Breast Cancer Rates Research Articles

Systematic review and meta-analysis: The incidence rate of breast cancer among ovarian cancer patients with BRCA mutation

Systematic review and meta-analysis: The incidence rate of breast cancer among ovarian cancer patients with BRCA mutation

Obesity and lack of breastfeeding: a perfect storm to augment risk of breast cancer?

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with higher rates of recurrence and distant metastasis, as well as decreased 5-year survival rates. Racial disparities are evident in the incidence and mortality rates of triple negative breast cancer particularly increased in young African American women. Concurrently, young African American women have multiple risk factors for TNBC including higher rates of premenopausal abdominal obesity (higher waist-hip ratio) and lower rates of breastfeeding with higher parity, implicating these factors as potentially contributors to poor outcomes. By understanding the mechanisms of how premenopausal obesity and lack of breastfeeding may be associated with increased risk of triple negative breast cancer, we can determine the best strategies for intervention and awareness to improve outcomes in TNBC.

The role of ethnic enclaves and neighborhood socioeconomic status in invasive breast cancer incidence rates among Asian American, Native Hawaiian, and Pacific Islander females in California.

Few studies have examined whether the incidence rates of invasive breast cancer among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations differ by the neighborhood social environment. Thus, we examined associations of ethnic enclave and neighborhood socioeconomic status (nSES) with breast cancer incidence rates among AANHPI females in California. A total of 14,738 AANHPI females diagnosed with invasive breast cancer in 2008-2012 were identified from the California Cancer Registry. AANHPI ethnic enclaves (culturally distinct neighborhoods) and nSES were assessed at the census tract level using 2007-2011 American Community Survey data. Breast cancer age-adjusted incidence rates and incidence rate ratios (IRRs) were estimated for AANHPI ethnic enclave, nSES, and their joint effects. Subgroup analyses were conducted by stage of disease. The incidence rate of breast cancer among AANHPI females living in lowest ethnic enclave neighborhoods (quintile (Q)1) were 1.21 times (95% Confidence Interval (CI) 1.11, 1.32) that of AANHPI females living highest ethnic enclave neighborhoods (Q5). In addition, AANHPI females living in highest vs. lowest SES neighborhoods had higher incidence rates of breast cancer (Q5 vs. Q1 IRR = 1.30, 95% CI 1.22 to 1.40). The incidence rate of breast cancer among AANHPI females living in low ethnic enclave + high SES neighborhoods was 1.32 times (95% CI 1.25, 1.39) that of AANHPI females living in high ethnic enclave + low SES neighborhoods. Similar patterns of associations were observed for localized and advanced stage disease. For AANHPI females in California, incidence rates of breast cancer differed by nSES, ethnic enclave, when considered independently and jointly. Future studies should examine whether the impact of these neighborhood-level factors on breast cancer incidence rates differ across specific AANHPI ethnic groups and investigate the pathways through which they contribute to breast cancer incidence.

Quantum classical hybrid convolutional neural networks for breast cancer diagnosis.

The World Health Organization states that early diagnosis is essential to increasing the cure rate for breast cancer, which poses a danger to women's health worldwide. However, the efficacy and cost limitations of conventional diagnostic techniques increase the possibility of misdiagnosis. In this work, we present a quantum hybrid classical convolutional neural network (QCCNN) based breast cancer diagnosis approach with the goal of utilizing quantum computing's high-dimensional data processing power and parallelism to increase diagnosis efficiency and accuracy. When working with large-scale and complicated datasets, classical convolutional neural network (CNN) and other machine learning techniques generally demand a large amount of computational resources and time. Their restricted capacity for generalization makes it challenging to maintain consistent performance across multiple data sets. To address these issues, this paper adds a quantum convolutional layer to the classical convolutional neural network to take advantage of quantum computing to improve learning efficiency and processing speed. Simulation experiments on three breast cancer datasets, GBSG, SEER and WDBC, validate the robustness and generalization of QCCNN and significantly outperform CNN and logistic regression models in classification accuracy. This study not only provides a novel method for breast cancer diagnosis but also achieves a breakthrough in breast cancer diagnosis and promotes the development of medical diagnostic technology.

