Risk Of Breast Cancer Mortality Research Articles

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p=.03), 53% more deaths after breast cancer (p<.001), and 44% higher breast cancer mortality (p=.03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p<.001), more total breast cancers (p<.001), and more deaths after breast cancer (p<.001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p<.001). MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Statin use and risks of breast cancer recurrence and mortality.

Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis statin use and risks of breast cancer recurrence and breast cancer-specific mortality. Over a median follow-up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post-diagnosis statin use was 2.2 years. Statin use post-diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91-1.21), but was associated with a reduced risk of cancer-specific mortality (HR, 0.85; 95% CI, 0.75-0.96). The reduction was more pronounced in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR, 0.71; 95% CI, 0.57-0.88). These findings suggest that post-diagnosis statin use is associated with improved cancer-specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.

Abstract PO3-19-03: Addressing USPSTF 2023 Identified Key Gaps in Knowledge in Breast Cancer Screening through TMIST (ECOG-ACRIN EA1151) or its Ancillary Studies

Abstract Background The United States Preventative Services Task Force in their 2023 recommendations identified areas where more research data is needed to inform future breast cancer screening recommendations. Research areas identified are: improve clinicians and patients understanding and evaluation of dense breast tissue on a screening mammogram, benefits and harms of supplemental screening using ultrasound or MRI for women with dense breasts, health outcomes such as rates of breast cancer diagnosis requiring treatment, rates of advanced breast cancers diagnosed across consecutive screening rounds, and breast cancer-associated morbidity and mortality, causes of increased risk of breast cancer mortality in black women across spectrum of stages and biomarker patterns, understand why black women are more likely to be diagnosed with breast cancers that have biomarker patterns that are indicative of poor health outcomes, assess benefits/harms differences between annual and biennial screening for breast cancer in women overall and if there are differences between black and white women, approaches to reduce the risk of overdiagnosis leading to overtreatment of breast lesions found at screening that may not cause morbidity and mortality, natural history of DCIS, and identify prognostic indicators of breast tumors that are unlikely to affect quality or length of life. Methods The ongoing TMIST study, currently with 88,801 asymptomatic women presenting for screening mammography ages 45-74 enrolled out of 128,905, could contribute to scientific evidence to support the above research areas through existing study aims and planned ancillary studies. Supplemental Screening with US and MRI: TMIST PreSCRIB will utilize Machine Learning applied to TMIST and All of Us data, including genetics, mammograms, social determinates of health and other data to recommend individualized screening strategies for women. DxMRI is a study where women will get AbMRI at time of Dx work-up. There are plans to use these examinations plus supplemental screening MRIs performed on TMIST subjects in an enriched reader study to evaluate the role of supplemental screening MRI in moderate risk women. Rates of breast cancer treatment, consecutive screening, morbidity, and mortality: TMIST’s primary outcome is the proportion of women experiencing an advanced breast cancer and needing treatment. TMIST is also collecting information on health care utilization following a cancer diagnosis, including types of treatment given, and costs data from the screening and diagnostic work-up visits, and mortality data for study participants. Increased risk of breast cancer mortality in black women: TMIST is performing PAM50 plus p53 status, immune profile, DNA repair phenotype, and 21-gene recurrence assay on all breast cancers and a subset of benign tissue. Blood and buccal smears might also help address this issue. Ongoing work, funded by the Susan B. Komen Foundation, focuses on improving Black participation in TMIST Biorepository (currently about 45% participation of the 21% of TMIST US black subjects). Surveys are planned on perceived racism and social determinates of health as part of DxMRI Study. Screening Frequency: We are developing a collaboration with the UK-based clinical trial PROSPECTS to compare rates of all cancers and advanced cancers for annual, biennial, and 3-year screening. Overdiagnosis, natural history of DCIS, prognostic indicators of breast tumors not impacting quality of life: PRoGram- will use radiomics, genomics and pathomics to develop a greater understanding of the variability of the non-advanced cancers diagnosed in the TMIST population, including DCIS. It is hoped that this model will provide greater understanding of the risk of poor outcomes for women diagnosed with lower risk cancers, including DCIS. Citation Format: Etta Pisano, Constantine Gatsonis, Mitchell Schnall, Melissa Troester, Elodia Cole, Jean Cormack, Ilana Gareen, Martin Yaffe, Laura Collins, Amarinthia Curtis, Ruth Carlos, Kathy Miller, Christopher Comstock. Addressing USPSTF 2023 Identified Key Gaps in Knowledge in Breast Cancer Screening through TMIST (ECOG-ACRIN EA1151) or its Ancillary Studies [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 PO3-19-03.

