Using a cultural dance program to increase sustainable physical activity for breast cancer survivors-A pilot study.

BACKGROUND: Studies have shown that physical activity can reduce the risk of mortality for female breast cancer patients and improve quality of life, reduce weight, and alter circulating biomarker levels. We conducted a pilot trial to determine the feasibility of increasing physical activity through a cultural dance intervention to achieve similar benefits. METHODS: Conducted a pilot trial implementing a cultural dance intervention to increase and sustain physical activity for breast cancer survivors, which consisted of a six-month group-based intervention of Hula Dance. Anthropometric measures, fasting blood draws, and self-reported questionnaires to assess physical activity, mood, and quality of life, were completed at baseline, at the end of the 6-month intervention (time point month-6), and at two additional post-intervention time points (month-12 and month-24) to assess sustainability. RESULTS: A total of 11 women with a median age of 63 years were enrolled in the intervention trial. Eight of the 11 (73%) completed the trial to month-12 and demonstrated an overall significant increase in weekly moderate exercise. There were no significant changes in intra-individual body mass index (BMI). However, there was a sustained post-intervention reduction in waist circumference and significant changes in circulating biomarker levels. For the self-reported measures, there was a significant increase in vigor/activity (p < 0.001; Profile of Mood States-Short Form). CONCLUSION: Our intervention pilot trial demonstrated that a cultural dance program could achieve a sustainable increase in physical activity for breast cancer survivors, with potential to improve quality of life, increase vigor, and decrease levels of circulating cytokines associated with obesity and inflammation.

Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model.

Aberrant sphingolipid metabolism has been reported to promote breast cancer progression. Sphingosine kinase 1 (SphK1) is a key metabolic enzyme for the formation of pro-survival S1P from pro-apoptotic ceramide. The role of SphK1 in breast cancer has been well studied in estrogen receptor (ER)-positive breast cancer; however, its role in human epidermal growth factor 2 (HER2)-positive breast cancer remains unclear. Here, we show that genetic deletion of SphK1 significantly reduced mammary tumor development with reduced tumor incidence and multiplicity in the MMTV-neu transgenic mouse model. Gene expression analysis revealed significant reduction of claudin-2 (CLDN2) expression in tumors from SphK1 deficient mice, suggesting that CLDN2 may mediate SphK1's function. It is remarkable that SphK1 deficiency in HER2-positive breast cancer model inhibited tumor formation by the different mechanism from ER-positive breast cancer. In vitro experiments demonstrated that overexpression of SphK1 in ER-/PR-/HER2+ human breast cancer cells enhanced cell proliferation, colony formation, migration and invasion. Furthermore, immunostaining of SphK1 and CLDN2 in HER2-positive human breast tumors revealed a correlation in high-grade disease. Taken together, these findings suggest that SphK1 may play a pivotal role in HER2-positive breast carcinogenesis. Targeting SphK1 may represent a novel approach for HER2-positive breast cancer chemoprevention and/or treatment.

Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients.

There is limited knowledge about the biological basis of racial/ethnic disparities in breast cancer outcomes. Aberrations in IGF signaling induced by obesity and other factors may contribute to these disparities. This study examines the expression profiles of the insulin-like growth factor (IGF)-axis proteins and the association with breast cancer survival across a multiethnic population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF-binding proteins), and IGFBP3 proteins in breast tumor tissue and their relationships with all-cause and breast cancer-specific survival up to 17 years postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native Hawaiians, Caucasians, and Japanese were compared. Covariates included demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian patients, IGFBP2 and IGFBP3 expression were each independently associated with overall and breast cancer mortality (IGFB2: HR(mort) = 10.96, 95% CI: 2.18-55.19 and HR(mort) = 35.75, 95% CI: 3.64-350.95, respectively; IGFBP3: HR(mort) = 5.16, 95% CI: 1.27-20.94 and HR(mort) = 8.60, 95% CI: 1.84-40.15, respectively). IGF1R expression was also positively associated with all-cause mortality in Native Hawaiians. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients. The interaction of race/ethnicity and IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have variable influence on breast cancer progression across different racial/ethnic groups. Expression of binding proteins and receptors in breast tumors may influence survival in breast cancer patients by inducing aberrations in IGF signaling and/or through IGF-independent mechanisms. Additional studies to evaluate the role of the IGF-axis in breast cancer are critical to improve targeted breast cancer treatment strategies.

Building Native Hawaiian capacity in cancer research and programming. A legacy of 'Imi Hale.

