Breast Cancer Screening Strategies Research Articles

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [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 PO4-19-02.

Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement.

Among all US women, breast cancer is the second most common cancer and the second most common cause of cancer death. In 2023, an estimated 43 170 women died of breast cancer. Non-Hispanic White women have the highest incidence of breast cancer and non-Hispanic Black women have the highest mortality rate. The USPSTF commissioned a systematic review to evaluate the comparative effectiveness of different mammography-based breast cancer screening strategies by age to start and stop screening, screening interval, modality, use of supplemental imaging, or personalization of screening for breast cancer on the incidence of and progression to advanced breast cancer, breast cancer morbidity, and breast cancer-specific or all-cause mortality, and collaborative modeling studies to complement the evidence from the review. Cisgender women and all other persons assigned female at birth aged 40 years or older at average risk of breast cancer. The USPSTF concludes with moderate certainty that biennial screening mammography in women aged 40 to 74 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening mammography in women 75 years or older and the balance of benefits and harms of supplemental screening for breast cancer with breast ultrasound or magnetic resonance imaging (MRI), regardless of breast density. The USPSTF recommends biennial screening mammography for women aged 40 to 74 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of supplemental screening for breast cancer using breast ultrasonography or MRI in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Modeling correlated pairs of mammogram images.

Mammography remains the primary screening strategy for breast cancer, which continues to be the most prevalent cancer diagnosis among women globally. Because screening mammograms capture both the left and right breast, there is a nonnegligible correlation between the pair of images. Previous studies have explored the concept of averaging between the pair of images after proper image registration; however, no comparison has been made in directly utilizing the paired images. In this paper, we extend the bivariate functional principal component analysis over triangulations to jointly characterize the pair of imaging data bounded in an irregular domain and then nest the extracted features within the survival model to predict the onset of breast cancer. The method is applied to our motivating data from the Joanne Knight Breast Health Cohort at Siteman Cancer Center. Our findings indicate that there was no statistically significant difference in model discrimination performance between averaging the pair of images and jointly modeling the two images. Although the breast cancer study did not reveal any significant difference, it is worth noting that the methods proposed here can be readily extended to other studies involving paired or multivariate imaging data.

Outcomes of Breast Cancer Screening Strategies Based on Cancer Intervention and Surveillance Modeling Network Estimates.

Background There is ongoing debate about recommendations for breast cancer screening strategies, specifically regarding the frequency of screening and the age at which to initiate screening. Purpose To compare estimates of breast cancer screening outcomes published by the Cancer Intervention and Surveillance Modeling Network (CISNET) to understand the benefits and risks of different screening scenarios. Materials and Methods Modeling estimates published by CISNET are based on hypothetical cohorts in the United States and compare women, starting at 40 years of age, who do and do not undergo breast cancer screening with mammography. The four scenarios assessed in this study, of multiple possible scenarios, were biennial screening ages 50-74 years (2009 and 2016 U.S. Preventive Services Task Force [USPSTF] recommendations), biennial screening ages 40-74 years (2023 USPSTF draft recommendation), annual screening ages 40-74 years, and annual screening ages 40-79 years. For each scenario, CISNET estimates of median lifetime benefits were compared. Risks that included false-positive screening results per examination and benign biopsies per examination were also calculated and compared. Results Estimates from CISNET 2023 showed that annual screening ages 40-79 years improved breast cancer mortality reduction compared with biennial screening ages 50-74 years and biennial screening ages 40-74 years (41.7%, 25.4%, and 30%, respectively). Annual screening ages 40-79 years averted the most breast cancer deaths (11.5 per 1000) and gained the most life-years (230 per 1000) compared with other screening scenarios (range, 6.7-11.5 per 1000 and 121-230 per 1000, respectively). False-positive screening results per examination were less than 10% for all screening scenarios (range, 6.5%-9.6%) and lowest for annual screening ages 40-79 years (6.5%). Benign biopsies per examination were less than 1.33% for all screening scenarios (range, 0.88%-1.32%) and lowest for annual screening ages 40-79 years (0.88%). Conclusion CISNET 2023 modeling estimates indicate that annual breast cancer screening starting at 40 years of age provides the greatest benefit to women and the least risk per examination. © RSNA, 2024 See also the editorial by Joe in this issue.

