Breast Cancer Mortality Research Articles

Differences in risk factors for mortality between T2N1M0 and T3N0M0 lobular breast cancer patients: a comparative study

ObjectiveThis study aimed to explore the differences in risk factors for mortality between T2N1M0 and T3N0M0 lobular breast cancer, and investigate the factors associated with non-lobular breast cancer mortality.MethodsData from 2,693 T2N1M0 and 1,384 T3N0M0 lobular breast cancer patients from the SEER database (2008–2018) were analyzed. The lobular breast cancer-specific and non-lobular breast cancer mortality were compared using the Kaplan-Meier curve and Log-rank test. The Cox proportional hazards regression analysis was used to determine the risk factors associated with non-lobular breast cancer mortality.ResultsThe total survival time showed a significant difference between the T2N1M0 and T3N0M0 groups (p = 0.0011). Statistically significant difference were found in lung-related disease mortality (p = 0.0023), with the survival rate of T2N1M0 higher than that of T3N0M0. Age, surgery, radiotherapy, and chemotherapy were independent factors associated with mortality in lung-related disease patients with both subtypes, and compared with T2N1M0, radiotherapy in T3N0M0 increased the risk of lung-related disease mortality (HR = 2.076, 95% CI: 1.4318–3.011).ConclusionThe T3N0M0 group had a higher mortality rate from lung-related diseases compared to the T2N1M0 group, and radiotherapy may increase the risk of lung-related disease death in T3N0M0 patients. These findings provide valuable information for treatment strategies for T2N1M0 and T3N0M0 subtypes of patients and assist physicians and patients make better treatment choices.

Recent Trends in Breast Cancer Mortality Rates for U.S. Women by Age and Race/Ethnicity.

To analyze recent trends in U.S. breast cancer mortality rates by age group and race and ethnicity. This retrospective analysis of female breast cancer mortality rates used National Center for Health Statistics data from 1990 to 2022 for all women, by age group, and by race or ethnicity. Joinpoint analysis assessed trends in breast cancer mortality rates. Breast cancer mortality rates for women 20 to 39 years old decreased 2.8% per year from 1999 to 2010 but showed no decline from 2010 to 2022 (annual percentage change [APC], -0.01; P = .98). For women of ages 40 to 74 years, breast cancer mortality rates decreased 1.7% to 3.9% per year from 1990 to 2022 (P <.001); a decline was found for all cohorts in this age group except Asian women. For women ≥75 years of age, breast cancer mortality rates declined significantly from 1993 to 2013 (APC, -1.26; P = .01) but showed no evidence of decline from 2013 to 2022 (APC, -0.2; P = .24). Across all ages, breast cancer mortality rates declined for White and Black women but not for Asian, Hispanic, and Native American women. Asian women ≥75 years of age had significantly increasing mortality rates (APC, 0.73; P <.001). For 2004 to 2022, breast cancer mortality rates were 39% higher in Black women than White women and varied strongly by age group: 104% for ages 20 to 39 years, 51% for ages 40 to 74 years, and 13% for ages ≥75 years. Female breast cancer mortality rates have stopped declining in women <40 years of age and >74 years of age. The higher mortality rates in Black women compared with White women are age dependent and substantially higher in younger women.

Breast Cancer Screening Participation and Internet Search Activity in a Japanese Population: Decade-Long Time-Series Study.