Abstract GS02-05: Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials

Abstract Background: In early breast cancer, the optimal management of the axilla is uncertain. To better understand the long-term benefits and risks of different approaches, we undertook an individual patient data meta-analysis of randomised trials comparing varying types of axillary treatment. Methods: Information was available on 20,273 women in 29 trials of axillary surgery or axillary radiotherapy. The trial comparisons included in this overview are summarised in Table 1. Randomisation took place during 1958–2009. Median follow-up was 10.0 years (IQR 7.4–11.5). Findings: In the trials of more extensive versus less extensive axillary treatment, the rate ratios (RR) for locoregional recurrence varied by site (p=0.003), however, 82% of these locoregional recurrences (552/670) occurred either in the breast or were of unspecified location (Table 2). Considering locoregional recurrence at any site, there was little difference in the risk from more versus less axillary treatment (10-year risk 4.3% vs 4.7%; RR 0.90 95% CI 0.77–1.05; p = 0.20), even in women treated for node-positive disease (3.7% vs 3.6%; RR 1.01, 95% CI 0.74–1.36, p=0.97). There was, however, a substantial difference in lymphoedema for trials of more versus less axillary surgery (odds ratio (OR) 2.35, 95% CI 2.05–2.70; p&amp;lt; 0.00001) and for trials of axillary treatment (surgery or radiotherapy) compared with no further axillary treatment (OR 3.08, 95% CI 2.01–4.71; p&amp;lt; 0.00001). In the four trials comparing axillary node clearance to axillary radiotherapy, the risk of locoregional recurrence appeared to be somewhat reduced in women allocated to clearance (43 vs. 56 events, 10-year risk 4.4% vs. 6.9%; RR 0.64, 95% CI 0.43-0.96, p=0.03) whilst their risk of lymphoedema was increased (OR 1.79, 95% CI 1.42–2.27; p&amp;lt; 0.00001). The risks of distant recurrence, breast cancer, non-breast-cancer, or all-cause mortality did not differ significantly by extent of axillary treatment or when comparing axillary clearance to radiotherapy. Interpretation: This is the most comprehensive overview of axillary treatment to date. Less extensive surgery, such as sentinel lymph node biopsy, or using axillary radiotherapy, resulted in a substantial reduction in lymphoedema compared to axillary node clearance. While there was no evidence of a difference in locoregional recurrence, a moderate effect cannot be excluded. Funding: Cancer Research UK, British Heart Foundation, Medical Research Council Table 1: Summary of the trials of treatment of the axilla in early breast cancer that began prior to 2012. Table 2: Numbers of locoregional recurrences as first event and rate ratios in the trials of more versus less axillary treatment. Citation Format: Gurdeep Mannu, Graham Beake, Richard Berry, David Dodwell, Robert Hills, Paul McGale, Stewart Anderson, Ian Campbell, Armando E. Giuliano, Reshma Jagsi, Thorsten Kuehn, Rebecca Llewellyn-Bennett, Eleftherios Mamounas, Robert Mansel, Pascal Roy, Emiel Rutgers, Nisha Sharma, Sandra Swain, Jonas Bergh, On behalf of the EBCTCG. Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials [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 GS02-05.

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received &amp;lt; 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p&amp;lt; 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p&amp;lt; 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p&amp;lt; 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p&amp;lt; 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p&amp;lt; .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [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 PO5-18-02.

