Reduction In Breast Cancer Mortality Research Articles

Surgical treatment of breast cancer, national and international standards of care

Breast cancer shall continue to be a public health problem because of its constantly ascending incidence and its high mortality. In the last decades, several positive changes happened in the treatment of this disease, as breast cancer screening, and introducing more effective oncological and surgical therapeutical methods. Qualitative and methodological development of breast surgery, the centralisation and the daily practice of quality assurance principles together will play an important role in reduction of breast cancer mortality in the future.

Scientific uncertainty and perceived mammography benefits in women screened for breast cancer

Personal aversion to scientific uncertainty may influence how women perceive the benefits of mammography, a breast cancer screening practice with conflicting scientific opinions and guidelines. Such associations may even exist among women who participate in screening. We evaluated the distribution of aversion to ambiguous medical information (AA-Med), using a 6-item scale capturing the level of agreement with statements about obtaining a cancer screening test with conflicting medical recommendations in 665 women (aged 40-60years; 79.5% Hispanic) recruited during screening mammography appointments in New York City. We assessed the association of AA-Med with perceptions of benefits of mammography (breast cancer mortality reduction, worry reduction, early detection, treatment improvement) using multivariable logistic regression. Over a quarter of participants expressed negative reactions to medical ambiguity about a cancer screening test (e.g., fear, lower trust in experts), but a majority endorsed intention to undergo screening. AA-Med was higher in women who were U.S.-born, non-Hispanic black, and had marginal to adequate health literacy, but there were no differences by clinical factors or screening experiences (e.g., family history, prior breast biopsy). Women with higher AA-Med were more likely to perceive treatment benefits from mammography (OR = 1.37, 95% CI = 0.99-1.90), but AA-Med was not associated with other perceived mammography benefits. Aversion to uncertainty regarding cancer screening varies by sociodemographic characteristics but has limited associations with perceived mammography benefits in women who already participate in screening.

MiRNA-128 and miRNA-223 regulate cholesterol-mediated drug resistance in breast cancer.

Breast cancer is the second most common malignancy worldwide and 70% of all breast cancer cases are estrogen receptor-positive (ER+). Endocrine therapy, Tamoxifen (TAM), is a popular treatment for ER+ breast cancer patients; however, despite its success in reducing breast cancer mortality, cancer drug resistance remains a significant challenge. A major contributor to this resistance is the dysregulation of cholesterol homeostasis, where breast cancer cells have elevated cholesterol levels. MicroRNAs (miRNAs) are master regulators of cholesterol-related and cancer drug resistance pathways, and their aberrant expression often confers resistance. Therefore, we aimed to investigate the roles of miRNA-128 and miRNA-223 in cholesterol-mediated TAM resistance. Three breast cancer cell lines were treated with a combination of 1 μM TAM and 10 μM of a cholesterol depleting agent (Acetyl Plumbagin: AP) following transfection with a miR-128 inhibitor or a miR-223 mimic. Cell viability and cholesterol levels were assessed using an MTT assay and fluorescence staining, respectively. In addition, expression levels of several genes and proteins involved in cancer drug resistance and cholesterol homeostasis were also assessed using RT-qPCR and western blotting. The combination treatment with altered miRNA expression led to reduced cell viability due to a reduction in free cholesterol and lipid rafts in MCF-7, MDA-MB-231, and long-term estrogen-deprived cells (resistant breast cancer cells). Moreover, reduced miR-128 expression was favoured in all breast cancer cell lines as this alteration lowered the expression of genes involved in cholesterol synthesis and transport, drug resistance, and cell signalling. Investigating the gene expression profiles in different breast cancer cell lines was important to elucidate further the molecular mechanisms involved in miRNA-regulated cholesterol homeostasis and cancer drug resistance. Therefore, our findings demonstrated that miR-128 and miR-223 could be potential targets in reducing TAM resistance through the depletion of excess cholesterol.