Breast cancer is a major health concern in various countries. Routine mammography screening has been shown to reduce breast cancer mortality, and Japan has set national targets to improve screening participation and increase public attention. However, collecting nationwide data on public attention and activity is not easy. Google Trends can reveal changes in societal interest, yet there are no reports on the relationship between internet search volume and nationwide participation rates in Japan. This study aims to reveal and discuss the relationship between public awareness and actual behavior in breast cancer screening by examining trends in internet search volume for the keyword "breast cancer screening" and participation rates over a decade-long period. This time-series study evaluated the association between internet search volume and breast cancer screening participation behavior among women aged 60-69 years in Japan from 2009 to 2019. Relative search volume (RSV) data for the search term "breast cancer screening (nyuugan-kenshin)" were extracted from Google Trends as internet search volume. Breast cancer screening and further assessment participation rates were based on government municipal screening data. Joinpoint regression analyses were conducted with weighted BIC to evaluate the time trends. An ethics review was not required because all data were open. The RSV for "breast cancer screening (nyuugan-kenshin)" peaked in June 2017 (100) and showed clear spikes in June 2016 (94), September (69), and October (77) 2015. No RSVs above 60 were observed except around these three specific periods, and the average RSV for the entire period was 30.7 (SD 16.2). Two statistically significant joinpoints were detected, rising in December 2013 and falling in June 2017. Screening participation rates showed a temporary increase in 2015 in a slowly decreasing trend, and no joinpoints were detected. Further assessment participation rates showed a temporary spike in 2015 in the middle of an increasing trend, with a statistically significant point of slowing increase detected in 2015. Post hoc manual searches revealed that Japanese celebrities' breast cancer diagnoses were announced on the relevant dates, and many Japanese media reports were found. This study found a notable association between internet search activity and celebrity cancer media reports and a temporal association with screening participation in breast cancer screening in Japan. Celebrity cancer media reports triggered internet searches for cancer screening, but this did not lead to long-term changes in screening participation behavior. This finding suggests what information needs to be provided to citizens to encourage participation in screening.

Smart Breast Cancer Detection: Enhancing Early Breast Cancer Diagnosis-Transitioning from Convolutional Neural Network to Involutional Neural Network and Using Smart Wearable Devices

Breast cancer is the most prevalent form of tumor in women, and this is the leading cause of mortality in women. Accurately detecting and classifying breast cancer is crucial for effective treatment and diagnosis preparation. Internet of Things (IoT) wearable devices (smart bra) are considered one of the best methods for early detection and, thereby, reducing breast cancer mortality. This study proposes a unique approach for breast cancer classification that combines involutional neural networks (InvNets) with wearable devices to reduce the parameter-intensive nature of convolutional neural networks. Specifically, the involution kernel differs from the convolution kernel because it is location-specific and channel-agnostic. This location-specific operation enhances the network's ability to acquire detailed elements in medical images by adapting to diverse visual patterns across spatial regions. In that regard, magnetic resonance imaging (MRI) has become an important modality for breast cancer detection. This work investigates the use of IoT devices such as wearables and sensors to collect patient health data and monitor changes in breast tissue. If symptoms are present, an MRI scan is performed for a reliable diagnosis of breast cancer utilizing deep learning (InvNets). Our findings show that InvNets achieves 100% training accuracy, 98.5% validation accuracy, and 98.6% testing accuracy after data augmentation, indicating its potential for breast cancer classification. InvNets are highly successful for medical image processing, particularly in circumstances with limited computer resources, as seen by enhanced accuracy and reduced parameter count. As a result, the findings show that InvNets provided consistent and reliable features for breast cancer detection and faster diagnosis.

Incidence, Prevalence, Mortality, and Direct Costs of Breast Cancer in Iran: Using the Iran Health Insurance Organization Database