Abstract ED03-03: Impact of exercise on breast cancer outcomes

Abstract Background: Exercise may improve breast cancer outcomes; however, current research is limited in its ability to inform clinical exercise trials and clinical oncology practice. The purpose of this presentation is to summarize the current research on exercise and breast cancer outcomes using a framework proposed to improve the clinical utility of this research. The Exercise as Cancer Treatment (EXACT) Framework organizes and characterizes the critical aspects of a clinical oncology setting to allow for a more systematic and clinically informative approach to the study of exercise as a cancer treatment. The EXACT Framework proposes that two key clinical oncology variables—tumor/disease status (i.e., primary tumor present, primary tumor removed, metastatic disease present) and treatment status (i.e., treatment naïve, actively being treated, previously treated)—are critical for understanding the effects of exercise on cancer outcomes, but few studies have addressed these variables. Application of the EXACT Framework to existing studies may improve their interpretation and identify directions for future research. Results: Presently, there are no adequately powered randomized controlled trials that have examined the effects of exercise on breast cancer outcomes in any clinical oncology scenario, although secondary analysis of smaller phase II trials have been reported. Preclinical research using rodent models has generally shown that exercise slows the growth and spread of treatment naïve breast tumors through various mechanisms including immune response, tumor metabolism, apoptosis, and DNA synthesis and repair. More recently, these preclinical studies have enhanced their clinical utility by including an existing cancer treatment in their design and have generally shown that exercise enhances the delivery and/or efficacy of concurrent cancer treatments through mechanisms related to improved tumor vasculature and perfusion. Most human evidence on exercise and breast cancer outcomes has been gleaned from secondary analysis of observational studies involving healthy cohorts or breast cancer survivor cohorts. These studies have generally included early-stage breast cancer patients who received heterogeneous cancer treatments. Physical activity data was typically collected either well before diagnosis and/or well after treatments. Overall, these studies have generally shown that higher prediagnosis and postdiagnosis physical activity are associated with a lower risk of breast cancer recurrence and mortality. Discussion: There is a disconnect between the clinical oncology scenarios addressed by animal and human studies of exercise and breast cancer outcomes. Moreover, most studies do not adequately address treatment combinations and sequencing. Future observational studies of exercise and breast cancer outcomes may improve their clinical utility by: (a) recruiting breast cancer patients with the same tumor/disease status receiving the same or similar first-line treatment protocols, (b) collecting detailed data on all planned and unplanned cancer treatments, (c) assessing exercise in relation to those cancer treatments (i.e., before, during, between, after) rather than in relation to the cancer diagnosis (i.e., various time periods before and after diagnosis), (d) collecting data on cancer-specific outcomes (e.g., disease response, progression, recurrence) in addition to mortality, and (e) conducting subgroup analyses based on cancer treatments received. Conclusions: Preclinical and observational studies may contribute important knowledge regarding the role of exercise as a cancer treatment; however, modifications to study design and analysis are necessary if they are to inform clinical research and practice. The ultimate goal of precision exercise oncology is to provide the right exercise prescription to the right breast cancer patient at the right time postdiagnosis. Citation Format: K. Courneya. Impact of exercise on breast cancer outcomes [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 ED03-03.

Abstract LB418: Time to adjuvant chemotherapy and its predictors among postoperative breast cancer patients at Cancer Treatment Center of Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia in 2022: A retrospective follow-up study

Abstract Background The incidence of breast cancer is rising and is becoming a major public health problem in Ethiopia, posing a substantial threat to countries with limited oncology centers. Adjuvant chemotherapy is the most important treatment option for breast cancer initiated after definitive surgical management. Adjuvant chemotherapy decreases the risk of breast cancer mortality, reduces the recurrence rate, and improves the long-term overall survival. The time between surgery and the first adjuvant chemotherapy appears to have an impact on the overall survival (OS) and disease-free survival (DFS) in patients with breast cancer. Objective This study aimed to determine the time to start adjuvant chemotherapy and its predictors in post-operative breast cancer patients at oncology center of Hawassa University Comprehensive Specialized Hospital between September 2020 and March 2022. Method This institution based retrospective follow-up study was conducted at the Hawassa University Comprehensive Hospital Cancer Treatment Center between September 2020 and March 2022, among all women with breast cancer. All eligible patients whose medical records were available and accessed in the hospital during the study period were enrolled. The checklists were prepared using Google Forms. The data were then exported to Excel and sent to SPSS software version 26 for data analysis. A stratified Cox regression model was used to identify potential predictors. The adjusted hazard ratio (AHR) with 95% confidence interval (CI) was reported to indicate the strength of the association. This study was conducted between February 22 and April 8, 2022. Result In this study, the median time to adjuvant chemotherapy was 69 days Interquantile range (IQR)=26) with a range of 28-157 days. Twenty (12.9%) patients started chemotherapy in less than 30 days, 36 (23.2%) patients waited for 31-60 days, 68 (43.9%) patients initiated chemotherapy within 61-90 days while 31 (20%) patients took more than 90 days to start their adjuvant chemotherapy. Patients who experienced surgical complications were 1.5 times more likely to initiate adjuvant chemotherapy earlier than those without such complications, with an adjusted hazard ratio (AHR) of 1.512 (95% CI: 1.287-3.140). Patients with a BMI classified as underweight were1.5 times high likely to receive adjuvant chemotherapy earlier (AHR 1.569, 95% CI: (1.336-3.887)). Post-operative breast cancer patients with co-morbidity had a 25% lower likelihood of receiving adjuvant chemotherapy earlier than those without comorbidity (AHR=0.751,95%CI: 0.474-0.817), and illiteracy (AHR=0.829, 95% CI: (0.458-0.950)) was also a significant predictor of time to adjuvant chemotherapy. Conclusion The duration of initiation of the adjuvant chemotherapy was longer than the recommended initiation time. Body Mass Index, presence of surgical complications, presence of comorbidity, and educational status were predictors of delayed time to adjuvant chemotherapy Citation Format: Adugna Getahun Deboch. Time to adjuvant chemotherapy and its predictors among postoperative breast cancer patients at Cancer Treatment Center of Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia in 2022: A retrospective follow-up study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB418.