Breast Cancer Screening in Georgia: Choosing the Most Optimal and Cost-Effective Strategy

ObjectivesTo define the optimal and cost-effective breast cancer screening strategy for Georgia. MethodsWe used the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model that has been adapted to the Georgian situation to evaluate 736 mammography screening strategies varied by interval (biennial and triennial), starting ages (40-60 years), stopping ages (64-84 years), and screening modality (with and without clinical breast examination [CBE]). Quality-adjusted life-years (QALYs) and additional cost (healthcare perspective) compared with no screening per 1000 women were calculated with 3% discount. Major uncertainties (eg, costs) are addressed as sensitivity analyses. ResultsStrategies using a combination of mammography and CBE yielded in substantially higher costs with minimal differences in outcomes compared with mammography-only strategies. The current screening strategy, biennial mammography screening from the age of 40 until 70 years with CBE, is close to the frontier line but requires high additional cost given the QALY gains (€16 218/QALY), well above the willingness-to-pay threshold of €12 720. The optimal strategy in Georgia would be triennial mammography-only screening from age 45 to 66 years with an incremental cost-effectiveness ratio of €12 507. ConclusionsBiennial screening strategies are resource-intensive strategies and may not be feasible for Georgia. By switching to triennial mammography-only strategy from the age of 45 until 66 years, it is possible to offer screening to more eligible women while still gaining substantial screening benefits. This is to address capacity issues which is a common barrier for many Eastern European countries.

Impact of Mammography Screening Frequency on Breast Cancer Mortality Rates.

The frequency of mammography screening remains a topic of ongoing debate. This meta-analysis aimed to investigate the impact of annual vs. biennial mammography screenings on breast cancer mortality rates. A comprehensive search of relevant literature published up to 2021 was performed, with the primary outcome being the difference in breast cancer mortality rates between annual and biennial screenings. The extracted data included relative risks and 95% confidence intervals (CIs), with studies selected based on predetermined inclusion and exclusion criteria, emphasizing the quality of methodology and minimization of bias. Of the included studies, thirteen met the criteria, covering diverse demographic cohorts and screening frequencies. The synthesized data revealed a pattern of lower relative risk in annual screenings compared to biennial screenings across all studies. Notably, subgroup analyses indicated that age and racial background might modulate the effectiveness of screening frequency. In conclusion, this meta-analysis offers strong evidence suggesting that annual mammography screenings could be more effective than biennial screenings in reducing breast cancer mortality rates, especially in certain high-risk demographics. The results emphasize the importance of personalized, evidence-based approaches to mammography, with a call for future research to validate these findings and delve deeper into optimizing breast cancer screening strategies.

Availability of mammographs in Mexico: Is it possible to expand coverage

Breast cancer screening coverage in Mexico is limited. It is necessary to configure the Mexican health system to make it capable of producing more mammograms, without neglecting quality and diagnostic opportunity. To project the coverage of breast cancer screening programs according to the mammographs availability in the Mexican Health System. An exploratory study was conducted correlating the number mammographs available in the Mexican Health System with women between 40 and 69 who are the target of screening programs in Mexico. The analysis consisted of calculating the coverage of breast cancer screening programs if each mammograph could perform 6336 screening mammograms per year. All the calculations were made with the information of the year 2020 as the most current data in terms of population density. It was determined that the number of mammographs is enough to raise the offer of screening studies to ≈50% at the national level. There are even states whose coverage capacity is projected above 70%. Some of them are Mexico City, Colima, Durango, Quintana Roo, Zacatecas, Baja California Sur and Coahuila. Also, it was observed that the distribution of mammographs is not equitable in the national territory, suggesting investment both in equipment and in screening strategies for breast cancer. Our data show that it is possible to advance in preventing breast cancer in Mexico, although the improvement of the management capacities of the Mexican Health System is required to improve both the coverage and quality of the breast cancer screening programs.

