Breast Cancer Research Articles

Prognostic Significance of Immunohistochemical Expression of Cyclin D1 and β-Catenin in Invasive Ductal Carcinoma (IDC)

Introduction: Invasive ductal carcinoma (IDC) is the most prevalent subtype of breast cancer, distinguished by diverse clinical manifestations and molecular heterogeneity. Prognostic outcomes are influenced by multiple factors, including the patient’s age at diagnosis, tumor size, histological grade, disease stage, lymph node metastasis (LNM), and hormone receptor status (ER, PR, HER2). This research has highlighted the potential of emerging molecular biomarkers such as Cyclin D1 and β-Catenin in enhancing prognostic precision. Methodology: This retrospective, cross-sectional study analyzed the medical records of female patients diagnosed with IDC. Tumor size, grade, and stage were examined alongside lymph node involvement to assess the extent of disease dissemination. Immunohistochemistry (IHC) was employed to determine the expression of ER, PR, and HER2 receptors. Additionally, emerging biomarkers such as Cyclin D1 and β-Catenin were evaluated to explore their prognostic value. A total of 150 tumor samples were collected from multiple cancer treatment facilities across Rawalpindi, Punjab, Pakistan. Findings and Discussion: The mean age at diagnosis was 50.6 years, with the majority of patients (68%) between 36 and 55 years. Tumor analysis revealed that 76.7% of lesions were <30 mm in size, and 46.7% were classified as grade II. LNM was detected in 39.3% of patients, indicating significant metastatic potential. Regarding receptor expression, 45.5% of tumors were ER-positive, 42.9% PR-positive, and 54.8% HER2-positive, aligning with global incidence trends. The investigation of molecular markers showed Cyclin D1 overexpression in 60% of cases, predominantly in ER-positive tumors, suggesting better endocrine therapy responsiveness. β-Catenin was detected in 33.3% of samples and correlated with aggressive tumor phenotypes, emphasizing its potential role in identifying high-risk patients. These molecular markers align with globally research. Conclusion: This study emphasizes the significance of early detection and comprehensive molecular profiling in IDC management. Smaller tumors and receptor-positive cases are generally associated with more favorable outcomes. Additionally, emerging biomarkers such as Cyclin D1 and β-Catenin hold promise for refining prognostic models and optimizing individualized treatment plans. Incorporating these biomarkers into clinical practice can further enhance therapeutic decision-making and patient care.

Relationship Between Posttraumatic Growth and Illness Uncertainty in Young Women With Breast Cancer: The Mediating Role of Self-compassion

Background The recovery process for young women with breast cancer is influenced by several factors, including the uncertainty of disease, posttraumatic growth, and self-compassion. Objective To examine the association between illness uncertainty and posttraumatic growth in young women with breast cancer and to determine the mediating role of self-compassion in this association. METHODS This cross-sectional, descriptive and correlational study was conducted in Western Turkey between September 2023 and December 2023. Data were collected from 153 young women with breast cancer using the demographic and clinical questionnaire, the Posttraumatic Growth Inventory, Mishel Uncertainty in Illness Scale—Community, and the Self-compassion Scale. RESULTS Posttraumatic growth was negatively correlated with illness uncertainty (r = −0.304, P < .001) and positively correlated with self-compassion (r = 0.581, P < .001). Illness uncertainty negatively predicted posttraumatic growth (P < .001), whereas self-compassion positively predicted posttraumatic growth (P < .001). When self-compassion was included in the model, the effect of illness uncertainty on posttraumatic growth became insignificant (P > .05). Conclusion Results of the study indicate that self-compassion has a fully mediating effect on the relationship between illness uncertainty and posttraumatic growth in young women with breast cancer. Implications for Practice Psychosocial care of young women with breast cancer by oncology nurses can significantly improve self-compassion, reduce illness uncertainty, and promote posttraumatic growth.

Beyond pink ribbons: The unmet needs of women with breast cancer.