Abstract 5250: Effect of the β-blocker carvedilol in preventing DMBA-induced mammary gland tumor growth

Abstract According to global cancer statistics, breast cancer has now become the most diagnosed cancer and has become the fifth leading cause of cancer-related deaths worldwide. A promising method of retarding cancer-related mortality is cancer chemoprevention. However, there is no drug available that can be used routinely as a breast cancer-preventative agent. As carvedilol (CAR), an FDA-approved beta-adrenergic receptor blocker, reduces breast cancer mortality, we hypothesized that CAR might act as a breast cancer preventative agent. Three protocols were utilized to evaluate the ability of CAR to prevent 7,12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. In protocol 1, two doses of CAR (2 and 10 mg/kg) were administered in drinking water as a 7-day pretreatment and throughout the study. In protocol 2, 10 mg/kg tamoxifen and 10 mg/kg carvedilol were provided as a 7-day pretreatment, and treatment was halted after six weeks. In protocol 3, CAR and the non-β-blocking enantiomer R-carvedilol (10 mg/kg) were given as a 7-day pretreatment and throughout the study. In all studies, animals were palpated weekly beginning at week 5 to detect the presence and location of mammary tumors. Tumors were measured using a caliper, and the experiments terminated at week 13. In protocol 1, only 10 mg/kg CAR was effective in delaying DMBA-mediated tumor occurrence (p = 0.0002); the first appearance of tumors and median tumor appearance in CAR-treated rats were separated from rats receiving DMBA alone by 2 and 4 weeks, respectively. However, tumors that did form grew at the same rate in all groups. In protocol 2, tamoxifen served as a control to prevent DMBA-mediated tumors; only one tamoxifen-treated rat developed a tumor at the end of the study. The tamoxifen-treated rats tumor formation was not statistically different than negative controls; however, the CAR group was not statistically different from the DMBA group. In protocol 3, CAR and R-CAR treatment showed delayed tumor formation and growth compared to the DMBA-only group, although not statistically significant. Combining all DMBA and 1-week pretreatment CAR data (n = 58 and 40, respectively), CAR effectively prevents DMBA-induced tumor incidence (p = 0.001), with a 3-week differential in the median tumor formation between the two groups. Therefore, continuous CAR treatment is essential to achieve the observed chemopreventive effects. As carvedilol is a clinically used beta-blocker, the results provide significant implications in breast cancer chemoprevention. Citation Format: Pabitra Kumar Sardar, Steven Yeung, Ayaz Shahid, Bradley T. Andresen, Ying Huang. Effect of the β-blocker carvedilol in preventing DMBA-induced mammary gland tumor growth. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5250.

Abstract 1938: Germline mutations in breast cancer genes are associated with early age of diagnosis and triple negative disease in Guatemalan and US Hispanic women

Abstract Abstract Background: Mutations in hereditary breast cancer genes play an essential role in cancer risk. Little is known of the type and frequency of mutations in Hispanic populations in the United States and Central American countries, including Guatemala. Methods: We used exome sequencing to identify mutations in blood DNA from unselected Hispanic breast cancer cases from community recruitment and from two hospitals each in Texas and Guatemala. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes. Variants were annotated with ClinVar and VarSome. Results: We recruited 262 Hispanic US women, 37 (14%) from community-based recruitment and 225 (86%) from hospitals in Texas. In addition, we ascertained 633 patients from two hospitals in Guatemala City. A total of 91 out of 895 subjects (10%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were the high penetrance BRCA1 (44/895, 4.9%) followed by BRCA2 (23/895, 2.6%), PALB2 (5/895, 0.6%), CHEK2 (5/895 0.6%), ATM (6/895, 0.7%) and TP53 (6/895, 0.7%). Pathogenic variants were also detected in the moderate penetrance genes BARD1 and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212+1G>A splice mutation (18 cases) and BRCA1 c.799delT (9 cases) in Guatemala. Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs. 52 years, P<0.001) and were more likely to have a diagnosis before menopause. A higher percentage of mutation carriers had a relative with any cancer (51% vs. 37%, P=0.038) or breast cancer (33% vs. 15%, P<0.001). Patients with pathogenic mutations had a significantly higher percentage of triple-negative disease (60% vs. 13%, P=0.00046). Finally, mammography usage was less frequent in women with a lower socioeconomic status, indicating that this group is less likely to be screened for breast cancer (P<0.001). Conclusions: Guatemalan women have rates of hereditary breast cancer mutations like other populations, and these women are more likely to have early age at diagnosis, triple-negative disease, and family history. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Hispanic women. Citation Format: Jesica Godinez Paredes, Isabel Rodriguez, Megan Ren, Anali Orozco, Jeremy Ortiz, Anaseidy Albanez, Catherine Jones, Zeina Nahleh, Lilian Barreda, Lisa Garland, Dongjing Wu, Jiahui Wang, Victor Argueta, Roberto Orozco, Eduardo Gharzouzi, Michael Dean. Germline mutations in breast cancer genes are associated with early age of diagnosis and triple negative disease in Guatemalan and US Hispanic women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1938.

