A spatial attention guided deep learning system for prediction of pathological complete response using breast cancer histopathology images.

MOTIVATION: Predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients accurately is direly needed for clinical decision making. pCR is also regarded as a strong predictor of overall survival. In this work, we propose a deep learning system to predict pCR to NAC based on serial pathology images stained with hematoxylin and eosin and two immunohistochemical biomarkers (Ki67 and PHH3). To support human prior domain knowledge-based guidance and enhance interpretability of the deep learning system, we introduce a human knowledge-derived spatial attention mechanism to inform deep learning models of informative tissue areas of interest. For each patient, three serial breast tumor tissue sections from biopsy blocks were sectioned, stained in three different stains and integrated. The resulting comprehensive attention information from the image triplets is used to guide our prediction system for prognostic tissue regions. RESULTS: The experimental dataset consists of 26 419 pathology image patches of 1000×1000 pixels from 73 TNBC patients treated with NAC. Image patches from randomly selected 43 patients are used as a training dataset and images patches from the rest 30 are used as a testing dataset. By the maximum voting from patch-level results, our proposed model achieves a 93% patient-level accuracy, outperforming baselines and other state-of-the-art systems, suggesting its high potential for clinical decision making. AVAILABILITY AND IMPLEMENTATION: The codes, the documentation and example data are available on an open source at: https://github.com/jkonglab/PCR_Prediction_Serial_WSIs_biomarkers. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Drivers of racial, regional, and socioeconomic disparities in late-stage breast cancer mortality.

BACKGROUND: The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia. METHODS: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low- versus high-SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated. RESULTS: Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (HR, 1.27; 95% CI, 1.13, 1.41) and rurality (HR, 1.14; 95% CI, 1.00, 1.30), but not by SES (HR, 1.04; 95% CI, 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR, 2.30; 95% CI, 1.53, 3.45). Residing in a rural county was associated with increased mortality among uninsured women (HR, 2.25; 95% CI, 1.31, 3.86), and the most pronounced SES disparities were among younger women (<40 years: HR, 1.46; 95% CI, 0.88, 2.42). CONCLUSIONS: There is considerable variation in racial, regional, and socioeconomic disparities in late-stage BC mortality by tumor, treatment, and patient characteristics.

Neighborhood characteristics and breast tumor methylation: using epigenomics to explore cancer outcome disparities.

BACKGROUND: Social exposures may drive epigenetic alterations that affect racial disparities in breast cancer outcomes. This study examined the association between neighborhood-level factors and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. METHODS: Genome-wide DNA methylation was measured using the EPIC array in the tumor tissue of 96 women. Linear regression models were used to examine the association between nine neighborhood-level factors and methylation, regressing ß values for each cytosine-phosphate guanine dinucleotide (CpG) site on neighborhood-level factors while adjusting for covariates. Neighborhood data were obtained from the Opportunity Atlas. We used a false discovery rate (FDR) threshold < 0.05, and for CpGs below this threshold, we examined interactions with race. We employed multivariable Cox proportional-hazards models to estimate whether aberrant methylation was associated with all-cause mortality. RESULTS: 26 of the CpG sites were associated with job density or college education (FDR < 0.05). Further exploration of these 26 CpG sites revealed no interactions by race, but a single probe in TMEM204 was associated with all-cause mortality. CONCLUSION: We identified novel associations between neighborhood-level factors and the breast tumor DNA methylome. Our data are the first to show that dysregulation in neighborhood associated CpG sites may be associated with all-cause mortality. Neighborhood-level factors may contribute to differential tumor methylation in genes related to tumor progression and metastasis. This contributes to the increasing body of evidence that area-level factors (such as neighborhood characteristics) may play an important role in cancer disparities through modulation of the breast tumor epigenome.

Barriers to breast cancer screening in Atlanta, GA: results from the Pink Panel survey at faith-based institutions.