Cancer stages and mortality risk of breast cancer between women with and without disabilities: A national population-based cohort study in Taiwan

BackgroundThe second-most common cause of cancer-related death for women worldwide is breast cancer. However, there is little information about breast cancer among women with disabilities in Taiwan. ObjectivesThis study investigated differences between women with and without disabilities regarding breast cancer stages and evaluated the probability of developing an advanced stage and the mortality risk of breast cancer. MethodsThis study conducted a nationwide retrospective cohort study using the National Health Insurance Research Database and other nationwide databases. Our participants were newly diagnosed breast cancer patients, including women with and without disabilities, between 2004 and 2010. We matched both of them with propensity score matching methods (1:5), and all were followed up until the end of 2016. ResultsThis study included 50,683 participants with breast cancer. After matching, women with disabilities who did not receive breast cancer screening had a more significant proportion of advanced-stage breast cancer (19.95 %) than those without disabilities who did not receive breast cancer screening (16.87 %). After adjusting for related variables, women with disabilities were 1.27 times more likely to have advanced-stage breast cancer than those without disabilities. Additionally, after suffering from breast cancer, individuals with disabilities had a 1.23 times greater mortality risk compared to those without disabilities. ConclusionsAlthough cancer stages were controlled, women with disabilities still had a higher mortality risk of breast cancer. Hence, policymakers should pay more attention to women with disabilities to treat them at an early stage, which can reduce the mortality risk attributable to advanced stages.

Abstract 2218: Dietary insulinemic potential and survival after breast cancer diagnosis

Abstract Background: Hyperinsulinemia may promote the growth and metastasis of breast cancers by activating the insulin/insulin-like growth factor 1 signaling pathways. Whether the insulinemic potential of the diet contributes to breast cancer prognosis has not been examined previously. Here, we focused on a food-based empirical dietary index for hyperinsulinemia (EDIH), an index previously designed as most predictive of fasting plasma C-peptide. We aimed to investigate whether EDIH (at different time settings) is associated with overall and breast cancer-specific mortality. Methods: For 9,640 women with stage I-III breast cancer from the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII), we calculated the cumulative average EDIH, using repeated measures of post-diagnostic diet from food frequency questionnaires (FFQ). We also considered the pre-diagnostic EDIH score (using the last FFQ reported before diagnosis), the first postdiagnostic EDIH score, as well as a simple updated EDIH score. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. Deaths were ascertained by report from family members or by searching the National Death Index. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: Participants were followed up for a median of 12 years after breast cancer diagnosis. We documented 1,120 deaths due to breast cancer and 2,762 all-cause deaths. Women with higher post-diagnostic EDIH had a 40% higher risk of all-cause mortality (HR for quintile 5 vs. quintile 1 [HRQ5vs.Q1], 1.40; 95% CI, 1.22, 1.61; P-trend&amp;lt;0.0001). EDIH was also associated with a 19% increased risk of breast cancer mortality, although the confidence interval included the null (HRQ5vs.Q1, 1.19; 95% CI, 0.95, 1.48; P-trend=0.17). Findings for overall mortality were similar for EDIH measured at other timings/settings: last pre-diagnosis dietary assessment (HRQ5vs.Q1,1.21; 95% CI, 1.06, 1.39; P-trend&amp;lt;0.0001) and first post-diagnosis dietary assessment (HRQ5vs.Q1,1.23; 95% CI, 1.08, 1.40; P-trend&amp;lt;0.0001). Conclusions: In this large prospective study of breast cancer survivors, higher hyperinsulinemic dietary scores (reflecting higher dietary insulinemic potential) were associated with worse survival outcomes following diagnosis. Thus, dietary recommendations emphasizing the importance of avoiding high insulinemic dietary patterns (i.e., processed meat and red meat) and prioritizing low insulinemic dietary patterns (i.e., coffee, whole fruit and green-leafy vegetables) as components of a healthy diet may improve overall survival. Citation Format: Andrea Romanos-Nanclares, Tengteng Wang, Bernard A. Rosner, Michelle D. Holmes, Wendy Y. Chen, Walter C. Willett, Rulla M. Tamimi, A. Heather Eliassen. Dietary insulinemic potential and survival after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2218.