Background: Breast cancer (BC) is the most common cancer and the leading cause of cancer-related death among women worldwide. The BC is a costly disease for health care payers and patients. Objectives: This study aimed to determine the incidence, prevalence, mortality, and costs of BC using the database of the Iran Health Insurance Organization (IHIO). Methods: This study was conducted as a descriptive, cross-sectional, and retrospective study using the database of the IHIO. Data were extracted and collected using a census method from the profiles of 42,296,124 individuals in 2021 and 44,303,244 individuals in 2022 who were covered by the IHIO. The international classification of diseases, 10th revision (ICD-10), was used to diagnose BC patients. Descriptive statistical methods were used to analyze the data, and the analyses were performed using SPSS version 21 and Microsoft Excel 2016. Results: The prevalence of BC in the population covered by the IHIO was 29.16 per 100,000 population in 2021 and 36.88 per 100,000 population in 2022. The incidence rate in 2022 was 7.02 per 100,000 population. Out-of-pocket (OOP) costs accounted for 33.72% of total direct BC costs in 2021 and 29.45% in 2022. The mortality rate was 0.68 per 100,000 in 2021 and 0.86 per 100,000 in 2022. The annual cost per patient was 305$ in 2021 and 446$ in 2022. Conclusions: The incidence, prevalence, and mortality rates of BC in Iran are rising, imposing a significant financial burden on families and increasing the risk of catastrophic health expenditures. Enhancing public awareness, implementing effective prevention strategies, and ensuring equitable access to timely medical treatment are essential steps in mitigating the impact of BC.

Measuring the WHO Global Breast Cancer Initiative Pillars' keyperformance indicators in Sub-Saharan Africa: experience in the African Breast Cancer-Disparities in Outcomes hospital-based cohort study.

Measuring the WHO Global Breast Cancer Initiative Pillars' keyperformance indicators in Sub-Saharan Africa: experience in the African Breast Cancer-Disparities in Outcomes hospital-based cohort study.

Breast, Colorectal, and Pancreatic Cancer Mortality With Pathogenic Variants in ATM, CHEK2, or PALB2.

Oncologists encounter patients with pathogenic variants (PVs) in ATM, CHEK2, or PALB2, but little is known about their cancer mortality. Patients who were 20 years or older, diagnosed in 2013-2019 with breast, colorectal, or pancreatic cancer, and reported to SEER registries in California and Georgia were linked to germline genetic testing results from four clinical laboratories and followed through 2021. Multivariable models of cancer mortality were fit; for each cancer, the reference group was the average hazard across all genetically tested patients with that diagnosis. Each cancer was modeled separately, followed by a single model that interacted the cancer type with all covariates. In addition to fixed effects models, random effects models were used as a regularization approach to reduce overfitting. A total of 70,272 tested patients with breast (48,473 estrogen receptor-/progesterone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative; 9,957 HER2-positive; 11,842 triple-negative) cancer, 5,822 with colorectal cancer, and 1,861 with pancreatic cancer were analyzed; the mean follow-up was 3.9 years. Patients with ATM, CHEK2, or PALB2 PVs had no differences in breast, colorectal, or pancreatic cancer mortality. Patients with ATM PVs in triple-negative breast cancer appeared to have higher mortality in fixed effects models (hazard ratio [HR], 3.7 [95% CI, 1.8 to 7.8]), but not in random effects models (HR, 1.2 [95% CI, 0.8 to 1.6]) that reduce overfitting. Patients with BRCA1/2 PVs had lower triple-negative breast cancer mortality in both models (fixed HR, 0.6 [95% CI, 0.5 to 0.9], random HR, 0.7 [95% CI, 0.6 to 0.8]). Patients with Lynch syndrome gene PVs had lower colorectal cancer mortality in both models (fixed HR, 0.5 [95% CI, 0.4 to 0.8], random HR, 0.7 [95% CI, 0.5 to 0.9]). Patients with ATM, CHEK2, or PALB2 PVs had similar breast, colorectal, and pancreatic cancer mortality to the average genetically tested patient with their cancer type.

