Insulin Resistance Increases TNBC Aggressiveness and Brain Metastasis via Adipocyte-derived Exosomes.

Patients with triple negative breast cancer (TNBC) and comorbid Type 2 Diabetes (T2D), characterized by insulin resistance of adipose tissue, have higher risk of metastasis and shorter survival. Adipocytes are the main non-malignant cells of the breast tumor microenvironment (TME). However, adipocyte metabolism is usually ignored in oncology and mechanisms that couple T2D to TNBC outcomes are poorly understood. Here we hypothesized that exosomes, small vesicles secreted by TME breast adipocytes, drive epithelial-to-mesenchymal transition (EMT) and metastasis in TNBC via miRNAs. Exosomes were purified from conditioned media of 3T3-L1 mature adipocytes, either insulin-sensitive (IS) or insulin-resistant (IR). Murine 4T1 cells, a TNBC model, were treated with exosomes in vitro (72h). EMT, proliferation and angiogenesis were elevated in IR vs. control and IS. Brain metastases showed more mesenchymal morphology and EMT enrichment in the IR group. MiR-145a-3p is highly differentially expressed between IS and IR, and potentially regulates metastasis. Significance: IR adipocyte exosomes modify TME, increase EMT and promote metastasis to distant organs, likely through miRNA pathways. We suggest metabolic diseases such as T2D reshape the TME, promoting metastasis and decreasing survival. Therefore, TNBC patients with T2D should be closely monitored for metastasis, with metabolic medications considered.

Risk of contralateral breast cancer among Asian/Pacific Islander women in the United States.

PURPOSE: While breast cancer studies often aggregate Asian/Pacific Islander (API) women, as a single group or exclude them, this population is heterogeneous in terms of genetic background, environmental exposures, and health-related behaviors, potentially resulting in different cancer outcomes. Our purpose was to evaluate risks of contralateral breast cancer (CBC) among subgroups of API women with breast cancer. METHODS: We conducted a retrospective cohort study of women ages 18 + years diagnosed with stage I-III breast cancer between 2000 and 2016 in the Surveillance, Epidemiology and End Results registries. API subgroups included Chinese, Japanese, Filipina, Native Hawaiian, Korean, Vietnamese, Indian/Pakistani, and other API women. Asynchronous CBC was defined as breast cancer diagnosed in the opposite breast 12 + months after first primary unilateral breast cancer. Multivariable-adjusted subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) were estimated and stratified by API subgroups. RESULTS: From a cohort of 44,362 API women with breast cancer, 25% were Filipina, 18% were Chinese, 14% were Japanese, and 8% were Indian/Pakistani. API women as an aggregate group had increased risk of CBC (SHR 1.15, 95% CI 1.08-1.22) compared to NHW women, among whom Chinese (SHR 1.23, 95% CI 1.08-1.40), Filipina (SHR 1.37, 95% CI 1.23-1.52), and Native Hawaiian (SHR 1.69, 95% CI 1.37-2.08) women had greater risks. CONCLUSION: Aggregating or excluding API patients from breast cancer studies ignores their heterogeneous health outcomes. To advance cancer health equity among API women, future research should examine inequities within the API population to design interventions that can adequately address their unique differences.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

INTRODUCTION: Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. RESULTS: A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). CONCLUSION: At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Breast cancer survivorship experiences among Black women.

BACKGROUND: Black women experience significant disparities in breast cancer across the care continuum, including survivorship. Ensuring that Black women obtain high-quality follow-up care is critical but understudied. This study was aimed at understanding the experiences and needs of Black women during breast cancer survivorship. METHODS: Black patients diagnosed with invasive breast cancer within the past 5 years were invited to participate in a focus group and complete a survey. Focus groups examined the following: (1) the transition from active treatment to survivorship; (2) interactions with health care providers; (3) survivorship experiences, information needs, and preferences; and (4) existing educational materials. Results were thematically coded and analyzed for main themes. Surveys collected information on sociodemographics, health care experiences, quality of life, lifestyle, and education needs. RESULTS: The study enrolled 53 participants, 43 of whom completed a survey and participated in one of 11 focus groups. The median age was 54 years, 44% had private insurance, 81% were English speaking, and 86% had completed their treatment more than a year before. Participants identified the importance of relationships with health care providers, gaps in survivorship care, experiences with cancer-related symptoms, challenges with mental health, worry about recurrence, body image, cancer financial toxicity, and coping through religion and spirituality. Unmet needs were centered around preparation for long-term symptoms, diet and physical activity, emotional support, and more explanations of information resources. Participants reported preferences for educational videos, personal stories, and culturally relevant content. CONCLUSIONS: Some Black breast cancer survivors may have specific challenges and preferences. Supportive interventions that address these concerns can be responsive and help to ameliorate disparities.

