Breast Cancer Death Research Articles

Methodological Considerations in Evaluating Breast Cancer Screening Studies.

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations.

Tracking the epidemiological trends of female breast cancer in Saudi Arabia since 1990 and forecasting future statistics using global burden of disease data, time-series analysis

BackgroundFemale breast cancer stands as the prime type of cancer in the Kingdom of Saudi Arabia (KSA), with a high incidence and mortality rates. This study assessed the burden of female breast cancer in KSA by analyzing and forecasting its incidence, mortality, and disability-adjusted life years (DALYs).MethodsWe retrieved data from the Global Burden of Disease (GBD) about female breast cancer from 1990 to 2021. Time-series analysis used the autoregressive integrated moving average (ARIMA) model to forecast female breast cancer statistics from 2022 to 2026.ResultsFrom 1990 to 2021, KSA reported 77,513 cases of female breast cancer. The age groups with the highest number of cases are 45–49 years, followed by 40–44 years, 50–54 years, and 35–39 years. The analysis also showed fewer cases in the younger age groups, with the lowest number in the less than 20-year-old age group. From 1990 to 2021, KSA reported 19,440 deaths due to breast cancer, increasing from 201 cases in 1990 to 1,190 cases in 2021. The age-standardized incidence rate/100,000 of breast cancer increased from 15.4 (95% confidence interval (CI) 11.2–21.0) in 1990 to 46.0 (95%CI 34.5–61.5) in 2021. The forecasted incidence rate of female breast cancer will be 46.5 (95%CI 45.8–46.5) in 2022 and 49.6 (95%CI 46.8–52.3) in 2026. The age-standardized death rate per 100,000 Saudi women with breast cancer increased from 6.73 (95%CI 6.73–9.03) in 1990 to 9.77 (95%CI 7.63–13.00) in 2021. The forecasted female breast cancer death rate will slightly decrease to 9.67 (95%CI 9.49–9.84) in 2022 and to 9.26 (95%CI 8.37–10.15) in 2026. DALYs increased from 229.2 (95%CI 165.7–313.6) in 1990 to 346.1 (95%CI 253.9–467.2) in 2021. The forecasted DALYs of female breast cancer will slightly decrease to 343.3 (95%CI 337.2–349.5) in 2022 reaching 332.1 (95%CI 301.2–363.1) in 2026.ConclusionsFemale breast cancer is still a significant public health burden that challenges the health system in KSA, current policies and interventions should be fashioned to alleviate the disease morbidity and mortality and mitigate its future burden.

GAPVD1 Promotes the Proliferation of Triple-Negative Breast Cancer Cells by Regulating the ERK/MAPK Signaling Pathway.

Triple-Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancers and approximately 50% of breast cancer deaths. Chemotherapy remains the mainstay of systemic treatment due to the lack of effective therapy targets. Thus, more studies are urgently needed to identify new therapeutic targets in TNBC patients. GAPVD1 expression and prognosis value in breast cancer samples were explored in The Cancer Genome Atlas database (TCGA). GAPVD1 knockdown and overexpression TNBC cell lines were constructed. CCK-8 and colony formation assays were performed to detect cell viability. Flow cytometry analysis was performed to detect cell cycle variation. Western blotting was conducted to determine the levels of target genes. Finally, an enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. GAPVD1 is overexpressed in breast cancer tissues and predicts poor prognosis. In vitro experiments demonstrated that GAPVD1 is correlated with cell proliferation and the cell cycle of TNBC cells. Mechanistically, alteration in GAPVD1 expression was found to be associated with cell cycle-related proteins PCNA, Cyclin A, and the activity of the ERK/MAPK signaling pathway. Consistent with these findings, enrichment analysis of GAPVD1-involving partners and signaling pathways revealed that the cellular biosynthetic process, macromolecule biosynthetic process, and cell cycle signaling are related to GAPVD1. In vivo experiment demonstrated that GAPVD1 inhibition impedes tumor growth and expression of cell cyclerelated proteins. Taken together, our results indicate that GAPVD1 may participate in TNBC cell growth by regulating the cell cycle and ERK/MAPK signaling pathway.