Knowledge and practice of breast self-examination among women of reproductive age group in Palakkad district of Kerala: a cross-sectional study

Background: In India, non-communicable diseases (NCDs) are estimated to be 63% of all deaths, and cancer is one of the leading causes (9%). In 2022, there were 2.3 million women diagnosed with breast cancer and 670,000 deaths globally. Breast cancer mortality rates are primarily due to inadequate knowledge about the disease's risk factors, warning signals, and breast self-examination (BSE). Methods: A Hospital-based cross-sectional survey was conducted among 106 reproductive age group women excluding those diagnosed with breast cancer by nonprobability sampling. A structured questionnaire was used to assess the knowledge of breast cancer and BSE. Data was analyzed using SPSS 20 with inferential statistics using chi-square test. Results: Breast cancer knowledge was good in 70 (66%). 79 (74.5%) of the respondents had heard about BSE and out of them only 31 (29.2%) of respondents had practiced BSE. Not knowing the correct method was the most frequently reported reason for non-performance in 59 (55.7%). Only 8 (7.5%) of the women had received information about breast cancer from health professionals while a majority 53 (50%) stated that their source of information was family and friends. Higher educational level was found to be significantly associated with knowledge of breast cancer (p=0.003). A significant association was observed between knowledge and practice of BSE. (p=0.003). Conclusions: A two third of the Participants had good knowledge of breast cancer; however, the practice of BSE is still lacking. Therefore, BSE practice needs to be promoted among women for early detection of breast cancer and prompt management.

The impact of sleep on breast cancer-specific mortality: a Mendelian randomisation study

BackgroundThe relationship between sleep traits and survival in breast cancer is uncertain and complex. There are multiple biological, psychological and treatment-related factors that could link sleep and cancer outcomes. Previous studies could be biased due to methodological limitations such as reverse causation and confounding. Here, we used two-sample mendelian randomisation (MR) to investigate the causal relationship between sleep and breast cancer mortality.MethodsPublicly available genetic summary data from females of European ancestry from UK Biobank and 23andme and the Breast Cancer Association Consortium were used to generate instrumental variables for sleep traits (chronotype, insomnia symptoms, sleep duration, napping, daytime-sleepiness, and ease of getting up (N = 446,118–1,409,137)) and breast cancer outcomes (15 years post-diagnosis, stratified by tumour subtype and treatment (N = 91,686 and Ndeaths = 7,531 over a median follow-up of 8.1 years)). Sensitivity analyses were used to assess the robustness of analyses to MR assumptions.ResultsInitial results found some evidence for a per category increase in daytime-sleepiness reducing overall breast cancer mortality (HR = 0.34, 95% CI = 0.14, 0.80), and for insomnia symptoms reducing odds of mortality in oestrogen receptor positive breast cancers not receiving chemotherapy (HR = 0.18, 95% CI = 0.05, 0.68) and in patients receiving aromatase inhibitors (HR = 0.23, 95% CI = 0.07, 0.78). Importantly, these relationships were not robust following sensitivity analyses meaning we could not demonstrate any causal relationships.ConclusionsThis study did not provide evidence that sleep traits have a causal role in breast cancer mortality. Further work characterising disruption to normal sleep behaviours and its effects on tumour biology, treatment compliance and quality of life are needed.

Breast cancer mortality and prediction trends in Pakistani women: alarming public health concern

Breast cancer is the most common cancer in Pakistani women. The incidence and mortality rates have been continuously increasing over the last three decades in the country. The number of estimated new breast cancer cases in Pakistan will increase to 66562 (R2= 0·9928) by the end of 2050. However, strengthening local collaboration between public authorities and clinical settings is a way forward for early cancer detection and proper treatment.

Mathematical Modeling to Address Questions in Breast Cancer Screening: An Overview of the Breast Cancer Models of the Cancer Intervention and Surveillance Modeling Network.

The National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer mathematical models have been increasingly utilized by policymakers to address breast cancer screening policy decisions and influence clinical practice. These well-established and validated models have a successful track record of use in collaborations spanning over 2 decades. While mathematical modeling is a valuable approach to translate short-term screening performance data into long-term breast cancer outcomes, it is inherently complex and requires numerous inputs to approximate the impacts of breast cancer screening. This review article describes the 6 independently developed CISNET breast cancer models, with a particular focus on how they represent breast cancer screening and estimate the contribution of screening to breast cancer mortality reduction and improvements in life expectancy. We also describe differences in structures and assumptions across the models and how variation in model results can highlight areas of uncertainty. Finally, we offer insight into how the results generated by the models can be used to aid decision-making regarding breast cancer screening policy.

