De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer.

BACKGROUND: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. METHODS: The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. RESULTS: More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. CONCLUSIONS: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

Racial and ethnic disparities in outcomes with radiation therapy for rectal adenocarcinoma.

BACKGROUND: Race/ethnicity may modify cancer outcomes and manifest as survival disparities for patients with rectal cancer. Our objective was to determine whether disparate rectal cancer outcomes result from variable efficacy of radiation therapy for major racial/ethnic groups. METHODS: The Los Angeles County Cancer Surveillance Program (CSP) identified patients with rectal adenocarcinoma between the years 1988 and 2006. Patients who underwent curative-intent surgery were grouped by race/ethnicity and by receipt (yes vs. no) and timing (neoadjuvant vs. adjuvant) of radiation therapy. The impact of receipt and timing of radiation therapy on overall survival was then assessed. RESULTS: Of 4,961 patients in CSP, 2,229 (45%) received radiation therapy. Overall, there was no difference in survival among patients according to receipt of radiation therapy. We then examined the radiation cohort, wherein 919 (41%) and 1,310 (59%) patients received neoadjuvant or adjuvant radiation, respectively. Overall, patients who received neoadjuvant compared to adjuvant radiation had improved survival (median survival (MS), 9.4 vs. 6.8 years, respectively; p < 0.001). Among those patients who received neoadjuvant radiation, whites, Hispanics, and Asians had significantly longer survival than blacks (MS, 10.4, 10.4, and 10.4 vs. 4.4 years, respectively; p = 0.003). On multivariate analysis, race/ethnicity was an independent predictor of survival (p = 0.001). CONCLUSIONS: To our knowledge, this is the first study examining the efficacy of radiation therapy for racial/ethnic groups with rectal cancer. Disparate outcomes were observed for the administration of radiation therapy for select racial/ethnic groups. The reasons for these disparities in outcomes should be investigated to better optimize radiation therapy for patients with rectal cancer.

The contextual model of HRQoL: a paradigm for expanding the HRQoL framework.

Cancer is the second leading cause of death in most US populations. Unfortunately, ethnic minority status is associated with increased later stage at diagnosis, greater incidence for many cancer sites, differential treatments, greater mortality and morbidity. The government and public health focus on health disparities, evident in several documents including Healthy People 2010, Unequal Treatment and the Nation's Investment in Cancer Research, are spurring interest in research with ethnic minority populations. Research investigating the health-related quality of life (HRQoL) among ethnic minority cancer survivors is new and growing. However, there is a dearth of research that addresses theoretical frameworks in cross cultural research. In conducting research with diverse populations, appropriate theoretical grounding that is responsive to cultural and socioecological contexts must be considered. This paper will discuss the contextual model of HRQoL, a comprehensive framework developed to expand the traditional HRQoL framework to facilitate culturally and socioecologically responsive research. This model may provide a more comprehensive theoretical framework to investigate certain areas of health disparities and risk factors for poor outcomes in HRQoL research with cancer survivors.

Can a culturally responsive model for research design bring us closer to addressing participation disparities? Lessons learned from cancer survivorship studies.

INTRODUCTION: Health disparities research demands the inclusion of traditionally excluded peoples. Additional complex issues weigh into health disparities or multicultural research including sociopolitical context, cultural context, network or community context, and micro-level or personal dimensions. CONCEPTUAL FRAMEWORK: This paper will present a work in progress based on psycho-oncology research: A Culturally Responsive Model for Research Design. The manuscript will describe the model's governing principles and practices employed to address these study components: 1) purpose of the research; (2) utilization of modified or new conceptual framework and operationalization; (3) methods and procedures; (4) participant and data safety and monitoring; (5) reliable and valid instrumentation; (6) drawing valid conclusions; (7) dissemination of findings; and (8) staff training. This paper will define these issues and present the guiding principles modeled to conduct culturally responsive research and increase research integrity. DISCUSSION: Cancer control research is an important part of the stated commitment to reduce cancer incidence, morbidity, and mortality and to increase health-related quality of life. Ethnic minorities are overrepresented in cancer burden, yet underrepresented in research. This paper is part of a movement to articulate practical models for designing culturally responsive, multicultural research. The model may have implications for increasing ethnic minority participation in research.

Understanding the breast cancer experience of women: a qualitative study of African American, Asian American, Latina and Caucasian cancer survivors.

Breast cancer is the most common form of cancer in American women across most ethnic groups. Although the psychosocial impact of breast cancer is being studied, there is little information on women from diverse ethnic and socioeconomic backgrounds. We conducted a qualitative study with breast cancer survivors (BCS) of various ethnicities. A total of 102 BCS participated in focus group interviews (24 African Americans, 34 Asians, 26 Latinas and 18 Caucasians); 20 health professionals participated in key informant interviews. Important ethnic differences in type of treatment were noted, Asians and Latinas were more likely to receive mastectomies and African American BCS were least likely to receive adjuvant therapies, including radiation and chemotherapy. These BCS enjoyed a fairly good overall health-related quality of life (HRQOL) with some persistent concerns. The prevailing concerns among all women included overall health, moderate physical concerns, cancer recurrence or metastases, psychosocial concerns related to worry about children and burdening the family, and body image and sexual health concerns. Additional challenges included: lack of knowledge about breast cancer; medical care issues such as insurance, cost and amount of time spent with physician; cultural sensitivity of providers, language barriers, cultural factors related to beliefs about illness, gender role and family obligations (e.g. self-sacrifice). These BCS, particularly the women of color, voiced that their spiritual beliefs and practices are central to their coping. This study accomplishes two goals; it adds to the sparse literature concerning the psychosocial sequelae of breast cancer among women of color, and it increases our knowledge of specific cultural influences (e.g. dietary practices, coping) and socio-ecological factors on HRQOL. More importantly, the study addressed areas that have not been studied before, specifically, an in-depth study on BCS QOL comparing multiple ethnic groups in the US. The results of this investigation will provide preliminary information to survivors and health-care providers about the impact of culture and socio-ecological contexts on survivorship. Among women of all major ethnic groups, breast cancer is the most common form of cancer and the second leading cause of cancer death (American Cancer Society (ACS), 2002). In 2002, over 203,000 women in the United States will be diagnosed with breast cancer (ACS, 2002). Ethnic disparities exist for cancer stage, diagnosis, survival, morbidity and mortality. In general, ethnic minority women are diagnosed with more advanced disease and experience greater morbidity and mortality (Haynes & Smedley, 1999; Miller et al., 1996; Ries et al., 2000; Shinagawa, 2000). In general, increases in survival rates have prompted greater interest in the quality of life (QOL) of breast cancer survivors (BCS) over the past two decades. Additionally, the QOL of cancer survivors from diverse ethnic, cultural and socioeconomic backgrounds is an emerging priority area for studies on survivorship research and clinical care (Haynes and Smedley, 1999; National Cancer Institute (NCI), 2002; President's Cancer Panel, 2000).