.16, 95% CI, 1.02-1.31) and Arab (RR = 1.3, 95% CI, 1.02-1.65) women aged 50-59. Median age at diagnosis was 63 among White women and 52-60 among other race/ethnicity groups, with 22.4%-41.1% of cases (P < .001) diagnosed before age 50 compared to 16.6% among White women. BC was diagnosed at stage I less frequently among Filipina (38.6%), Black (39.2%), South Asian (40.6%), and First Nations (40.7%) compared to White (46.5%) and Chinese (49.6%) (P < .05) women. Black women had higher proportions of BC diagnoses at stages III and IV combined (26.3%) than White women (17.0%, P = .001). The proportion of triple-negative BC among Black women (20.5%) was higher than among White (9.5%, P < .001). Compared to White, age-specific BC mortality rates were higher among Black women aged 40-49 (RR = 1.4, 1.06-1.85) as well as First Nations (RR = 1.21, 1.01-1.45) and Métis (RR = 1.48, 1.15-1.91) women aged 60-69. Compared to White women, other Canadian women had an earlier peak age of BC diagnosis and higher proportions of cases diagnosed under age 50. Although many race/ethnicity groups had lower BC incidence and mortality than White, the higher age-specific BC mortality among Black 40-49 and First Nations and Métis women 60-69 merits further investigation.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer – A Swedish cohort study

IntroductionPerfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited. This study aims to investigate the association between PFAS exposure and hormone receptor-positive breast cancer. Materials and MethodsIn 2013, high levels of PFAS (sum of PFAS > 10,000 ng/L), dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were found in the drinking water from one of the two waterworks in Ronneby, Sweden. Breast cancer diagnoses and information of adjuvant endocrine therapy were retrieved from the Swedish Cancer Register and The Prescribed Drug Register 2006–2016 for a cohort of women residing in the municipality between 1985 and 2013 (n = 24,509). Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential addresses. Cox proportional hazards models were used in the analysis. The highest achieved educational level was used as an indicator of socioeconomic position. Sensitivity and subgroup analysis were performed for prepubertal exposure and diagnosis before or after age 50 (assumed menopause). ResultsThere were 313 cases of malignant breast cancer among women ≤ 85 years between 2006 and 2016. Of these, 224 cases (72 %) were considered hormone receptor-positive based on the first prescription of adjuvant endocrine therapy, antiestrogens (40 %) or aromatase inhibitor (60 %). Among women ever living at a residential address with high PFAS exposure, the hazard ratio (HR) for breast cancer classified as hormone receptor-positive was 0.84; 95 % confidence interval (CI) 0.61, 1.14. Findings were similar before and after menopause. ConclusionHigh PFAS exposure from drinking water, dominated by PFOS and PFHxS, was not associated with an elevated risk of hormone receptor-positive breast cancer.

Clinical Significance of FAM83G in Breast Cancer: Association With Triple-negative Subtype and Prognosis.

Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer. Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients. FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases. This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.