Survival outcomes after breast cancer surgery among older women with early invasive breast cancer in England: population-based cohort study.

This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer. Women aged over 50 years with early invasive breast cancer diagnosed in England (2014-2019) who had breast surgery were identified from Cancer Registry data. Survival estimates were calculated from a flexible parametric survival model. A competing risk approach was used for breast cancer-specific survival (BCSS). Standardized survival probabilities and cumulative incidence functions for breast cancer death were calculated for each treatment by age. Among 101 654 women, 72.2% received BCS + RT and 27.8% received mastectomy. Age, co-morbidity and frailty were associated with overall survival (OS), but only age and co-morbidity were associated with BCSS. Survival probabilities for OS were greater for BCS + RT (90.3%) versus mastectomy (87.0%), and the difference between treatments varied by age (50 years: 1.9% versus 80 years: 6.5%). Cumulative incidence functions for breast cancer death were higher after mastectomy (5.1%) versus BCS + RT (3.9%), but there was little change in the difference by age (50 years: 0.9% versus 80 years: 1.2%). The results highlight the change in baseline mortality risk by age for OS compared to the stable baseline for BCSS. For OS, the difference in survival probabilities for BCS + RT and mastectomy increased slightly with age. The difference in cumulative incidence functions for breast cancer death by surgery type was small regardless of age. Evidence on real-world survival outcomes among older populations with breast cancer is informative for treatment decision-making.

Functional exploration of copy number alterations in a Drosophila model of triple-negative breast cancer.

Accounting for 10-20% of breast cancer cases, triple-negative breast cancer (TNBC) is associated with a disproportionate number of breast cancer deaths. One challenge in studying TNBC is its genomic profile: with the exception of TP53 loss, most breast cancer tumors are characterized by a high number of copy number alterations (CNAs), making modeling the disease in whole animals challenging. We computationally analyzed 186 CNA regions previously identified in breast cancer tumors to rank genes within each region by likelihood of acting as a tumor driver. We then used a Drosophila p53-Myc TNBC model to identify 48 genes as functional drivers. To demonstrate the utility of this functional database, we established six 3-hit models; altering candidate genes led to increased aspects of transformation as well as resistance to the chemotherapeutic drug fluorouracil. Our work provides a functional database of CNA-associated TNBC drivers, and a template for an integrated computational/whole-animal approach to identify functional drivers of transformation and drug resistance within CNAs in other tumor types.

Breast cancer trends in Chile: Incidence and mortality rates (2007–2018)

Breast cancer (BC) is one of the most common cancers in women worldwide and in Chile. Due to the lack of a Chilean national cancer registry, there is partial information on the status of BC in the country. We aim to estimate BC incidence and mortality rates by health care providers and regions for Chilean women. We used two public anonymized databases provided by the Ministry of Health: the national death and hospital discharges datasets. We considered a cohort of 58,254 and 16,615 BC hospital discharges and deaths for the period 2007–2018. New BC cases increased by 43.6%, from 3,785 in 2007 to 5,435 in 2018. Total BC deaths increased by 33.6% from 1,158 to 1,547 during the same period. Age-adjusted incidence rates were stable over time, with an average rate of 44.0 cases/100,000 women (SD 2.2). There were considerable differences in age-adjusted incidence rates among regions, with no clear geographical trend. Women affiliated to a private provider (ISAPRE) have an average age-adjusted incidence rate of 60.6 compared to 38.8 (both cases/100,000 women) for women affiliated with the public provider (FONASA). Age-adjusted mortality rates have an average of 10.5 cases/100,000 women (SD 0.4). This study shows important differences in incidence rates between private and publicly insured women, with no significant differences in mortality rates. Such differences may be associated with women’s lifestyles, dietary compositions, comorbidities, and differences in healthcare systems. These hypotheses should be studied in greater depth. Additionally, differences in BC incidence found in this study compared to incidences reported from other estimations reinforce the need of a national cancer registry that should lead to more accurate indicators regarding BC in Chile.