Breast cancer is the most frequently diagnosed cancer worldwide. The treatment options for breast cancer can cause side effects and adversely impact quality of life. Side effects, including fatigue, pain, cognitive changes, and psychosocial complications, can be life altering and continue beyond treatment into survivorship. Traditionally, health professionals focused almost entirely on achieving cancer survival; however, due to significant success in cancer treatment outcomes, most women now live beyond their breast cancer treatment. Consequently, addressing side effects and compromises in quality of life are becoming more important issues to include in a comprehensive approach to breast cancer treatment. For women, these unmet needs may involve body image concerns, sexual dysfunction, and other lifestyle challenges, and may not have previously been given sufficient recognition or priority. It is necessary for us, as oncology healthcare professionals, to modify our delivery of cancer care and ensure that more comprehensive care is provided to women. By addressing women's unmet needs, we can contribute to achieving the United Nations' Sustainable Development Goals regarding improving health and equality. This commentary seeks to emphasise the advantages of providing comprehensive care for women with breast cancer and advocates for cancer care professionals to actively participate in initiating and implementing this care.

Artificial intelligence-based computer-aided diagnosis for breast cancer detection on digital mammography in Hong Kong.

Research concerning artificial intelligence in breast cancer detection has primarily focused on population screening. However, Hong Kong lacks a population-based screening programme. This study aimed to evaluate the potential of artificial intelligence-based computer-assisted diagnosis (AI-CAD) program in symptomatic clinics in Hong Kong and analyse the impact of radio-pathological breast cancer phenotype on AI-CAD performance. In total, 398 consecutive patients with 414 breast cancers were retrospectively identified from a local, prospectively maintained database managed by two tertiary referral centres between January 2020 and September 2022. The full-field digital mammography images were processed using a commercial AI-CAD algorithm. An abnormality score <30 was considered a false negative, whereas a score of ≥90 indicated a high-score tumour. Abnormality scores were analysed with respect to the clinical and radio-pathological characteristics of breast cancer, tumour-to-breast area ratio (TBAR), and tumour distance from the chest wall for cancers presenting as a mass. The median abnormality score across the 414 breast cancers was 95.6; sensitivity was 91.5% and specificity was 96.3%. High-score cancers were more often palpable, invasive, and presented as masses or architectural distortion (P<0.001). False-negative cancers were smaller, more common in dense breast tissue, and presented as asymmetrical densities (P<0.001). Large tumours with extreme TBARs and locations near the chest wall were associated with lower abnormality scores (P<0.001). Several strengths and limitations of AI-CAD were observed and discussed in detail. Artificial intelligence-based computer-assisted diagnosis shows potential value as a tool for breast cancer detection in symptomatic setting, which could provide substantial benefits to patients.

Collagen Density Is Associated With Pathological Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

The tumor-associated stroma is an essential compartment in breast cancer, and collagen fiber organization in the stroma has been reported to be correlated with prognosis. In this study, we sought to evaluate collagen fiber characteristics in relation to pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 388 breast cancer patients receiving NAC were enrolled. The stroma type was manually assessed on pretreatment hematoxylin and eosin (HE)-stained slides, and the collagen fiber features were quantified by a computer tool. The relationship between syndecan-1 expression and collagen fibers and its correlation with treatment efficacy were detected by immunohistochemistry. The pCR rate of patients with collagen-dominant stroma was lower than that of patients with lymphocyte-dominant stroma (19.6% vs. 40.0%, p = 0.001). Patients who achieved pCR had straighter and less dense fibers in pretreatment biopsied tissue than non-pCR patients (p = 0.031, p = 0.044). Additionally, the pCR group had greater syndecans-1 expression on the tumor epithelium than the non-pCR group (p < 0.001), while there was no statistically significant difference in the stroma (p = 0.333). Collagen fiber density was the only factor associated with pCR after correction for other clinicopathological variables in triple-negative breast cancer (TNBC)patients (OR 0.466, 95% CI 0.227-0.956, p = 0.037); patients with lower fiber density had a greater pCR rate (37.5% vs. 12.5%, p = 0.021). Collagen fiber density was associated with pCR in patients with breast cancer, and it could be a potential candidate for discriminating between responders and nonresponders for TNBC patients receiving NAC.

Cardiovascular mortality trends and disparities in U.S. breast cancer patients, 1999–2020: a population-based retrospective study