Association of Race, Ethnicity, Insurance, and Language and Rate of Breast-Conserving Therapy Among Women With Nonmetastatic Breast Cancer at an Urban, Safety-Net Hospital.

INTRODUCTION: Breast-conserving therapy (BCT), specifically breast-conserving surgery (BCS) and adjuvant radiation, provides an equivalent alternative to mastectomy for eligible patients. However, previous studies have shown that BCT is underused in the United States, particularly among marginalized demographic groups. In this study, we examine the association between race, ethnicity, insurance, and language and rate of BCS among patients treated at an academic, safety-net hospital. MATERIALS AND METHODS: We conducted a retrospective cohort study of 520 women with nonmetastatic breast cancer diagnosed and treated at an academic, safety-net hospital (2009-2014). We assessed eligibility for BCT and then differences in the rate of BCT among eligible patients by race, ethnicity, insurance, and language. Reasons for not undergoing BCT were documented. RESULTS: Median age was 60 y; 55.9% were non-White, 31.9% were non-English-speaking, 15.6% were Hispanic, and 47.4% were Medicaid/uninsured. Three hundred seventy one (86.3%) underwent BCS; within this group, 324 (87.3%) completed adjuvant radiation. Among patients undergoing mastectomy, 30 patients (36.7%) were eligible for BCT; within this group, reasons for mastectomy included patient preference (n = 28) and to avoid possible re-excision or adjuvant radiation in patients with significant comorbidities (n = 2). Eligibility for BCT varied by ethnicity (Hispanic [100%], Non-Hispanic [92%], P = 0.02), but not race, language, or insurance. Among eligible patients, rate of BCS varied by age (<50 y [84.9%], ≥50 y [92.9%], P = 0.01) and ethnicity (Hispanic [98.5%], Non-Hispanic [91.3%], P = 0.04), but not race, language, or insurance. CONCLUSIONS: At our safety-net hospital, the rate of BCS among eligible patients did not vary by race, language, or insurance. Excluding two highly comorbid patients, all patients who underwent mastectomy despite being eligible for BCT were counseled regarding BCS and expressed a preference for mastectomy. Further research is needed to understand the value of BCT in the treatment of breast cancer, to ensure informed decision-making, address potential misconceptions regarding BCT, and advance equitable care for all patients.

Axillary Lymph Node Dissection is Associated with Improved Survival Among Men with Invasive Breast Cancer and Sentinel Node Metastasis.

BACKGROUND: Male breast cancer (MBC) is rare, and management is extrapolated from trials that enroll only women. It is unclear whether contemporary axillary management based on data from landmark trials in women may also apply to men with breast cancer. This study aimed to compare survival in men with positive sentinel lymph nodes after sentinel lymph node biopsy (SLNB) alone versus complete axillary dissection (ALND). PATIENTS AND METHODS: Using the National Cancer Database, men with clinically node-negative, T1 and T2 breast cancer and 1-2 positive sentinel nodes who underwent SLNB or ALND were identified from 2010 to 2020. Both 1:1 propensity score matching and multivariate regression were used to identify patient and disease variables associated with ALND versus SLNB. Survival between ALND and SLNB were compared using Kaplan-Meier methods. RESULTS: A total of 1203 patients were identified: 61.1% underwent SLNB alone and 38.9% underwent ALND. Treatment in academic centers (36.1 vs. 27.7%; p < 0.0001), 2 positive lymph nodes on SLNB (32.9 vs. 17.3%, p < 0.0001) and receipt or recommendation of chemotherapy (66.5 vs. 52.2%, p < 0.0001) were associated with higher likelihood of ALND. After propensity score matching, ALND was associated with superior survival compared with SLNB (5-year overall survival of 83.8 vs. 76.0%; log-rank p = 0.0104). DISCUSSION: The results of this study suggest that among patients with early-stage MBC with limited sentinel lymph node metastasis, ALND is associated with superior survival compared with SLNB alone. These findings indicate that it may be inappropriate to extrapolate the results of the ACOSOG Z0011 and EORTC AMAROS trials to MBC.

