Association between Neighborhood Stressors and Allostatic Load in Breast Cancer Survivors: The Pathways Study.

Allostatic load (AL) is an intermediary outcome through which neighborhood drivers of health may impact cancer survivorship outcomes. We examined associations of neighborhood stressors and AL in 2,553 women with breast cancer recruited into the Pathways Study in 2006-2013. AL score was derived from biomarkers in the cardiovascular, metabolic, and immune domains of physiological stress measured within 3 years after baseline. Neighborhood data were appended to participants' geocoded baseline addresses. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate associations between neighborhood stressors and risk of higher AL score. Adjusting for age and stage, high AL was positively associated with low versus high neighborhood socioeconomic status (nSES; OR=2.24, 95% CI=1.61-3.12) and green space (OR=1.55, 95% CI=1.18-2.03); high versus low traffic (OR=1.32, 95% CI=1.01-1.72), crime (OR=1.32, 95% CI=1.05-1.67), and household crowding (OR=1.57, 95% CI=1.22-2.01); and more versus no fast-food restaurants (OR=1.50, 95% CI=1.21-1.84). Associations remained for nSES and fast-food restaurants after co-adjustment with other neighborhood stressors, and for fast-food restaurants after additional adjustment with individual sociodemographic and lifestyle factors. Our preliminary findings can inform further studies of the physiological effects of neighborhood stressors, which collectively may help improve survivorship outcomes for the growing population of breast cancer survivors.

The Impact of Insider Researcher Trainees in Recruiting and Retaining Latinx in an Outdoor Health Promotion Research Study.

Latinx represent the second largest ethnic group in the USA and remain significantly underrepresented in research studies. Efforts to better include Latinx make use of community-engaged research (CEnR) approaches, peer-navigators, and cultural humility training for research teams. While these efforts have led to slight increases in Latinx participation, studies to identify strategic practices for better inclusion of Latinx participants are needed. The objective of this study was to qualitatively examine factors leading to successful recruitment and retention of Latinx participants in the Promoting Activity and Stress Reduction in the Outdoors (PASITO) intervention. For this intervention, 99 low-income Latinx clients in a local community were contacted and 52 participants were recruited (53%). All were retained in the 3-month intervention. Of these, 12 were interviewed within 6 months of the close of PASITO by bi-cultural and bi-lingual non-research staff. They conducted one-on-one structured telephone interviews. Of the twelve participants, three (25%) were men, nine (75%) were women, and the mean age was 43.7 (SD = 8.7). Four critical themes for the recruitment and retention of Latinx populations emerged from the interviews: (1) importance of insider researchers; (2) sense of community and belonging; (3) responsive programming; and (4) health-promoting activities. These findings support the significant role insider researchers can play, and social identity theory provides a useful framework for understanding the role of insider researchers in recruiting and retaining Latinx, and likely other minoritized groups, in clinical studies. Insider researchers possess the skills, training, community cultural wealth, in-depth understanding of their communities, and structural competencies that position them to carry out more inclusive studies to address the needs of marginalized communities and advance science.

Cortisol levels in rural Latina breast cancer survivors participating in a peer-delivered cognitive-behavioral stress management intervention: The Nuevo Amanecer-II RCT.