BackgroundBreast cancer survivors face a higher risk of cardiovascular disease (CVD) compared to non-breast cancer patients, yet contemporary data on CVD-related mortality within this group remains scarce.ObjectiveTo investigate trends and disparities in CVD mortality among breast cancer patients.MethodsWe queried the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC Wonder) and conducted serial cross-sectional analyses on national death certificate data for CVD mortality in breast cancer patients aged 25 and above from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and analyzed trends over time using the Joinpoint Regression Program, with further analyses stratified by age, race, census region, and urbanization level.ResultsA total of 74,733 CVDs with comorbid breast cancer in the United States were identified between 1999 and 2020. The AAMR from CVDs with comorbid breast cancer decreased from 2.57 (95% CI [2.50–2.65]) in 1999 to 1.20 (95% CI [1.15–1.24]) in 2020, with an average annual percent change (AAPC) of − 4.3. The three most common causes of CVDs were ischemic heart disease (47.8%), cerebrovascular disease (17.1%), and hypertensive disease (10.6%). Our analysis revealed a significant decrease in AAMR for all CVD subtypes, except for hypertensive diseases and arrhythmias. The decrease in annual percent change (APC) was more pronounced in individuals aged ≥ 65 years compared to those < 65 years (-4.4, 95%CI [-4.9, -3.9] vs. -2.9, 95%CI [-4.1, -1.7], respectively. Notably, non-Hispanic Blacks consistently exhibited the highest AAMR (1.95, 95%CI [1.90–1.99]), whereas Hispanic or Latina patients had the lowest AAMR (0.75, 95% CI [0.72–0.78]). The AAMR was also higher in rural regions than in urban areas (1.64, 95%CI [1.62–1.67] vs. 1.55, 95%CI [1.53–1.56]).ConclusionThe study highlights a significant decline in CVD mortality among breast cancer patients over two decades, with persistent disparities by race and region. Exceptionally, hypertensive diseases and arrhythmias did not follow this declining trend.

Risk-based breast cancer screening: What are the challenges?

Population-based screening programs aim to detect the disease at an early stage, so less treatment will be needed as well as having better oncological outcomes when diagnosed earlier. In the majority of European countries, breast cancer screening programs are designed based on women age.Meta-analysis of randomized clinical trial data demonstrates a reduction in the relative risk of breast cancer mortality due to screening, which has been estimated to be approximately 20%.One of the controversies about the population breast screening programs is that age-based screening ignores women's individual breast cancer risk. Identification of high-risk women may intensify the screening measures and will optimize the population screening programs to align them to individual risks.Family history of breast cancer is one of the risk factors to consider along with the recently developed polygenic risk scores to stratify women into a risk group. Other factors to assess risk include: mammographic breast density; B3 lesions with atypia in breast biopsy specimens; hormonal and lyfestyle and, potentially, epigenetic markers. Still, there are some difficulties in validating these factors and reflecting the interaction between risk factors in the models.Ongoing screening trials (e.g., WISDOM and MyPebs) are currently evaluating the clinical acceptability and utility of risk-stratified screening programs in the general population, and should provide valuable information for the possible implementation of such programs.Communication of complex risk information to the women, as well as assessing ethical concerns need to be addressed before implementation of risk stratified programs.

Factors associated with post acute care utilization after mastectomy for breast cancer patients.

Although the demand for care immediately after mastectomy is rising, and such medical services are referred to as post-acute care (PAC), there is limited evidence on the factors influencing PAC choices among these patients in Korea. A total of 106,670 patients diagnosed with breast cancer and undergoing mastectomy were extracted from the Central Cancer Registry data from 2012 to 2019 using Public Cancer Library data of KCURE. PAC was defined as utilization of long-term care hospital (LTCH), hospital-based nursing care (HBNC), or HBC (hospital-based care) within 2 months post-surgery. Multinomial logistic regression was used to identify factors associated with different types of PAC utilization. The utilization patterns of different types of PAC within 2 months after mastectomy were associated with age, income, cancer severity, and particularly the region of residence (Metropolitan; HBNC, OR 0.16, 95% CI 0.10-0.26; LTCH, OR 2.35, 95% CI 2.21-2.50; HBC, OR 2.17, 95% CI 1.97-2.39), as well as the location (capital areas; HBNC, OR 12.46, 95% CI 4.97-31.25; LTCH, OR 1.21, 95% CI 1.15-1.28; HBC, OR 1.90, 95% CI 1.74-2.07) and type of the hospital (tertiary hospital; HBNC, OR 13.70, 95% CI 7.86-23.86; LTCH, OR 1.45, 95% CI 1.37-1.53; HBC, OR 3.38, 95% CI 3.00-3.80) where the surgery was performed. In this study, we found the factors associated with PAC utilization on mastectomy patients. Our study found that middle-aged breast cancer patients, residents of metropolitan or rural areas, and those who underwent surgery at hospitals in capital area were particularly associated with higher utilization of inpatient-related PAC services. Breast cancer patients with higher income, older adults, metropolitan residents, patients who underwent breast cancer surgery at metropolitan hospitals, and those treated at tertiary hospitals were strongly associated with higher utilization of HBNC services. Identifying factors that determine the use of PAC has meaningful implications for patients and healthcare systems.