Abstract 4353: Utilizing scRNA sequencing to understand biomarkers of response and resistance to Sacitizumab Govetican in localized TNBC

Abstract Triple-Negative Breast Cancer (TNBC) is an aggressive breast cancer subset, which lacks expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2. This subset of breast cancer disproportionately affects Black and African American women and improving TNBC treatment options is vital to reducing breast cancer mortality. The novel antibody-drug conjugate, Sacitizumab Govetican (SG), which targets TROP2 at the cell surface, has shown promising clinical results from the NeoSTAR trial (NCT04230109), a phase II study evaluating neoadjuvant SG therapy in a localized TNBC setting. As part of the NeoSTAR clinical trial, we have collected and processed pre- and post- SG treatment patient samples, with the aim of understanding response to this monotherapy. Herein, we identify biomarkers of response and resistance to SG monotherapy through the use of single cell RNA sequencing of matched pre- and post-treatment patient biopsies combined with exome sequencing these patient samples. Pre-treatment core needle biopsy samples, and if applicable, post-treatment residual disease biopsies were dissociated into single cell suspensions and subjected to single cell RNA sequencing. Additionally, fixed patient tissue samples were processed accordingly for exome sequencing analyses. Overall, we analyzed over 144,000 cells from 37 total scRNA seq libraries with an average of 3800 cells per biopsy sample, demonstrating the feasibility of this method. From these analyses, we observed several cell-type differences between patients who achieved a pathological complete response (pCR) and patients who had residual disease (RD). Specifically, our data shows that tumor infiltrating lymphocytes are a potential prognostic biomarker of response to SG. Furthermore, we detected alterations in among stromal and immune cell subsets, among non-responders, indicating that these cell types maybe indicative of SG resistance. Taken together, we outline biomarkers of response to SG treatment for an improved understanding of resistance mechanisms in the neoadjuvant setting to improve TNBC outcomes among patients. Citation Format: Nicole Peiris, Simona Cristea, Mengran Zhang, Siang Koh, James Coates, Ilze Smidt, Veerle Bossuyt, Laura Spring, Aditya Bardia, Leif Ellisen. Utilizing scRNA sequencing to understand biomarkers of response and resistance to Sacitizumab Govetican in localized TNBC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4353.

233 Uganda-based Survey of Challenges in Breast Cancer Detection in Low and Middle Income Countries

OBJECTIVES/GOALS: Low and middle income countries (LMICs) face challenges in early detection of breast cancer resulting in high breast cancer mortality. This study serves to identify gaps and opportunities for innovators seeking to address problems in early detection of breast cancer in Uganda and other LMICs. METHODS/STUDY POPULATION: Two methods were used: 1) Three weeks of ethnographic research in Uganda through primary stakeholder interviews and clinical observations. Interviews were conducted with patients, clinicians, NGOs, and key opinion leaders from the Uganda Cancer Institute, Makerere University, and JHPIEGO. Clinical observations were performed to note the workflow and availability of resources across diverse health centers ranging from village health teams in rural settings to the national referral hospital in the urban center. 2) A targeted literature search focused on breast cancer detection in LMICs. Keywords included breast cancer’, screening’, and diagnosis’. Identified challenges were validated through stakeholder interviews and categorized. Potential solutions to each challenge were explored. RESULTS/ANTICIPATED RESULTS: Three broad categories of challenges and suggested innovation targets were identified. 1) Ineffective clinical processes: deskilling and improving training around the process of clinical breast examinations, imaging operation and interpretation, and pathology preparation and interpretation; 2) Accessibility: increasing screening throughput, improving rural community access to breast cancer care, and increasing opportunistic screening; 3) Sensitization: increasing patient and health worker awareness of clinical presentations of breast cancer, reducing cultural barriers, and improving trust in the medical community. DISCUSSION/SIGNIFICANCE: Innovators seeking to solve problems in early breast cancer detection in LMICs should focus on ineffective clinical processes, accessibility, and sensitization. In conjunction with prompt treatment, there is potential to reduce breast cancer mortality rates in line with the Global Breast Initiative.

Breast cancer screening programmes and self-reported mammography use in European countries.