Background: Compared to their White counterparts, Latina breast cancer survivors have poorer survival rates and health-related quality of life, and higher rates of depression and anxiety which may be a result of chronic stress. Chronic stress impacts the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol dysregulation which may be associated with breast cancer survival. However, cortisol levels and cortisol profiles of Latina breast cancer survivors are poorly characterized due to their underrepresentation in biomedical research. Objective: The objective of this study was to describe cortisol levels and patterns of cortisol secretions in rural Latina breast cancer survivors participating in an RCT study of Nuevo Amanecer-II, an evidence-based peer-delivered cognitive behavioral stress management intervention. Methods: Participant-centered recruitment and collection strategies were used to obtain biospecimens for cortisol analysis. Nine saliva samples (3/day for 3 days) and a hair sample were obtained at baseline and 6-months (3-months post-intervention). We describe cortisol levels and profiles, explore correlations of biomarkers with self-report measures of stress and psychological distress, and compare women who received the intervention with a delayed intervention group on biomarkers of stress. Mean hair cortisol concentration (HCC) was used to assess chronic stress. Based on daily measures of cortisol (awakening, 30 min post-awakening, and bedtime), we calculated three summary measures of the dynamic nature of the cortisol awakening response (CAR): 1) the CAR slope, 2) whether CAR demonstrates a percent change ≥40, and 3) total daily cortisol output (AUCg). Linear and log-binomial regression, accounting for multiple samples per participant, were used to compare cortisol measures at 6-month follow-up by treatment arm. Results: Participants (n = 103) were from two rural California communities; 76 provided at least one saliva sample at baseline and follow-up and were included in the analysis. At baseline, mean age was 57 years, mean years since diagnosis was 2 years, 76% had a high school education or less, and 34% reported financial hardship. The overall median CAR slope was 0.10, and median cortisol AUCg (in thousands) was 11.34 (range = 0.93, 36.66). Mean hair cortisol concentration was 1751.6 pg/mg (SD = 1148.6). Forty-two percent of samples had a ≥40% change in CAR. We found no statistically significant correlations between the cortisol measures and self-reported measures of stress and psychological distress. At follow-up, no differences were seen in HCC (mean difference between intervention and control: -0.11, 95% CI -0.48, 0.25), CAR slope (0.001, 95% CI -0.005, 0.008), cortisol AUCg (-0.15, 95% CI -0.42, 0.13), or ≥40% change in CAR (prevalence ratio 0.87, 95% CI 0.42, 1.77) between treatment arms. Conclusion: Our findings of flattened cortisol profiles among more than half of the sample suggest potential HPA-axis dysregulation among rural Spanish-speaking Latina breast cancer survivors that merits further study due to its implications for long-term survival. Trial registration: http://www.ClinicalTrials.gov identifier NCT02931552.

Sharing research results with Latina breast cancer survivors who participated in a community-engaged behavioral RCT study: a descriptive cross-sectional survey study.

BACKGROUND: An often heard and justifiable concern of ethnic minorities is related to researchers' lack of attention to sharing the results of a study with participants after the study has concluded. Few studies have examined the effects of returning overall study results on participants' attitudes, especially among populations underrepresented in research. Among Latina research participants, providing a summary of study results could enhance participation in research. We assess Latina breast cancer survivors' reactions to receiving study results and their attitudes about participating in future studies. METHODS: For this cross-sectional survey study, all women who had participated in two behavioral randomized controlled trials (RCTs) were mailed a letter summarizing the study results (using written and graphic formats) and a questionnaire assessing problems and understanding the results, importance of sharing results, willingness to participate in future studies, and format preferences for receiving the results. A postage-paid envelope for returning the completed questionnaire was included. Logistic regression examined the associations of age, education, and rural/urban residence on format preferences and willingness to participate. The survey sample consisted of 304 low-income, predominantly Spanish-speaking Latina breast cancer survivors (151 from urban and 153 from rural communities) who had participated in two RCTs testing a stress management program designed for Latina breast cancer survivors. RESULTS: Ninety-two women returned the questionnaires (30.3%). Most of the women (91.1%) indicated that they had no trouble understanding the results of the study, and 97% agreed that it is very/extremely important for researchers to share the study result with the participants. The majority (60.2%) reported that receiving the results increased their willingness to participate in future studies. About half (51.7%) did not have a format preference, 37.4% preferred written summaries, and 10.9% preferred graphs. CONCLUSIONS: This study is an important first step to understanding the impact of returning study results among a population that is underrepresented in research. Returning the results of studies and understanding the impact of doing so is consistent with maintaining community involvement in all phases of research. The findings suggest that sharing aggregate research results in simple language yields few problems in participants' understanding of the results and is viewed as important by participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02931552 Date registered: October 13, 2016 and NCT01383174 Date registered: June 28, 2011.

Self-Efficacy for Coping with Breast Cancer Treatment Among Spanish-Speaking Latinas.

Background: Cancer-related self-efficacy, a multidimensional construct, is the confidence that one can overcome challenges associated with cancer and its treatment; higher levels have been associated with better psychosocial outcomes of breast cancer survivors. Little is known about factors that influence it among Latina breast cancer survivors. Purpose: Assess associations of several aspects of health care processes and of spirituality with self-efficacy for coping with breast cancer treatment among primarily Spanish-speaking Latina breast cancer survivors. Methods: We analyzed baseline data from a randomized controlled trial of a cognitive-behavioral stress management intervention that enrolled 151 Spanish-speaking Latinas within 1 year of breast cancer diagnosis. Multivariate linear regression models examined associations of health care processes (quality of breast cancer care and information, participating in medical care, difficulty engaging with doctors) and spirituality (meaning/peace, faith, acceptance) with self-efficacy for coping with breast cancer treatment. Results: Mean age was 51 (standard deviation [SD]=11), 66% completed high school or less, and most reported financial hardship in the past year (78%). Average time since diagnosis was 3.8 months (SD=2.7). In bivariate analyses, all six determinants were significantly associated with self-efficacy for coping with breast cancer treatment; participating in medical care (B=0.56, p<0.001) and having a sense of meaning/peace (B=0.76; p<0.001) were independently associated, controlling for sociodemographic and treatment characteristics. Discussion: Interventions that promote participation in treatment decisions and sense of meaning and peace could improve confidence in coping with breast cancer treatment, and potentially quality of life, among Latinas living with breast cancer (Trial Registration Number: NCT01383174 [ClinicalTrials.gov]).

