ACR Appropriateness Criteria® Imaging of Invasive Breast Cancer.

As the proportion of women diagnosed with invasive breast cancer increases, the role of imaging for staging and surveillance purposes should be determined based on evidence-based guidelines. It is important to understand the indications for extent of disease evaluation and staging, as unnecessary imaging can delay care and even result in adverse outcomes. In asymptomatic patients that received treatment for curative intent, there is no role for imaging to screen for distant recurrence. Routine surveillance with an annual 2-D mammogram and/or tomosynthesis is recommended to detect an in-breast recurrence or a new primary breast cancer in women with a history of breast cancer, and MRI is increasingly used as an additional screening tool in this population, especially in women with dense breasts. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update.

Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Her-2/neu gene amplification and its correlation with other prognostic factors in Iranian breast cancer patients.

BACKGROUND: Breast cancer is one of the most common diseases in females, arising from overexpression of a variety of oncogenes like HER2/neu. The amplification rate of this gene is variable in different breast cancer patients. In this study, the amplification of the HER2/neu oncogene was distinguished in breast cancer patients and its correlation with prognostic factors. Also, the simultaneous effect of prognostic factors on the occurrence of a specific prognostic factor was investigated. MATERIALS AND METHODS: The multiplex PCR technique was used to assay the amplification of the HER2/neu oncogene in breast cancer patients. After extracting DNA from 100 tumor tissue and 8 normal breast tissue samples, the amplification of the HER2/neu gene was distinguished by the co-amplification of a single-copy reference gene, γ-IFN, and the target gene HER2/neu in the PCR reaction and using the Gel analyzer software. SPSS 23 and STATA 9.1 software were used for statistical analysis. RESULTS: The HER2/neu gene was amplification in 30% of the tumor samples. The statistical analysis showed a statistically significant relationship between HER2/neu gene amplification and progesterone receptors. Amplification of the HER2/neu gene significantly increases the chance of lymph node involvement. Also, the amplification of this gene in tumors with histological grade II tissue is more than grade I. CONCLUSION: The amplification of the HER2/neu gene can be used as an independent prognostic factor in predicting lymph node involvement and histological grade in breast cancer patients.

Formulation of quinoa oil-alginate loaded nanoemulsion and its anticancer efficacy as a therapy for chemically induced breast cancer.

BACKGROUND: Quinoa seeds (Chenopodium quinoa Willd.) have gained interest due to their naturally occurring phytochemicals and antioxidants. They possess potent anticancer properties against human colorectal cancer. METHODS AND RESULTS: Fatty acids in quinoa oil were studied using gas chromatography-mass spectrometry. Rats were used to test the acute oral toxicity of the nanoemulsion loaded with sodium alginate. The DPPH radical scavenging method was employed to assess the nanoemulsion's ability to scavenge free radicals. It was examined the in vivo anticancer potential of quinoa oil nanoemulsion on rats with breast cancer induced by 7, 12-dimethylbenz (a) anthracene (DMBA). DMBA-breast cancer models received daily quinoa oil nanoemulsions for 30 days. The anticancer effect of the nanoemulsion was assessed by measuring ROS, protein carbonyl, gene expression of anti-oncogenes, and histopathological analysis. Supplying quinoa oil nanoemulsion significantly reduced the increase in serum ROS and PC levels induced in breast cancer tissue. The expression levels of antioncogenes in breast cancer tissue were decreased by the quinoa oil nanoemulsion. Nanoemulsions also improved the cellular morphology of breast tumors. CONCLUSION: The study results indicate that quinoa oil nanoemulsion has anticancer activity against breast cancer, effectively modulating oxidative stress markers, anti-oncogene expressions, and tissue architecture. It can be inferred from the results that quinoa oil nanoemulsion is a chemoprotective medication that may hinder breast cancer progression in rats.

Prognostic significance of CHCHD2P9 and ZNF204P in breast cancer: exploring their expression patterns and associations with malignancy-related genes.