Mammography screening has been shown to be able to reduce breast cancer mortality, leading most European countries to implement mammography-based screening programmes. In our study, we analysed key characteristics of breast cancer screening programmes and mammography use in European countries. Information on screening programmes were obtained from the 2017 European Union (EU) screening report, websites from governments and cancer registries, and through literature search in PubMed (studies published up to 20 June 2022). Data on self-reported mammography use in the past 2 years were obtained from Eurostat and had been derived from the European health interview survey (cross-sectional survey), conducted in the 27 EU countries, Iceland, Norway, Serbia, Turkey and the UK in 2013 to 2015 and 2018 to 2020. Data were analysed for each country according to their human development index (HDI). By 2022, all included countries besides Bulgaria and Greece had introduced an organised mammography-based screening programme; Romania and Turkey had only pilot programmes. Screening programmes differ substantially across countries, particularly in timing of implementation (e.g., in Sweden, the Netherlands before 1990; Belgium, France between 2000 and 2004; Denmark, Germany between 2005 and 2009; Austria, Slovakia after 2010). Self-reported mammography use also differed considerably across countries, and went along with HDI-from <36% in all countries with HDI <0.85 to >70% in most countries with HDI >0.90. The data call for efforts to improve mammography screening use across Europe, particularly in countries with lower development levels where breast cancer mortality rates are also among the highest in the region.

Contribution of Mammography in the Screening of Suspicious Breast Cancer Lesions in Congolese Women in Kinshasa

Background: Mammography is a particular mammary imaging technique, an important tool for screening, diagnosis and monitoring of breast disease in general and breast cancer in particular, for which incidence and mortality are well established. Several studies have shown a reduction in breast cancer mortality reaching 40% in women screened by mammography. Thus, the prognosis after treatment is better because of early detection. In the DRC, in developing countries, the mortality rate is high because the diagnosis is late and therefore responsible for a bad prognosis. However, no studies on early detection by mammography have been performed to our knowledge. Our goal was to determine the mammography contribution in suspicious lesions detection of breast cancer in Kinshasa. Method: A retrospective and descriptive study of 1738 mammograms at the Gombe Imaging Center from January 2012 to December 2015. The reports were prepared by radiologists. We re-read approximately 230 images under supervision to complete the missing data related to interpretation. Age, clinical information, breast density (BIRADS type), elemental or associated lesions, and ACR radiological diagnosis were the key parameters collected on an epidemiological data questionnaire and analyzed on the SPSS 20 software.Results: 347 screening mammograms or 20% were performed with an average age of 48.6 years ; 25 of these (7.2%) had mammographic lesions suspected of malignancy, among which 23 were considered in situ. In addition, our study showed that high breast density is a radiologically visible risk factor. Conclusion: This study has shown that mammography is a tool to integrate into cancer screening in our country. Because it allowed to detect suspicious lesions in asymptomatic women.

Abstract P3-03-05: A randomized study assessing interventions to improve comfort during screening mammography

Abstract Background: Although screening mammography leads to an early detection of breast cancer and a reduction in breast cancer mortality, many women have apprehension about mammograms due to reported discomfort and pain [would cite the source]. A study showed that pain was the cause of non-reattendance of screening mammograms in 25-46% of reported cases by women. Despite this, there is limited research on strategies to reduce discomfort and anxiety associated with mammography screening and improve patient experience and compliance with national screening recommendations. Herein, we performed a double-blind randomized clinical study to determine if the use of local analgesia and calming music can improve patient satisfaction during routine screening mammogram. Methods: This study was designed as a double-blind randomized clinical trial with a 2 × 2 factorial design. A total of 251 patients who presented for mammographic screening were randomized to receive: breast lidocaine gel at a dose of 1200 mg or placebo gel on both breast and experience calming music or no music Patients with history of mastectomy, breast cancer or recent (within 24 hours) analgesic use were excluded. Pain was measured with a 5-point face pain scale. Benjamini-Hochberg false discovery rate was used for analysis Results: Of the 251 patients who were randomized between June 2017 and October 2019, 195 self-identified as Hispanics (77%). Median age was 58.5 years old and there were no differences in between groups. 100% were female. 99.3% presented for screening with no concerning symptoms. A total of 126 patients were randomized to music vs 125 to no Music. 79 patients in music group and 51 patients in no music group were randomized to lidocaine. Regarding pain assessment, 18.96% of patients had a pain score of 4 and 5 in the music group randomized to lidocaine gel as opposed to 10.64% to placebo gel. In the non-music group, 17.65% of patients expressed pain score of 4 and 5 to lidocaine gel vs. 18.91% to placebo gel. (P value music: 0.95, P value lidocaine: 0.93 P value music and lidocaine: 1). Patients randomized to lidocaine gel to music reported their prior mammogram to be at a pain score of 4 to 5 in 41.7% of the subjects vs 45% of patients in the no music group. (P value music: 0.45, P value lidocaine: 0.93 P value music and lidocaine: 1). Despite this, majority patients in both groups expressed no reluctance for future mammograms. Conclusion: The addition of calming music and breast lidocaine gel did not show a statistically significant difference in the level of pain perceived by patients getting screening mammography. The data appear to suggest less severe pain (pain score 4 and 5) when these strategies are combined. Further prospective trials with larger patient populations are needed to explore these interventions. Despite the perceived pain most patients were still willing to return for a mammogram the following year. Citation Format: Marcela Mazo-Canola, Heidi C. Ko, Kenneth Kist, Joel Michalek, Lillian Franco, Pamela Otto, Virginia Kaklamani. A randomized study assessing interventions to improve comfort during screening mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-05.