Effect of screening mammography on the risk of breast cancer deaths and of all-cause deaths: a systematic review with meta-analysis of cohort studies

ObjectivesObservational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on causes of death other than breast cancer (BC), cohort studies should show reductions in the risk of BC death substantially greater than possible reductions in the risk of all-cause death. We assessed the risk of BC deaths and of all-cause (or of nonBC) deaths associated with screening mammography attendance reported in cohort studies. Study Design and SettingCohort studies published from 2002 to 2022 on women invited to screening mammography were searched in PubMed, Web of Sciences, Scopus, and in review articles. Random effect meta-analyses were performed using relative risks (RRs) of death between women who attended screening compared to women who did not attend screening. ResultsEighteen cohort studies were identified, nine that reported RRs of BC deaths only, five that reported RRs of all-cause deaths only, and four that reported RRs for both BC deaths and all-cause deaths. The latter four cohort studies reported 12–76 times more all-cause deaths than BC deaths. The random-effect summary of RR for BC mortality in screening attendees vs nonattendees was 0.55 (95% CI: 0.50–0.60) in 13 cohort studies. The summary of RR for all-cause mortality was 0.54 (0.50–0.58) in 10 cohort studies. In the four cohort studies that evaluated both outcomes, the summary of RRs were 0.63 (0.43–0.83) for BC mortality and of 0.54 (0.44–0.64) for all-cause mortality. ConclusionThe similar relative reductions in breast- and all-cause (or nonBC) mortality indicates that screening mammography attendance is an indicator of characteristics associated with a lower risk of dying from any cause, including from BC, which observational studies have falsely interpreted as a screening effect.

Neighborhood Deprivation and Breast Cancer Mortality Among Black and White Women

Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who experience different neighborhood contexts. Accounting for interactions among neighborhood deprivation, race, and other neighborhood characteristics may enhance understanding of the association. To investigate whether neighborhood deprivation is associated with breast cancer mortality among Black and White women and whether interactions with rurality, residential mobility, and racial composition, which are markers of access, social cohesion, and segregation, respectively, modify the association. This population-based cohort study used Georgia Cancer Registry (GCR) data on women with breast cancer diagnosed in 2010 to 2017 and followed-up until December 31, 2022. Data were analyzed between January 2023 and October 2023. The study included non-Hispanic Black and White women with invasive early-stage (I-IIIA) breast cancer diagnosed between 2010 and 2017 and identified through the GCR. The Neighborhood Deprivation Index (NDI), assessed in quintiles, was derived through principal component analysis of 2011 to 2015 block group-level American Community Survey (ACS) data. Rurality, neighborhood residential mobility, and racial composition were measured using Georgia Public Health Department or ACS data. The primary outcome was breast cancer-specific mortality identified by the GCR through linkage to the Georgia vital statistics registry and National Death Index. Cox proportional hazards regression was used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% CIs for the association between neighborhood deprivation and breast cancer mortality. Among the 36 795 patients with breast cancer (mean [SD] age at diagnosis, 60.3 [13.1] years), 11 044 (30.0%) were non-Hispanic Black, and 25 751 (70.0%) were non-Hispanic White. During follow-up, 2942 breast cancer deaths occurred (1214 [41.3%] non-Hispanic Black women; 1728 [58.7%] non-Hispanic White women). NDI was associated with an increase in breast cancer mortality (quintile 5 vs 1, HR, 1.36; 95% CI, 1.19-1.55) in Cox proportional hazards models. The association was present only among non-Hispanic White women (quintile 5 vs 1, HR, 1.47; 95% CI, 1.21-1.79). Similar race-specific patterns were observed in jointly stratified analyses, such that NDI was associated with increased breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women, irrespective of the additional neighborhood characteristics considered. In this cohort study, neighborhood deprivation was associated with increased breast cancer mortality among non-Hispanic White women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women, suggesting that factors beyond those explored here may contribute to breast cancer mortality in this racial group.