Abstract 3425: Genetic predisposition to obesity and survival in women with breast cancer

Abstract Background. Higher body mass index (BMI) is associated with poor survival after breast cancer diagnosis. BMI is a heritable trait. A polygenic risk score (PRS) for BMI has been associated with cardiometabolic traits and found to modify weight loss interventions. Whether BMI genetic scores affect survival in women with breast cancer is unknown. Methods. This analysis was conducted in the Cancer Prevention Study II Nutrition cohort. Women diagnosed with non-metastatic breast cancer between 1992 and 2017 were included in the analysis if they had genotype data. Analyses were restricted to unrelated, postmenopausal women at the time of diagnosis who were of European ancestry (N=3,566). Deaths through 2020 were identified through linkage with the National Death Index. Primary cause of death was based on the International Classification of Disease codes. Pre-diagnosis BMI was self-reported (median 1.3 years from BMI measurement to diagnosis, interquartile range (IQR): 0.6, 1.9). We constructed a PRS using findings from a published meta-analysis of BMI genome wide association studies (GWAS) that included ~700,000 individuals and the PRSice tool.Hazard ratios (HR) and 95% confidence intervals (CI) between the PRS and all-cause mortality were estimated using Cox proportional hazards regression and Fine and Gray models for cause-specific mortality to account for competing risks. Models were adjusted for age and GWAS-specific statistically significant (P&amp;lt;0.05) principal components for population stratification. Mediation was estimated using the mediation R package. Results. The median age at diagnosis was 71.5 years (IQR: 66.3, 76.8). Most women were overweight (33.5%) or obese (18.4%) and were diagnosed with localized stage (63%) and estrogen receptor positive (65%) breast cancer. During a median follow-up of 14.5 years (IQR: 9.7-19.8), there were 1,825 (51.2%) deaths, including 301 breast cancer and 337 cardiovascular disease (CVD) specific deaths. In multivariable models, a 5 Kg/m2 increase in BMI was associated with increased risks of all-cause mortality (HR=1.09, 95% CI: 1.04, 1.15), breast cancer-specific mortality (HR=1.27, 95% CI: 1.13, 1.42), and CVD-specific mortality (HR=1.25, 95% CI: 1.11, 1.41). The PRS was highly predictive of pre-diagnostic BMI (P&amp;lt;0.001). A 1-standard deviation increase in the PRS was associated with statistically increased risk of all-cause mortality (HR=1.06, 95% CI: 1.02, 1.11). Risks of breast cancer (HR=1.07, 95% CI: 0.96, 1.19) or CVD (HR=1.01, 95% CI: 0.90, 1.12) specific mortality did not reach statistical significance. We estimated that 27% of the PRS and all-cause mortality association was mediated by BMI (95% CI: 12%, 91%; P=0.004). Conclusions. Women with breast cancer predisposed to higher BMI were at increased risk of all-cause mortality. A BMI-related PRS may be a useful tool to identify women with breast cancer in need of additional interventions and/or surveillance. Citation Format: Clara Bodelon, Adriana Lori, Mariah Landry, James Hodge, Parichoy Pal Choudhury, Ying Wang, Lauren E. McCullough, Alpa V. Patel, Lauren R. Teras. Genetic predisposition to obesity and survival in women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3425.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil

Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

Omission of radiation therapy post breast conserving surgery

Radiation therapy (RT) after breast conserving surgery decreases the risks of local recurrence and breast cancer mortality in the multidisciplinary management of patients with breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of post-operative RT in individual patients varies substantially.Clinical trials aiming to identify patients with low-risk early breast cancer in whom post-operative RT may be safely omitted, based on conventional clinical-pathologic variables alone, have not provided sufficiently tailored information on local recurrence risk assessment to guide treatment decisions. The majority of patients with early breast cancer continue to be routinely treated with RT after breast conserving surgery. This approach may represent over-treatment for a substantial proportion of the patients.The clinical impact of genomic signatures on local therapy decisions for early breast cancer has been remarkably modest due to the lack of high-level evidence supporting their clinical validity for assessment of the risk of local recurrence. Efforts to personalise breast cancer care must be supported by high level evidence to enable balanced, informed treatment decisions. These considerations underpin the importance of ongoing biomarker-directed clinical trials to generate the high-level evidence necessary for setting the future standard of care in personalised local therapy for patients with early breast cancer.

Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part II - Microscopic scales.