Abstract OT3-20-02: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial

Abstract Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman’s lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis cancers. The main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery; with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Non-inferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion: Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32 Citation Format: Stuart A. McIntosh, Charlotte E. Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-02.

Abstract P1-06-04: IMPACTS OF TREATMENT DELAY ON BREAST CANCER MORTALITY AND BENEFIT OF TIMELY CARE IN BLACK AND NON-BLACK WOMEN

Abstract BACKGROUND: The impact of treatment delays on cancer outcomes has been well documented, but few published studies explicitly attempt to identify subgroups which would benefit the most from potential interventions improving timeliness of care. Using the state of North Carolina and breast cancer as an example, we sought to quantify race-specific associations between frontline treatment delay and breast cancer mortality, and estimate the potential impact of improvements in timeliness by racial sub-group. METHODS: We conducted a retrospective cohort study, utilizing multipayer insurance claims linked to cancer registry data from the Cancer Information and Population Health Resource, of females diagnosed with stage I-III breast cancer from 2004 to 2014. Our exposure of interest was treatment delay, defined as initial cancer directed therapy received ≥ 60 days after diagnosis. Our outcome was death certificate identified breast cancer mortality within 5-years of follow-up. To quantify the association between treatment delay and mortality we estimated hazard ratios (HR) and 95% confidence limits (CL) where non-breast cancer deaths were treated as competing events. We then simulated the effect of treating all patients within 60 days using inverse probability of treatment weighting (IPTW), and estimated the potential impact by comparing the simulated data with observed data. Models were adjusted for age and stage at diagnosis, tumor grade, hormone receptor status, and modality of first treatment. Models were stratified by race, dichotomized as Black or non-Black, and geographic subregion for evaluation. RESULTS: Our analytic cohort comprised 21,200 patients, of whom 19% were Black. Treatment delays &amp;gt;60 days were twice as frequent among Black compared with non-Black patients (13.5% vs. 6.5%). We found a positive association between treatment delay and breast cancer mortality in the overall cohort (HR=1.3; CL: 1.1, 1.6). The association differed between Black (HR=1.4; CL: 1.1, 1.8) and Non-Black (HR=1.2; CL: 0.9, 1.6) patient subgroups. For both racial groups, the strength of the relationship between treatment delay and mortality varied across geographic subregions. The estimated potential improvement in 5-year cumulative breast cancer mortality from delivering timely care to all patients differed in magnitude across sub-populations. The magnitude of potential improvement in breast cancer mortality at 5 years in the overall analytic cohort was 0.3% (5-year risk of breast cancer mortality in observed cohort: 7.2% vs 6.9% with simulated universal timely treatment). In the Black subcohort, the potential decrease in mortality for timely treatment was 1.0% (observed: 12.3% vs simulated: 11.4%), while in the non-Black population the potential decrease was 0.1% (observed: 6.1% vs simulated: 5.9%). CONCLUSIONS: The magnitude of association between delayed treatment of stage I-III breast cancer and breast cancer mortality differed between Black and non-Black patients, highlighting that interventions to avert treatment delays may have a meaningful impact for this group. Further research is needed to identify factors underlying this difference, which may include a direct effect of differences in timeliness, or downstream differences in the intensity and quality of cancer care beyond the 60-day landmark for delayed patients. Our findings suggest that comprehensive intervention at the state level to improve the timeliness of breast cancer treatment could potentially reduce breast cancer mortality, and that targeting such intervention to patient groups with larger projected benefit, such as Black patients, may be a more efficient use of resources. We have illustrated how a counterfactual approach may be useful in identifying subgroups where focused intervention efforts may yield greater improvements in outcomes. Citation Format: Bradford Jackson, Stephanie Wheeler, Juan Yanguela, Matthew LeBlanc, Tzy-Mey Kuo, Christopher Baggett, Katherine Reeder-Hayes. IMPACTS OF TREATMENT DELAY ON BREAST CANCER MORTALITY AND BENEFIT OF TIMELY CARE IN BLACK AND NON-BLACK WOMEN [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-04.