Parameter map guided explainable segmentation framework for breast cancer using amide proton transfer weighted imaging.

Amide proton transfer weighted (APTw) imaging has demonstrated extensive clinical applications in diagnosing, treating evaluating, and prognosis prediction of breast cancer. There is a pressing need to automatically segment breast lesions on APTw original images to facilitate downstream quantification, which is however challenging. To build a segmentation model on the original images of APTw imaging sequence by leveraging the varying contrasts between breast lesions and their surrounding glandular and fat tissues displayed on the original images of APTw imaging at different frequency offsets. This paper proposes a network with multiple tasks, including a breast lesion segmentation model (task I) incorporating multiple images at different frequencies with different contrasts between tumor and surrounding tissues, an automatic classification of pathological task (task II), and an APTw parameter map fitting (task III). Compared with these advanced segmentation methods such as U-Net, segment anything model (SAM), segment anything in medical images (Med-SAM), and transfomer for MRI brain tumor segmentation (TransBTS), our method achieves higher accuracy (ACC). Furthermore, the model's interpretability facilitates the evaluation of how maps with varying gray contrasts contribute to the segmentation. Moreover, improving the ACC of segmentation can be accomplished through tasks such as pathological classification and parametric mapfitting. The pathological classification task and parameter fitting task could improve the ACC ofsegmentation.

Does T1c–2N0–1M0 triple negative breast cancer derive a benefit from neoadjuvant chemotherapy?

ObjectivesAlthough neoadjuvant chemotherapy (NCT) is a standard approach for operable triple negative breast cancer (TNBC), the potential risks brought by it should also be noticed. Is the expanding indication of NCT to T1cN0M0 population appropriate? We conducted an investigation to compare the long-term survival of small tumor TNBC between NCT and adjuvant chemotherapy (ACT).MethodsFor this propensity-matched analysis, we used data from Surveillance, Epidemiology, and End Results (SEER) database. We enrolled 1183 cases with NCT and 2550 cases with ACT who are AJCC clinical T1c–T2 N0–N1, diagnosed with invasive triple-negative breast cancer, from 2016 to 2017. The propensity score matching was utilized to minimize baseline characteristics bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression model.ResultsCompared with patients receiving ACT, patients with NCT in this study presented a higher proportion of younger age, T2 stage, N1 stage, and underwent more mastectomy. Multivariate analysis in matched patients showed that NCT had no significant survival benefit compared with ACT in T1c–2N0–1M0 TNBC patients. Stratified analyses by T stage and N stage demonstrated NCT mainly presented a survival advantage in patients with N1 stage. Further investigation found that NCT didn’t improve BCSS (HR, 0.472; 95% CI 0.135–1.647; P = 0.239) and OS (HR, 0.392; 95% CI 0.147–1.047; P = 0.062) for patients with T1cN0M0 TNBC; however, it was associated with improved OS (HR, 1.951; 95% CI 1.003–3.797; P = 0.049) only for patients with T2N1M0 TNBC.ConclusionsIn this study, we did not find any profit brought by NCT in the stage I and stage IIa cohorts, but even more unfavorable outcomes appeared in the T1cN0M0 cohort. Therefore, whether the candidates of NCT should be extended to T1cN0M0 still need to be cautious.

Cardiovascular adverse events in patients with HER2-positive breast cancer treated with trastuzumab-drug conjugates : a Bayesian disproportional real world study for signal detection leveraging the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background The cardiovascular risk profiles of trastuzumab drug conjugates (T-DCs) in the treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer are uncertain. This study analyzed real-world adverse events data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to investigate the association between T-DCs and major adverse cardiovascular events (MACE). Methods We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). The primary endpoint was MACE and the secondary endpoint was other cardiovascular events. Results Between January 2015 and April 2024, out of the 135,226 drug-adverse event pairs analyzed, 8,497 were cardiovascular events, with 4,457 classified as MACE and 4,040 as other cardiovascular events. Trastuzumab reached pharmacovigilance for MACE (ROR = 1.39, 95%CI: 1.30–1.49, IC025 = 0.25), while neither T-DM1 (ROR = 0.78, 95%CI: 0.69–0.88, IC025=-0.51) nor T-Dxd (ROR = 0.63, 95%CI: 0.52–0.76, IC025=-0.93) reached MACE-related pharmacovigilance. Among MACE, stroke linked to T-DM1 (ROR = 1.86, 95%CI: 1.42–2.43, IC025 = 0.35) and T-Dxd (ROR = 2.44, 95%CI: 1.68–3.56, IC025 = 0.57) both reached pharmacovigilance in younger patients (<65 years). Proportionate analysis showed age and weight were the two key factors contributing to the occurrence of T-DCs induced MACE. Conclusion HER2-positive breast cancer patients receiving T-DCs require additional cardiac monitoring, particularly for stroke in younger patients.