Although the benefits of breast screening and early diagnosis are known for reducing breast cancer mortality rates, the effects and risks of low radiation doses to the cells in the breast are still ongoing topics ofstudy. To study specific energy distributions ( ) in cytoplasm and nuclei of cells corresponding to glandular tissue for different x-ray breast imagingmodalities. A cubic lattice (500 μm length side) containing 4064 spherical cells was irradiated with photons loaded from phase space files with varying glandular voxel doses ( ). Specific energy distributions were scored for nucleus and cytoplasm compartments using the PENELOPE (v. 2018) + penEasy (v. 2020) Monte Carlo (MC) code. The phase space files, generated in part I of this work, were obtained from MC simulations in a voxelized anthropomorphic phantom corresponding to glandular voxels for different breast imaging modalities, including digital mammography (DM), digital breast tomosynthesis (DBT), contrast enhanced digital mammography (CEDM) and breast CT (BCT). In general, the average specific energy in nuclei is higher than the respective glandular dose scored in the same region, by up to 10%. The specific energy distributions for nucleus and cytoplasm are directly related to the magnitude of the glandular dose in the voxel ( ), with little dependence on the spatial location. For similar values, for nuclei is different between DM/DBT and CEDM/BCT, indicating that distinct x-ray spectra play significant roles in . In addition, this behavior is also present when the specific energy distribution ( ) is considered taking into account the GDD in thebreast. Microdosimetry studies are complementary to the traditional macroscopic breast dosimetry based on the mean glandular dose (MGD). For the same MGD, the specific energy distribution in glandular tissue varies between breast imaging modalities, indicating that this effect could be considered for studying the risks of exposing the breast to ionizingradiation.

Abstract A014: Connecting with Black patients through targeted, breast cancer messaging in the clinic setting

Abstract Background: While overall breast cancer incidence among Black women is lower than among white women, Black women are, on average, about 40 percent more likely to die of the disease as compared to white women. And the incidence rates are higher among Black women under age 40 (where incidence is the number of new cases that develop in a specific time period). Black women experience higher rates of death from breast cancer due to a combination of factors, including barriers to early diagnosis, the aggressive nature of certain breast cancers that are more prevalent in Black women (Triple Negative Breast Cancer and Inflammatory Breast Cancer, for example), and a lack of quality care. One of the key findings from Komen’s report ‘Closing the Gap: A Roadmap to Save the Lives of Black Women in America’ (2021) indicated a need for better education and resources for patients to support health decisions. Specifically, qualitative data from focus groups across 10 cities with significant disparities in breast cancer outcomes showed information was needed about breast cancer screening guidelines and family health history in the community to identify high-risk families. Hypothesis: To determine if targeted, patient-faced educational messages in point-of-care settings would connect with Black patients and educate them on breast cancer resources provided by Susan G. Komen. Our efforts focused particularly in cities with the greatest breast cancer disparities (Atlanta, GA; Chicago, IL; Dallas, TX; Houston, TX; Los Angeles, CA; Memphis, TN; Philadelphia, PA; St. Louis, MO; Tidewater, VA; Washington, DC) . Methods: In 11 focus cities, select educational messaging over a six-month period appeared through static digital content in patient exam rooms featuring Black imagery and patient-empowering breast cancer resources content. The 20-second reels appeared every 15-20 minutes in 471 primary care and OB/GYN offices/2,336 exam rooms. Patients in these offices responded (n=315) through an online survey to share demographic information including gender and ethnicity and to identify how aware they were of Black women’s risk of breast cancer mortality, that resource programs exist to support breast health including those offered by Susan G. Komen and that Komen has a program aimed at addressing this disparity within the Black community. Results: By sharing educational messaging directly to patients in the clinic, significant awareness was achieved. Those who responded to the survey included 38% Black women. The targeted messaging campaign reached the intended audience and connected Black patients with additional resources to take action on their breast health. In particular, increased awareness of specific interventions was achieved. In future efforts to empower Black women and improve outcomes, direct, culturally tailored education presented in the clinic setting may be a useful tool and lead to better utilization of key resource programs and overall improved health education. Citation Format: Nikki Hopewell, Brady Kazar, Michelle Strong, Krissa Smith. Connecting with Black patients through targeted, breast cancer messaging in the clinic setting [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A014.