A Joint Optimization Scheme for Enhanced Breast Cancer Diagnosis Using Particle Swarm Optimization (PSO) and Binary Particle Swarm Optimization (BPSO)

One of the leading diseases globally is cancer and breast cancer is not exempted. The objective of the WHO Global Breast Cancer Initiative (GBCI) is to reduce global breast cancer mortality by 2.5% per year, thereby averting 2.5 million breast cancer deaths globally between 2020 and 2040. The three pillars toward achieving these objectives are: health promotion for early detection; timely diagnosis; and comprehensive breast cancer management. In this study we propose an early and comprehensive detection technique in combatting breast cancer diagnosis by combining the strength of both PSO (Particle Swarm Optimization) and BPSO (Binary Particle Swarm Optimization) to achieve optimal solution. The results obtained indicated the superiority of the Hybrid PSO-BPSO model in detection over an existing solution by achieving an accuracy of 98.82% on both the WBCD and WDBC datasets.

Global patterns and trends in breast cancer incidence and mortality across 185 countries.

Updates of current and projected estimates of the burden are critical to monitoring the success of ongoing efforts in breast cancer control, such as the World Health Organization Global Breast Cancer Initiative, which aims to reduce breast cancer mortality by 2.5% per year. We investigated the current (2022) and future (2050) global burden of female breast cancer overall, and by age group, in 185 countries using the GLOBOCAN database, and 10-year trends in incidence and mortality rates in 50 and 46 countries, respectively, using the Cancer Incidence in Five Continents plus and World Health Organization mortality databases. Globally, 2.3 million new cases and 670,000 deaths from female breast cancer occurred in 2022. Annual rates increased by 1-5% in half of examined countries. Mortality rates decreased in 29 countries with very high Human Development Index (HDI), and seven countries (for example, Belgium and Denmark) are meeting the Global Breast Cancer Initiative goal of at least a 2.5% decrease each year. By 2050, new cases and deaths will have increased by 38% and 68%, respectively, disproportionately impacting low-HDI countries. High-quality cancer and vital status data, and continued progress in early diagnosis and access to treatment, are needed in countries with low and medium HDI to address inequities and monitor cancer control goals.

Abstract B055: Macrophage and T reg expression of PD-L1 in the tumor draining lymph node and not the primary tumor is associated with anti-PD-1 resistance in a model of metastatic triple negative breast cancer