BACKGROUND: Non-coding RNAs (ncRNAs) have a crucial impact on diverse cellular processes, influencing the progression of breast cancer (BC). The objective of this study was to identify novel ncRNAs in BC with potential effects on patient survival and disease progression. METHODS: We utilized the cancer genome atlas data to identify ncRNAs associated with BC pathogenesis. We explored the association between these ncRNA expressions and survival rates. A risk model was developed using candidate ncRNA expression and beta coefficients obtained from a multivariate Cox regression analysis. Co-expression networks were constructed to determine potential relationships between these ncRNAs and molecular pathways. For validation, we employed BC samples and the RT-qPCR method. RESULTS: Our findings revealed a noteworthy increase in the expression of AC093850.2 and CHCHD2P9 in BC, which was correlated with a poor prognosis. In contrast, ADAMTS9-AS1 and ZNF204P displayed significant downregulation and were associated with a favorable prognosis. The risk model, incorporating these four ncRNAs, robustly predicted patient survival. The co-expression network showed an effective association between levels of AC093850.2, CHCHD2P9, ADAMTS9-AS1, and ZNF204P and genes involved in pathways like metastasis, angiogenesis, metabolism, and DNA repair. The RT-qPCR results verified notable alterations in the expression of CHCHD2P9 and ZNF204P in BC samples. Pan-cancer analyses revealed alterations in the expression of these two ncRNAs across various cancer types. CONCLUSION: This study presents a groundbreaking discovery, highlighting the substantial dysregulation of CHCHD2P9 and ZNF204P in BC and other cancers, with implications for patient survival.

Study on the mechanism of heterogeneous tumor-associated macrophages in three subtypes of breast cancer through the integration of single-cell RNA sequencing and in vitro experiments.

BACKGROUND: Tumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2. MATERIALS AND METHODS: This investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells. RESULTS: Our findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-ß1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance. CONCLUSION: Our study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.

Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

A survey of cancer patients' interest in undertaking exercise to promote relaxation during radiotherapy for breast cancer and metastatic cancer.

BACKGROUND: Approximately 25-50% of patients undergoing radiotherapy (RT) experience psychological distress and anxiety, which can detrimentally affect both their quality of life and treatment outcomes. While previous research has demonstrated that relaxation exercises can enhance the tolerability of RT and alleviate associated stress and anxiety, the specific needs for such therapies in radiation oncology remain under-explored. This study aims to investigate the demand for and preferences toward relaxation exercises among radiotherapy patients, addressing a critical gap in patient-centered care. METHODS: A prospective pseudonymized survey study using a one-time paper-based questionnaire was conducted from 2022 to 2023 among patients undergoing curative-intent RT for breast cancer or patients undergoing palliative RT for bone metastases. Patients were asked in a 11-item questionnaire about their anxiety, pre-existing practice of relaxation exercises/interventions, their interest in relaxation exercises, and preferences on the type and format of instruction. Data were analyzed descriptively. RESULTS: 100 patients (74 female and 26 male) responded, of whom 68 received curative-intent adjuvant RT and 32 palliative RT. Median age was 62 years. 78% of patients indicated a desire to be actively involved in their radiotherapy, but only 27% had used relaxation exercises prior to RT. 44.8% of both curatively and palliatively treated patients who wanted to be actively involved in their therapy desired to learn how to best relax. 56.4% of respondents were willing to spend extra time learning offered exercises. CONCLUSION: The survey indicates that patients undergoing RT, both for curative or palliative intent, desire relaxation exercises to relieve stress and anxiety from RT. It is therefore important to assess the need for relaxation interventions in individual patients and to develop suitable programs or collaborate with other healthcare professionals to meet these needs.

Effect of Perioperative Docetaxel-induced Limb Edema on Health-related Quality of Life in Patients with Early-stage Breast Cancer: A Prospective Observational Study.

