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.

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.

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.