Background: This study investigated the association of vitamin D3 levels with breast cancer risk and progression in African-Americans and Hispanics. Methods: A total of 237 African-American (Cases = 119, Control = 118) and 423 Hispanic women (Cases = 124, Control = 299) were recruited in the study. Blood samples were collected at the time of breast cancer screening and prior to cancer treatment for 4 weeks on average for the cases. The serum 25-hydroxyvitamin D (25(OH)D3) was measured at a Quest-Diagnostics facility. Results: The results showed that 69.2% of African-Americans and 37.8% of Hispanics had 25(OH)D3 levels below 20 ng/mL. The 25(OH)D3 level below 20 ng/mL was significantly associated with breast cancer in both African-Americans (OR = 2.5, 95% CI = 1.3-4.8) and Hispanics (OR = 1.9, 95% CI = 1.1-3.0). However, the predicted probabilities of breast cancer in African-Americans were significantly higher than in Hispanics (p < 0.001). The 25(OH)D3 below 20 ng/mL was significantly associated with triple negative breast cancer (TNBC) in African-Americans (OR = 5.4, p = 0.02, 95% CI = 1.4-15), but not in Hispanics in our cohort of participants. Levels of 25(OH)D3 below 26 ng/mL predicts a decrease in disease-free survival, but it was not an independent predictor. Conclusions: Our data shows an association between 25(OH)D3 levels and the risk of breast cancer. Further studies on the relationship between 25(OH)D3 level and breast cancer risk are warranted.

Background

With the growing number of survivors of breast cancer outpacing the capacity of oncology providers, there is pressure to transition patients back to primary care. Primary care providers (PCPs) working in safety-net settings may have less experience treating survivors, and little is known about their knowledge and views on survivorship care. The current study was performed to determine the knowledge, attitudes, and confidence of PCPs in the safety net at delivering care to survivors of breast cancer.

Methods

A modified version of the National Cancer Institute's Survey of Physician Attitudes Regarding Care of Cancer Survivors was given to providers at 2 county hospitals and 5 associated clinics (59 providers). Focus groups were held to understand barriers to survivorship care.

Results

Although the majority of providers believed PCPs have the skills necessary to provide cancer-related follow-up, the vast majority were not comfortable providing these services themselves. Providers were adherent to American Society of Clinical Oncology recommendations for mammography (98%) and physical examination (87%); less than one-third were guideline-concordant for laboratory testing and only 6 providers (10%) met all recommendations. PCPs universally requested additional training on clinical guidelines and the provision of written survivorship care plans before transfer. Concerns voiced in qualitative sessions included unfamiliarity with the management of endocrine therapy and confusion regarding who would be responsible for certain aspects of care.

Conclusions

Safety-net providers currently lack knowledge of and confidence in providing survivorship care to patients with breast cancer. Opportunities exist for additional training in evidence-based guidelines and improved coordination of care between PCPs and oncology specialists.

Purpose

The aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment.

Methods

The effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay. Secreted Wnt3 level was determined by ELISA assay.

Results

HER2-overexpressing breast cancer cells treated with TGF-β have a reduced response to trastuzumab and exhibited EMT-like phenotype. The TGF-β-induced EMT in HER2-cells was concordant with upregulation of Wnt3 and β-catenin pathways. The TGF-β-induced induction of Wnt3 during EMT was found to be Smad3-dependent. ChIP analysis identified occupancy of Twist at promoter region of Wnt3. Knock-down of Twist by shRNA confirmed the significance of Twist in response to TGF-β regulating Wnt3 during EMT. Subsequently, TGF-β-induced matrix metalloproteinases, MMP1, MMP7, MMP9, MMP26, Vascular endothelial growth factors (VEGF), and activation of Wnt/β-catenin signaling were repressed by the shRNA treatment. TGF-βR1 ALK5 kinase inhibitor, A83-01 can effectively prevent the TGF-β-induced Twist and Wnt3. Co-treating A83-01 and trastuzumab inhibited TGF-β-induced cell invasion significantly in both trastuzumab responsive and resistant cells.

Conclusions

Our data demonstrated an important interdependence between TGF-β and Wnt/β-catenin pathways inducing EMT in HER2-overexpressing breast cancer cells. Twist served as a linkage between the two pathways during TGF-β-induced EMT. A83-01 could inhibit the TGF-β-initiated pathway interactions and enhance HER2-cells response to trastuzumab treatment.