PURPOSE: Our research sought to describe barriers to mammography screening among a sample of predominantly Black women in metropolitan Atlanta, Georgia. METHODS: The Pink Panel project convened community leaders from faith-based institutions to administer an offline survey to women via convenience sampling at fourteen churches in Atlanta in late 2019 and early 2020. With the COVID-19 pandemic, the research team switched to an online survey. The survey included seven questions about breast cancer awareness, barriers to breast cancer screening, and screening status. We used residence information to attain the 9-digit zip code to link to the Area Deprivation Index at the Census Block Group neighborhood level. We report results as descriptive statistics of the barriers to mammography screening. RESULTS: The 643 women represented 21 counties in Georgia, predominantly from metropolitan Atlanta, and 86% identified as Black. Among women aged 40 and older, 90% have ever had a mammogram. Among all women, 79% have ever had a mammogram, and 86% indicated that they would get a mammogram if offered in their neighborhood. The top barriers to mammography screening were lack of health insurance and high cost. Barriers to mammography screening did not differ substantially by Area Deprivation Index. CONCLUSION: Among metropolitan Atlanta women aged 40+ , nearly all reported ever having a mammogram. However, addressing the barriers, including lack of health insurance and high cost, that women reported may further improve mammography screening rates.

Pilot Feasibility Study of a Video Intervention to Educate Patients with Breast Cancer About Clinical Trials.

The purpose of this project was to develop and test the feasibility and preliminary efficacy of a video about cancer clinical trials (CCTs) developed for breast cancer patients. We developed 2 brief 7-min videos that focused on breast cancer patients describing their experiences participating in CCTs, supplemented with doctors and research staff explaining key research concepts. One video was culturally tailored to Black patients and the other to White patients. To assess feasibility study, participants and their care providers completed a survey to evaluate their satisfaction with the video. Eligibility criteria for the study included ≥ 21 years of age, English-speaking, no prior experience participating in a CCT, and being potentially eligible for breast CCT enrollment. Preliminary efficacy was evaluated with a pretest-posttest design using a single item asking about intent to enroll in a clinical trial. The mean age of the patient sample (n = 50) was 53.0 years, and 50.0% were Black. Participants reported that the video was in the right length, useful, and easy to understand. Providers' evaluation (n = 5) revealed that viewing the video helped prepare patients for further CCT discussion. Preliminary efficacy showed no statistically significant difference in participant interest in CCT enrollment pre- and post-video. Changes in patients' intent in enrollment were associated with age and education. Culturally adapted video interventions can be helpful in supporting both patients and providers throughout the CCT education process but additional work is needed to improve enrollment into clinical trials.

Undercutting efforts of precision medicine: roadblocks to minority representation in breast cancer clinical trials.

Precision (or personalized) medicine holds great promise in the treatment of breast cancer. The success of personalized medicine is contingent upon inclusivity and representation for minority groups in clinical trials. In this article, we focus on the roadblocks for the African American demographic, including the barriers to access and enrollment in breast oncology trials, the prevailing classification of race and ethnicity, and the need to refine monolithic categorization by employing genetic ancestry mapping tools for a more accurate determination of race or ethnicity.

Receipt of Guideline-Concordant Care Does Not Explain Breast Cancer Mortality Disparities by Race in Metropolitan Atlanta.

BACKGROUND: Racial disparities in breast cancer mortality in the United States are well documented. Non-Hispanic Black (NHB) women are more likely to die of their disease than their non-Hispanic White (NHW) counterparts. The disparity is most pronounced among women diagnosed with prognostically favorable tumors, which may result in part from variations in their receipt of guideline care. In this study, we sought to estimate the effect of guideline-concordant care (GCC) on prognosis, and to evaluate whether receipt of GCC modified racial disparities in breast cancer mortality. PATIENTS AND METHODS: Using the Georgia Cancer Registry, we identified 2,784 NHB and 4,262 NHW women diagnosed with a stage I-III first primary breast cancer in the metropolitan Atlanta area, Georgia, between 2010 and 2014. Women were included if they received surgery and information on their breast tumor characteristics was available; all others were excluded. Receipt of recommended therapies (chemotherapy, radiotherapy, endocrine therapy, and anti-HER2 therapy) as indicated was considered GCC. We used Cox proportional hazards models to estimate the impact of receiving GCC on breast cancer mortality overall and by race, with multivariable adjusted hazard ratios (HRs). RESULTS: We found that NHB and NHW women were almost equally likely to receive GCC (65% vs 63%, respectively). Failure to receive GCC was associated with an increase in the hazard of breast cancer mortality (HR, 1.74; 95% CI, 1.37-2.20). However, racial disparities in breast cancer mortality persisted despite whether GCC was received (HRGCC: 2.17 [95% CI, 1.61-2.92]; HRnon-GCC: 1.81 [95% CI, 1.28-2.91] ). CONCLUSIONS: Although receipt of GCC is important for breast cancer outcomes, racial disparities in breast cancer mortality did not diminish with receipt of GCC; differences in mortality between Black and White patients persisted across the strata of GCC.