A Breast Cancer Polygenic Risk Score Is Feasible for Risk Stratification in the Norwegian Population.

Statistical associations of numerous single nucleotide polymorphisms with breast cancer (BC) have been identified in genome-wide association studies (GWAS). Recent evidence suggests that a Polygenic Risk Score (PRS) can be a useful risk stratification instrument for a BC screening strategy, and a PRS test has been developed for clinical use. The performance of the PRS is yet unknown in the Norwegian population. To evaluate the performance of PRS models for BC in a Norwegian dataset. We investigated a sample of 1053 BC cases and 7094 controls from different regions of Norway. PRS values were calculated using four PRS models, and their performance was evaluated by the area under the curve (AUC) and the odds ratio (OR). The effect of the PRS on the age of onset of BC was determined by a Cox regression model, and the lifetime absolute risk of developing BC was calculated using the iCare tool. The best performing PRS model included 3820 SNPs, which yielded an AUC = 0.625 and an OR = 1.567 per one standard deviation increase. The PRS values of the samples correlate with an increased risk of BC, with a hazard ratio of 1.494 per one standard deviation increase (95% confidence interval of 1.406-1.588). The individuals in the highest decile of the PRS have at least twice the risk of developing BC compared to the individuals with a median PRS. The results in this study with Norwegian samples are coherent with the findings in the study conducted using Estonian and UK Biobank samples. The previously validated PRS models have a similar observed accuracy in the Norwegian data as in the UK and Estonian populations. A PRS provides a meaningful association with the age of onset of BC and lifetime risk. Therefore, as suggested in Estonia, a PRS may also be integrated into the screening strategy for BC in Norway.

A microneedle patch for breast cancer screening via minimally invasive interstitial fluid sampling

Early diagnosis and treatment are crucial for breast cancer patients. Interstitial fluid (ISF) shows promise for early disease screening, but its extraction for biomarker detection is challenging. To address this, we designed a microneedle (MN) patch for minimally invasive and rapid ISF extraction through materials engineering, which could improve cancer detection, ease the burden on medical resources, and increase patient compliance. Via UV crosslinking, the water absorbing moiety, acrylic acid (AA), can be polymerized and crosslinked with gelatin methacrylate (GelMA). The resulting GelMA-AA MN (G-A MN) can rapidly extract different analytes. One piece of G-A MN patch can aspirate about 1.29 mg (≈ 1.29 µL) of ISF from mice within 60 s. We further applied G-A MN for breast cancer screening in the 4T1 orthotopic mice breast cancer model and genetically engineered breast cancer model. By measuring the tumor markers carcinoembryonic antigen (CEA) and glycoantigen CA15-3, G-A MN could detect the cancer occurrence earlier than other standard screening methods, including blood tests, ultrasound, or Micro-CT. Furthermore, earlier diagnosis led to timely chemotherapy treatment and resulted in prolonged survival in the mice 4T1 breast cancer model. In conclusion, G-A MN enabled rapid ISF extraction for biomarker analysis in a minimally invasive manner. G-A MN facilitated detection outperformed other common diagnostic methods, representing a promising alternative breast cancer screening strategy.

SA54 A Scoping Review of Economic Evaluation of Breast Cancer Screening in China

The cost-effectiveness of conventional population-based breast cancer screening strategies (e.g., mammography) has been found controversial, while evidence shows that genetic testing for early detection of pathogenic variants is cost-effective.

Causal mediation analysis using high-dimensional image mediator bounded in irregular domain with an application to breast cancer.

Mammography is the primary breast cancer screening strategy. Recent methods have been developed using the mammogram image to improve breast cancer risk prediction. However, it is unclear on the extent to which the effect of risk factors on breast cancer risk is mediated through tissue features summarized in mammogram images and the extent to which it is through other pathways. While mediation analysis has been conducted using mammographic density (a summary measure within the image), the mammogram image is not necessarily well described by a single summary measure and, in addition, such a measure provides no spatial information about the relationship between the exposure risk factor and the risk of breast cancer. Thus, to better understand the role of the mammogram images that provide spatial information about the state of the breast tissue that is causally predictive of the future occurrence of breast cancer, we propose a novel method of causal mediation analysis using mammogram image mediator while accommodating the irregular shape of the breast. We apply the proposed method to data from the Joanne Knight Breast Health Cohort and leverage new insights on the decomposition of the total association between risk factor and breast cancer risk that was mediated by the texture of the underlying breast tissue summarized in the mammogramimage.