In 2000, cancer health indicators for Native Hawaiians were worse than those of other ethnic groups in Hawai'i, and Native Hawaiians were under-represented in research endeavors. To build capacity to reduce cancer health disparities, 'Imi Hale applied principles of community-based participatory research (CBPR) and empowerment theory. Strategies included: 1) engaging Native Hawaiians in defining cancer priorities; 2) developing culturally appropriate processes and products; 3) supplementing primary and secondary cancer prevention activities; 4) offering skills training and technical assistance; and 5) providing an infrastructure to support culturally appropriate research. Between 2000 and 2005, 'Imi Hale involved more than 8000 Native Hawaiians in education, training, and primary and secondary prevention activities; developed 24 culturally tailored educational products (brochures, curricula, and self-help kits); secured $1.1 million in additional program and research funds; trained 98 indigenous researchers, 79 of whom worked on research projects; and engaged more than 3000 other Native Hawaiians as research participants and advisors. Evidence of empowerment was seen in increased individual competence, enhanced community capacity and participation, reduced barriers, and improved supports to address cancer in Hawaiian communities. Operationalizing CBPR and empowerment requires a commitment to involving as many people as possible, addressing community priorities, following cultural protocol, developing and transferring skills, and supporting an infrastructure to reduce barriers and build supports to sustain change. This approach is time consuming, but necessary for building competence and capacity, especially in indigenous and minority communities. Cancer 2006. (c) 2006 American Cancer Society.

Ethnicity and breast cancer in Hawaii: increased survival but continued disparity.

OBJECTIVES: To examine ethnic variation in survival among 7722 women diagnosed with invasive breast cancer in Hawaii between 1990 and 2002 and to extend previous multivariate analyses by adding a new prognostic variable: estrogen receptor/progesterone receptor (ER/PR) status. DESIGN: Cox regression analysis of retrospective data. SETTING: Population-based data from the Hawaii Tumor Registry, which is part of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. PARTICIPANTS: 7722 women in 5 ethnic groups--Caucasian, Chinese, Japanese, Filipino, and Native Hawaiian--diagnosed with invasive breast cancer between 1990 and 2002. MAIN OUTCOME MEASURE: Survival, examining death from breast cancer and death from a cause other than breast cancer. RESULTS: Compared to Caucasians, significantly smaller proportions of Japanese and Chinese women and larger proportions of Native Hawaiian and Filipino women were diagnosed in later stages of disease and at earlier ages. The four minority ethnic groups had higher rates of ER+PR+ tumors than Caucasians. For both causes of death, ethnic disparities in survival were reduced, but still existed, after controlling for age, stage, and ER/PR status. Japanese had the highest rates of survival for either cause of death. Native Hawaiians and Filipinos had the lowest rates of survival for breast cancer, and Native Hawaiians and Caucasians had the lowest rates of survival for other causes of death. CONCLUSIONS: Future studies should examine other reasons for continued ethnic differences in breast cancer survival in Hawaii, including socioeconomic status, access to insurance, adequacy of recommended screening frequency, comorbid conditions, treatment appropriateness and compliance, and genetic markers of tumor aggressiveness.

Ethnic differences in breast cancer in Hawai'i: age, stage, hormone receptor status, and survival.

Previous examinations of breast cancer and survival in Hawai'i's 5 major ethnic groups have found that Native Hawaiian women have the highest breast cancer mortality rates. Although ethnic disparities in survival are reduced when age and stage at diagnosis are controlled for statistically, prior studies could not explain ethnic variation in survival among women who were diagnosed at the same stage. We examined variations in breast tumor characteristics for a multiethnic sample of 4,583 women diagnosed in 1990-1997 by stage and age group and extended previous multivariate analyses by adding a new prognostic variable: estrogen receptor (ER) and progesterone receptor (PR) status. Logistic regression was used to examine the influence of age, stage, and hormone status on 5-year survival. With a few exceptions, greater proportions of Native Hawaiian women were diagnosed both in later stages of disease and at earlier ages compared to women of other ethnicities, and smaller proportions of Native Hawaiians survived 5 years post diagnosis in each stage and age group. Surprisingly, greater proportions of Native Hawaiian women in all age groups had ER/PR positive tumors, which is a prognostic indicator for better, not worse, survival. Native Hawaiian women had an increased risk of death and Japanese women had an increased chance of survival after controlling for age, stage, and ER/PR status. Future studies should examine other reasons for better survival of Japanese women and worse survival of Native Hawaiian women, including socioeconomic status, access to health insurance, adequacy of recommended screening frequency, co-morbid conditions, treatment appropriateness and compliance, and genetic markers of tumor aggressiveness.