Docetaxel (DTX) is a key drug used in perioperative chemotherapy for breast cancer. Edema is a known adverse effect of DTX, but its effect on health-related QOL (HRQOL) is unclear. In this study, we evaluated the effects of edema caused by administration of DTX on HRQOL in patients with early-stage breast cancer. We prospectively investigated patients diagnosed with early-stage breast cancer (stage I-III) who received 4 cycles of DTX as preoperative or postoperative chemotherapy between September 2021 and December 2022 at Yamanashi Prefectural Central Hospital. The circumference of each extremity was measured at each administration of DTX, and limb edema was evaluated by Common Terminology Criteria for Adverse Events version 5.0. HRQOL was evaluated using SF-12 version 2, which has a range of 0-100 (national standard, 50), and compared between the presence and absence of grade 2 or higher edema and between before and after administration of DTX. Twenty patients met the eligibility criteria and were included in the study. There was no difference in the HRQOL score according to whether grade 2 limb edema was present. The median HRQOL summary scores before and after administration of DTX were 51.1 and 50.8 (p=0.763), respectively, for mental health, 52.6 and 49.4 (p=0.005) for physical health, and 38.9 and 37.5 (p=1.000) for role/social health. We found no direct effect of DTX-induced limb edema on HRQOL in patients with early-stage breast cancer. However, HRQOL summary scores indicated that administration of DTX reduced physical health in these patients.

Quercetin inhibits breast cancer cell proliferation and survival by targeting Akt/mTOR/PTEN signaling pathway.

Recently, natural compounds such as quercetin have gained an increasing amount of attention in treating breast cancer. However, the exact mechanisms responsible for the antiproliferative functions of quercetin are not completely understood. Therefore, we aimed to examine quercetin impacts on breast cancer cell proliferation and survival and the involvement of PI3K/Akt/mTOR pathway. Breast cancer MDA-MB-231 and MCF-7 cells were exposed to quercetin, and cell proliferation was assessed by MTT assay. ELISA was applied to evaluate cell apoptosis. The expression levels of apoptotic mediators such as caspase-3, Bcl-2, Bax and PI3K, Akt, mTOR, and PTEN were assessed via qRT-PCR and western blot. We found that quercetin suppressed dose dependently cell growth capacity in MDA-MB-231 and MCF-7 cells. In addition, quercetin treatment increase apoptosis in both cells lines via modulating the pro- and antiapoptotic markers. Quercetin upregulated PTEN and downregulated PI3K, Akt, and mTOR, hence suppressing this signaling pathway in cells. In conclusion, we showed antiproliferative and pro-apoptotic function of quercetin in breast cancer cell lines, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.

Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria.

BACKGROUND: Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer. METHODS: The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05. RESULTS: Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants' permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices. CONCLUSION: This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Targeting the core program of metastasis with a novel drug combination.

BACKGROUND: We previously reported that metastases are generally characterized by a core program of gene expression that activates tissue remodeling/vascularization, alters ion homeostasis, induces the oxidative metabolism, and silences extracellular matrix interactions. This core program distinguishes metastases from their originating primary tumors as well as from their destination host tissues. Therefore, the gene products involved are potential targets for anti-metastasis drug treatment. METHODS: Because the silencing of extracellular matrix interactions predisposes to anoiks in the absence of active survival mechanisms, we tested inhibitors against the other three components. RESULTS: Individually, the low-specificity VEGFR blocker pazopanib (in vivo combined with marimastat), the antioxidant dimethyl sulfoxide (or the substitute atovaquone, which is approved for internal administration), and the ionic modulators bumetanide and tetrathiomolybdate inhibited soft agar colony formation by breast and pancreatic cancer cell lines. The individual candidate agents have a record of use in humans (with limited efficacy when administered individually) and are available for repurposing. In combination, the effects of these drugs were additive or synergistic. In two mouse models of cancer (utilizing 4T1 cells or B16-F10 cells), the combination treatment with these medications, applied immediately (to prevent metastasis formation) or after a delay (to suppress established metastases), dramatically reduced the occurrence of disseminated foci. CONCLUSIONS: The combination of tissue remodeling inhibitors, suppressors of the oxidative metabolism, and ion homeostasis modulators has very strong promise for the treatment of metastases by multiple cancers.

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Extracellular vesicle proteins as breast cancer biomarkers: Mass spectrometry-based analysis.