Preferences for Breast and Cervical Cancer Screening Among Women and Men in Kenya: Key Considerations for Designing Implementation Strategies to Increase Screening Uptake.

Breast and cervical cancer incidence rates and mortality rates in Kenya are high. Screening is globally accepted as a strategy for early detection and downstaging of these cancers for better outcomes, but despite the efforts established by the Kenyan government to provide these services to eligible populations, uptake has remained disproportionately low. Using data from a larger study aimed at understanding the implementation and scale-up of cervical cancer screening services, we analyzed data to compare the preferences for breast and cervical cancer screening services between men and women (25-49years) in rural and urban communities in Kenya. Participants were recruited in concentric circles starting at the center of six subcounties. One woman and one man per household were enrolled for data collection on a continuous basis. More than 90% of both men and women had a monthly income of less than US $500. The top three preferred sources of information on screening for cancers affecting women were health care providers; community health volunteers; and media such as television, radio, newspapers, and magazines. More women (43.6%) than men (28.0%) trusted community health volunteers to provide health information on cancer screening. Printed materials and mobile phone messages were preferred by approximately 30% of both genders. Over 75% of both men and women preferred an integrated model of service delivery. These findings show that there are many similarities that can be leveraged when designing implementation strategies for population-wide breast and cervical cancer screening hence reducing the challenge of addressing diverse preferences of men and women which may not be easy to reconcile.

Breast Cancer Screening Should Embrace Precision Medicine: Evidence by Reviewing Economic Evaluations in China.

The cost-effectiveness of conventional population-based breast cancer screening strategies (e.g. mammography) has been found controversial, while evidence shows that genetic testing for early detection of pathogenic variants is cost-effective. We aimed to review the economic evaluations of breast cancer screening in China to provide an information summary for future research on this topic. We searched the literature to identify the economic evaluations that examined breast cancer screening and testing in China, supplemented by hand-searching the reference lists of the included studies. We finally included five studies satisfying our inclusion criteria. Four articles examined mammography while the rest investigated multigene testing. The existing breast cancer screening programmes were found to be cost-effective among urban Chinese women, but one study concluded that they might cause harm to women in rural areas. Contextual factors, such as data absence, urban-rural disparity, willingness-to-pay threshold, and model design, imposed barriers to cost-effectiveness analysis. Multigene testing was found to be cost-effective and has a promising population impact among all women with breast cancer in China. Future research should investigate the cost-effectiveness of screening and identifying breast cancer through precision medicine technologies, including genetic testing, genome sequencing, cascade testing, and the return of secondary findings.

An optimization approach for parameter selection in natural history of breast cancer in China

Breast cancer is one of the most common cancers for females. In order to propose efficient screening strategies and evaluate the effect, one fundamental and important step is to choose proper parameters, i.e., transition rates, in the natural history model of breast cancer in China. There are two challenges to choosing reasonable transition rates. Firstly, the transition rates used in other countries may be not applicable to China, due to the cancer epidemiology. Secondly, little screening sample data are available, making the traditional statistical based approaches such as maximum likelihood methods fail. In this paper, we propose an optimization approach for parameter selection in the natural history of breast cancer in China. A mathematical optimization model is established based on the published statistical data. A coordinate descent algorithm is proposed to solve the resulting box-constrained and highly nonlinear problem, whose objective function does not have an explicit form. Finally, the best matching method is proposed to estimate the distributions of each transition rate. Our approach provides solid foundations to further propose reasonable screening strategies for breast cancer in China and analyze the economic burden of breast cancer.

Physician knowledge and attitudes toward breast cancer screening strategies in transgender population.

