Racial disparities in breast cancer preclinical and clinical models.

Breast cancer (BCa) has long been a health burden to women across the globe. However, the burden is not equally carried across races. Though the manifestation and behavior of BCa differs among racial groups, the racial representation of models used in preclinical trials and clinical trial participants lacks this heterogeneity. Women of African Ancestry (WAA) are disproportionately afflicted by having an increased risk of developing BCas that are more aggressive in nature, and consequently suffer from poorer outcomes relative to women of European ancestry (WEA). Notwithstanding this, one of the most commonly used tools in studying BCa, cell lines, exhibit a sizeable gap in cell line derivatives of WEA relative to WAA. In this review, we summarize the available BCa cell lines grouped by race by major suppliers, American Type Culture Collection (ATCC) and the European Collection of Authenticated Cell Cultures (ECACC). Next, examined the enrollment of WAA in clinical trials for BCa. Of the cell lines found provided by ATCC and ECACC, those derived from WEA constituted approximately 80% and 94%, respectively. The disparity is mirrored in clinical trial enrollment where, on average, WEA made up more than 70% of participants in trials found where ancestry information was provided. As both experimental models and clinical trial participants primarily consist of WEA, results may have poorer translatability toward other races. This highlights the need for greater racial diversity at the preclinical and clinical levels to more accurately represent the population and strengthen the translatability of results.

Breast cancer screening patterns in Jamaican women: review of the largest national mammography clinic.

BACKGROUND: Breast cancer is the leading cause of cancer and cancer related deaths in Jamaican women. In Jamaica, women often present with advanced stages of breast cancer, despite the availability of screening mammography for early detection. The utilization of screening mammography for early breast cancer diagnosis seems to be limited, and this study investigated the national patterns of mammographic screening and the impact of mammography on the diagnosis of breast cancer in Jamaica. METHODS: A retrospective analysis of the records of the largest mammography clinic in Jamaica was done for the period January 2011 to December 2016. Descriptive statistics was performed on relevant patient characteristics with calculation of rates and proportions; cross-tabulations were utilized to assess relationship of covariates being studied on the outcomes of interest. Results are reported in aggregate form with no identifiable patient data. RESULTS: 48,203 mammograms were performed during the study period. 574 women (1.2%) had mammograms suspicious for breast cancer with median age of 57 years (range 30-95 years); 35% were under the age of 50. 4 women with suspicious findings had undergone 'screening mammography', with the remaining having 'diagnostic mammography'. 38% reported previous mammograms, with a mean interval of 8 years between previous normal mammogram and mammogram suspicious for breast cancer. Median age at first screening mammogram was 51 years (range 41-77). CONCLUSION: Breast cancer screening mammography is underutilized in Jamaica. An organized national breast cancer screening programme is recommended to improve adherence to international breast cancer screening guidelines.

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population. Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations. Design, Setting, and Participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020. Exposures: Breast and/or ovarian cancer diagnosis. Main Outcomes and Measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants. Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P < .001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P = .001). Conclusions and Relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.

Molecular Targets and Angiogenesis in Renal Cell Carcinoma, A Multitarget Approach: Mini Review.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2% of all adult malignancies and is associated with a case fatality rate as high as 40%. RCC has been on the rise for the last 6 decades at a steady increase of 2% per annum. Much work has been done to uncover the pathogenesis of the disease and the role of angiogenesis has been a recurrent denominator connected to vascular endothelial growth factor (VEGF) and its downstream effectors along with the mammalian target of rapamycin (mTOR) mediated signal transduction pathway. OBJECTIVE: This review will discuss relevant inhibitors of key biomarkers to the disease in hopes of paving the way for novel treatments geared towards improving RCC morbidity and mortality rates. RESULTS AND CONCLUSION: Currently, treatment of advanced RCC includes one or more of the following: partial or radical nephrectomy, systemic therapy, immunotherapy and targeted therapy. Still drug resistance continues to be a challenge to many of the approved drugs and those undergoing clinical trials. However, the inclusion of targeted therapies has improved advanced RCC treatment success rates over that of surgery alone, and over that of the use of traditional chemotherapy for this relatively chemo-resistant disease. In an era of personalized medicine, research utilizing a polypharmacology approach could enhance efficacy of drug leads to treating RCC.

Concomitant urothelial cancer and renal tuberculosis.

We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer.

Lynch syndrome in a predominantly Afrocentric population: a clinicopathological and genetic study.