Breast cancer treatment receipt and the role of financial stress, health literacy, and numeracy among diverse breast cancer survivors.

PURPOSE: Disparities in breast cancer treatment for low-income and minority women are well documented. We examined economic hardship, health literacy, and numeracy and whether these factors were associated with differences in receipt of recommended treatment among breast cancer survivors. METHODS: During 2018-2020, we surveyed adult women diagnosed with stage I-III breast cancer between 2013 and 2017 and received care at three centers in Boston and New York. We inquired about treatment receipt and treatment decision-making. We used Chi-squared and Fisher's exact tests to examine associations between financial strain, health literacy, numeracy (using validated measures), and treatment receipt by race and ethnicity. RESULTS: The 296 participants studied were 60.1% Non-Hispanic (NH) White, 25.0% NH Black, and 14.9% Hispanic; NH Black and Hispanic women had lower health literacy and numeracy and reported more financial concerns. Overall, 21 (7.1%) women declined at least one component of recommended therapy, without differences by race and ethnicity. Those not initiating recommended treatment(s) reported more worry about paying large medical bills (52.4% vs. 27.1%), worse household finances since diagnosis (42.9% vs. 22.2%), and more uninsurance before diagnosis (9.5% vs. 1.5%); all P < .05. No differences in treatment receipt by health literacy or numeracy were observed. CONCLUSION: In this diverse population of breast cancer survivors, rates of treatment initiation were high. Worry about paying medical bills and financial strain were frequent, especially among non-White participants. Although we observed associations of financial strain with treatment initiation, because few women declined treatments, understanding the scope of impact is limited. Our results highlight the importance of assessments of resource needs and allocation of support for breast cancer survivors. Novelty of this work includes the granular measures of financial strain and inclusion of health literacy and numeracy.

Mitigating disparities in breast cancer treatment at an academic safety-net hospital.

PURPOSE: Among women with non-metastatic breast cancer, marked disparities in stage at presentation, receipt of guideline-concordant treatment and stage-specific survival have been shown in national cohorts based on race, ethnicity, insurance and language. Little is published on the performance of safety-net hospitals to achieve equitable care. We evaluate differences in treatment and survival by race, ethnicity, language and insurance status among women with non-metastatic invasive breast cancer at a single, urban academic safety-net hospital. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2014 at an urban, academic safety-net hospital. Demographic, tumor and treatment characteristics were obtained. Stage at presentation, stage-specific overall survival, and receipt of guideline-concordant surgical and adjuvant therapies were analyzed. Chi-square analysis and ANOVA were used for statistical analysis. Unadjusted survival analysis was conducted by Kaplan-Meier method using log-rank test; adjusted 5 year survival analysis was completed stratified by early and late stage, using flexible parametric survival models incorporating age, race, primary language and insurance status. RESULTS: 520 women with stage 1-3 invasive breast cancer were identified. Median age was 58.5 years, 56.1% were non-white, 31.7% were non-English-speaking, 16.4% were Hispanic, and 50.1% were Medicaid/uninsured patients. There were no statistically significant differences in stage at presentation between age group, race, ethnicity, language or insurance. The rate of breast conserving surgery (BCS) among stage 1-2 patients did not vary by race, insurance or language. Among patients indicated for adjuvant therapies, the rates of recommendation and completion of therapy did not vary by race, ethnicity, insurance or language. Unadjusted survival at 5 years was 93.7% for stage 1-2 and 73.5% for stage 3. Adjusting for age, race, insurance status and primary language, overall survival at 5 years was 93.8% (95% CI 86.3-97.2%) for stage 1-2 and 83.4% (95% CI 35.5-96.9%) for stage 3 disease. Independently, for patients with early- and late-stage disease, age, race, language and insurance were not associated with survival at 5-years. CONCLUSION: Among patients diagnosed and treated at an academic safety-net hospital, there were no differences in the stage at presentation or receipt of guideline-concordant treatment by race, ethnicity, insurance or language. Overall survival did not vary by race, insurance or language. Additional research is needed to assess how hospitals and healthcare systems mitigate breast cancer disparities.