Abstract Introduction: The main cause of breast cancer mortality is metastasis. Triple negative breast cancer (TNBC) is an aggressive subtype with high rates of metastasis to the regional tumor draining lymph nodes (TDLN) and visceral organs, which is driven in part by immune escape. Recently, the addition of pembrolizumab (anti-PD-1) to neo-adjuvant chemotherapy gained FDA approval for both the management of metastatic and early stage TNBC. However, only about 20% of patients benefit and responses are completely independent of PD-L1 tumor expression, indicating a need to better elucidate the complexities the TNBC immune microenvironment. A major hurdle in identifying the mechanisms of immune escape and anti-PD-1 resistance in TNBC, is the lack of clinically representative mouse models of metastatic progression. We hypothesized that the serial re-implantation of metastatic lesions from a relatively slow growing syngeneic mouse model of TNBC would faithfully recapitulate the immune microenvironment of primary, lymphatic and distant metastatic disease. Methods: We previously reported the establishment of a syngeneic basal TNBC mouse model KPB25Luv (KLuv) that has comparable mutational burden, genomic profile, B-T cell cooperativity and IgG signature to human TNBC. The KLuv model develops both primary and TDLN tumors over several months, with rare liver metastases. KPB25Luv tumors were maintained in vivo and liver metastases were harvested and re-transplanted orthotopically over 1 year to develop the KLuv_LVMMR tumor line. Confocal microscopy, immunohistochemistry, bulk and single cell RNseq characterize and contrast the tumor microenvironments of each site. Longitudinal flow cytometry and TCR and BCR sequencing assess changes in adaptive lymphocyte dynamics. Findings are validated with corresponding patient data. Results: We report the development of the KLuv_LVMMR tumor line which is innately metastatic and reliably develops primary tumors, TDLN and liver metastases over 10 weeks. Gene expression signatures were comparable to human tumor tissues, including a significant decrease in immune activity (p=0.02) in metastases relative to primary tumors. This was associated with a reduction in MHCI and PD-L1 expression in metastatic lesions (p &amp;lt; 0.05). As metastatic tumors progress, CD8+ PD1+ T-cells increase 20-fold, with only a 2.5-fold increase in cytotoxic activity and IFN-gamma production, while T regulatory cells increase by 10-fold. No significant change was seen in CD4+ T cells or B220+ B cells. Confocal microscopy and single cell RNAseq reveal that PD-L1 expression localizes to macrophages and T-regs in the tumor draining lymph node rather than primary or metastatic tumor cells. Anti-PD-1 response is lost. Conclusions: The KLuv_LVMMR tumor line faithfully models the TNBC metastatic cascade, and immune microenvironment. This model represents the large population of anti-PD-1 resistant patients and has potential utility in identifying mechanisms of immune escape that can be harnessed into novel therapeutics for patients with advanced TNBC. Citation Format: Monika J Quackenbush, Asona Lui, Daniel P Hollern. Macrophage and T reg expression of PD-L1 in the tumor draining lymph node and not the primary tumor is associated with anti-PD-1 resistance in a model of metastatic triple negative breast cancer [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B055.

When “One Size Fits All” Fits None: A Commentary on the Impacts of the“Draft Canadian Breast Cancer Screening Guidelines” on Racialized Populations in Canada

Epidemiological data show racial and ethnic differences exist in breast cancer morbidity and mortality amongst Black, Indigenous, Asian, and Hispanic populations, with non-white females experiencing earlier age at diagnosis, more aggressive breast cancer subtypes and advanced cancer stages, and earlier mortality than white females. However, the current Canadian breast cancer screening guidelines recommend biannual screening for all females starting from age 50 to age 74 and suggest not to screen individuals aged 40–49. In May 2024, the Canadian Task Force for Preventative Health released updated draft breast cancer screening guidelines, maintaining such recommendations for screening. Both the existing and the proposed guidelines fail to account for the unique cancer burden amongst racialized populations in Canada and risk further perpetuation of existing racial and ethnic disparities by underscreening racialized females. This commentary will present data regarding racial disparities in cancer burden, highlighting the role social and biological factors play in impacting cancer risk and age of disease and presenting perspectives from stakeholder groups reflecting the impacts of current screening guidelines. Ultimately, we critique the current “one-size-fits-all” approach to breast cancer screening in Canada, emphasizing the need for adapted screening practices with the understanding that the current approaches overlook the needs of racialized Canadian populations.

Adjuvant radiotherapy in postmenopausal women with early-stage ER-positive breast cancer: A systematic review and meta-analysis.