71 Background: Transgender people experience intersecting forms of marginalization and suffer significant healthcare disparities. There is evidence that healthcare providers are insufficiently equipped to provide adequate healthcare to this population. Hormone-replacement therapy for trans-women requires blockade of androgen production and estrogen supplementation, which increases the risk of breast cancer (BC) compared to cis-males. Also, trans-women without gender-affirming mastectomy should undergo BC screening (BCS). We seek to explore the knowledge and attitudes among physicians regarding current strategies for breast cancer screening in trans-women and men. Methods: We adapted an online 15-item survey exploring knowledge and attitudes among physicians on strategies for BCS in trans people. The first 6-items evaluated attitudes, and the last 9-items knowledge. We conducted a pilot phase to assess physicians' understanding before the final data collection and adjusted it after corrections. Participants were invited through social media and directly peer-to-peer in June 2022. Descriptive statistics and Chi-square test were used for statistical analysis using SPSS ver. 26. Results: A total of 165 participants completed the survey, 96 (58.2%) self-identified as male, 66 (40%) female, and 2 (1.2%) non-binary gender with a mean age of 30 years (23 – 60 years). Most participants were residents and fellows (70.3%), and 29.7% were attendings. Overall, only 7.3% of participants felt confident in their knowledge of BCS in trans-people, 55.2% felt that had an inadequate preparation regarding transgender health during medical school and 86.1 and 83% agreed that it should be thoroughly addressed during medical school and residency, respectively. Regarding knowledge, 10.9% recognized that BC risk is different between trans- and cis-women, 9.7% identified that trans-women had a lower BC risk, and 77% answered that transgender people have insufficient access to health services. Finally, as for specific BC screening strategies, only 49.1% correctly identified BCS strategies for trans-women, 61.2% correctly answered the recommended age to start BCS in trans-women, 40.6% the periodicity for BCS, and 63% identified the correct recommendation for BCS trans-men without a gender-affirming mastectomy. Conclusions: Current physician knowledge regarding BCS strategies in the transgender population is limited. Nonetheless, respondents identified transgender health as an area of opportunity that might be addressed with widespread information. These findings reinforce that education of healthcare providers is required to end health inequalities faced by this diverse group of patients.

Breast Cancer Risk and Screening Mammography Frequency Among Multiethnic Women

In 2009, the U.S. Preventive Services Task Force updated recommended mammography screening frequency from annual to biennial for average-risk women aged 50-74 years. The association between estimated breast cancer risk and mammography screening frequency was evaluated. A single-center retrospective cohort study was conducted among racially/ethnically diverse women, aged 50-74 years, who underwent screening mammography from 2014 to 2018. Data on age, race/ethnicity, first-degree family history of breast cancer, previous benign breast biopsies, and mammographic density were extracted from the electronic health record to calculate Breast Cancer Surveillance Consortium 5-year risk of invasive breast cancer, with a 5-year risk ≥1.67% defined as high risk. Multivariable analyses were conducted to determine the association between breast cancer risk factors and mammography screening frequency (annual versus biennial). Data were analyzed from 2020 to 2022. Among 12,929 women with a mean age of 61±6.9 years, 82.7% underwent annual screening mammography, and 30.7% met high-risk criteria for breast cancer. Hispanic women were more likely to screen annually than non-Hispanic Whites (85.0% vs 79.8%, respectively), despite fewer meeting high-risk criteria. In multivariable analyses adjusting for breast cancer risk factors, high- versus low/average-risk women (OR=1.17; 95% CI=1.04, 1.32) and Hispanic versus non-Hispanic White women (OR=1.46; 95% CI=1.29, 1.65) were more likely to undergo annual mammography. A majority of women continue to undergo annual screening mammography despite only a minority meeting high-risk criteria, and Hispanic women were more likely to screen annually despite lower overall breast cancer risk. Future studies should focus on the implementation of risk-stratified breast cancer screening strategies.

Distribution of breast cancer molecular subtypes within receptor classifications: Lessons from the I-SPY2 Trial and FLEX Registry.