OPTIMAL Breast Cancer Care: Effect of an Outpatient Pharmacy Team to Improve Management and Adherence to Oral Cancer Treatment.

PURPOSE: Since the approval of cyclin-dependent kinase 4/6 inhibitors in 2015, this oral cancer (OC) therapy has been combined with oral endocrine therapy as first-line treatment in metastatic hormone receptor-positive breast cancer, adding unique toxicity and complexity to the successful administration of this oral medication. Implementation of OC is challenging because of delays in treatment and nonadherence and is worse among vulnerable patient populations. Pharmacists may mitigate these barriers with facilitation of prior authorizations, communication with pharmacies, toxicity management, adherence counseling, and optimization of dosing schedules and regimens. MATERIALS AND METHODS: We conducted a quality improvement project to decrease the average number of treatment day delays during the first six cycles of OC. Patients were enrolled on the OPTIMAL protocol, a high-touch pharmacy intervention incorporating pharmacists within outpatient oncology clinic visits with the providers. Pharmacists met with patients, identified individual barriers to treatment, and performed counseling including toxicity and adherence assessments. RESULTS: A preintervention assessment identified an average treatment day delay of 7.7 (range, 3.2-15.3) days during the first six cycles of OC. During the intervention period, 53 patients were enrolled on the OPTIMAL protocol and experienced an average treatment day delay of 2.1 (0.6-4) days, P < .0001. Delays were characterized as modifiable and unmodifiable. Pharmacists documented 640 interventions, including medication reconciliations and clinical recommendations. Forty-two patients reported treatment-related toxicities, resulting in 33 therapy and 20 dose modifications. CONCLUSION: Our initiative to incorporate pharmacists in clinic visits at an outpatient breast cancer clinic was associated with decreased treatment day delays during the first six cycles of treatment. Pharmacists performed a multitude of meaningful interventions to facilitate treatment in a particularly vulnerable population and play a valuable role in comanaging patients.

Impact of Race, Ethnicity, Primary Language, and Insurance on Reconstruction after Mastectomy for Patients with Breast Cancer at an Urban, Academic Safety-Net Hospital.

BACKGROUND: Disparities in breast reconstruction have been observed in national cohorts and single-institution studies based on race, ethnicity, insurance, and language. However, little is known regarding whether safety-net hospitals deliver more or less equitable breast reconstruction care in comparison with national cohorts. STUDY DESIGN: We performed a retrospective study of patients with either invasive breast cancer or ductal carcinoma in situ diagnosed and treated at our institution (January 1, 2009, to December 31, 2014). The rate of, timing of, and approach to breast reconstruction were assessed by race, ethnicity, insurance status, and primary language among women who underwent mastectomy. Reasons for not performing reconstruction were also analyzed. RESULTS: A total of 756 women with ductal carcinoma in situ or nonmetastatic invasive cancer were identified. The median age was 58.5 years, 56.2% were non-White, 33.1% were non-English-speaking, and 48.9% were Medicaid/uninsured patients. A total of 142 (18.8%) underwent mastectomy during their index operation. A total of 47.9% (n = 68) did not complete reconstruction. Reasons for not performing reconstruction included patient preference (n = 22), contraindication to immediate reconstruction (ie, locoregionally advanced disease prohibiting immediate reconstruction) without follow-up for consideration of delayed reconstruction (n = 12), prohibitive medical risk or contraindication (ie, morbid obesity; n = 8), and progression of disease, prohibiting reconstruction (n = 7). Immediate and delayed reconstruction were completed in 43.7% and 8.5% of patients. The rate of reconstruction was inversely associated with tumor stage (odds ratio 0.52, 95% CI 0.31 to 0.88), but not race, ethnicity, insurance, or language, on multivariate regression. CONCLUSIONS: At a safety-net hospital, we observed rates of reconstruction at or greater than national estimates. After adjustment for clinical attributes, rates did not vary by race, ethnicity, insurance or language. Future research is needed to understand the role of reconstruction in breast cancer care and how to advance shared decision-making among diverse patients.