Quadruple-negative breast cancer: novel implications for a new disease.

Based on the androgen receptor (AR) expression, triple-negative breast cancer (TNBC) can be subdivided into AR-positive TNBC and AR-negative TNBC, also known as quadruple-negative breast cancer (QNBC). QNBC characterization and treatment is fraught with many challenges. In QNBC, there is a greater paucity of prognostic biomarkers and therapeutic targets than AR-positive TNBC. Although the prognostic role of AR in TNBC remains controversial, many studies revealed that a lack of AR expression confers a more aggressive disease course. Literature characterizing QNBC tumor biology and uncovering novel biomarkers for improved management of the disease remains scarce. In this comprehensive review, we summarize the current QNBC landscape and propose avenues for future research, suggesting potential biomarkers and therapeutic strategies that warrant investigation.

Detection of crown-like structures in breast adipose tissue and clinical outcomes among African-American and White women with breast cancer.

BACKGROUND: Crown-like structures in breast adipose tissue (CLS-B), composed of necrotic adipocytes encircled by macrophages, are associated with obesity and hypothesized to worsen breast cancer prognosis; however, data are sparse, particularly in multi-racial populations. METHODS: We assessed specimens for CLS-B from 174 African-American and 168 White women with stage I-III breast cancer treated by mastectomy. Benign breast tissue from an uninvolved quadrant was immunohistochemically stained for CD68 to determine CLS-B presence and density (per cm2 of adipose tissue). Demographic and lifestyle factors, collected via medical record review, were analyzed for associations with CLS-B using logistic regression. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CLS-B and overall (OS) or progression-free (PFS) survival. RESULTS: Detection of any CLS-B was similar between African-American (32%) and White (29%) patients with no evidence of an association between race and CLS-B in multivariable models (OR = 0.82, 95% CI = 0.49-1.36). Detection of CLS-B was associated with obesity (OR = 4.73, 95% CI = 2.48-9.01) and age ≥ 60 years at diagnosis (OR = 1.78, 95% CI = 0.99-3.21). There was some evidence of associations with parity and current smoking status. Detection of CLS-B was not associated with OS (HR = 1.02, 95% CI = 0.55-1.87) or PFS (HR = 0.99, 95% CI = 0.59-1.67). CONCLUSIONS: Our results show a strong, positive association between BMI and CLS-B in non-tumor tissue similar to previous findings. Detection of CLS-B did not vary by race and was not associated with worse OS or PFS.

Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?

PURPOSE: As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. METHODS: Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used-regressing methylation ß value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) < 0.05. In the top 20 CpG sites, we explored the interactions with race and estrogen receptor (ER) status. We used multivariable Cox-proportional hazard models to examine whether methylation in the top 20 sites was associated with all-cause mortality. RESULTS: While none of the CpG sites passed the FDR threshold for significance, among the top 20 CpG sites, we observed interactions with race (TOMM20) and ER status (PSMB1, QSOX1 and PHF1). The same CpG sites in TOMM20, PSMB1, and QSOX1 were associated with all-cause mortality. CONCLUSIONS: We identified novel interactions between obesity-associated methylation and both race and ER status in genes that have been associated with tumor regulation. Our data suggest that dysregulation in two sites may associate with all-cause mortality.