Exploring Neighborhood-Level Environmental Justice to Tackle County-Level Disparities in Breast Cancer Outcomes

Breast cancer is a disease in which cells, originating from the breast epithelium, grow out of control and form tumors. The progression of breast cancer can vary, and its severity is often categorized by stages ranging from early, localized forms to more advanced stages involving widespread dissemination. Breast cancer cases can be hereditary or non-hereditary; Hereditary cases are caused by a penetrant gene mutation: one that is pathogenic and has the potential to promote the development of cancer whereas non-hereditary cases can be caused by a variety of day-to-day exposures affected by socioeconomic disparities and health literacy rates. Despite scientific and technological advancements, researchers and health officials still do not know enough about the disease and breast cancer incidence rates in the United States have steadily increased. This literature review aims to synthesize the relationship between breast cancer health outcomes and environmental justice, health literacy, and socioeconomic disparities. This relationship was first examined from a county-level in the state of Florida. We first examined three Florida counties with varying socioeconomic profiles (Broward, Miami-Dade, and Palm Beach) and then examined neighborhoods within the county of Miami-Dade (selected because it has the highest breast cancer rates out of all Florida counties). This examination revealed higher incidences of breast cancer in Latinx and African American communities with high environmental exposures and lower socioeconomic statuses. The identification of specific neighborhoods primarily affected by environmental exposures and low socioeconomic statuses emphasizes the need for neighborhood level modeling to inform future breast cancer research and intervention strategies.

Comprehensive analysis of the expression level, prognostic value, and immune infiltration of cuproptosis-related genes in human breast cancer.

As a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer. The expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above. Compared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years. This study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.

7609 Androgen Receptor Positive DCIS in a Transmasculine Individual on Testosterone Therapy

Abstract Disclosure: J. Kelly: None. B. Cohen: None. Introduction: The rate of breast cancer in transgender men is lower than in cisgender women, perhaps due to lower estrogen levels in the setting of suppression from exogenous testosterone, lack of clear guidelines on screening after top surgery, and increase in mastectomies. However, the impact of testosterone therapy on existing breast cancer is not known. Concerns regarding use of testosterone in patients with breast cancer include the potential for conversion of testosterone to estradiol, as well as direct androgen receptor (AR) stimulation. However, for some patients, hormone therapy is lifesaving and stopping gender affirming hormone therapy (GAHT) will negatively impact patient well-being. This creates a challenging clinical scenario when transgender patients on testosterone are diagnosed with breast cancer.Case Presentation: We present a case of a 29-year-old self-identified transmasculine nonbinary individual (assigned female at birth) who underwent chest reconstruction surgery after several months on daily transdermal testosterone therapy. A 4 cm DCIS ER+/AR+ with possible micro invasion was incidentally noted on pathology. They had no family history of breast cancer. The patient underwent chest MRI which was negative for persistent disease. The treating oncologist did not recommend Tamoxifen. The patient chose to discontinue testosterone therapy due to uncertainty regarding future breast cancer risk. However, due to worsening depression and fatigue, the patient chose to resume GAHT after receiving counseling of possible risk, though likely low, of cancer recurrence. Given that they had undergone bilateral mastectomy which, unlike chest reconstruction surgery where some breast tissue is left for contouring, all breast tissue was removed and given that chest MRI was negative for disease, cancer recurrence was felt to be low. Furthermore, though AR positivity was noted, the clinical implications are unclear and it is not known whether testosterone would stimulate tumor growth or potentially have antagonistic effects on ER signaling. Additionally, any stimulatory effects of AR signaling may be balanced by androgen suppression of gonadotroph production and reduction in estrogen production; this is more clearly associated with stimulatory effects on cancer growth. And finally, the potential risks of therapy must be weighed against the benefits provided to the patient’s well-being and mental health. Ultimately, the patient resumed testosterone therapy and has been doing well.Teaching Point: This case illustrates the uncertainties regarding the management of gender affirming testosterone therapy in patients with DCIS or breast cancer. It also highlights the need for a patient centered approach to decisions regarding changes to GAHT, to appropriately weigh the risks and benefits of continuing therapy. Presentation: 6/2/2024

9260 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

9260 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

Interval breast cancer rates for tomosynthesis vs mammography population screening: a systematic review and meta-analysis of prospective studies.