Extracellular vesicles (EVs) are membrane-surrounded vesicles released by various cell types into the extracellular microenvironment. Although EVs vary in size, biological function, and components, their importance in cancer progression and the potential use of EV molecular species to serve as novel cancer biomarkers have become increasingly evident. Cancer cells actively release EVs into surrounding tissues, which play vital roles in cancer progression and metastasis, including invasion and immune modulation. EVs released by cancer cells are usually chosen as a gateway in the search for biomarkers for cancer. In this review, we mainly focused on molecular profiling of EV protein constituents from breast cancer, emphasizing mass spectrometry (MS)-based proteomic approaches. To further investigate the potential use of EVs as a source of breast cancer biomarkers, we have discussed the use of these proteins as predictive marker candidates. Besides, we have also summarized the key characteristics of EVs as potential therapeutic targets in breast cancer and provided significant information on their implications in breast cancer development and progression. Information provided in this review may help understand the recent progress in understanding EV biology and their potential role as new noninvasive biomarkers as well as emerging therapeutic opportunities and associated challenges.

Pooled analysis of NeoCARH and NeoCART trials: patient-reported outcomes in patients with early-stage breast cancer receiving platinum-based or anthracycline-based neoadjuvant chemotherapy.

PURPOSE: Anthracycline-based or platinum-based neoadjuvant chemotherapy belongs to the standard treatment for early-stage breast cancer (EBC) that is either triple-negative or human epidermal growth factor receptor 2 positive (HER2 +). Currently, there is a paucity of data comparing their impact on health-related quality of life (HRQoL). METHODS: Triple-negative or HER2 + EBC from our two prospective randomized controlled trials, neoCARH and neoCART, were divided into two groups based on the neoadjuvant chemotherapy regimens they received: anthracycline-based or platinum-based group. HRQoL was the exploratory endpoint in these two trials, which was assessed using the European Organization for Research and Treatment of Cancer Quality of Life-Core30 and Breast23 questionnaires. The primary variable of interest was the C30 summary score (C30-SumSc). Assessments were carried out at baseline, after neoadjuvant chemotherapy, and 1 year and 2 years after diagnosis. RESULTS: The mean questionnaires' compliance rate was 95.0%. After neoadjuvant chemotherapy, 210 patients had evaluable HRQoL data, the mean least square change from baseline for the platinum-based group was - 15.997 (95% confidence interval (CI): - 17.877 to - 14.117), and it was - 20.156 (95% CI: - 22.053 to - 18.258) for the anthracycline-based group (difference: 4.159, 95% CI: 1.462 to 6.855, P = 0.003, minimal important difference = 3). For the majority of the domains of interest assessed by the C30 and BR23 questionnaires, the platinum-based group demonstrated superior outcomes in comparison to the anthracycline-based group. CONCLUSION: Patients receiving platinum-based or anthracycline-based regimens both experienced worsened HRQoL after neoadjuvant chemotherapy; however, the former provided relatively better HRQoL compared with the latter. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03140553. Registered 4 May 2017 (neoCARH). NCT03154749. Registered 16 May 2017 (neoCART).

Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China.

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.

Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation.

Breast cancer is the leading cause of cancer-related deaths in women worldwide, with Hormone Receptor (HR)+ being the predominant subtype. Tamoxifen (TAM) serves as the primary treatment for HR+ breast cancer. However, drug resistance often leads to recurrence, underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates. Artemisinin (ART) has demonstrated efficacy in inhibiting the growth of drug-resistant cells, positioning art as a viable option for counteracting endocrine resistance. This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation. Five characterized genes (ar, cdkn1a, erbb2, esr1, hsp90aa1) and seven drug-disease crossover genes (cyp2e1, rorc, mapk10, glp1r, egfr, pgr, mgll) were identified using WGCNA crossover analysis. Subsequent functional enrichment analyses were conducted. Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and -sensitized patients. scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells, suggesting artemisinin's specific impact on tumor cells in estrogen receptor (ER)-positive BC tissues. Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes. These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.