Determinants of breast cancer screening mammography uptake: Results from Jordan population and family health survey.

Screening for breast cancer utilizing mammography is associated with reduced advanced cancer diagnosis and reduced breast cancer mortality. We aimed to assess the lifetime history of breast cancer screening utilization for Jordanian women aged 40 and 49 years and determinants of this utilization. This paper reports the analyzed data from the seventh cycle of the Jordan Population and Family Health Survey (JPFHS). For this study, the analysis was confined to 4486 women aged between 40 and 49 years at the time of data collection who reported their nationality as Jordanian. We used multivariate logistic regression analysis to assess whether any socio-demographic variables could predict greater breast cancer screening utilization. Only 14% of all respondents aged 40-49 years reported ever having a mammogram. Results of multivariate logistic regression showed that area of residence, husband's level of education, younger age, and living in a wealthy status were strong predictors of lifetime history of breast cancer screening. This study elucidates that breast cancer screening mammography among Jordanian women has remained opportunistic and underutilized despite the efforts of national entities to promote screening and early detection of breast cancer. There is a geographic and social disparity in the utilization of mammography screening among Jordanian women.

Tumour Growth Models of Breast Cancer for Evaluating Early Detection-A Summary and a Simulation Study.

With the advent of nationwide mammography screening programmes, a number of natural history models of breast cancers have been developed and used to assess the effects of screening. The first half of this article provides an overview of a class of these models and describes how they can be used to study latent processes of tumour progression from observational data. The second half of the article describes a simulation study which applies a continuous growth model to illustrate how effects of extending the maximum age of the current Swedish screening programme from 74 to 80 can be evaluated. Compared to no screening, the current and extended programmes reduced breast cancer mortality by 18.5% and 21.7%, respectively. The proportion of screen-detected invasive cancers which were overdiagnosed was estimated to be 1.9% in the current programme and 2.9% in the extended programme. With the help of these breast cancer natural history models, we can better understand the latent processes, and better study the effects of breast cancer screening.

Radiation-Free Microwave Technology for Breast Lesion Detection Using Supervised Machine Learning Model.

Mammography is the gold standard technology for breast screening, which has been demonstrated through different randomized controlled trials to reduce breast cancer mortality. However, mammography has limitations and potential harms, such as the use of ionizing radiation. To overcome the ionizing radiation exposure issues, a novel device (i.e. MammoWave) based on low-power radio-frequency signals has been developed for breast lesion detection. The MammoWave is a microwave device and is under clinical validation phase in several hospitals across Europe. The device transmits non-invasive microwave signals through the breast and accumulates the backscattered (returned) signatures, commonly denoted as the S21 signals in engineering terminology. Backscattered (complex) S21 signals exploit the contrast in dielectric properties of breasts with and without lesions. The proposed research is aimed to automatically segregate these two types of signal responses by applying appropriate supervised machine learning (ML) algorithm for the data emerging from this research. The support vector machine with radial basis function has been employed here. The proposed algorithm has been trained and tested using microwave breast response data collected at one of the clinical validation centres. Statistical evaluation indicates that the proposed ML model can recognise the MammoWave breasts signal with no radiological finding (NF) and with radiological findings (WF), i.e., may be the presence of benign or malignant lesions. A sensitivity of 84.40% and a specificity of 95.50% have been achieved in NF/WF recognition using the proposed ML model.

SNSVM: SqueezeNet-Guided SVM for Breast Cancer Diagnosis.