We aimed to synthesise evidence from prospective studies of digital breast tomosynthesis (DBT) screening to assess its effectiveness compared to digital mammography (DM). Specifically, we examined whether DBT reduces interval cancer rates (ICRs) in population breast cancer screening. We performed a systematic review and meta-analysis of DBT screening studies (identified from January 2013 to March 2024). We included both RCTs and non-randomised prospective studies that used an independent comparison for our primary outcome ICRs. The risk of bias was assessed with QUADAS-2. We compared the ICR, cancer detection rate (CDR), and recall rate of DBT and DM screening using random effects meta-analysis models. Subgroup analyses estimated outcomes by study design. Sensitivity analyses estimated absolute effects from relative effects. Ten prospective studies (three RCTs, seven non-randomised) were eligible; all had a low risk of bias. There were 205,245 DBT-screened and 306,476 DM-screened participants with follow-up for interval cancer data. The pooled absolute ICR did not significantly differ between DBT and DM: -2.92 per 10,000 screens (95% CI: -6.39 to 0.54); however subsequent subgroup analysis indicated certain study designs may have biased this ICR estimate. Pooled ICR from studies that only sampled groups from the same time and region indicated DBT led to 5.50 less IC per 10,000 screens (95% CI: -9.47 to -1.54). Estimates from subgroup analysis that compared randomised and non-randomised trials did not significantly differ. This meta-analysis provides suggestive evidence that DBT decreases ICR relative to DM screening; further evidence is needed to reduce uncertainty regarding ICR differences between DBT and DM. Question Does DBT have long-term benefits over standard DM? Finding We find suggestive evidence in our primary analysis and stronger evidence in a follow-up analysis that DBT reduces interval cancers. Clinical relevance This meta-analysis provides the first indication that DBT may detect additional cancers that are clinically meaningful, based on suggestive evidence of a reduction in ICR. This finding does not preclude the simultaneous possibility of overdiagnosis.

Quality improvement of breast and cervical cancer screening satisfaction rate at a resident-led clinic.

308 Background: In the US, 77.3% of women aged 21-65 years have had a Pap smear within the past three years and around 75.9% of women aged 50-74 years reported having a mammogram within the past two years as recommended according to the U.S. Preventive Services Task Force (USPSTF). In UTRGV Resident-led Clinic located in Hidalgo County, the quality metrics data demonstrated screening satisfactory rate for cervical and breast cancer to be 18% in August 2023. This Quality Improvement project is aimed at enhancing the screening satisfactory rate of breast and cervical cancer by 20% at UTRGV Knapp IM Clinic by December 2023. Methods: First, we focused on the education of the residents through noon conference and 1:1 education. This included comprehensive instruction on latest USPSTF guidelines and proper documentation on the electronic health record system, Athena. Second, we introduced a patient screening questionnaire, available in both English and Spanish. These efforts were evaluated through a pre-and-post-intervention survey designed to assess changes in residents' confidence, aligning with quality metrics data. We obtained and filtered the quality metrics raw data to include all the current residents in PGY1-3 and summed the number of patients who had records of breast and cervical cancer screening and divided the sum of all patients that required the record. The satisfaction rate was rounded to the 2nd decimal place. Results: The raw data from 8/2023 showed screening satisfactory rate for cervical and breast cancer to be 18%. With the initiation of intervention, the data from 9/2023 showed rate of 35%, finally reaching 39% on 12/2023, fulfilling our aim of 20% increase in the screening satisfactory rate. Survey data shows that there was an improvement of confidence observed in both breast and cervical cancer screening. Respectively, 27.5% and 30.9% increase in the residents who responded confident in breast cancer and cervical cancer screening were observed. 84.4% of residents responded that they are less forgetfulness in screening patients after the intervention. There was 22.9% increase in residents who know how to record the cancer screening result in Athena. 87.5% of the residents responded that they experienced improvement in implementing and documenting the breast and cervical cancer screening. Conclusions: Despite several limitations in acquiring and analyzing the data, this QI project positively impacted both subjective and objective data for the improvement of the breast and cervical cancer screening, fulfilling our aim of 20% increase in screening satisfactory rate by December 2023. Breast and cervical screening satisfactory Rate. Month/year Number of patients requiring breast and cervical cancer screening Number of patients with satisfaction in breast and cervical cancer screening Satisfactory rate (%) 08/2023 42 229 18 9/2023 999 2844 35 10/2023 454 1458 31 11/2023 649 1771 37 12/2023 113 287 39

Discovering Explainable Biomarkers for Breast Cancer Anti-PD1 Response via Network Shapley Value Analysis