Breast cancer knowledge and understanding treatment rationales among diverse breast cancer survivors.

PURPOSE: The degree to which breast cancer survivors know about their tumors and understand treatment rationales is not well understood. We sought to identify information gaps within a diverse sample and explore whether knowledge about breast cancer and treatment may impact care. METHODS: We conducted a one-time, interviewer-administered survey of women who were diagnosed with breast cancer during 2013-2017 and received care at one of three centers in Boston, MA, and New York, NY. We examined knowledge of breast cancer and treatment rationales, information preferences, and treatment receipt. RESULTS: During 2018-2020, we interviewed 313 women (American Association for Public Opinion Research Cooperation Rates 58.4-76.5% across centers) who were 56.9% White, 23.6% Black, 14.1% Hispanic, and 5.4% other. Among the 296 included in analyses, we observed high variability in knowledge of breast cancer and treatment rationales, with a substantial number demonstrating limited knowledge despite feeling highly informed; > 25% actively avoided information. Black and Hispanic (vs. White) women consistently knew less about their cancers. Lack of understanding of treatment rationales for chemotherapy, radiation, and hormonal therapy was common but not consistently different by race and ethnicity. Understanding treatment rationale (but not cancer knowledge) was associated with treatment initiation, but small sample sizes limited in-depth examination. CONCLUSIONS: Our study highlights the need for enhanced informational support for breast cancer survivors, who are challenged with complex information during the decision-making process and beyond. More research is needed to understand how to further educate and empower diverse populations of patients with breast cancer.

Predictors of long-term durable response in de novo HER2-positive metastatic breast cancer and the real-world treatment experience at two institutions.

PURPOSE: HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR). Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature. Patient factors that predict DR continue to be elucidated. METHODS: This is a retrospective study of patients with de novo HER2 + MBC. DR is defined as absence of progression/death at any point after diagnosis. Controls are patients with evidence of progression/death. Age, ER/PR status, sites of metastasis, surgical resection of primary tumor, and initial treatment were analyzed. RESULTS: 96 patients with de novo HER2 + MBC, 28 with DR, and 68 with progression were identified. 75% of patients with DR had a single metastatic site, compared with 47% of patients with progression (OR 3.7, p = 0.01). 64% of patients with DR received a regimen containing trastuzumab, pertuzumab, and a taxane, while 28% of patients who progressed did (OR 4.5, p < 0.001). 57% of patients with DR underwent surgical removal of breast primary, compared with 24% of patients who progressed (OR 4.3, p = 0.002.) Among patients with DR, nine patients have been receiving trastuzumab for over ten years with no evidence of disease and one patient opted to discontinue trastuzumab. CONCLUSION: Nearly a third of patients with de novo HER2 + MBC achieved DR. Factors that correlate with DR include single metastatic site, initial trastuzumab, pertuzumab and taxane therapy, and surgical resection of primary tumor. Among patients with DR, indefinite trastuzumab administration is the norm.

The Role of Race and Insurance Status in Access to Genetic Counseling and Testing Among High-Risk Breast Cancer Patients.

PURPOSE: The role of germline genetic testing in breast cancer patients is crucial, especially in the setting of the recent trials showing the benefit of PARP inhibitors. The goal of this study was to identify racial disparities in genetic counseling and testing in patients with high-risk breast cancer. METHODS: Patients with 2 unique breast cancer diagnoses were examined to understand demographics, insurance coverage, characteristics of breast cancer, and whether they were recommended for and received genetic counseling and testing. RESULTS: A total of 69 patients with a dual diagnosis of breast cancer between the years 2000 and 2017 were identified (42% identified as White compared to 58% that identified as non-White). White patients were more likely to be recommended for genetic counseling (OR = 2.85; 95% CI, 1.07-7.93, P < .05), be referred for genetic counseling (OR = 3.17; 95% CI, 1.19-8.86, P < .05), receive counseling (OR = 3.82; 95% CI, 1.42-10.83, P < .01), and undergo genetic testing (OR = 2.88; 95% CI, 0.97-9.09, P = .056) compared to non-White patients. Patients with private insurance were significantly more likely to be recommended for genetic counseling (OR 5.63, P < .005), referred (OR 6.11, P < .005), receive counseling (OR 4.21, P < .05), and undergo testing (OR 4.10, P < .05). When controlled for insurance, there was no significant racial differences in the rates of GC recommendation, referral, counseling, or testing. CONCLUSION: The findings of this study suggest that disparities in genetic counseling and testing are largely driven by differences in health insurance.