Abstract B077: Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women

Abstract Background: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who are more likely to die from the disease. To improve our understanding of the relation, we investigated the joint effects of race and neighborhood racial composition, residential mobility, and rurality on the neighborhood deprivation-breast cancer mortality association among White and Black women. Methods: In 2010-2017, 31,358 non-Hispanic White and Black women diagnosed with invasive stage I-IIIA breast cancer were identified by the Georgia Cancer Registry and were followed through 2019 for breast cancer mortality. The neighborhood deprivation index (NDI) was derived through principal component analysis of 2011-2015 block group-level American Community Survey (ACS) data on poverty, income, housing, unemployment, occupation, and education. Neighborhood racial composition and residential mobility were measured using 2011-2015 ACS data. Rurality was measured using Georgia Department of Public Health data. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for the association between NDI, in quintiles, and breast cancer mortality, overall and according to joint effects of race and neighborhood characteristics (neighborhood racial composition, residential mobility, and rurality). Results: During follow-up, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Living in the most deprived neighborhoods was associated with a 30% increased risk of breast cancer mortality (quintile 5 vs. 1: HR=1.30, 95% CI 1.13-1.49). The association was present among non-Hispanic White (quintile 5 vs. 1: HR=1.47, 95% CI 1.20-1.79) but not non-Hispanic Black women. We observed similar race-specific patterns when assessing jointly stratified associations. For example, among non-Hispanic White women, neighborhood deprivation was associated with breast cancer mortality irrespective of the additional neighborhood characteristics considered, with the strongest association observed among non-Hispanic White women living in the most deprived rural neighborhoods compared to those living in the least deprived urban neighborhoods (HR=1.70, 95% CI 1.30-2.22). In contrast, no association was found among non-Hispanic Black women in any strata of neighborhood racial composition, residential mobility, or rurality (non-Hispanic Black women living in the most deprived rural neighborhoods vs. those living in the least deprived urban neighborhoods: HR=1.05, 95% CI 0.78-1.41). Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White but not non-Hispanic Black women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women. Other factors beyond neighborhood may contribute to the high breast cancer mortality rate among this racial group. Citation Format: Lauren E. Barber, Leah Moubadder, Maret L. Maliniak, Jasmine M. Miller-Kleinhenz, Jeffrey M. Switchenko, Lauren E. McCullough. Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B077.

Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay

Increased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE2/EP2 feedforward loop, which favors M2 polarization and its associated pro-metastatic changes but are abrogated by oral treatment with COX-2 or EP2 inhibitors in estrogen-receptor-positive (ER+) syngeneic mouse tumor models. Therefore, we conclude that needle biopsy of ER+ BC provokes progressive pro-metastatic changes, which may explain the mortality risk posed by surgery delay after diagnosis.

Alcohol, Smoking, and Risks of Breast Cancer Recurrence and Mortality among Women with Luminal, Triple-Negative, and HER2-Overexpressing Breast Cancer.

This study evaluates the relationship between smoking, alcohol, and breast cancer outcomes according to molecular subtype. This population-based prospective cohort consisted of 3,876 women ages 20 to 69 diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 expressions: luminal (ER+), triple-negative (TN; ER-/PR-/HER2-), and HER2-overexpressing (H2E; ER-/HER2+). We fit Cox proportional hazards models to assess the association between alcohol consumption and smoking status at diagnosis and risks of recurrence, breast cancer-specific mortality, and all-cause mortality. Histories of ever smoking [HR, 1.33; 95% confidence interval (CI), 1.01-1.74] and current smoking (HR, 1.59; 95% CI, 1.07-2.35) were associated with greater risk of breast cancer recurrence among TN cases. Smoking was also associated with greater risk of recurrence to bone among all cases and among luminal cases. Elevated risks of breast cancer-specific and all-cause mortality were observed among current smokers across all subtypes. Alcohol use was not positively associated with risk of recurrence or mortality overall; however, TN patients who drank four or more drinks per week had a decreased risk of recurrence (HR, 0.71; 95% CI, 0.51-0.98) and breast cancer-specific mortality (HR, 0.73; 95% CI, 0.55-0.97) compared with non-current drinkers. Patients with breast cancer with a history of smoking at diagnosis have elevated risks of recurrence and mortality. These findings underscore the need to prioritize smoking cessation among women diagnosed with breast cancer.

RRIMS: Radiation Risk In Mammography Screening - model evaluation.