Background and objectiveImmunotherapy holds promise in enhancing pathological complete response rates in breast cancer, albeit confined to a select cohort of patients. Consequently, pinpointing factors predictive of treatment responsiveness is of paramount importance. Gene expression and regulation, inherently operating within intricate networks, constitute fundamental molecular machinery for cellular processes and often serve as robust biomarkers. Nevertheless, contemporary feature selection approaches grapple with two key challenges: opacity in modeling and scarcity in accounting for gene-gene interactions MethodsTo address these limitations, we devise a novel feature selection methodology grounded in cooperative game theory, harmoniously integrating with sophisticated machine learning models. This approach identifies interconnected gene regulatory network biomarker modules with priori genetic linkage architecture. Specifically, we leverage Shapley values on network to quantify feature importance, while strategically constraining their integration based on network expansion principles and nodal adjacency, thereby fostering enhanced interpretability in feature selection. We apply our methods to a publicly available single-cell RNA sequencing dataset of breast cancer immunotherapy responses, using the identified feature gene set as biomarkers. Functional enrichment analysis with independent validations further illustrates their effective predictive performance ResultsWe demonstrate the sophistication and excellence of the proposed method in data with network structure. It unveiled a cohesive biomarker module encompassing 27 genes for immunotherapy response. Notably, this module proves adept at precisely predicting anti-PD1 therapeutic outcomes in breast cancer patients with classification accuracy of 0.905 and AUC value of 0.971, underscoring its unique capacity to illuminate gene functionalities ConclusionThe proposed method is effective for identifying network module biomarkers, and the detected anti-PD1 response biomarkers can enrich our understanding of the underlying physiological mechanisms of immunotherapy, which have a promising application for realizing precision medicine.

Integration of big data analytics in the investigation of the relationship between acromegaly and cancer

ObjectiveTo evaluate the association between acromegaly and cancer and different types of cancer by using natural language processing systems and big data analytics. Material and methodsWe conducted an observational, retrospective study utilizing data from the electronic health records (EHRs) of Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. Information from the EHRs was extracted using artificial intelligence techniques and analyzed using Savana Manager 4.0 software. ResultsOut of a total of 708,047 registered patients (54.7% females), 544 patients (0.08%; 330 women, 60.7%; mean age at diagnosis 53.0±15.8 yr) were diagnosed with acromegaly. The incidence of cancer was higher in patients with acromegaly vs those without this condition (7.7% vs 3.9%, p<0.001; OR, 2.047, 95%CI, 1.493–2.804). Male acromegalic patients had a higher prevalence of cancer vs females (57.1% vs 42.9%, p=0.012). A significantly higher prevalence of colorectal cancer (2.9% vs 1.4%, p=0.006), bladder cancer (1.1% vs 0.3%, p=0.005), and lymphoma (1.1% vs 0.3%, p=0.009) was observed in patients with acromegaly vs those without the condition. Acromegalic men had significantly higher prevalence rates of colorectal cancer (4.7% vs 1.3%, p=0.001), bladder cancer (2.8% vs 0.4%, p<0.001), breast cancer (0.9% vs 0.2%, p=0.042), gastric cancer (0.9% vs 0.1%, p=0.011), lymphoma (1.4% vs 0.3%, p=0.037), and liver cancer (0.9% vs 0.1%, p=0.012) vs non-acromegalic men. On the other hand, acromegalic women showed a higher prevalence of thyroid cancer (1.2% vs 0.4%, p=0.043) vs non-acromegalic women. ConclusionOur study, based on artificial intelligence techniques and analysis of real-world data and information, revealed a significant association between acromegaly and cancer in our hospital population, mainly acromegalic men, with a higher frequency of colorectal cancer, bladder cancer and lymphoma in particular.

Zn2+ enhanced the anti-breast cancer activity of fucoidan based nanoparticles by activating the cGAS-STING pathway

The incidence rate of breast cancer remains high, and lung metastasis often leads to treatment failure. Immunotherapy based on the cyclic guanosine monophosphate synthesis (cGAS) − interface gene stimulatory factor (STING) pathway is expected to bring benefits to the treatment of breast cancer. This study provided a delivery system based on fucoidan (Fu) and polyvinylpyrrolidone (PVP) for the potential molecule resveratrol (Res). The study confirmed that Fu and PVP were assembled into nanoparticles through hydrogen bonding and effectively loaded Res (Fu/PVP/Res). Interestingly, the adsorption of Zn2+ (Fu/PVP/Res Zn2+) was expected to provide impetus for the treatment of breast cancer. The results in vitro confirmed that Fu/PVP/Res Zn2+ significantly inhibited the proliferation of breast cancer 4T1 cells, induced the accumulation of mitochondrial reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP), and further induced the cytoplasmic release of mtDNA, which was the direct cause of the activation of cGAS-STING pathway. In vivo studies confirmed that Fu/PVP/Res Zn2+ treatment inhibited the growth of 4T1 transplanted tumors. Excitingly, Fu/PVP/Res Zn2+ treatment also prevented lung metastasis of in situ tumors. The in vivo mechanism confirmed that Fu/PVP/Res Zn2+ treatment activated the cGAS-STING pathway and induced abnormal expression of tumor apoptosis factors such as Bax/Bcl-2. In conclusion, our research provided potential for the treatment of breast cancer.

