Faculty Bibliography

Black women in the United States experience disproportionately high breast cancer mortality and have high rates of comorbid hypertension; however, the associations of hypertension and antihypertensive medication use with breast cancer survival are unclear. We examined these associations among 2474 Black Women's Health Study participants with invasive breast cancer. Hypertension and antihypertensive medication use were assessed biennially, and breast cancer diagnoses were confirmed through medical records and cancer registries. We used Cox proportional hazards models, adjusted for clinical and lifestyle factors and cancer treatment, to estimate hazard ratios (HR) for breast cancer-specific death. In the full study population, the HR for untreated hypertension compared to no hypertension was 1.17 (95% CI = 0.75-1.82), while the HR for treated hypertension compared to no hypertension was 0.81 (95% CI = 0.60-1.10). For ER+ cases, there was no association between untreated hypertension and breast cancer specific-death (HR = 0.96, 95% CI = 0.50-1.82), but a strong inverse association between treated hypertension and breast cancer-specific death (HR = 0.53, 95% CI = 0.34-0.83). In contrast, for ER- cases, we observed an increased risk of breast cancer specific death among those with untreated hypertension (HR = 2.19, 95% CI = 1.09-4.39), but there was little evidence of an association with treated hypertension (HR = 1.32, 95% CI = 0.80-2.19). Overall, our findings indicate that Black breast cancer patients with hypertension have better survival when their hypertension is treated, possibly due to regular healthcare engagement or the tumor suppressing actions of antihypertensive medications. Randomized trials are needed to establish causality and inform optimal cardiovascular management in oncology.

Breast cancer disparities in outcomes remain a persistent challenge in the USA, with survival influenced by neighborhood context, access to resources, and the applicability of existing scientific evidence across populations. These disparities arise from complex, intersectional factors spanning social, structural, and biologic domains. While social determinants of health (SDOH) are strongly associated with breast cancer incidence and outcomes, the causality of biologic mechanisms underlying these associations remain incompletely understood. This review examines breast cancer disparities at the societal level and highlights emerging research that links social epidemiology with tumor biology, emphasizing the need for continued investigation using advanced genomic and epigenetic approaches to better understand and ultimately reduce inequities in breast cancer outcomes.

Cancer disparities among populations in the United States are a persistent and ongoing challenge. Medical mistrust (MM), or the tendency to distrust individuals and systems even at the cost of one's own well-being, has been implicated in contributing to worse health outcomes. Thus, understanding the relationship between MM and cancer care disparities may inform effective interventions to improve outcomes for all. We conducted a two-step review: (1) a standard review to examine the relationship between MM and the cancer continuum of care, and (2) a systematic review to assess interventions targeted to mitigate MM in cancer care. The standard review included eleven studies, which revealed that MM impacted cancer screening, treatment adherence, clinical trial participation, and access to social support. Key mediators of MM included patient-provider discordance, health-related and sociodemographic-related discrimination, perceptions of Western medicine, low quality care, and health insurance. Our systematic review yielded twelve interventions-67% tailored towards screening, 17% towards patient navigation services, and 17% towards clinical trial participation. Key methods included adapting patient-centered (e.g. gathering patient perspectives, increasing racial and ethnic representation) and community-based approaches (e.g. use of churches and training family members to disseminate patient education) to overall create culturally tailored interventions against MM across the cancer continuum of care.

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. Implications: IR adipocyte exosomes modify the TME, enhance EMT, and promote brain metastasis-likely via miRNA pathways-suggesting that metabolic diseases like T2D foster a pro-metastatic TME, reducing survival, warranting close monitoring and potential metabolic interventions in TNBC patients with T2D.

Discrimination can contribute to worse health outcomes, but its prevalence in breast cancer is not well studied. We aimed to understand how women with stage I-III breast cancer faced discrimination in health care and everyday settings through the Everyday Discrimination Scale, cross-sectional survey. 296 women, 178 (60%) Non-Hispanic White (NHW), 76 (26%) Non-Hispanic Black (NHB), and 42 (14%) Hispanic participated. NHB women reported significantly more discrimination in everyday life compared to NHW women (score 20.1 vs 16.1, p < 0.001) and Hispanic women (score 20.1 vs 16.0, p < 0.001). In the health care setting, NHB had statistically more frequent reports of being ignored (23.7% vs. 5.6%), treated with less respect (21.1% vs. 7.3%), and treated with less courtesy (18.7% vs. 6.2%; all P = < 0.001) when compared to NHW women. NHB women experience a higher degree of discrimination both inside and outside of health care. Further research to understand discrimination on breast cancer outcomes is warranted.