Transferrin Protein Corona-Targeted Codelivery of Tirapazamine and IR820 Facilitates Efficient PDT-Induced Hypoxic Chemotherapy on 4T1 Breast Cancer.

Protein corona (PC) formation confers novel biological properties to the original nanomaterial, impeding its uptake and targeting efficacy in cells and tissues. Although many studies discussing PC formation have focused on inert proteins that may inhibit the function of nanomaterials, some functional plasma proteins with intrinsic targeting capabilities can also be adsorbed to the surface of nanomaterials, with active ligand properties to improve the targeting ability. In this approach, nanomaterials are surface-engineered to promote the adsorption of specific functional plasma proteins that are directly targeted to transport nanomaterials to the target site. In this study, T10 peptide-modified liposomes were employed to construct an in situ transferrin (Tf) PC-mediated liposome carrying a hypoxia-sensitive chemotherapy drug (tirapazamine, TPZ) and a photosensitizer (indocyanine green, IR820). The water-soluble drug TPZ was encapsulated in mesoporous silica nanoparticles (MSNs) and coated with IR820 (IR)-loaded liposome. Lipid-coated MSNs can inhibit aggregation in the body and significantly reduce the rapid release of water-soluble drugs, resulting in improved system stability and sustained release. Upon entering the in vivo circulation, T10 bound specifically to Tf in plasma to form an in situ Tf liposome-PC complex with enhanced targeting efficacy compared to traditional ligand-modified active-targeting strategies. However, large-sized PC particles faced challenges in penetrating deep into tumor tissues. IR could kill tumors through photodynamic therapy (PDT) and elicit complementary antitumor effects with the hypoxia-sensitive drug TPZ. This study demonstrates the novel design of in situ PC-mediated multifunctional liposomes for hypoxia-activated chemotherapy combined with PDT, a promising approach to cancer therapy.

Quest for discovering novel CDK12 inhibitor.

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology. Targeting CDK12 offers a promising strategy to develop therapy. Various monoclonal antibodies have drawn wide attention, but they are expensive compared to small-molecule inhibitors, limiting their accessibility and affordability for patients. Consequently, this research aims to identify effective CDK12 inhibitors using comprehensive high-throughput virtual screening. RASPD protocol has been employed to screen three different databases against the target followed by drug-likeness, molecular docking, ADME, toxicity, Consensus molecular docking, MD Simulation, and in-vitro studies MTT assay. The research conducted yielded one compound ZINC11784547 has demonstrated robust binding affinity, favorable ADME features, less toxicity, remarkable stability, and cytotoxic effect. The identified compound holds promise for promoting cancer cell death through CDK12 inhibition.

Ultrasound nanodroplets loaded with Siglec-G siRNA and Fe3O4 activate macrophages and enhance phagocytosis for immunotherapy of triple-negative breast cancer

BackgroundThe progression of triple-negative breast cancer is shaped by both tumor cells and the surrounding tumor microenvironment (TME). Within the TME, tumor-associated macrophages (TAMs) represent a significant cell population and have emerged as a primary target for cancer therapy. As antigen-presenting cells within the innate immune system, macrophages are pivotal in tumor immunotherapy through their phagocytic functions. Due to the highly dynamic and heterogeneous nature of TAMs, re-polarizing them to the anti-tumor M1 phenotype can amplify anti-tumor effects and help mitigate the immunosuppressive TME.ResultsIn this study, we designed and constructed an ultrasound-responsive targeted nanodrug delivery system to deliver Siglec-G siRNA and Fe3O4, with perfluorohexane (PFH) at the core and mannose modified on the surface (referred to as MPFS@NDs). Siglec-G siRNA blocks the CD24/Siglec-G mediated “don’t eat me” phagocytosis inhibition pathway, activating macrophages, enhancing their phagocytic function, and improving antigen presentation, subsequently triggering anti-tumor immune responses. Fe3O4 repolarizes M2-TAMs to the anti-tumor M1 phenotype. Together, these components synergistically alleviate the immunosuppressive TME, and promote T cell activation, proliferation, and recruitment to tumor tissues, effectively inhibiting the growth of primary tumors and lung metastasis.ConclusionThis work suggests that activating macrophages and enhancing phagocytosis to remodel the TME could be an effective strategy for macrophage-based triple-negative breast cancer immunotherapy.