The importance of patient engagement to quality of breast cancer care and health-related quality of life: a cross-sectional study among Latina breast cancer survivors in rural and urban communities.

BACKGROUND: Compared to their white counterparts, Latina breast cancer survivors experience poorer quality of care and worse health-related quality of life. Limited English proficiency (LEP) and patient engagement in cancer care could help explain these disparities. We assessed associations between LEP status and difficulty engaging with physicians, with self-reported quality of breast cancer care and health-related quality of life (physical and emotional well-being) among rural and urban Latina breast cancer survivors. METHODS: Analyses used cross-sectional baseline survey data from two studies that tested a stress management program among rural and urban Latina breast cancer survivors in California. Medical information was collected through medical records review. Linear regression models examined bivariate and multivariable associations of LEP status (yes or no), difficulty engaging with doctors (asking questions and participating in treatment decisions) (1-4; higher score = greater difficulty), and rural versus urban site, with three outcomes: (1) quality of breast cancer care and information; (2) physical well-being; and (3) and emotional well-being, controlling for demographic and medical factors. RESULTS: The total sample included 304 women (151 from urban and 153 from rural sites). Mean age was 52.7 years (SD 10.9). Most were limited English proficient (84.5%) and had less than a high school education (67.8%). Difficulty engaging with doctors was inversely associated with patient ratings of quality of breast cancer care and information (B = - 0.190, p = 0.014), emotional well-being (B = - 1.866, p < 0.001), and physical well-being (B = - 1.272, p = 0.002), controlling for demographic and treatment factors. LEP (vs. not; B = 1.987, p = 0.040) was independently associated with physical well-being only. Rural/urban status was not related independently to any outcome. CONCLUSIONS: Rural and urban Latina breast cancer survivors who report greater difficulty engaging with physicians experienced worse quality of breast cancer care and health-related quality of life. Promoting greater engagement of Latina breast cancer survivors in cancer care and providing medical interpreters when needed could improve patient outcomes among this vulnerable group. TRIAL REGISTRATION: http://www.ClinicalTrials.gov identifier NCT02931552 and NCT01383174.

Nuevo Amanecer-II: Results of a randomized controlled trial of a community-based participatory, peer-delivered stress management intervention for rural Latina breast cancer survivors.

OBJECTIVE: We report results of a community-based multisite, randomized controlled trial of Nuevo Amanecer (NA-II), a 10-week stress management program for rural, low literacy Latina breast cancer survivors. METHODS: Trained peers delivered NA-II to Spanish-speaking Latinas with non-metastatic breast cancer in three rural communities. Women were randomized to receive the program immediately or wait 6 months. Assessments were conducted at baseline, 3 months, and 6 months. Primary outcomes were breast cancer-specific quality of life domains; secondary outcomes included general distress symptoms and stress management skills. Intention-to-treat analyses using repeated-measures linear regression models estimated changes in slope between groups. RESULTS: Of 153 participants (76 randomized to intervention, 77 to control group), 92% were retained at 6 months. Mean age was 54.8 years (SD = 10.5); 80% had less than high school education. There were no statistically significant treatment × time effects on quality of life. Compared to women in the control group, intervention group women reported greater improvements in anxiety at 6 months (-0.20 vs -0.02, P = .049; range 0-4) as well as three stress management skills: relaxation at 3 months (+0.98 vs -0.07, P < .0001; range 0-4) and 6 months (+0.82 vs +0.04, P < .001), awareness of tension at 3 months (+0.31 vs -0.19, P < .01; range 0-4) and 6 months (+0.29 vs -0.11, P < .05), and coping confidence at 3 months (+0.12 vs -0.23, P < .01; range 0-4). CONCLUSIONS: Stress management programs delivered by trained peers in rural community settings can reduce anxiety and improve stress management skills among Latina breast cancer survivors.

Participant-Centered Strategies for Overcoming Barriers to Biospecimen Collection among Spanish-Speaking Latina Breast Cancer Survivors.

