Satisfaction With Clinician-Led Germline Genetic Counseling in Patients With Prostate Cancer.

PURPOSE: Indications for germline testing in prostate cancer patients have expanded substantially over the past decade. With a near-universal shortage of genetic counselors and increasing demand, increased access to genetic counseling is crucial. We sought to prospectively implement and assess a clinician-led approach to genetic counseling and testing. MATERIALS AND METHODS: Patients with metastatic or localized prostate cancer meeting National Comprehensive Cancer Network® criteria for consideration of genetic testing were offered pre-test genetic counseling by their urologist or medical oncologist as part of their routine clinical care and concurrently approached for enrollment in the Germline Genetics in Prostate Cancer Study. Consented patients filled out a post-counseling survey using validated instruments to assess the quality of counseling. For patients who elected to undergo genetic testing, an additional validated questionnaire was completed following disclosure of results. The primary outcome was the proportion of patients undergoing testing, with a target >60% of patients. The secondary outcome was overall satisfaction with counseling, with a target >85% of patients. RESULTS: A total of 275 patients enrolled, and 203 patients elected to undergo genetic testing. Post-counseling surveys were obtained from 265 patients, and post-genetic testing surveys were obtained from 132 patients. Patient satisfaction was high, with 98% of patients reporting being satisfied with the overall quality of pre-test counseling, and 74% of patients elected to undergo genetic testing. CONCLUSIONS: These results support the effectiveness of clinician-led genetic counseling in prostate cancer. With clinician training, this approach can be utilized to expand access to appropriate germline genetic testing.

Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.

PURPOSE: The burden of cancer in Africa is an enlarging public health challenge. Breast cancer in Ghana is the second most common cancer among Ghanaian women and the proportion of diagnosed patients who complete prescribed treatment is estimated to be very limited, thereby potentially adding to lower survival and poor quality of life after diagnosis. The objective of this study was to identify the patient and system factors related to incomplete treatment of breast cancer among patients. METHODS: This study was conducted at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. We interviewed 117 breast cancer patients and next of kin of breast cancer patients diagnosed from 2008 to 2010. RESULTS: Islamic religion, seeking treatment with traditional healers, and lack of awareness about national health insurance coverage of breast cancer treatment were predictors of incomplete treatment. CONCLUSIONS: The results of this study support that Ghanaian women with diagnosed breast cancer have multiple addressable and modifiable patient factors that may deter them from completing the prescribed treatment. The results highlight the need for developing and testing specific interventions about the importance of completing treatment with a special focus on addressing religious, cultural, and system navigation barriers in developing countries.

A comparison of criteria to identify inflammatory breast cancer cases from medical records and the Surveillance, Epidemiology and End Results data base, 2007-2009.

Inflammatory breast cancer (IBC) is a relatively rare and extremely aggressive form of breast cancer that is diagnosed clinically. Standardization of clinical diagnoses is challenging, both nationally and internationally; moreover, IBC coding definitions used by registries have changed over time. This study aimed to compare diagnostic factors of IBC reported in a U.S. Surveillance, Epidemiology, and End Results (SEER) registry to clinical criteria found in the medical records of all invasive breast cancer cases at a single institution. We conducted a medical record review of all female invasive breast cancers (n = 915) seen at an NCI-designated comprehensive cancer center in Detroit from 2007 to 2009. IBC cases were identified based on the presence of the main clinical characteristics of the disease (erythema, edema, peau d'orange). We compared the proportion of IBC out of all breast cancers, using these clinical criteria and the standard SEER IBC codes. In the reviewed cases, the clinical criteria identified significantly more IBC cases (n = 74, 8.1%) than the standard IBC SEER definition (n = 19, 2.1%; p < 0.0001). No IBC cases were identified in the cancer center records using the SEER pathologic coding, which requires the diagnosis of inflammatory carcinoma on the pathology report, a notation that is rarely made. Emphasis must be placed on the documentation of clinical and pathologic characteristics of IBC in the medical record, so that analysis of putative IBC subtypes will be possible. Our results indicate the need for a consensus on the definition of IBC to be utilized in future research.

Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer.

Introduction This phase II trial investigated chemoradiation followed by surgery and 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60 mg/m(2) (days 1 and 22), paclitaxel 60 mg/m(2) (days 1, 8, 15, and 22), and 45 Gy hyperfractionated radiotherapy for 3 weeks followed by transhiatal esophagectomy. TM 20 mg PO QD was started 4 weeks post-op, and continued for 2 years to maintain the ceruloplasmin level between 5 and 15 mg/dl. Results Sixty-nine patients were enrolled (median age, 60 years). Sixty-six patients underwent surgery and 61 patients had a complete resection. Histologic complete response rate was 10 %. Twenty-one patients did not receive TM (metastases noted in the peri-operative period, prolonged post-operative recovery time, or patient refusal). Forty-eight patients started TM; 14 completed 24 months of treatment, 11 completed 10-18 months, 15 completed 2-8 months, and 8 completed ≤1 month. Twenty-seven patients had disease recurrence. With a median follow-up of 55 months, 25 patients were alive without disease, 1 was alive with disease, and 43 have died. Three-year recurrence-free survival was 44 % (95 % CI, 32-55 %) and the three-year overall survival was 45 % (95 % CI 33-56 %). Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation.