Patient-reported quality of life in Asian patients with ER+/HER2- advanced breast cancer treated with palbociclib plus letrozole in the PALOMA-4 trial.

Palbociclib plus an aromatase inhibitor is approved for treatment of patients with ER+/HER2- advanced breast cancer (ABC). In the PALOMA-4 trial, adding palbociclib to letrozole prolonged median progression-free survival in Asian women with ER+/HER2- ABC. Here, we report patient-reported outcomes (PROs) from PALOMA-4. PALOMA-4 was a randomized, double-blind, phase 3 trial of palbociclib plus letrozole vs. placebo plus letrozole treatment in postmenopausal Asian women with ER+/HER2- ABC. PROs were longitudinally assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQoL 5D three level (EQ-5D-3L) questionnaires. Group comparisons were analyzed using longitudinal, mixed-effects models. Patients were randomly assigned to palbociclib plus letrozole (n=169) or placebo plus letrozole (n=171) treated groups. No significant between-arm differences in change from baseline were observed in FACT-B and its subscales, or the EQ-5D-3L index. A significant, but not clinically meaningful difference was observed in change from baseline in mean EQ-VAS score favoring palbociclib plus letrozole (3.36; 95% confidence interval [CI], 0.88-5.83; P =0.008). When patients from both arms were combined, significant differences in the mean change from baseline for FACT-B total were observed favoring treatment responders vs. non-responders (3.84; 95% CI, 0.33-7.36; P =0.032) and for the Breast Cancer Subscale favoring patients without disease progression vs. those with progression (0.97; 95% CI, 0.05-1.89; P =0.038). Quality of life was maintained when palbociclib was added to letrozole in Asian women with ABC. These findings are consistent with PALOMA-2 results and support the use of palbociclib as first-line treatment in postmenopausal Asian patients with ER+/HER2- ABC. clinicaltrials.gov, NCT02297438.

Genetic overlap between breast cancer and sarcopenia: exploring the prognostic implications of SLC38A1 gene expression

BackgroundSarcopenia, an age-related syndrome characterized by a decline in muscle mass, not only affects patients’ quality of life but may also increase the risk of breast cancer recurrence and reduce survival rates. Therefore, investigating the genetic mechanisms shared between breast cancer and sarcopenia is significant for the prevention, diagnosis, and treatment of breast cancer.MethodsThis study downloaded gene expression datasets and clinical data related to breast cancer and skeletal muscle aging from the GEO database. Data preprocessing, integration, differential gene identification, functional enrichment analysis, and construction of protein-protein interaction networks were performed using R language. Subsequently, COX proportional hazards model analysis and survival analysis were conducted, and survival curves and nomograms were generated. The expression levels of genes in tissues were detected using qRT-PCR, and the Radiant DICOM viewer software was used to delineate the pectoralis major muscle area in CT images.ResultsWe identified 152 differentially expressed genes (P < .05) and 226 sarcopenia-related genes (r > .4) associated with skeletal muscle aging. The TCGA-BRCA dataset revealed 106 genes associated with breast cancer (P < .05, logFC = 1). Functional enrichment analysis indicated significant enrichment in cell proliferation and growth pathways. The PPI network identified critical molecules involved in muscle aging and tumor progression. After dimensionality reduction, a strong correlation was observed between the expression of the muscle aging-related gene set and the prognosis of breast cancer patients (P < .01). The expression of SLC38A1 identified through multivariate COX analysis was significantly associated with poor prognosis in breast cancer patients (P = .03). Incorporating SLC38A1 expression, the prognostic model precisely forecasted breast cancer survival (P < .01). External validation confirmed the higher expression of the SLC38A1 gene in breast cancer tissues compared to adjacent non-cancerous tissues (P < .01). The SLC38A1 index, calculated in combination with the patient’s age and BMI, can optimize the prognostic prediction model, providing a powerful tool for personalized treatment of breast cancer.ConclusionHigh SLC38A1 gene expression was significantly associated with poor prognosis in breast cancer patients. The combination of SLC38A1 expression and the pectoralis major muscle area provided an optimized prognostic prediction model, offering a potential tool for personalized breast cancer treatment.