Trastuzumab deruxtecan (T-DXd) is approved for HER2-low (HER2 immunohistochemistry (IHC)1+ or 2+ with non-amplified in situ hybridization (ISH)), but not HER2-0 (IHC 0) metastatic breast cancer. The impact of repeat biopsies (Bxs) in identifying new potential candidates with triple negative breast cancer (TNBC) for T-DXd treatment remains unknown. 512 consecutive patients with TNBC at diagnosis were included in the study cohort. Bxs were categorized as core, surgical, or metastatic based on the timing and method of biopsy (Bx) acquisition, and the total number of Bxs was determined for each patient. Additionally, matched biopsies were identified, and the rate of discordance in HER2 status was calculated. The proportion of patients with at least one HER2-low result increased as the number of successive Bxs increased [59%, 73%, 83%, 83%, and 100% when 1 (196 patients), 2 (231 patients), 3 (48 patients), 4 (29 patients), and ≥ 5 (8 patients) Bxs were obtained, respectively]. Among patients without a prior HER2-low result, approximately one-third demonstrated HER2-low status with each additional successive Bx. HER2 status exhibited variability between matched Bxs, with observed discordance rates of 26%, 44%, and 33% between matched core-surgical, early-metastatic, and two metastatic matched Bxs, respectively. Our findings indicate that HER2 status can vary between different Bxs taken during the disease course of patients with TNBC with the highest discordance rate observed between the primary and metastatic Bxs. For patients with metastastic HER2-0 TNBC, repeat Bxs can increase the chance of obtaining a HER2-low result, thereby offering patients a promising therapeutic option.

Women with obesity-driven diabetes are predisposed to more aggressive breast cancers. However, patient metabolic status does not fully inform the current standard of care. We previously identified plasma exosomes as functionally critical actors in intercellular communication and drivers of tumor progression. Here, we generated patient-derived organoids (PDOs) from breast tumor resections to model signaling within the tumor microenvironment (TME). Novel techniques and a short (1-week) culture preserved native tumor-infiltrating lymphocytes for the first time in breast tumor PDOs. After 3-day exosome treatment, we measured the impact of exosomal signaling on PDOs via single-cell RNA sequencing. Exosomes derived from Type 2 diabetic patient plasma significantly upregulated pathways associated with epithelial-to-mesenchymal transition, invasiveness, and cancer stemness, compared to non-diabetic exosome controls. Intratumoral heterogeneity and immune evasion increased in the diabetic context, consistent with enhanced tumor aggressiveness and metastatic potential of these PDOs. Our model of systemic metabolic dysregulation and perturbed transcriptional networks enhances understanding of dynamic interactions within the TME in obesity-driven diabetes and offers new insights into novel exosomal communication.

PURPOSE:We aimed to determine the availability of existing web-based educational materials on breast cancer survivorship and assess their readability and understandability. METHODS:We identified materials eligible for review in two ways: (1) reviews of websites of major cancer-related organizations (e.g., American Cancer Society); (2) Google searches for breast cancer survivorship, breast cancer, breast cancer follow-up care, and cancer survivorship. We measured Flesch-Kincaid and New Dale Readability of existing breast cancer and breast cancer survivorship materials. Readability grade levels 5 to 8 were considered ideal to acceptable. We used the Patient Education Materials Assessment Tool (PEMAT) to measure the understandability of 53 videos and 152 written materials, such as booklets and manuals. A resource was considered understandable and/or actionable if it scored ≥ 70% on either the understandability section or the actionability section of the PEMAT. RESULTS:grade reading level. According to the New Dale-Chall readability assessment, most of the materials were in the 9 to 10 grade level range. The average PEMAT score was 88.6% (range 56-100%). CONCLUSION:grade reading level. The PEMAT results, however, suggest that materials are easy to understand regarding word choice and style, use of numbers, organization, layout and design, and use of visual aids. IMPLICATIONS FOR CANCER SURVIVORS:Understandable patient education materials are essential for guiding breast cancer survivors towards improving their health outcomes and optimizing their quality of life.

PURPOSE/OBJECTIVE: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/CONCLUSIONS: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.