BACKGROUND: We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. METHODS: We identified patients aged 40 years or younger in whom primary CRC was diagnosed at the University Hospital of the West Indies from January 2004 to December 2008. We reviewed the medical records and hematoxylin and eosin (H&E)-stained histopathology slides. Tumour blocks were tested for microsatellite instability (MSI). Patients with MSI-high phenotype (MSI-H) tumours had genetic counselling, after which genomic DNA was extracted from peripheral blood to test for MLH1 and MSH2 germline mutations. Patients also had pedigree mapping. RESULTS: There were 25 patients with CRC aged 40 years or younger with no history of hereditary colon cancer syndrome. The patients' mean age was 33 (range 21-40) years. Histopathologic review confirmed CRC in all patients; 8 of 25 (32%) showed morphologic features suggestive of MSI. We detected MSI-H in 5 of 23 (22%) tumour blocks tested. Review with H&E staining correctly identified 80% of cases positive for MSI-H. The false-positive rate and positive predictive value on H&E review was 50%. The negative predictive value of histomorphologic H&E review was 94%. Three patients were available for and had mutational analysis of DNA mismatch repair genes; 2 were positive for mutations in keeping with Lynch syndrome and 1 had MLH1 alterations of uncertain significance. All 3 met the Amsterdam criteria for hereditary nonpolyposis CRC. CONCLUSION: Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.

Hepatic steatosis secondary to capecitabine: a case report.

INTRODUCTION: There are no known case reports of hepatic steatosis caused by oral fluoropyrimidines such as capecitabine. With increasing use of capecitabine since its approval for the treatment of metastatic colon cancer in 2001, and more recently for adjuvant treatment of colon cancer and treatment of metastatic breast cancer, we can anticipate increased recognition of potential toxicities associated with this 5-fluorouracil derivative. CASE PRESENTATION: We report the case of a 74-year-old Armenian woman who received capecitabine as adjuvant treatment for colon cancer and subsequently developed abnormal liver biochemical tests and radiographic findings in keeping with hepatic steatosis. There was complete reversal of liver enzyme abnormalities with discontinuation of the drug and this patient represents a case of reversible liver injury due to capecitabine. CONCLUSION: In this original case report, capecitabine use was associated with hepatic steatosis. It is important for clinicians to recognize and monitor for this potential toxicity, which may be a cause of abnormal liver enzymes in this patient population.

Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer.

BACKGROUND: Data from randomized trials in postmenopausal women receiving endocrine therapy for breast cancer would suggest that the incidence of significant urogenital symptoms is around 40%. As there are inherent reporting biases associated with clinical trials, we sought to assess the prevalence, severity, and effect of urogenital side effects of endocrine therapy in the non-trial setting. PATIENTS AND METHODS: A cross-sectional survey study was undertaken and questionnaires used to assess vulvovaginal and urinary tract symptoms in a group of postmenopausal women receiving endocrine therapy for breast cancer. RESULTS: A total of 251 women were surveyed. Sixty-three percent (158) reported urogenital symptoms. Vaginal dryness was the most common vaginal symptom, occurring in 121 women (48%). This was rated as severe or very severe in 56 of 121 (46%). Thirty-one of 251 (12%) women experienced urinary symptoms. A total of 68 women (27%) had used some form of treatment for vaginal symptoms. Nine women (4%) had considered discontinuing treatment because of urogenital side effects. CONCLUSION: Urogenital side effects are common and often severe in women receiving endocrine therapy for breast cancer. The prevalence in this study was 63%, which is higher than that reported in the clinical trial literature. Less than one third of patients had used some form of treatment for these symptoms. This highlights the need for increased recognition and management of the urogenital side effects of estrogen deprivation therapy and raises the concern of the risk of non-compliance with potentially curative adjuvant therapy.

Evaluation of an intraperitoneal chemotherapy program implemented at the Princess Margaret Hospital for patients with epithelial ovarian carcinoma.

OBJECTIVE: A prospective evaluation of an ambulatory intraperitoneal (IP) /intravenous (IV) chemotherapy regimen for women with epithelial ovarian carcinoma (EOC). METHODS: Cisplatin 100 mg/m(2) (option for 75 mg/m(2)) IP combined with paclitaxel 175 mg/m(2) IV (3 h infusion) administered every 21 days was adopted by our institution as a single day, outpatient regimen for women with stage III EOC who had undergone optimal cytoreductive (

Potential drug interactions in cancer patients receiving supportive care exclusively.

Cancer patients at the end of life often take many medications and are at risk for drug interactions. The purpose of this study was to describe the epidemiology of potential drug interactions in cancer patients receiving supportive care exclusively. We retrospectively reviewed the charts of consecutive adult cancer outpatients attending palliative care clinics at the Princess Margaret Hospital, Toronto, Canada. Drugs were screened for interactions by the Drug Interaction Facts software, which classifies interactions by levels of severity (major, moderate, and minor) and scientific evidence (1-5, with 1=the strongest level of evidence). Among 372 eligible patients, 250 potential drug interactions were identified in 115 patients (31%, 95% confidence interval 26%-36%). The most common involved warfarin and phenytoin. Most interactions were classified as being of moderate severity (59%) and 42% of them were supported by Levels 1-3 of evidence. In multivariable analysis, increasing age (P<0.001), presence of comorbidity (P=0.001), cancer type (brain tumors, P<0.001), and increasing number of drugs (P<0.001) were associated with risk of drug interactions. Potential drug interactions are common in palliative care and mostly involve warfarin and anticonvulsants. Older patients, those with comorbid conditions, brain tumor patients, and those taking many medications are at greater risk of drug interactions.

Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer.

BACKGROUND: A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. METHODS: Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. CONCLUSIONS: The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.