The Impact of Genetic Counseling Educational Tools on Patients' Knowledge of Molecular Testing Terminology.

Molecular testing is increasingly being integrated into cancer management. Despite rapid advancements, little work has been done to explore strategies for communicating with patients undergoing molecular tumor testing. This study evaluated the impact of genetic counseling educational tools on improving patients' understanding of key terms related to molecular testing. A genetic counseling intern designed a picture book to explain six words found in prior research to be difficult to understand (mutation, germline mutation, somatic mutation, biomarker, molecular testing, and targeted therapy). Participants who had previously discussed molecular testing with their oncologist were asked to define the terms. The same participants then received an explanation of each term either from the intern using the picture book in person or from a video presentation of the picture book. They were then asked to redefine each term afterward. The difference between the number of terms defined correctly pre- and post-intervention was compared between presentations. Sixty-three patients with melanoma, colon, lung, or breast cancer were recruited. After both interventions, correct understanding rates improved for all six terms, with significant improvement for germline mutation (p < 0.001), somatic mutation (p < 0.001), biomarker (p < 0.001), and molecular testing (p < 0.001). Understanding of targeted therapy improved significantly (p = 0.011) for the video presentation only. Mean change in knowledge scores did not differ between the two interventions (intern presentation 3.2 vs. video 2.9, p = 0.428). Our data suggest that genetic counseling educational tools can increase patient understanding of terms used to describe molecular testing.

Benefits and risks of contralateral prophylactic mastectomy in women undergoing treatment for sporadic unilateral breast cancer: a decision analysis.

The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.

Leveraging Mobile Health to Improve Capecitabine Adherence Among Women With Breast Cancer: A Pilot Randomized Controlled Trial.

PURPOSE: Oral capecitabine improves convenience compared to intravenous therapies but presents monitoring challenges. We conducted a randomized pilot trial to evaluate a mobile health intervention to remotely monitor capecitabine adherence and patient-reported outcomes (PROs) among women with breast cancer. METHODS: Patients with breast cancer prescribed capecitabine, an oral chemotherapy with a complex, cyclical regimen, were randomly assigned to enhanced usual care (EUC) or PRO arm. Participants were asked to use a smart pill bottle to measure adherence (timing and dose) and complete baseline and 90-day follow-up surveys. PRO participants received text messages for missed or incorrect doses and weekly text-based symptom assessments, and their oncologists received alerts for severe symptoms or missed doses. We compared nonadherence (<80%) and changes from enrollment to follow-up on reported physical and mental health quality-of-life scores and number of severe symptoms by study arm. RESULTS: Overall, 32 women were randomly assigned (17 EUC and 15 PRO): 28 (87.5%) received the intervention and 24 (78.1%) completed the follow-up survey. Among participants who received the intervention, PRO participants responded to 83.3% of symptom questions; 7.7% of PRO participants were nonadherent compared with 40.0% of EUC participants (P = .049). Among those who completed the follow-up survey, 12.5% of PRO participants had reductions in their mental health composite scores compared with 69.2% of EUC participants (P = .011); 10% of PRO participants had more severe symptoms at follow-up compared with 57.1% of EUC participants (P = .019). CONCLUSION: A mobile health intervention using text message reminders and symptom assessments improved medication adherence and mental health quality-of-life scores and lowered symptom burden of patients with breast cancer prescribed capecitabine. Future work should evaluate the longer-term impacts of this intervention.

Sunitinib in Patients With Breast Cancer With FGFR1 or FGFR2 Amplifications or Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with FGFR1 and FGFR2 alterations treated with sunitinib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Forty patients with BC with FGFR1 (N = 30; amplification only n = 26, mutation only n = 1, both n = 3) or FGFR2 (N = 10; amplification only n = 2, mutation only n = 6, both n = 2) alterations were enrolled. Three patients in the FGFR1 cohort were not evaluable for efficacy; all patients in the FGFR2 cohort were evaluable. For the FGFR1 cohort, two patients with partial response and four with SD16+ were observed for DC and OR rates of 27% (90% CI, 13 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected (P = .169). No patients achieved DC in the FGFR2 cohort (P = 1.00). Thirteen of the 40 total patients across both cohorts had at least one grade 3-4 adverse event or serious adverse event at least possibly related to sunitinib. CONCLUSION: Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either FGFR1 or FGFR2 alterations. Other treatments and clinical trials should be considered for these patient populations.