The Radiation Risk In Mammography Screening (RRIMS) model was introduced as a novel tool to help females accurately calculate their lifetime mean glandular dose (MGD) and estimate their population-level risk of radiation-induced breast cancer incidence and mortality. The model's accuracy was evaluated by comparing the received MGD of 317 women who had undergone a total of 733 visits across one to four rounds of screening. This was achieved by comparing the RRIMS predicted dose values with the same examination dose calculated manually by hand. Qualitative and quantitative statistical analyses were performed to assess the percentage difference (% diff) or agreement between the two values. Qualitative statistical analysis using the Bland-Altman plots demonstrated a statistically significant bias for the % diff between the manually calculated and RRIMS predicted dose values, where the mean (bias) was -2.02% with an upper and lower limit of agreement of 40.24% and -44.27%, respectively. Quantitative statistical analysis revealed an intraclass correlation coefficient (ICC, 3,1) of 0.64 (p-value < 0.001) and a Kendall's W of 0.83 (p-value < 0.001). The results indicate a statistically significant and reasonably good level of agreement between the manually calculated vs RRIMS predicted dose values. This work was focused on one of the major mammography equipment manufacturers that is Hologic, however there is potential for a multivendor applicability study of this model with future iterations. This will further improve upon this innovative dose and risk prediction tool that can empower healthcare professionals when making informed decisions and enhance patient care. This paper assesses the precision of the dose and risk model that our team has previously established. The results bring us one step closer to providing females and clinicians with a useful tool that can help explain and contextualise the benefits and risks associated with screening mammography.

53 The Patient Demographic Details of Referrals for Risk Reducing Breast Surgery and Reconstruction to St Helen’s and Knowsley Teaching Hospitals Over a 5 Year Period

Abstract Background Breast cancer is the most common cause of cancer in women affecting 1 in 7 women in the UK. Hereditary breast cancers are present in up to 10% of all cases and are most commonly related to BRCA gene mutations. Bilateral risk reducing mastectomy (RRM) +/- reconstruction is the most effective strategy reducing breast cancer mortality risk. Reconstruction options can be classified into immediate vs delayed reconstruction and autologous vs alloplastic reconstruction. Complete reconstruction may take considerable time depending on waiting lists and may include additional aesthetic corrections such as lipomodelling and nipple reconstruction. Method Retrospective analysis of referrals (all ages) to a single surgeon at Whiston Hospital for breast reconstruction following RRM between 1/04/2015-1/04/2020. Results There were a total of 467 referrals. Of these, 76 (16%) were referred for breast reconstruction following RRM, 51 (67%) of these patients had confirmed genetic mutations and 24 (32%) had no genetic mutation. 48 (94%) patients were BRCA gene carriers of which 32 (63%) were BRCA2 carriers, 14 (27%) were BRCA1 carriers and 2 patients with unknown BRCA variants. There were 2 (4%) patients with CHEK2 mutations and 1 (2%) patient with Cowden’s syndrome. Conclusions There is currently no standardised guidance on the timing of RRM and reconstruction in high-risk patients. The risk of breast cancer in high-risk patients increases with age, and there is need for a risk stratification tool for RRM and reconstruction waiting lists, to identify patients with the highest risk of breast cancer development considering their personal and family history.

Predicting 10-year breast cancer mortality risk in the general female population in England: a model development and validation study

Identifying female individuals at highest risk of developing life-threatening breast cancers could inform novel stratified early detection and prevention strategies to reduce breast cancer mortality, rather than only considering cancer incidence. We aimed to develop a prognostic model that accurately predicts the 10-year risk of breast cancer mortality in female individuals without breast cancer at baseline. In this model development and validation study, we used an open cohort study from the QResearch primary care database, which was linked to secondary care and national cancer and mortality registers in England, UK. The data extracted were from female individuals aged 20-90 years without previous breast cancer or ductal carcinoma in situ who entered the cohort between Jan 1, 2000, and Dec 31, 2020. The primary outcome was breast cancer-related death, which was assessed in the full dataset. Cox proportional hazards, competing risks regression, XGBoost, and neural network modelling approaches were used to predict the risk of breast cancer death within 10 years using routinely collected health-care data. Death due to causes other than breast cancer was the competing risk. Internal-external validation was used to evaluate prognostic model performance (using Harrell's C, calibration slope, and calibration in the large), performance heterogeneity, and transportability. Internal-external validation involved dataset partitioning by time period and geographical region. Decision curve analysis was used to assess clinical utility. We identified data for 11 626 969 female individuals, with 70 095 574 person-years of follow-up. There were 142 712 (1·2%) diagnoses of breast cancer, 24 043 (0·2%) breast cancer-related deaths, and 696 106 (6·0%) deaths from other causes. Meta-analysis pooled estimates of Harrell's C were highest for the competing risks model (0·932, 95% CI 0·917-0·946). The competing risks model was well calibrated overall (slope 1·011, 95% CI 0·978-1·044), and across different ethnic groups. Decision curve analysis suggested favourable clinical utility across all age groups. The XGBoost and neural network models had variable performance across age and ethnic groups. A model that predicts the combined risk of developing and then dying from breast cancer at the population level could inform stratified screening or chemoprevention strategies. Further evaluation of the competing risks model should comprise effect and health economic assessment of model-informed strategies. Cancer Research UK.