PH-responsive coacervate with adrenergic nerve blockade function inhibits triple-negative breast cancer metastasis by blocking nerve-tumor-immune loop

Chronic stress, a common comorbidity of breast cancer, is shown to promote tumor progression by affecting tumor microenvironment. Metastasis is the leading cause of death in triple-negative breast cancer (TNBC), and clarifying the specific role of chronic stress on TNBC metastasis will facilitate the development of new targets and improve its prognosis. In this study, a reciprocal nerve-tumor-immune loop is firstly depicted to promote TNBC metastasis under chronic stress and can be interrupted by propranolol (Pro), which shows rapid clinical translation potential due to “new uses for old drugs”. However, low bioavailability and insufficient efficacy of Pro when applied systemically may hinder its clinical translation in cancer patients. Based on this, an injectable and pH-responsive Pro-loaded coacervate (Pro@Coa) is further developed, which can accumulate and sustainably release Pro within the tumor. For the first time, the study demonstrates that Pro@Coa not only inhibits TNBC metastasis by interrupting the reciprocal loop but also suppresses distant tumor growth by inducing systemic immunity. Compared to traditional free Pro administration, Pro@Coa improves treatment efficiency and has no side effects on normal tissues. Overall, this work delineates a nerve-tumor-immune loop that promotes TNBC metastasis under chronic stress and provides a reference for applying Pro@Coa for safer and more effective treatment of TNBC metastasis, which is more promising for clinical translation.

Health literacy and mammography screening behaviors among women living in a rural area of Turkey.

Breast cancer is the most common cause of cancer-related deaths. and early diagnosis could reduce breast cancer deaths. Therefore, health literacy is one of the most important determinants of participation in cancer screening for early diagnosis. This study aimed to determine the relationship between women's mammography screening behaviors and health literacy levels. The cross-sectional study included 312 women aged 40-69 years living in a rural area. Data were collected through face-to-face interviews using a personal information form and the Turkish Health Literacy Scale (THLS-32). Of the women, 28.5% had mammography in the last 2 years. Of concern was the low health literacy levels. In addition, there were significant differences in the THLS-32 subgroup scores, including the THLS-32 total score, among the mammography screening groups. Health literacy levels of women were related to mammography screening rates. For this reason, effective intervention studies aiming to increase society's health literacy levels may contribute to an increase in breast cancer screenings.

Tamoxifen for breast cancer prevention among survivors of pediatric lymphoma previously treated with chest radiation: Clinical benefits, harms and tradeoffs.

10025 Background: Survivors of pediatric lymphoma previously treated with chest radiation are at high risk for subsequent breast cancer. Although early initiation of breast cancer screening is recommended, the clinical benefits and harms of adding tamoxifen to reduce breast cancer deaths among these women are unknown. Methods: We adapted a Cancer Intervention and Surveillance Modeling Network (CISNET) breast model using data from the Childhood Cancer Survivor Study (CCSS) to reflect the elevated risks for breast cancer and competing mortality for 5-year survivors previously treated with chest radiation (RT). Breast cancer risk was based on age, chest RT field, timing of RT relative to menarche, menopause status, anthracycline exposure, and family history. Premature menopause risk varied by cumulative ovarian RT and alkylator dose. Based on the US Preventive Services Task Force 2019 Evidence Summary, we assumed tamoxifen (20mg daily for 5 years) reduced estrogen receptor positive (ER+) breast cancer risk by 42% (RR = 0.58 [0.42-0.81]) for 20 years and increased risks for venous thromboembolism, deep vein thrombosis, coronary heart disease, stroke and endometrial cancer during treatment. Strategies included no screening or tamoxifen, annual screening with mammography and MRI starting at age 25, annual screening with mammography and MRI starting at age 25 with the addition of tamoxifen at ages 25, 30 or 35. Model outcomes included cumulative breast cancer risk, number of childbearing years before age 45 (defined as years menstruating without tamoxifen use or a breast cancer diagnosis or having survived breast cancer for at least 3 years), and number of tamoxifen-related side-effects. Results: Among a cohort of 20-year-old 5-year lymphoma survivors previously treated with mediastinal RT without primary ovarian failure, an estimated 20% were projected to develop breast cancer and 2.6% would die from the disease before age 50 in the absence of screening or tamoxifen use. Survivors would have on average 22 childbearing years before age 45. Early initiation of breast cancer screening at age 25 would reduce breast cancer deaths before age 50 by 56.3%. Depending on age at initiation, tamoxifen would further reduce breast cancer deaths by 8.0 to 9.6 percentage points for an overall 64.3% to 65.9% reduction and reduce the average number of childbearing years by 17% to 21%. For each breast cancer death averted, a reduction of 1950 to 3740 childbearing life years and 11 to 20 side-effects would occur and varied by the tamoxifen start age compared to mammography and MRI screening. Conclusions: Tamoxifen use for primary breast cancer prevention among pediatric lymphoma survivors may further reduce breast cancer deaths but decisions might depend on survivor preferences for side effects vs. avoiding breast cancer and consideration of timing for childbearing.