The management of early breast cancer (BC) includes breast-conserving surgery (BCS), postoperative radiation therapy (PORT) and systemic therapy. Therefore, we aim at evaluating all the efficacy endpoints for PORT compared to no PORT in older women with early-stage BC. We searched PubMed, Web of Science, Cochrane, and Scopus databases from inception up to May 2024 for randomized controlled trials (RCTs) where patients were randomized into either PORT vs no PORT. The following outcomes were studied: any local recurrence, nodal recurrence, contralateral BC, distant relapse, all-causes and cancer-specific mortality. Seven eligible RCTs with a total of 4860 patients were included; 2435 of them received PORT; and 2425 did not. All patients had a node-negative disease, with 84.4% older than 60 years and only 10.4% had tumors larger than 2 cm. Patients in both treatment arms were offered adjuvant endocrine therapy e.g. tamoxifen and anastrozole. The median follow-up was 9.7 years (95% CI: 5.1-11.3). The survival risk for any local recurrence for patients with no radiotherapy was significantly higher than for those who used PORT (HR: 6.3; 95% CI: 4.17-9.52). Also, patients in the PORT arm had a significantly lower risk of nodal recurrence (risk of recurrence (RR): 0.28, 95% CI: 0.11-0.72, P = .009). However, PORT was not associated with a significant reduction in the risk of contralateral BC, distant relapse, BC-specific mortality or all-cause mortality (RR: 0.883, 1.52, 1.12, 0.995, respectively). Postoperative radiotherapy significantly reduces local and regional recurrence following BCS in early estrogen receptor-positive elderly BC with limited value on distant recurrence or mortality. The risk-benefit ratio should be determined for every patient to avoid overtreatment of a significant proportion of patients.

Biennial Mammography Performance in the Korean National Cancer Screening Program From 2009 to 2020.

Mammography is essential for reducing breast cancer mortality; however, its performance varies globally. This study aimed to evaluate mammography screening outcomes in Korea over 12 years and investigate regional variations. We analyzed mammography data from 42 million Korean women, aged 40 years and older, who participated in the Korean National Cancer Screening Program (KNCSP) from 2009 to 2020. Performance metrics-including recall rate (RR), positive predictive value (PPV), sensitivity, specificity, false positive rate (FPR), cancer detection rate (CDR), interval cancer rate (ICR), and dense breast rate (DBR), were computed. Twelve-year trends in these metrics were analyzed using Joinpoint regression. Regional variations were also examined across Korea's 237 districts, stratified by age groups. From 2009 to 2020, 42165405 mammography screenings were conducted through the KNCSP, increasing from 2821132 screenings in 2009 to 3596204 in 2020. The RR decreased from 17.2% in 2009 to 11.2% in 2020 (average annual percent change [AAPC] = -3.7%), while the PPV increased from 0.8% to 2.8%; AAPC = 10.7%), the CDR increased from 1.5 to 3.1 per 1000; AAPC = 7.3%), and the ICR rose from 0.9 to 1.6 per 1000; (AAPC = 5.2%). Regional variations were noted; however, differences in the RR, sensitivity, specificity, and FPR decreased over time. While mammography performance improved from 2009 to 2020, the PPV and sensitivity remain suboptimal, underscoring the need for continuous monitoring. Regional disparities in performance, although reduced, persist. These findings provide essential baseline data for improving mammography quality and addressing inequities in breast cancer screening.

Outcomes of the Saudi breast cancer early detection program: a nine-year analysis (2012-2020).

This study aims to report the preliminary outcome of the Saudi breast cancer early detection program (SBCEDP). Mammography screens were done for Saudi women (age 40-69years old) who participated in the SBCEDP from April 2012 to December 2020. Independent double-blind reading of the mammograms was performed by two radiologists. Analysis of age at diagnosis, cancer characteristics, and available screening indicators will be reported within this timeframe. Among 72,774 screened women, 504 had breast cancer cases, yielding a cancer detection rate of 6.93 per 1000 screened women. DCIS detection rate was 0.87 per1000 screened women (n = 63). Mean age at diagnosis was 53.61years (SD = 8.85) and the majority women had fatty breast tissue (A and B, 65%). Luminal A subtype was predominant (N = 58.6%), whereas triple-negative breast cancers constituted about 12.6% of cases. Estrogen and progesterone positivity was common (more than 65% of cases). Early and localized breast cancer was reported among 28% and 45.8% of women, respectively. Lesions mean size was 23.88mm and mastectomy rate was 54.2%. Although not all screening indicators were available, the SBCEDP demonstrates encouraging results, with notable rates of early-stage diagnosis. Continuous evaluation and improvement of screening strategies are essential for further enhancing the program effectiveness in reducing breast cancer mortality and morbidity among Saudi women.

CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.

We evaluated the impact of systematic bias due to loss of heterozygosity (LOH) and incomplete phenotyping in studies examining the relationship between CYP2D6 variants and breast cancer recurrence among women treated with tamoxifen. We performed a systematic review of the literature on tamoxifen, CYP2D6 variants, and breast cancer recurrence. A quantitative bias analysis was performed to adjust for LOH and incomplete phenotyping. Bias-adjusted results were then combined in a meta-analysis. Thirty-three studies informed the bias analysis and meta-analysis on CYP2D6 variants and breast cancer recurrence and/or mortality. An unadjusted meta-analysis suggested increased risk of recurrence and/or mortality for poor relative to normal metabolizers [RR = 1.28; 95% simulation interval (SI), 1.04-1.58] with substantial heterogeneity (I2 = 27%; P for heterogeneity = 0.07). Adjusting for LOH and incomplete genotyping resulted in a slight change in the effect estimate and a decrease in heterogeneity (RR = 1.34; 95% SI, 1.10-1.63; I2 = 0%; P for heterogeneity = 0.17). Intermediate metabolizers had a slightly increased risk of recurrence and/or mortality relative to normal metabolizers (RR = 1.15; 95% SI, 1.00-1.34; I2 = 0%; P for heterogeneity = 0.89). Adjusting for biases such as LOH and incomplete genotyping reduced observed heterogeneity between studies. Individuals with poor CYP2D6 phenotypes were at increased risk for breast cancer outcomes compared with those with normal phenotypes. Reduction in CYP2D6 activity was associated with an increased risk of breast cancer recurrence and/or mortality, and results underscore the importance of quantitatively adjusting for biases when aggregating study results. See related In the Spotlight, p. 221.

Adaptive selection of p53 mutation metaplastic phenotypes in estrogen-independent progression of ER+ tumors: A mechanism for acquired resistance to hormonal therapy.

Estrogen receptor positive (ER + ) subtypes of mammary adenocarcinoma comprise 79% of all breast cancer diagnosis and 67% of all breast cancer mortality. The paucity of models of ER + mammary cancer that mimic human disease and response to treatment has limited critical preclinical study of mechanisms and new therapies for ER + breast cancer. The Stat1 knockout, 129S6/SvEvTac-Stat1 tm1Rds ( Stat1 -/- ), females develop luminal type FoxA1 + , ER + , and PR + mammary carcinomas after prolonged latencies. Initial studies showed that a cell line derived from a Stat1-/- mammary carcinoma was tumorigenic in syngeneic mice, but non-tumorigenic in ovariectomized (Ovx) mice. Here, data shows that Ovx performed after SSM2 tumors establish growth results in ovarian hormone independent growth. The viable post-Ovx tumors were primarily composed of metaplastic CK14 + basal type cells with a high percentage p53 immunohistochemistry (IHC) positive "mutation pattern", rather than the original luminal type tumors with low percent "wild type" pattern p53. Comparing whole exome sequences of ER + Stat1 -/- mammary tumors before and after Ovx, revealed basal keratins, mesenchymal (EMT) phenotypes, and unique mutation profiles in genes, including Trp53 and Prlr, in the estrogen-independent tumors. Our experimental findings are consistent with the clinical evidence of tumor heterogeneity of ER + breast cancers in patients in recent whole genome sequencing studies. Similarly, spontaneous Stat1-/- tumors with high percentage p53 "mutation pattern" were more basaloid and grew rapidly after Ovx, while retaining high expression of ER and FoxA1. This study demonstrates that the STAT1 -/- , ER + estrogen dependent breast cancers can become resistant to through clonal selection of mammary cells comprised of metaplastic p53 + /CK14 + basaloid cells.