Traditional herbalists and cancer management in Kumasi, Ghana.

Cancer incidence rates are increasing in sub-Saharan Africa where traditional medical practitioners (TMPs) are involved in cancer management. Little is known about the specific role that TMPs play in cancer management in Ghana; we hypothesize that an understanding of the practices of TMPs with regard to cancer patients would help to enhance literacy about cancer amongst TMPs and would contribute to the diagnosis of cancer at earlier stages, by avoiding the detrimental delays while enlisting their help in certain activities that enhance cancer care. To elucidate the nature of the involvement of TMPs in cancer management, we conducted semi-structured interviews with 42 TMPs who practice in Kumasi, Ghana. The interviews elicited information about their knowledge and practices regarding cancer management and interactions with local hospitals. The results showed that TMPs tended to identify cancers as diseases of visible masses, fungating lesions, ulceration, and bleeding reflecting the advanced stages and types of cancers they usually encounter. TMPs identified certain causes of cancer and believed that they can treat and prevent cancer. These results indicate that TMPs are significant health service delivery resources in Ghana for patients potentially affected with cancer. Our work suggests that dedicated efforts to further integrate TMPs into the overall health care system would be beneficial to patients. Future research should examine the role of cancer education and training programs for TMPs to enhance their knowledge, strengthen their ability to complement allopathic practitioners, and increase early detection and treatment efforts through appropriate and timely referrals.

Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.

Pomegranate fruit extract impairs invasion and motility in human breast cancer.

PURPOSE: Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. EXPERIMENTAL DESIGN: The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined. RESULTS: Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. CONCLUSION: Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.

Preclinical development of a bifunctional cancer cell homing, PKCepsilon inhibitory peptide for the treatment of head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide, comprising approximately 50% of all malignancies in some developing nations. Our recent work identified protein kinase Cepsilon (PKCepsilon) as a critical and causative player in establishing an aggressive phenotype in HNSCC. In this study, we investigated the specificity and efficacy of HN1-PKCepsilon, a novel bifunctional cancer cell homing, PKCepsilon inhibitory peptide, as a treatment for HNSCC. HN1-PKCepsilon peptide was designed by merging two separate technologies and synthesized as a capped peptide with two functional modules, HN1 (cancer cell homing) and PKCepsilon (specific PKCepsilon inhibitory), connected by a novel linker module. HN1-PKCepsilon preferentially internalized into UMSCC1 and UMSCC36 cells, two HNSCC cell lines, in comparison with oral epithelial cells: 82.1% positive for UMSCC1 and 86.5% positive for UMSCC36 compared with 1.2% positive for oral epithelial cells. In addition, HN1-PKCepsilon penetrated HNSCC cells in a dose- and time-dependent manner. Consistent with these in vitro observations, systemic injection of HN1-PKCepsilon resulted in selective delivery of HN1-PKCepsilon into UMSCC1 xenografts in nude mice. HN1-PKCepsilon blocked the translocation of active PKCepsilon in UMSCC1 cells, confirming HN1-PKCepsilon as a PKCepsilon inhibitor. HN1-PKCepsilon inhibited cell invasion by 72 +/- 2% (P < 0.001, n = 12) and cell motility by 56 +/- 2% (P < 0.001, n = 5) in UMSCC1 cells. Moreover, in vivo bioluminescence imaging showed that HN1-PKCepsilon significantly (83 +/- 1% inhibition; P < 0.02) retards the growth of UMSCC1 xenografts in nude mice. Our work indicates that the bifunctional HN1-PKCepsilon inhibitory peptide represents a promising novel therapeutic strategy for HNSCC.

Modulation of angiogenesis for cancer prevention: strategies based on antioxidants and copper deficiency.

Although anti- angiogenesis strategies have generated much enthusiasm for therapeutic applications, it is still unknown whether they would be feasible for prevention. The possibility of interfering very early in tumor progression by modulating the cancer angiogenic switch is appealing. In this chapter, we review progress with in vitro and in vivo models that show that anti-angiogenic interventions may be amenable to long- term chemopreventive measures. In particular, some approaches that are nearly ready for major applications are anti-oxidant nutraceuticals and copper deficiency. We use these strategies as paradigms of how to make progress in this difficult but important area of translational research.

Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review.

A new anticopper drug, tetrathiomolybdate (TM), developed for Wilson's disease, is a very promising antiangiogenic agent. Copper levels lowered into an antiangiogenic window by TM have shown efficacy against cancer in a variety of animal models as well as in patients. The only significant toxicity so far results from overtreatment and excessive bone marrow depletion of copper. The resulting anemia and/or leukopenia is easily treatable by dose reduction or drug holiday. The underlying concept for TM efficacy as an anticancer agent is that when the body's copper status is in the window, cellular copper needs are met and toxicity is avoided. Copper status is relatively easily monitored by following serum ceruloplasmin, a copper-containing protein secreted by the liver at a rate dependent upon the amount of copper in the liver available to incorporate into the protein. The authors speculate that the copper level is a primitive angiogenesis and growth-signaling regulator that has been retained throughout evolution.