Updated SEER database study of 21-gene assay to assess breast cancer–specific mortality and benefit of chemotherapy by race and ethnicity.

533 Background: In randomized studies (NSABP B-20, SWOG 8814, TAILORx, RxPONDER), the predictive effect of the 21-gene Breast Recurrence Score assay (RS) on chemotherapy (CT) benefit has been evaluated in patients with node-negative (N0) and node-positive (N+) breast cancer. Retrospective analyses of TAILORx and RxPONDER demonstrated differences in outcome by racial/ethnic groups (RG); however, there were no differences in CT benefit for any of the clinical outcome measures. In this study we characterized the association between the RS result and breast cancer-specific mortality (BCSM) and chemotherapy benefit in BCSM in RG in the recently updated, population-based SEER registries. Methods: Eligible patients were from the SEER 17 registries, November 2022 submission, and had non-metastatic, hormone receptor-positive, HER2-negative, node negative (N0) breast cancer diagnosed between 2006 and 2019 with a RS result. Analyses were weighted using the inverse of estimated propensity of using CT (yes vs. none/unknown). Prognosis was ascertained by estimating breast cancer specific survival (BCSS) at 9 years among patients with CT recorded as none/unknown by RG. The log-rank test was used to compare BCSM by RG. Multivariable Cox models, including RS result (26-100 vs. 0-25) x CT interaction, were used to assess whether RS result was predictive of CT benefit. Analyses were performed in the overall cohort and in Hispanic (H), non-Hispanic Asian and Pacific Islander (NHAPI), non-Hispanic Black (NHB), and non-Hispanic White (NHW) RGs. Results: There were 145,642 eligible patients and 3,212 breast cancer deaths. Median follow-up was 68 months. NHB patients had higher median RS result and CT usage than other groups (p < .001). In N0 patients, higher RS result was associated with lower 9-year BCSS, both overall and by race/ethnicity (p < .001). In Cox multivariable models (Table), the interaction between RS result by CT was significant among all N0 patients (p < .001) and in NHB patients (p = 0.005), NHW patients (p = 0.002), and H patients (p = 0.019), but not in NHAPI patients (p = 0.766). Analyses of patients with N+ disease and more detailed analysis of CT benefit according to RS results by RG are underway and will also be presented. Conclusions: Real-world evidence from the SEER registries in over 145,000 patients confirms the 21-gene assay is prognostic for BCSS in all groups by race and ethnicity. The RS result was predictive of CT benefit in N0 patients overall and in Hispanic, NHB, and NHW patients, but not in NHAPI patients in this analysis. [Table: see text]

Genetic counseling and subsequent cascade genetic testing for women with a family history of pathogenic BRCA1 mutation: A cost-effectiveness model.