Patient navigation to address sociolegal barriers for patients with cancer: A comparative-effectiveness study.

BACKGROUND: Sociolegal barriers to cancer care are defined as health-related social needs like affordable healthy housing, stable utility service, and food security that may be remedied by public policy, law, regulation, or programming. Legal support has not been studied in cancer care. METHODS: The authors conducted a randomized controlled trial of patients who had newly diagnosed cancer at a safety-net medical center in Boston from 2014 through 2017, comparing standard patient navigation versus enhanced navigation partnered with legal advocates to identify and address sociolegal barriers. English-speaking, Spanish-speaking, or Haitian Creole-speaking patients with breast and lung cancer were eligible within 30 days of diagnosis. The primary outcome was timely treatment within 90 days of diagnosis. Secondary outcomes included patient-reported outcomes (distress, cancer-related needs, and satisfaction with navigation) at baseline and at 6 months. RESULTS: In total, 201 patients with breast cancer and 19 with lung cancer enrolled (response rate, 78%). The mean patient age was 55 years, 51% of patients were Black and 22% were Hispanic, 20% spoke Spanish and 8% spoke Haitian Creole, 73% had public health insurance, 77% reported 1 or more perceived sociolegal barrier, and the most common were barriers to housing and employment. Ninety-six percent of participants with breast cancer and 73% of those with lung cancer initiated treatment within 90 days. No significant effect of enhanced navigation was observed on the receipt of timely treatment among participants with breast cancer (odds ratio, 0.88; 95% CI, 0.17-4.52) or among those with lung cancer (odds ratio, 4.00; 95% CI, 0.35-45.4). No differences in patient-reported outcomes were observed between treatment groups. CONCLUSIONS: Navigation enhanced by access to legal consultation and support had no impact on timely treatment, patient distress, or patient needs. Although most patients reported sociolegal barriers, few required intensive legal services that could not be addressed by navigators. LAY SUMMARY: In patients with cancer, the experience of sociolegal barriers to care, such as unstable housing, utility services, or food insecurity, is discussed. Addressing these barriers through legal information and assistance may improve care. This study compares standard patient navigation versus enhanced navigation partnered with legal advocates for patients with breast and lung cancers. Almost all patients in both navigation groups received timely care and also reported the same levels of distress, needs, and satisfaction with navigation. Although 75% of patients in the study had at least 1 sociolegal barrier identified, few required legal advocacy beyond what a navigator who received legal information and coaching could provide.

Physical functioning, frailty and risks of locally-advanced breast cancer among older women.

OBJECTIVE: Women with multiple comorbidities have competing health needs that may delay screening for early detection of breast cancer. Our objective was to determine associations between physical functioning and frailty with risk of locally-advanced breast cancer (BC). METHODS: We conducted a retrospective cohort study of women 65 years and older diagnosed with first primary stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Physical health-related quality of life was measured using Veterans RAND 12 Item Health Survey scales within two years before diagnosis; frailty was determined by calculating deficit-accumulation frailty index (DAFI) scores. Multivariable modified Poisson regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for risk of locally-advanced (stage III) versus early-stage (I-II) BC. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 2189 (91%) were diagnosed with incident stage I-II BC and 222 (9%) were diagnosed at stage III. Compared to women with early-stage disease, women with locally-advanced BC had lower physical component scores (37.8 vs. 41.4) and more classified as pre-frail or frail (55% vs. 50%). In multivariable models, frailty was not associated with increased risk of locally-advanced disease. However, worse physical function subscale scores (lowest vs. upper quartile; RR = 1.56, 95% CI 1.04-2.34) were associated with risk of locally-advanced BC. CONCLUSIONS: Breast cancer screening among non-frail older women should be personalized to include women with limited physical functioning if the benefits of screening and early detection outweigh the potential harms.