592 Background: Expression-based molecular subtypes of breast cancer (BC) predict tumor behavior and therapeutic response. Subtype distributions by age and sociodemographics can inform strategies for BC screening, treatment, and prognosis. The conventional approach, adopted by NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, uses HR and HER2 to label: “triple negative” (HR-HER2-), “HER2-enriched” (HR-HER2+), “luminal A” (HR+HER2-), and “luminal B” (HR+HER2+). However, immunohistochemical (IHC)-based receptor labels may not reflect clinically and epidemiologically relevant molecular subtypes that share the same nomenclature, e.g., luminal B. Methods: We compared IHC labels by HR/HER2 to molecular subtypes by MammaPrint (MP) and BluePrint (BP) for patients in the phase II neoadjuvant I-SPY2 TRIAL for high-risk, stage II-III BC (NCT01042379, n = 981) and in the multicenter, prospective FLEX Registry for stage I-III BC (NCT03053193, n = 5,679). Results: IHC labels were discordant with MP/BP in 52% of I-SPY2 and 43% of FLEX cases (Table 1). HR-HER2- had the highest concordance with basal-type (99% in I-SPY2, 88% in FLEX). HR+ labels had the least agreement with MP/BP: HR+HER2- tumors were molecularly luminal B and basal in 71% and 29% of I-SPY2 and 40% and 4% of FLEX cases, respectively. HR+HER2+ tumors were molecularly luminal A and HER2-type in 10% and 60% of I-SPY2 and 15% and 36% of FLEX cases, respectively. Of molecularly luminal B cases, only 14% in I-SPY2 and 7% in FLEX were HR+HER2+. Conclusions: IHC markers collected by population-based registries (SEER) enable BC surveillance. However, IHC labels cannot be used as surrogates for molecular subtypes by MP/BP, especially for luminal B tumors. Given the unmet need to improve management of luminal B BC, we anticipate the growing importance of molecular subtyping to inform treatment and epidemiological research. We propose that the BC research community work with SEER to update its IHC labels to avoid overlap with molecular subtype nomenclature and incorporate such modern classifications when available. [Table: see text]

Simulation modeling as a tool to support clinical guidelines and care for breast cancer prevention and early detection in high-risk women.

10525 Background: To evaluate the incremental short- and long-term benefits and harms of primary prevention with risk reducing medication in high-risk women receiving screening mammography. Methods: We adapted an established, validated Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer discrete event microsimulation model developed to synthesize data the impact of using risk-reducing medication and annual mammography among women with a 3% or higher five-year risk of developing breast cancer. We also examined the effects of supplemental MRI. The model follows a simulated cohort of millions of US women from birth to death. We used large observational and clinical trial data to derive input parameters for cohort-specific birth rates, breast cancer risk, incidence and stage, screening performance, survival by age, stage, and subtype, treatment efficacy, and other cause mortality. Breast cancer risk was modeled based on family history, breast density, age and history of past breast biopsy. We compared two strategies, annual 3D mammography alone vs. annual 3D mammography and a 5-year course of risk reducing medication at various starting ages, and adding MRI to each approach. Outcomes included the benefits of risk-reducing drugs (avoiding breast cancer) and screening (stage, breast cancer death). Harms included drug side effects and screening false positives and overdiagnosis. Sensitivity analysis tested the impact of uncertainty in model inputs and assumptions on results. Results: Compared to mammography alone, adding risk reducing medication could decrease invasive breast cancer incidence by 30%, and breast cancer deaths by 30% (Table). However, due to reduction in breast cancer incidence, risk reducing medication could result in a 3% increase in false positive results; adding MRI increases benefits but also increases false-positive results. Benefits and harms of risk reducing medication and breast cancer screening strategies for women at high-risk of developing breast cancer. Conclusions: Risk-reducing mediation reduces the risk of hormone-receptor positive breast cancer, and combining this with mammography (and/or MRI) improves earlier detection. Additional work is ongoing to incorporate adverse effects of therapy. Simulation modeling can be used to provide individualized data to facilitate discussions about breast cancer prevention and early detection among high-risk women seen in clinical practice.[Table: see text]

Second primary malignancy in stage I and II breast cancer survivor: A United States population-based study.