Breast cancer is a major public health concern that affects women worldwide. It is a leading cause of cancer-related deaths among women, and early detection is crucial for successful treatment. Unfortunately, breast cancer can often go undetected until it has reached advanced stages, making it more difficult to treat. Therefore, there is a pressing need for accurate and efficient diagnostic tools to detect breast cancer at an early stage. The proposed approach utilizes SqueezeNet with fire modules and complex bypass to extract informative features from mammography images. The extracted features are then utilized to train a support vector machine (SVM) for mammography image classification. The SqueezeNet-guided SVM model, known as SNSVM, achieved promising results, with an accuracy of 94.10% and a sensitivity of 94.30%. A 10-fold cross-validation was performed to ensure the robustness of the results, and the mean and standard deviation of various performance indicators were calculated across multiple runs. This model also outperforms state-of-the-art models in all performance indicators, indicating its superior performance. This demonstrates the effectiveness of the proposed approach for breast cancer diagnosis using mammography images. The superior performance of the proposed model across all indicators makes it a promising tool for early breast cancer diagnosis. This may have significant implications for reducing breast cancer mortality rates.

Abstract A070: Association between socioeconomic and clinical factors on timely access to care among young Black women with breast cancer

Abstract Background: Young-onset breast cancer is associated with higher mortality due to multiple factors including tumor biology and delayed presentation. Young women with breast cancer with longer treatment delays have decreased survival time, with the impact on survival being more prominent in Black women. The factors contributing to the racial survival disparity are complex and are likely an interplay between tumor biology, genomics, patterns of care and socioeconomic factors. This study looked at socioeconomic and clinical factors that may affect timely access to care for breast cancer in young Black women, and thus impact survival. Methods: Data from the Black Women Etiology and Survival of Triple-negative Breast Cancers (BEST) Study, a population-based cohort of Black women diagnosed with breast cancer ≤ 50 years old between 2009 and 2015 from the Florida and Tennessee State Cancer Registries was used. The time to treatment (in days) was used as the exposure variable and defined as the time from breast cancer diagnosis to the date of first treatment. The primary outcome was determined by distant or local recurrence or death. Pearson chi-square test was conducted to assess the association between clinical and socioeconomic factors with time to treatment. The socioeconomic variables studied were insurance, income and education. Clinical factors evaluated were the stage of breast cancer at diagnosis, hormone subtype, neoadjuvant chemotherapy and type of surgery. Survival analysis and Cox proportional hazard model were performed to analyze the 10-year overall survival and recurrence rate while adjusting for income, breast cancer stage and hormone subtype. Results: There was a statistically significant association between time to treatment and hormone receptor subtype (p=0.04). More than 60% of women with triple-negative breast cancer (TNBC), and 57% of women with HER2+ breast cancer received treatment within a month of their breast cancer diagnosis. There was also a significant association between the time to treatment and type of surgery received (p=0.03). 64% of patients who had lumpectomies received treatment in ≤30 days, compared to 54% of patients who had a mastectomy. Survival analysis showed the highest mortality in patients with time to treatment &amp;gt;90 days, followed by patients who received treatment in ≤30 days. The study did not find a statistically significant association between insurance, income, or education on the timeliness of treatment for breast cancer. Conclusion: In our study of young Black women, delayed breast cancer treatment resulted in lower survival. While those with TNBC and HER2+ disease were more likely to receive treatment ≤30 days, i.e. neoadjuvant chemotherapy to assess response to chemotherapy and the amount of residual disease at the time of the surgery, the enrichment for aggressive disease is likely the reason for the low survival observed in this group. Timely access to treatment for breast cancer impacts survival and strategies to decrease treatment delays are crucial to reducing breast cancer mortality. Citation Format: Kikelola Oyeleye, Rebecca Lee, Sonya Reid, Tuya Pal, Anne Weidner, Lindsay Venton. Association between socioeconomic and clinical factors on timely access to care among young Black women with breast cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A070.

Abstract IA027: DCIS or cancer? Why all the confusion?