Impact of socioeconomic status and rurality on cancer-specific survival among women with de novo metastatic breast cancer by race/ethnicity.

PURPOSE: There are approximately 150,000 women living with metastatic breast cancer (mBC) in the United States. Disparities in de novo mBC incidence and mortality exist across race/ethnicity, socioeconomic status (SES), and rurality. However, how SES and rurality independently impact mBC outcomes across different racial/ethnic groups is not fully understood. The purpose of this study was to determine the impact of SES and rurality on cancer-specific mortality among women with mBC by race/ethnicity. METHODS: We conducted a large, population-based retrospective cohort study in women aged 18 + years diagnosed with de novo mBC using the Surveillance, Epidemiology and End Results Census Tract-level SES and Rurality Database (2000-2015). Associations between SES/rurality and cancer-specific mortality were determined using Fine and Gray regression models. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) by race/ethnicity and hormone receptor (HR) status were calculated. RESULTS: A cohort of 33,976 women were included with the majority being White (67%), 17% Black, 0.4% American Indian/Alaskan Native, 6% Asian/Pacific Islander, and 10% Latina/Hispanic. We observed the greatest increased risk of BC mortality among Black women with HR-negative mBC residing in neighborhoods with lower SES (lowest versus highest quintile: SHR 1.38, 95% CI 1.00-1.90) and in rural areas compared to urban areas (SHR 1.27, 95% CI 1.01-1.59). CONCLUSION: Overall, BC-specific survival among women with de novo mBC differs by race/ethnicity, with the greatest adverse impacts of SES and rurality affecting Black women with HR-negative disease.

Impact of time to distant recurrence on breast cancer-specific mortality in hormone receptor-positive breast cancer.

Women with hormone receptor (HR)-positive early-stage breast cancer (BC) have five-year survival rates of > 90% but remain at serious risk for developing distant metastases beyond five years from diagnosis. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to examine associations between distant recurrence-free interval (DRFI) and risk of BC-specific mortality following distant relapse. The analysis includes 1,057 women with second primary stage IV BC who were initially diagnosed with AJCC stages I-III HR-positive BC between1990 and 2016. Overall, 65% of women had a preceding DRFI of ≥ 5 years. Five-year BC-specific survival following development of distant recurrence was 52% for women with DRFI ≥ 5 years compared to 31% in women with DRFI of < 5 years. In multivariable analyses, risks of cancer-specific mortality following distant recurrence were lower in women with DRFI of 5 years or more (subdistribution hazard ratio = 0.72, 95% CI 0.58-0.89, p = 0.002). The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients who develop a distant recurrence of disease.

Assessment of patient navigation programs for breast cancer patients across the city of Boston.

PURPOSE: Healthcare systems contribute to disparities in breast cancer outcomes. Patient navigation is a widely cited system-based approach to improve outcomes among populations at risk for delays in care. Patient navigation programs exist in all major Boston hospitals, yet disparities in outcomes persist. The objective of this study was to conduct a baseline assessment of navigation processes at six Boston hospitals that provide breast cancer care in preparation for an implementation trial of standardized navigation across the city. METHODS: We conducted a mixed methods study in six hospitals that provide treatment to breast cancer patients in Boston. We administered a web-based survey to clinical champions (n = 7) across six sites to collect information about the structure of navigation programs. We then conducted in-person workflow assessments at each site using a semi-structured interview guide to understand site-specific implementation processes for patient navigation programs. The target population included administrators, supervisors, and patient navigators who provided breast cancer treatment-focused care. RESULTS: All sites offered patient navigation services to their patients undergoing treatment for breast cancer. We identified wide heterogeneity in terms of how programs were funded/resourced, which patients were targeted for navigation, the type of services provided, and the continuity of those services relative to the patient's cancer treatment. CONCLUSIONS: The operationalization of patient navigation varies widely across hospitals especially in relation to three core principles in patient navigation: providing patient support across the care continuum, targeting services to those patients most likely to experience delays in care, and systematically screening for and addressing patients' health-related social needs. Gaps in navigation across the care continuum present opportunities for intervention. TRIAL REGISTRATION: Clinical Trial Registration Number NCT03514433, 5/2/2018.