10621 Background: BRCA1 pathogenic mutations significantly increase the lifetime risk for breast and ovarian cancer, but risk reducing interventions such as bilateral salpingo-oophorectomy (RRBSO) and mastectomy (RRM) can improve outcomes. For women with a known family history of pathogenetic mutation, genetic counseling and testing is recommended. We sought to determine the cost-effectiveness (CE) of referral to genetic counseling with subsequent cascade testing. Methods: A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine genetics consultation with Ambry panel testing versus no referral. It was assumed that known BRCA1 carriers would undergo annual breast cancer screening with mammogram and MRI at 25yo, RRBSO at 35yo, and RRM at 40yo. Non-carriers underwent routine annual mammogram at 40yo. Additionally, women who did not undergo genetic testing initially do so at the time of diagnosis of first cancer (breast of ovary) and subsequently underwent all recommended risk reducing strategies if found to have a pathogenic BRCA1 mutation. Outcomes included cost, quality adjusted life years (QALYs), ovarian and breast cancer cases and deaths. Univariate and multi-variate analyses were used to investigate the impact of the strategies. Results: In a Monte Carlo Microsimulation cohort of 10,000 women with a first degree relative with a pathogenic BRCA1 mutation, referral to genetic counseling with testing was the dominate strategy. This strategy resulted in a similar mean cost ($185,543 vs $185,171), but with 2,322 additional QALYs and incremental CE ratio (ICER) of 1,605 per QALY. This dominant strategy also resulted in 73 fewer ovarian cancer cases and 545 fewer breast cancer cases. Sensitivity analysis for the age of RRM was remarkable for an annual reduction in breast cancer cases by 97 cases and an annual cost savings of 375,658 for year prior to age 40 that mastectomy was performed. Conclusions: Routine genetic counseling and screening for all patients with a known family history of pathogenic BRCA1 mutation reduces breast and ovarian cancer diagnoses by prompting risk-reducing procedures without significant increase in cost when compared to diagnosis-based testing. Routine access to genetic counseling in a high-risk population would help inform earlier counseling and further decrease cancer risk, particularly as earlier RRM may improve outcomes. This is further supported by the low cost to implement. Improvement in identification and early referral could be targeted. [Table: see text]

Understanding trends of US breast cancer hospitalization, mortality and costs using the National Inpatient Sample database.

11162 Background: Studies have shown a rising breast cancer incidence in the US. However, its impact on healthcare utilization is unclear. Our study delves into the previously unexplored territory of hospitalization and cost trends among breast cancer patients, aiming to shed light on resource allocation and potential areas for improvement. Methods: To investigate trends in breast cancer admissions and costs, we queried the National Inpatient Sample database. Patients admitted between January 2011 and December 2019 with following criteria were included in the analysis: female gender, age ≥ 18, and ICD diagnosis code corresponding to unspecified malignant neoplasm of the breast as their primary reason for admission. Our primary outcome was defined as the temporal trends in the number of admissions, discharge rates, length of stay, and cost of hospitalization and mortality rates. Analyses were performed using Stata version 15.1 College station TX: StataCorp LP 2017. Appropriate discharge weights were applied to the dataset during the analyses to account for critical elements of sampling design. A p-value of <0.05 was considered statistically significant. Results: Between 2011 and 2019, hospital admissions for breast cancer as the primary diagnosis declined significantly, from 32,126 to 12,742 (P < 0.001). However, while average length of stay increased slightly from 4.3 to 4.9 days (P < 0.01), hospital charges for breast cancer rose dramatically. Adjusted for inflation, mean charges per patient rose 38.8%, from $50,663.86 in 2011 to $70,334.11 in 2019 (P < 0.001). Despite this surge, the total aggregate cost ("national burden") of hospitalizations with breast cancer as main discharge diagnosis decreased, falling from $1.63 billion in 2011 to $896 million in 2019 (inflation adjusted) (P < 0.001). Discharges for breast cancer peaked in women between 45 and 64, followed by the 65-84 demographic. Compared to the overall decrease in hospitalization rates, the declines in the above age groups were notably steeper with declines of 62% for 45-64 and 48% for 65-84 (p<0.001). Although absolute number of breast cancer deaths decreased from 2011 to 2019, the mortality rate paradoxically increased from 4.3% to 5.8% over the same period (P < 0.001). This seemingly contradictory trend warrants further investigation to better understand contributing factors. Conclusions: While breast cancer diagnoses are on the rise in women, our study reveals a fascinating paradox: significant declines in hospitalization, associated costs, and overall mortality. This encouraging trend likely stems from widespread surveillance mammography with increases in early stage, curable disease diagnosis, and the flourishing landscape of outpatient therapies, including targeted treatments, with more tolerable toxicity profiles allowing for majority of breast cancer care to be completed in the outpatient setting.

A Potential Combination of Targeting HSP90 and mTOR in Breast Cancer Cell Growth, Migration, and Invasion Through Inhibiting AKT Phosphorylation and F-actin Organization.