Abstract Many women diagnosed with DCIS in the United States report they are confused about their chances of developing an invasive breast cancer or metastatic cancer. They are told that DCIS is not cancer but it holds the possibility of becoming a cancer. Nevertheless, DCIS is treated in much the same way as a small invasive cancer. Surgical options include lumpectomy alone, lumpectomy with radiotherapy, unilateral or bilateral mastectomy. Much of the confusion is generated by the current paradigm that separates DCIS and invasive cancer into distinct conditions. The mortality of DCIS is 3% over 20 years and that prevention of local invasive recurrence post-DCIS does not reduce breast cancer mortality. If the invasive recurrence were the real cancer then preventing it would reduce the risk of dying but this has not been shown. Further, the risk of an invasive in-breast recurrence following DCIS is the same as the risk of an invasive in-breast recurrence following invasive breast cancer. In the Banting database, the 15-year risk of invasive local recurrence following DCIS was 15.6%, following stage I breast cancer was 15.3% and following stage II breast cancer was 15.9%. In the Banting database, the 15-year risk of ipsilateral invasive recurrence was 14% for DCIS patients who receives radiotherapy and was 29% for DCIS patients who did not received radiotherapy – a difference of 15%. In the Banting database, the 15-year risk of ipsilateral invasive recurrence was 14% for Stage I/II patients who received radiotherapy and was 27% for Stage I/II patients who did not receive radiotherapy – a difference of 13%. The benefit of radiotherapy is the same in both groups. Similarly, the benefit of unilateral mastectomy versus lumpectomy on preventing local invasive recurrence is the same for DCIS patients as it is for early-stage invasive breast cancer patients. In our SEER-based analysis of 812,851 women with breast cancer, the 25-year actuarial risk of contralateral invasive breast cancer was 10.1% for patients with DCIS and was 9.9% for patients with invasive breast cancer. Based on this finding, the benefit of performing a contralateral mastectomy at the time of diagnosis is the same for both groups. We accept lumpectomy as standard of care for invasive breast cancer even though the risk of invasive ipsilateral recurrence is much higher after lumpectomy than after mastectomy. We consider contralateral mastectomy as an option for women with invasive cancer, but as overtreatment for women with DCIS even though the risk of contralateral breast cancer is almost exactly the same. The benefit of radiotherapy is the same for patients with DCIS and stage I/II breast cancer, but we are more likely to consider it overtreatment for DCIS patients. Much of the confusion can be resolved if we consider both types of cancer to be different points on the spectrum. Breast cancer is heterogeneous; DCIS is one end of the spectrum. Accepting this fact will make the rationale behind treatment decisions easier to explain. Citation Format: Steven A. Narod. DCIS or cancer? Why all the confusion? [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA027.

Thermography as a Breast Cancer Screening Technique: A Review Article.

Globally, breast cancer is the most frequently occurring cancer in women and is the reason for more disability-adjusted life years lost than any other type of cancer. Hence, early screening plays a vital role in reducing breast cancer mortality. Although mammography is the standard procedure used for screening and diagnosis of breast cancer, it still has some limitations. Other methods used for screening include ultrasound and clinical breast examination. Despite its limitations, mammography is the gold standard for screening breast malignancy. Another emerging method for screening is thermography. With recent technological advances, breast cancer screening through thermography has demonstrated several advantages over existing modalities. For this review, a literature search was performed using databases such as PubMed, Google Scholar, and ScienceDirect. The keywords searched included breast cancer, early detection, breast cancer screening, mammography, and thermography. This review discusses the benefits of thermography showing that it can be a significant modality for breast cancer screening. The recent developments in thermal sensors, imaging protocols, and computer-aided software diagnostics hold great promise for making this technique a mainstream screening method for cancer. Moreover, the use of artificial intelligence and thermal imaging to detect early-stage breast cancer can provide impressive results. Therefore, thermography will be a promising technology for the early detection of breast cancer.

Breast Cancer Screening: Is There Room for De-escalation?

Breast cancer screening is highly controversial and different agencies have widely varying guidelines. Yet it is currently used extensively in the USA and frequently the thought is "the more, the better." The purpose of this review is to objectively assess the risks and benefits of screening mammography and consider whether there may be areas where it could be de-escalated. Over the past few years, there have been several meta-analyses that are concordant, and it is now agreed that the main benefit of screening mammography is about a 20% reduction in breast cancer mortality. This actually benefits about 5% of patients with mammographically detected tumors. We now appreciate that the main harm of screening is overdiagnosis, i.e. detection of a cancer that will not cause the patient any harm and would not have ever been detected without the screening. This currently represents about 20 to 30% of screening detected cancers. Finding extra cancers with more intense screening is not always good, because in this situation, the risk of overdiagnosis increases and the benefit decreases. In some groups, the risk of overdiagnosis approaches 75%. Our goal should be not only to find more cancers, but to avoid finding cancers that would never have caused the patient any harm and lead to unnecessary treatment. The authors suggest some situations where it may be reasonable to de-escalate screening.