Associations between health insurance status, neighborhood deprivation, and treatment delays in women with breast cancer living in Georgia.

BACKGROUND: Little is known regarding the association between insurance status and treatment delays in women with breast cancer and whether this association varies by neighborhood socioeconomic deprivation status. METHODS: In this cohort study, we used medical record data of women diagnosed with breast cancer between 2004 and 2022 at two Georgia-based healthcare systems. Treatment delay was defined as >90 days to surgery or >120 days to systemic treatment. Insurance coverage was categorized as private, Medicaid, Medicare, other public, or uninsured. Area deprivation index (ADI) was used as a proxy for neighborhood-level socioeconomic status. Associations between delayed treatment and insurance status were analyzed using logistic regression, with an interaction term assessing effect modification by ADI. RESULTS: Of the 14,195 women with breast cancer, 54% were non-Hispanic Black and 52% were privately insured. Compared with privately insured patients, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 79%, 75%, and 27% higher odds of delayed treatment, respectively (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.32-2.43; OR: 1.75, 95% CI: 1.43-2.13; OR: 1.27, 95% CI: 1.06-1.51). Among patients living in low-deprivation areas, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 100%, 84%, and 26% higher odds of delayed treatment than privately insured patients (OR: 2.00, 95% CI: 1.44-2.78; OR: 1.84, 95% CI: 1.48-2.30; OR: 1.26, 95% CI: 1.05-1.53). No differences in the odds of delayed treatment by insurance status were observed in patients living in high-deprivation areas. DISCUSSION/CONCLUSION: Insurance status was associated with treatment delays for women living in low-deprivation neighborhoods. However, for women living in neighborhoods with high deprivation, treatment delays were observed regardless of insurance status.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing ß values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality. Results: Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (ß=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock. Conclusion: We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.

Current approaches to the management of Her2-negative metastatic breast cancer.

While metastatic breast cancer (MBC) remains incurable, a vast array of active therapeutic agents has provided the opportunity for long-term disease control while maintaining quality of life and physical function. Optimal management of MBC balances a multitude of factors, including a woman's performance status, social support, symptoms, disease burden, prior therapies, and surrogates for tumor biology. Choosing the most appropriate initial therapy and subsequent sequence of treatments demands flexibility as goals and patient preferences may change. Knowledge of the estrogen receptor (ER), progesterone receptor (PR), and Her2 receptor status of the metastatic tumor has become critical to determining the optimal treatment strategy in the metastatic setting as targeted therapeutic approaches are developed. Patients with ER+ or PR+ breast cancer or both have a wide array of hormonal therapy options that can forestall the use of cytotoxic therapies, although rapidly progressive phenotypes and the emergence of resistance may ultimately lead to the need for chemotherapy in this setting. So-called 'triple-negative' breast cancer - lacking ER, PR, and Her2 overexpression - remains a major challenge. These tumors have an aggressive phenotype, and clear targets for therapy have not yet been established. Chemotherapy remains the mainstay of treatment in this group, but biologically based clinical trials of new agents are critical to developing a more effective set of therapies for this patient population.

Study Protocol: Efficacy and Safety of Radioembolization (REM) as an Early Modality (EM) Therapy for Metastatic Breast Cancer (BR) to the Liver with Y90 (REMEMBR Y90).