e12579 Background: In United States, breast cancer accounts for over 260,000 cases each year and is responsible for over 40,000 deaths. Survival primarily depends on the stage at time of diagnosis. 5-year survival among early breast cancer is more than 50%. It is known that patients with cancer undergoing treatment have a significant risk of developing a second primary malignancy (SPM); we aimed to focus our study at the incidence of various SPM among patients surviving stage I and II breast cancer, which can help in their targeted surveillance. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to select adult patients (18 and above) diagnosed with stage I and II breast cancer as their first malignancy between January 2000 and December 2015. This is one of the largest cancer registries worldwide. SPM is metachronous cancer which develops six months after an index localized breast cancer diagnosis based on Warren and Gates criteria. Multiple primary standardized incidence ratios (MP-SIR) and absolute excess risk (AER) for an occurrence of SPM were obtained utilizing SEER. SIR is observed to expected incidence ratio (O/E) of SPM and AER, it is an actual number of excess SPMs in patients with early breast cancer per 10,000 person-years at risk. Statistical significance was defined as a p-value ≤ 0.05. Results: We localized 513,408 patients with a diagnosis of stage I and II breast cancer from 2000 - 2015. Patients were followed for a median duration of 8.92 years (range 0.5 to 15.92). Of these patients, 81.5% were white. About 8.6% (43938) of patients developed 47708 primary malignancies. These malignancies were significantly higher than the general population with O/E ratio of 1.15 and AER of 17.12. The median age of diagnosis of SPM was 69.8 years (range 22.8 – 105.08 years). The average latency to develop SPM was 5.28 years (range 0.5 – 15.92 years). Among solid tumors, a statistically significant increased risk was observed with salivary gland, tongue, gastric, colon, lung cancer, and genitourinary cancers. Among hematological malignancies, statistically significant risk was seen for ALL, AML and CML. The risk of hepatobiliary, CNS cancers and lymphoma were significantly lower among our cohort included in current study. The SPM was found significantly increased after the latency of 24 months, and the risk of SPM was greater across all age groups. Conclusions: Due to robust breast cancer screening strategies, a significantly higher proportion of the patients are diagnosed early in the course of the disease which tends to be curative and this group of patients has better survival rates. Our study recognizes that the risk of certain SPM is higher in stage I and II breast cancer survivals compared to general population; and they would benefit from guidelines that can identify cancer with increased risk in these patients population.

Finding the optimal mammography screening strategy: A cost-effectiveness analysis of 920 modelled strategies.

Breast cancer screening policies have been designed decades ago, but current screening strategies may not be optimal anymore. Next to that, screening capacity issues may restrict feasibility. This cost‐effectiveness study evaluates an extensive set of breast cancer screening strategies in the Netherlands. Using the Microsimulation Screening Analysis‐Breast (MISCAN‐Breast) model, the cost‐effectiveness of 920 breast cancer screening strategies with varying starting ages (40‐60), stopping ages (64‐84) and intervals (1‐4 years) were simulated. The number of quality adjusted life years (QALYs) gained and additional net costs (in €) per 1000 women were predicted (3.5% discounted) and incremental cost‐effectiveness ratios (ICERs) were calculated to compare screening scenarios. Sensitivity analyses were performed using different assumptions. In total, 26 strategies covering all four intervals were on the efficiency frontier. Using a willingness‐to‐pay threshold of €20 000/QALY gained, the biennial 40 to 76 screening strategy was optimal. However, this strategy resulted in more overdiagnoses and false positives, and required a high screening capacity. The current strategy in the Netherlands, biennial 50 to 74 years, was dominated. Triennial screening in the age range 44 to 71 (ICER 9364) or 44 to 74 (ICER 11144) resulted in slightly more QALYs gained and lower costs than the current Dutch strategy. Furthermore, these strategies were estimated to require a lower screening capacity. Findings were robust when varying attendance and effectiveness of treatment. In conclusion, switching from biennial to triennial screening while simultaneously lowering the starting age to 44 can increase benefits at lower costs and with a minor increase in harms compared to the current strategy.