PROFIL PENGOBATAN KEMOTERAPI PADA PASIEN KANKER PAYUDARA DI RUMAH SAKIT UMUM DAERAH KOTA BOGOR PADA TAHUN 2022

Breast cancer is cancer that starts in the breast tissue, which consists of milk-producing glands (lobules) and ducts that connect the lobules to the nipple. One of the efforts to reduce the morbidity rate of breast cancer is chemotherapy. Chemotherapy involves the use of cytostatic drugs aimed at stopping the growth and spread of cancer cells. The purpose of this study was to determine the pattern of drug use and evaluation of drug use in breast cancer patients. The study was conducted observational with retrospective data collection. The research was conducted from May to June 2023. The number of samples was 96 samples with the method of purposive sampling technique using the slovin formula, the data were analyzed qualitatively. The results of the chemotherapy treatment profile using single therapy 9 patients (9.38%), combination therapy 87 patients (90.63%) with a combination chemotherapy regimen of Epirubicin and Cyclophosphamide followed by Paclitaxel as many as 50 patients (57.47%). Evaluation of appropriate patient (98.96%), appropriate indication (100%), appropriate drug (100%), appropriate dose (19.79%), inappropriate dose (20.83%), under dose (34.48%), over dose (25%).

Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates

Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates

Cosmetic implant placement in the female breast yields an altered local and systemic immune response: evidence for breast cancer immunosurveillance.

Women with cosmetic implants have lower rates of future breast cancer than the general population. We hypothesized the implant foreign body response could induce a local protective anti-cancer immunosurveillance. We expanded on our previous finding which showed women with breast implants have elevated antibody responses to certain breast cancer proteins. Blood samples and breast tissue were collected from women undergoing first time breast augmentation (implant-naive, IN) and revision breast augmentation (implant-exposed, IE). Sera were collected and antibody levels to common breast cancer proteins were quantified by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed on breast tissue samples to quantify immune-related gene expression levels between IN and IE. Bulk RNA sequencing was performed to identify differentially expressed genes and altered signaling pathways in the breasts of IN versus IE. In total, 188 patients were recruited (117 IN, 71 IE). Data demonstrated that IE patients had higher levels of antibodies to MUC-1, ER, and mammaglobin A compared to IN patients. MUC-1 expression was found to be higher in IE compared to IN breast tissue. RNA-seq analysis demonstrated upregulated pathways in IE breast tissue for B cell activation and development, Th2 related genes, T cell activation, chemotactic factors, and responses to estrogen. This is the first study to demonstrate that peri-implant inflammation extends beyond the implant capsule to breast parenchyma. Women with breast implants have more activated B cells in the breast parenchyma and elevated antibody responses to breast cancer antigen.

Investigating the Relationship between Schizophrenia and Incidence Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Objective: Schizophrenia seems to have a complex association with various types of cancer, exerting a protective effect against some cancers while being a risk factor against some others. Therefore, we intended to conduct an updated systematic review and meta-analysis in order to examine the relationship between schizophrenia and the risk of breast cancer incidence. Method: We did a systematic search of databases, namely Web of Science, Scopus, Embase, PubMed, and PsycINFO up to August 15, 2024. Screening and data extraction were performed independently. Data was analyzed using Stata16 software. We used the random effect model to pool the results, while the heterogeneity between studies was calculated using Cochran's Q test and (I2) index. Results: We found 15 studies, among which 12 were included in this meta-analysis. The results indicated that the risk of breast cancer development is significantly increased in women with schizophrenia (SIR: 1.43, 95% CI: 1.08-1.85, P &lt; 0.01; IRR: 1.19, 95% CI: 1.13-1.26, P &lt; 0.01). Subgroup analysis revealed significant differences in the incidence of breast cancer rates among women with schizophrenia based on geographic location and duration of follow-up. Conclusion: The results indicate that schizophrenia increases the risk of developing breast cancer. Therefore, taking preventive measures concerning breast cancer among women with schizophrenia is crucial. Additionally, regular screening programs should be implemented to ensure early diagnosis and treatment in case breast cancer is detected.