PURPOSE: The primary objective of the REMEMBR Y90 study is to evaluate the efficacy of Yttrium-90 (Y90) radioembolization in patients with breast cancer metastases to the liver as a 2nd or 3rd line treatment option with systemic therapy by assessing liver-specific and overall progression-free survival. Secondary objectives include quality of life, overall survival benefit, and toxicity in relation to patients' tumor biology. MATERIALS AND METHODS: This trial is a multi-center, prospective, Phase 2, open-label, IRB-approved, randomized control trial in the final phases of activation. Eligible patients include those over 18 years of age with metastatic breast cancer to the liver with liver-only or liver-dominant disease, and history of tumor progression on 1-2 lines of chemotherapy. 60 patients will be randomized to radioembolization with chemotherapy versus chemotherapy alone. Permissible regimens include capecitabine, eribulin, vinorelbine, and gemcitabine within 2 weeks of enrollment for every patient. Patients receiving radioembolization will receive lobar or segmental treatment within 1-6 weeks of enrollment depending on their lesion. After final radioembolization, patients will receive clinical and imaging follow-up every 12-16 weeks for two years, including contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen and whole-body positron emission tomography/computed tomography. DISCUSSION: This study seeks to elucidate the clinical benefit and toxicity of Y90 in patients with metastatic breast cancer to the liver who are receiving minimal chemotherapy. Given previous data, it is anticipated that the use of Y90 and chemotherapy earlier in the metastatic disease course would improve survival outcomes and reduce toxicity. LEVEL OF EVIDENCE: Level 1b, Randomized Controlled Trial. TRIAL REGISTRATION NUMBER: NCT05315687 on clinicaltrials.gov.

Association of Race and Area Deprivation With Breast Cancer Survival Among Black and White Women in the State of Georgia.

Importance: Increasing evidence suggests that low socioeconomic status and geographic residence in disadvantaged neighborhoods contribute to disparities in breast cancer outcomes. However, little epidemiological research has sought to better understand these disparities within the context of location. Objective: To examine the association between neighborhood deprivation and racial disparities in mortality among Black and White patients with breast cancer in the state of Georgia. Design, Setting, and Participants: This population-based cohort study collected demographic and geographic data from patients diagnosed with breast cancer between January 1, 2004, and February 11, 2020, in 3 large health care systems in Georgia. A total of 19 580 patients with breast cancer were included: 12 976 from Piedmont Healthcare, 2285 from Grady Health System, and 4319 from Emory Healthcare. Data were analyzed from October 2, 2020, to August 11, 2022. Exposures: Area deprivation index (ADI) scores were assigned to each patient based on their residential census block group. The ADI was categorized into quartile groups, and associations between ADI and race and ADI × race interaction were examined. Main Outcomes and Measures: Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% CIs associating ADI with overall mortality by race. Kaplan-Meier curves were used to visualize mortality stratified across racial and ADI groups. Results: Of the 19 580 patients included in the analysis (mean [SD] age at diagnosis, 58.8 [13.2] years), 3777 (19.3%) died during the course of the study. Area deprivation index contributed differently to breast cancer outcomes for Black and White women. In multivariable-adjusted models, living in a neighborhood with a greater ADI (more deprivation) was associated with increased mortality for White patients with breast cancer; compared with the ADI quartile of less than 25 (least deprived), increased mortality HRs were found in quartiles of 25 to 49 (1.22 [95% CI, 1.07-1.39]), 50 to 74 (1.32 [95% CI, 1.13-1.53]), and 75 or greater (1.33 [95% CI, 1.07-1.65]). However, an increase in the ADI quartile group was not associated with changes in mortality for Black patients with breast cancer (quartile 25 to 49: HR, 0.81 [95% CI, 0.61-1.07]; quartile 50 to 74: HR, 0.91 [95% CI, 0.70-1.18]; and quartile ≥75: HR, 1.05 [95% CI, 0.70-1.36]). In neighborhoods with an ADI of 75 or greater, no racial disparity was observed in mortality (HR, 1.11 [95% CI, 0.92-1.36]). Conclusions and Relevance: Black women with breast cancer had higher mortality than White women in Georgia, but this disparity was not explained by ADI: among Black patients, low ADI was not associated with lower mortality. This lack of association warrants further investigation to inform community-level approaches that may mitigate the existing disparities in breast cancer outcomes in Georgia.