ERBB2/HOXB13 co-amplification with interstitial loss of BRCA1 defines a unique subset of breast cancers

BackgroundThe HOXB13/IL17RB gene expression biomarker has been shown to predict response to adjuvant and extended endocrine therapy in patients with early-stage ER+ HER2- breast tumors. HOXB13 gene expression is the primary determinant driving the prognostic and endocrine treatment-predictive performance of the biomarker. Currently, there is limited data on HOXB13 expression in HER2+ and ER- breast cancers. Herein, we studied the expression of HOXB13 in large cohorts of HER2+ and ER- breast cancers.MethodsWe investigated gene expression, genomic copy number, mutational signatures, and clinical outcome data in the TGGA and METABRIC breast cancer cohorts. Genomic-based gene amplification data was validated with tri-colored fluorescence in situ hybridization.ResultsIn the TCGA breast cancer cohort, HOXB13 gene expression was significantly higher in HER2+ versus HER2- breast cancers, and its expression was also significantly higher in the ER- versus ER+ breast cancers. HOXB13 is frequently co-gained or co-amplified with ERBB2. Joint copy gains of HOXB13 and ERBB2 occurred with low-level co-gains or high-level co-amplifications (co-amp), the latter of which is associated with an interstitial loss that includes the tumor suppressor BRCA1. ERBB2/HOXB13 co-amp tumors with interstitial BRCA1 loss exhibit a mutational signature associated with APOBEC deaminase activity and copy number signatures associated with chromothripsis and genomic instability. Among ERBB2-amplified tumors of different tissue origins, ERBB2/HOXB13 co-amp with a BRCA1 loss appeared to be enriched in breast cancer compared to other tumor types. Lastly, patients with ERBB2/HOXB13 co-amplified and BRCA1 lost tumors displayed a significantly shorter progression-free survival (PFS) than those with ERBB2-only amplifications. The difference in PFS was restricted to the ER- subset patients and this difference in PFS was not solely driven by HOXB13 gene expression.ConclusionsHOXB13 is frequently co-gained with ERBB2 at both low-copy number level or as complex high-level amplification with relative BRCA1 loss. ERBB2/HOXB13 amplified, BRCA1-lost tumors are strongly enriched in breast cancer, and patients with such breast tumors experience a shortened PFS.

Assessing the causal relationships between circulating metabolic biomarkers and breast cancer by using mendelian randomization

ObjectivePrevious studies have established a causal relationship between metabolites and breast cancer (BC), but the underlying mechanisms remain unclear. Thus, we aimed to investigate the genetic relationship between metabolites and BC, including its subtypes, using Mendelian randomization (MR) analysis.MethodsUtilizing the latest and most comprehensive summary statistics from genome-wide association studies we conducted an Mendelian randomization study. Data on 233 metabolites, used as exposure variables, were obtained from a study involving 136,016 participants. BC data, used as outcome variables, were sourced from a study comprising 122,977 cases and 105,974 controls. We used the inverse-variance weighted method as the primary approach, along with three supplementary methods, to assess the causal relationship. We also used Cochran’s Q test to detect heterogeneity and MR-Egger regression to examine the presence of horizontal pleiotropy.ResultsUpon analyzing 233 metabolites across 11 classes in relation to BC, we found six classes of metabolites (fatty acids glycerides and phospholipids, lipoprotein subclasses, lipids, apolipoproteins, and lipoprotein particle size) associated with overall BC. Five classes of metabolites (fatty acids glycerides and phospholipids, lipoprotein subclasses, lipids, and lipoprotein particle size) were related to estrogen receptor (ER) + BC, and eight classes of metabolites (fatty acids, amino acids, glycerides and phospholipids, lipoprotein subclasses, lipids, apolipoproteins, glycolysis-related metabolites, and lipoprotein particle size) were linked to ER- BC.ConclusionOur study demonstrates a genetic causal relationship between most metabolites and BC, confirming the link between these factors. This research provides a significant foundation for the prevention and treatment of BC.

Association Between Delayed/Forgone Medical Care and Resource Utilization Among Women with Breast Cancer in the United States.