BACKGROUND: Latinos are underrepresented in biomedical research, particularly biomarker research, yet they constitute the nation's largest ethnic/racial minority. Optimal methods for obtaining biospecimens for biomarker research among Latinos need to be identified. To minimize barriers and enhance participation, this study developed and tested tailored strategies for collecting biomarkers of chronic stress and premature aging among Spanish-speaking Latina breast cancer survivors. METHODS: This study used a community-based participatory approach and selected hair and saliva as noninvasive biospecimens to assess telomere length, the cortisol awakening response (CAR), and hair cortisol concentration. We developed bilingual multimedia instructional materials, and community health workers assisted in collections. Telephone surveys assessed willingness to participate in future studies, barriers to sample collection, and recommendations for improving the strategies. RESULTS: A total of 103 participants were recruited over 18 months from two rural sites in California, and 88 were retained at 6-month follow-up. At baseline, rates of donating salivary DNA for telomere length measurement, saliva for CAR analysis, and hair for cortisol concentration were 98%, 89%, and 52%, respectively. At follow-up, rates were 83%, 76%, and 55%, respectively. The majority of participants reported being very willing to provide hair (72%) or saliva (74%) for future studies. CONCLUSIONS: Our results support the feasibility of including minorities in biomedical research. We report excellent rates of saliva collection when community partners are engaged in the process, and when patient-centered and culturally tailored recruitment methods are implemented. IMPACT: The development of methods to facilitate the inclusion of minorities in biomedical research is critical to eliminate racial/ethnic health disparities.

Translating a stress management intervention for rural Latina breast cancer survivors: The Nuevo Amanecer-II.

OBJECTIVES: Adapt a cognitive-behavioral stress management program (Nuevo Amanecer or NA) to be generalizable to rural, low literacy Spanish-speaking Latinas with breast cancer survivors at all phases of survivorship. METHODS: Apply the Transcreation Framework, a community-engaged translational model, to develop the adapted program (Nuevo Amanecer or NA-II), design a randomized controlled trial for community settings, identify recruiters and interventionists, and recruit participants into the trial. RESULTS: Adaptations included expanding the program from eight to ten weeks, simplifying materials, and increasing skills practice. We added stress management videos, healthy lifestyles information, and survivorship information. Interventionists were trained Latina breast cancer survivors. All core components of NA were retained in NA-II including managing the impact of cancer, information on breast cancer and its treatment, finding cancer information, getting support, managing thoughts, stress management techniques, and setting goals. Participants receive a program manual. Each session includes a review of that week's content using the manual, practicing a stress-management skill, setting a specific goal, and reviewing videos. Spanish-speaking Latinas with non-metastatic breast cancer were recruited by community recruiters. Of 231 women approached, 24% refused, 10% were ineligible, and 153 (66%) were randomized to the intervention or a wait-list control group. The sample was vulnerable: 69% had < high school education, more than half had only Medicaid or no insurance, 91% was foreign born, and 48% reported financial hardship in the past year. CONCLUSIONS: Applying the Transcreation Framework to engage stakeholders in designing community-based RCTs enhanced congruence with community contexts and recruitment of this vulnerable population.

Therapeutic Use of Estrogen Receptor ß Agonists in Prevention and Treatment of Endocrine Therapy Resistant Breast Cancers: Observations From Preclinical Models.

Breast cancer is one of the most common cancers in the world. The majority of breast cancers express estrogen receptor (ER)α, and endocrine therapy is the primary therapeutic approach to treat ER positive breast cancers. However, developing resistance and side effects are common events of these therapeutic strategies. Recent studies have evaluated the role of ERs sub types and demonstrated that ERα is a tumorigenic and ERß functions as a tumor suppressor. In recent years, preclinical studies focused on the use of natural and synthetic ERß agonists to treat wide varieties of cancers, including breast cancer. Successful studies conducted so far, have established that ERß agonists are effective both alone and in combination with chemotherapeutic agents. These data have suggested that use of ERß agonists in combination with endocrine therapy may be an effective treatment strategy in hormone receptor positive breast cancers. The present review focuses on the tumor suppressive role of ERß, and the efficacy and mechanisms of several natural and synthetic ERß agonists against breast cancer.

PELP1 overexpression in the mouse mammary gland results in the development of hyperplasia and carcinoma.

Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents. Recent studies in our laboratory, as well as others, demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene. PELP1 interactions with histone demethylase KDM1 play a critical role in its oncogenic functions and PELP1 is a prognostic indicator of decreased survival in patients with breast cancer. However, the in vivo significance of PELP1 deregulation during initiation and progression of breast cancer remains unknown. We generated an inducible, mammary gland-specific PELP1-expressing transgenic (Tg) mouse (MMTVrtTA-TetOPELP1). We found more proliferation, extensive side branching, and precocious differentiation in PELP1-overexpressing mammary glands than in control glands. Aged MMTVrtTA-TetOPELP1 Tg mice had hyperplasia and preneoplastic changes as early as 12 weeks, and ER-positive mammary tumors occurred at a latency of 14 to 16 months. Mechanistic studies revealed that PELP1 deregulation altered expression of a number of known ER target genes involved in cellular proliferation (cyclin D1, CDKs) and morphogenesis (EGFR, MMPs) and such changes facilitated altered mammary gland morphogenesis and tumor progression. Furthermore, PELP1 was hyper-phosphorylated at its CDK phosphorylation site, suggesting an autocrine loop involving the CDK-cyclin D1-PELP1 axis in promoting mammary tumorigenesis. Treatment of PELP1 Tg mice with a KDM1 inhibitor significantly reduced PELP1-driven hyperbranching, reversed alterations in cyclin D1 expression levels, and reduced CDK-driven PELP1 phosphorylation. These results further support the hypothesis that PELP1 deregulation has the potential to promote breast tumorigenesis in vivo and represent a novel model for future investigation into molecular mechanisms of PELP1-mediated tumorigenesis.

Debunking 'race' and asserting social determinants as primary causes of cancer health disparities: outcomes of a science education activity for teens.

Cancer health disparities are often described as the unequal burden of cancer deaths in one racial/ethnic group compared to another. For example, national cancer statistics in the USA shows that Blacks die the most for 9 of the top 10 cancers in men and women. When asked about the underlying causes for this disparity, teen participants speculated that it is primarily due to genetics or biology. This speculation appears to be based on a false concept of 'race.' A science activity was created to counter the false concept that genetics/biology underlie the categorization of humans into different 'races.' This activity provided teen participants with first-hand evidence of how they are all related at one genetic locus, and how they are more genetically related across racial/ethnic groups than within them. Results of surveys given before and after the activity show that they change their perceptions of 'race.' Before the activity, they view themselves as most related at the genetic level to 1-2 well-known individuals (i.e., celebrities) who they perceive as members of their own 'race' mainly because of similar appearance. After the activity, they view themselves as related to more/all the celebrities or they state that they do not know to whom they are most related. This increased awareness of the uncertainty between the apparent 'race' of an individual and their genetics drives teens to dismiss genetics or biology as the primary cause of racial/ethnic disparities in cancer outcomes. Instead, they consider the unequal distribution of the social determinants of health as the primary cause of cancer disparities.

Factors influencing time to diagnosis after abnormal mammography in diverse women.

BACKGROUND: Abnormal mammograms are common, and the risk of false positives is high. We surveyed women in order to understand the factors influencing the efficiency of the evaluation of an abnormal mammogram. METHODS: Women aged 40-80 years, identified from lists with Breast Imaging Reporting and Data System (BIRADS) classifications of 0, 3, 4, or 5, were surveyed. Telephone surveys asked about the process of evaluation, and medical records were reviewed for tests and timing of evaluation. RESULTS: In this study, 970 women were surveyed, and 951 had chart reviews. Overall, 36% were college graduates, 68% were members of a group model health plan, 18% were Latinas, 25% were African Americans, 15% were Asian, and 43% were white. Of the 352 women who underwent biopsies, 151 were diagnosed with cancer (93 invasive). Median time to diagnosis was 183 days for BIRADS 3 compared to 29 days for BIRADS 4/5 and 27 days for BIRADS 0. At 60 days, 84% of BIRADS 4/5 women had a diagnosis. Being African American (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.49-0.97, p=0.03), income < $10,000 (HR 0.55, 95% CI 0.31-0.98, p<0.04), perceived discrimination (HR 0.22, 95% CI 0.09-0.52, p<0.001), not fully understanding the results of the index mammogram (HR 0.49, 95% CI 0.32-0.75, p=0.001), and being notified by letter (HR 0.66, 95% CI 0.48-0.90, p=0.01) or telephone (HR 0.62, 95% CI 0.42-0.92, p=0.02) rather than in person were all associated with significant delays in diagnosis. CONCLUSIONS: Evaluation of BIRADS 0, 4, or 5 abnormal mammograms was completed in most women within the recommended 60 days. Even within effective systems, correctible communication factors may adversely affect time to diagnosis.