Breast cancer is the most prevalent form of cancer among women worldwide, with a high mortality rate. While the most common cause of breast cancer death is metastasis, there is currently no potential treatment for patients at the metastatic stage. The present study investigated the potential of using a combination of HSP90 and mTOR inhibitor in the treatment of breast cancer cell growth, migration, and invasion. Gene Expression Profiling Interactive Analysis (GEPIA) was used to investigate the gene expression profiles. Western blot analysis and fluorescence staining were used for protein expression and localization, respectively. MTT, wound healing, and transwell invasion assays were used for cell proliferation, migration, and invasion, respectively. GEPIA demonstrated that HSP90 expression was significantly higher in breast invasive carcinoma compared to other tumor types, and this expression correlated with mTOR levels. Treatment with 17-AAG, an HSP90 inhibitor, and Torkinib, an mTORC1/2 inhibitor, significantly inhibited cell proliferation. Moreover, combination treatment led to down-regulation of AKT. Morphological changes revealed a reduction in F-actin intensity, a marked reduction of YAP, with interference in nuclear localization. Targeting HSP90 and mTOR has the potential to suppress breast cancer cell growth and progression by disrupting AKT signaling and inhibiting F-actin polymerization. This combination treatment may hold promise as a therapeutic strategy for breast cancer treatment that ameliorates adverse effects of a single treatment.

Prognostic Value of MRI Assessment of Residual Peritumoral Edema in Breast Cancer Treated With Neoadjuvant Chemotherapy.

Peritumoral edema (PE) identified on T2-weighted breast MRI is a factor for poor prognosis in breast cancer. To assess the prognostic value of residual PE (rPE) in patients with PE positive breast cancer prior to neoadjuvant chemotherapy (NACT) who subsequently underwent curative surgery. Retrospective. In total, 128 patients with nonmetastatic invasive breast cancer who underwent breast MRI before and after NACT. Axial precontrast 2D fast spin echo T2W fat-suppressed sequence. Axial dynamic 3D gradient echo T1W fat-suppressed sequence. PE was diagnosed when a signal intensity as high as water was detected surrounding the tumor on a T2-weighted breast MRI. PE was qualitatively evaluated by three readers with more than 20 years of experience in interpreting breast field imaging findings. Residual cancer burden (RCB) were assessed post-NACT. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as the endpoints of this study. Chi-square test; Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P-value <0.05 was considered statistically significant. Pre-PE was observed in 64 out of 128 patients. Of these, rPE was observed in 21. In the log-rank test, breast cancer with rPE had significantly worse RFS and OS than that without rPE. Cox proportional hazard analysis identified rPE as a significant prognostic factor for recurrence (hazard ratio, 11.6; 95% confidence interval [CI], 3.05-43.8) and death (hazard ratio, 17.8; 95% CI, 3.30-96.3). Breast cancer with rPE had significant worse RFS and OS than that without rPE in RCB class II, and significant worse OS in pathological complete response, class I and class II in the log-rank test. rPE on a T2-weighted breast MRI was a significant factor for breast cancer recurrence and death in patients with pre-PE-positive breast cancer treated with NACT. Stage 2.

The effect of the COVID-19 health disruptions on breast cancer mortality for older women: a semi-Markov modelling approach

ABSTRACT Public health measures necessitated by the COVID-19 pandemic have affected cancer pathways by halting screening, delaying diagnostic tests and reducing the numbers starting treatment. Specifically, this moves individuals from observed and treated pathways to unobserved and untreated pathways. We introduce a semi-Markov model that includes both, extending an industry-based multiple state model used for life and critical illness insurance. Our model includes events related to cancer diagnosis and progression based on publicly available population data for women aged 65–89 in England and on relevant medical literature. We quantify age-specific excess deaths, for a period up to 5 years, along with years of life expectancy lost and changes in cancer mortality by cancer stage. Our analysis suggests a 3–6% increase in breast cancer deaths, and a 4–6% increase in registrations of advanced breast cancer, robust under sensitivity analysis. This should be applicable to actuarial work in areas where longevity and advanced age morbidity affect healthcare, retirement and insurance.

Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.

Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation. Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death. In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis. Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

Risk Assessment Tool of Breast Cancer and Barriers against Breast Self-Examination among Nurses: An Educational Program

Purpose. Breast cancer is considered a huge health problem among women all over the world due to its increased mortality rate. Breast cancer deaths are decreased by 28–34% due to improvement in treatment and early detection. In order to detect breast cancer early and provide the best possible therapy, knowledge and awareness are essential. So, this study aimed to assess risk of breast cancer among nurses, the knowledge and practices of breast self-examination (BSE) and determine its barriers, and implement an educational program for them. Design. A quasiexperimental research design was used. Methods. This study was conducted at two university hospitals (main university hospital and woman’s health hospital). A purposive sample of 280 nurses with age more than thirty-five years were included in the study using three tools, namely, structure interview questionnaire, breast cancer risk assessment tool, and a structured breast cancer knowledge and practice questionnaire. Nurses’ knowledge and practices regarding breast cancer and BSE were first assessed and then they were provided with two educational courses covering theoretical and practical information. One month after the program ended, the nurses’ knowledge and practices were assessed again. Results. About 3.2% of the participants have five years high risk of developing breast cancer according the risk assessment tool, the main barriers of do not do BSE did not find any symptoms and scared from finding any abnormality. There was a significant increase in knowledge and practice of breast self-examination posteducation compared to pre-education (73.2 and 98.2%, respectively). Also, there was a statistically significant difference between pre- and postprogram with a p value of 0.0001. Conclusion. This study concluded that 3.2% of the nurses with high risk of developing breast cancer needed a follow-up; more than half of them do not perform breast self-examination because they think that do not have any symptoms in the breast and the educational program with a significant effect on knowledge and practices of nurses. So, the researchers recommend the nurses need for an empowerment program and support by providing assistance in places of work as done free clinical examination and mammography by female specialist for privacy.

Abstract PO2-23-10: Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer

Abstract Background - An inverse association has been described in a number of studies between mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (BC), implicating high MBD in chemotherapy resistance. However, this effect has not been seen in all there is a paucity of data exploring whether this relationship extends the relationship beyond pCR to overall survival. This study aims to validate the relationship between MBD and pCR in patients undergoing NAC for early BC as well as to assess the relation of MBD with clinical complete response (cCR), relapse-free (RFS) and BC-specific survival (BCSS). Further, this study examines these associations stratified by body mass index (BMI). Methods - MBD was measured in contralateral mammograms in 127 women before NAC, using Cumulus software. As the study spanned the transition period from film to digital mammography, film mammograms were digitised using a high-powered scanner and processed full-field digital mammograms were extracted from the imaging storage facility. Basic patient, tumour and treatment demographics were collated including BMI. Percent dense area (PDA) was correlated with patient and tumour characteristics, short-term (pCR/cCR incidences), and long-term chemotherapy outcomes (RFS and BCSS). Results - Overall rates of cCR and pCR of 49% and 21% were observed across the whole cohort. Mean PDA was higher in those not undergoing cCR (p=0.041) and relapsing patients (p=0.041) but did not significantly vary by pCR or BC-deaths. As a dichotomous variable, high PDA relative to low PDA corresponded to lower cCR (40 v 58%, p=0.027), but no significant difference was seen for pCR (17.5 v 25.0%, p=0.15), BC relapse (38 v 30%, p=0.15) or BC-death (32 v 25%, p=0.20). High PDA (relative to low PDA) in patients with obesity (BMI &amp;gt;30kg/m2) was associated with lower pCR (0% v 28.1%, p=0.036) and numerically higher relapse rates (56% v 28%, p=0.063) and breast cancer deaths (56 v 28%, p=0.071. No such relationship was observed in patients with a BMI&amp;lt; 30kg/m2. Conclusion - Higher MBD associated with lower cCR and higher relapse but not with pCR or BC death. The inferior outcomes with high MBD were confined to patients with obesity in our study. Further analysis of the relationship between MBD and outcomes, including by BMI, is warranted. Citation Format: Andrew Redfern, Veenoo Agarwal, Ellie Darcey, Lisa Spalding, Hilary Martin, Jennifer Stone. Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-10.