Although high treatment costs of breast cancer care are well documented, the relationship between delayed/forgone (D/F) care and resource utilization among patients with breast cancer is unknown. This study sought to investigate the relationship between D/F care, resource use, and healthcare expenditures among patients with breast cancer. Data on adult female patients with breast cancer were obtained from the Medical Expenditure Panel Survey to assess resource utilization and expenditures in the United States from 2007 to 2017. Weighted proportions of patients with ≥1 emergency department, ≥1 inpatient, ≥1 outpatient, and >5 office-based encounters were compared between those experiencing D/F care versus those who did not using Rao-Scott adjusted chi-squared tests. Annual, per capita total, out-of-pocket, emergency department, inpatient, outpatient, office-based visit, and prescription medication expenditures were compared by using two-part econometric models. Five percent of patients with breast cancer experienced D/F care, and 42.9% of patients cited financial barriers as the primary reason for D/F care. In unweighted estimates, there were higher proportions of patients with ≥1 hospitalizations (37% vs. 16%, P<0.001) among those experiencing D/F care versus those who did not. Patients with D/F care had $5372 (95% CI $35-$10,709, P=0.04) higher per capita inpatient expenditures than patients without D/F care. Delayed/forgone care is associated with increased resource utilization and healthcare spending among breast cancer patients. Further work is needed to address the root causes of D/F breast cancer care, with a view to mitigating disparate outcomes and increasing costs.

Characteristics of positive and negative effects on the quality of life of breast cancer patients

BackgroundPostoperative and ongoing treatment of breast cancer is traumatic to women with breast cancer and may lead to positive and negative psychological diseases, which can affect the prognosis of patients with breast cancer. Positive affect (PA) and negative affect (NA) significantly impact the prognosis of postoperative breast cancer patients. However, the effects of specific emotions on patient prognosis and the relationships between them are still unclear.MethodsA case–control study was conducted to investigate the characteristics of PA and NA and their effects on Quality of Life (QoL) in breast cancer patients. 442 postoperative breast cancer patients and 444 healthy women were recruited from November to December 2021. For the observation group, participants were eligible if they (1) were aged between 16 and 80 years and (2) had a confirmed pathological diagnosis of breast cancer and (3) possessed the ability to read text, voluntarily agreed to participate, provided informed consent, and cooperated with the study procedures. The control group consisted of individuals without breast cancer who met all other criteria, as stated above. Patients were excluded from the study if they (1) had severe comorbid conditions causing functional impairment or life-threatening risks or (2) suffered from mental disorders or were unconscious at the time of the study. For the control group, individuals with a pathological diagnosis of breast cancer were also excluded. All other exclusion criteria were consistent with those for the observation group. The demographic information and clinicopathological information of the participants were collected. The Positive Affect and Negative Affect Scale (PANAS) is a scale containing 20 emotional scores related to emotion and is used to assess the level of positive and negative affect. The Quality of Life Questionnaire Core 30 (QLQ-C30) was used to assess the quality of life of cancer patients in 15 domains. SPSS 24.0 was used to analyze and process the data. Independent-sample t-tests, one-way ANOVA and Pearson correlation analysis, were used to analyze PA and NA in different treatment phases. Polynomial regression and response surface analysis were conducted to assess the relationships among PA, NA, and QoL. The results were considered statistically significant at P < 0.05.ResultsCompared with healthy women, breast cancer patients had lower scores on "alert" and "distressed" but higher scores on "inspired," "scared," and "afraid." There were no significant differences in the relationships between PA and NA between patients and healthy women (P > 0.05). During the initial treatment phase, the highest proportion of patients had an NA greater than the PA (PA < NA). In the rehabilitation phase, the highest proportion of patients had PA greater than or equal to the NA (PA ≥ NA). The relationship between PA and QoL was an inverted U-shaped curve (P < 0.05), whereas the relationship between NA and QoL was a positive U-shaped curve (P < 0.05). There was an interaction effect between PA and NA (P < 0.001). The relationships among PA, NA, and QoL varied across treatment phases. In the initial treatment phase, the presence of both positive and negative affect improved QoL. In the endocrine therapy phase, excessive positive effects decrease QoL. During the rehabilitation phase, QoL improved as positive affect increased relative to negative affect.ConclusionThere are significant differences in the distributions of positive and negative effects in breast cancer patients at different treatment phases. The impact of PA and NA on QoL varies by treatment phase. Our findings have important implications for tailoring emotional interventions for breast cancer patients at different stages of treatment.