Publications by authors named "Gilian Wharfe"

15 Publications

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

JAMA Netw Open 2021 Mar 1;4(3):e210307. Epub 2021 Mar 1.

Sylvester Comprehensive Cancer Center, Miami, Florida.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921902PMC
March 2021

Assessment of commercial SARS-CoV-2 antibody assays, Jamaica.

Int J Infect Dis 2021 Feb 18;105:333-336. Epub 2021 Feb 18.

The University of the West Indies, Department of Microbiology, Kingston, Jamaica; Global Virus Network, Baltimore, MD, United States. Electronic address:

Background: The performance of the Roche Elecsys® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgM, Abbott Architect SARS-CoV-2 IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica.

Methods: Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons and diagnostic specificity was assessed by testing serum samples collected during 2018-2019 from healthy persons and from persons with antibodies to a wide range of viral infections.

Results: Serum samples collected ≥14 days after onset of symptoms, or an initial SARS-CoV-2 RT-PCR positive test for asymptomatics, showed diagnostic sensitivities ranging from 67.9 to 75.0% when including all possible disease severities and increased to 90.0-95.0% when examining those with moderate to critical disease. Grouping moderate to critical disease showed a significant association with a SARS-CoV-2 antibody positive result for all assays. Diagnostic specificity ranged from 96.7 to 100.0%. For all assays examined, SARS-CoV-2 real-time PCR cycle threshold (Ct) values of the initial nasopharyngeal swab sample testing positive were significantly different for samples testing antibody positive versus negative.

Conclusions: These data from a predominantly African descent Caribbean population show comparable diagnostic sensitivities and specificities for all testing platforms assessed and limited utility of these tests for persons with asymptomatic and mild infections.
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http://dx.doi.org/10.1016/j.ijid.2021.02.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891043PMC
February 2021

Breast Cancer in Jamaica: Trends From 2010 to 2014-Is Mortality Increasing?

JCO Glob Oncol 2020 06;6:837-843

The University of the West Indies, Mona Campus, Kingston, Jamaica.

Purpose: This study sought to provide a detailed analysis of breast cancer-specific mortality in Jamaica on the basis of reported deaths between 2010 and 2014.

Methods: A cross-sectional study was done to analyze breast cancer-specific mortality data from the Registrar General's Department, the statutory body responsible for registering all deaths across Jamaica.

Results: A total of 1,634 breast cancer-related deaths were documented among Jamaican women between 2010 and 2014, which accounted for 24% of all female cancer deaths. The age-standardized breast cancer mortality rate increased from 21.8 per 100,000 in 2010 to 28 per 100,000 in 2014 for the total female population. The overall difference in breast cancer mortality rates between the 2014 and 2010 rates was not statistically significant ( = .114). Analysis of the year-by-year trend reflected by the annual percentage of change did show, however, a statistically significant increasing trend in breast cancer mortality ( = .028). Mortality rates varied by age, with statistically significant annual increases observed in the 35-44-, 65-74-, and ≥ 75-year age groups ( = .04, .03, and .01, respectively).

Conclusion: Breast cancer remains the leading cause of death among Jamaican women. Despite global advances in breast cancer screening and management, breast cancer remains a major public health challenge and represents a public health priority in Jamaica. The increasing breast cancer-specific mortality in Jamaica over the 5-year period contrasts with decreasing mortality rates among US women with breast cancer. This study highlights the critical need to address the implementation of a national organized breast cancer screening program in Jamaica and to focus future research efforts on the biology of breast cancer, especially among young Jamaican women.
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http://dx.doi.org/10.1200/GO.20.00022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328114PMC
June 2020

Cancer control in the Caribbean island countries and territories: some progress but the journey continues.

Lancet Oncol 2019 09 5;20(9):e503-e521. Epub 2019 Aug 5.

Department of Public Health, University of Otago, Wellington, Wellington, New Zealand.

Cancer causes a fifth of deaths in the Caribbean region and its incidence is increasing. Incidence and mortality patterns of cancer in the Caribbean reflect globally widespread epidemiological transitions, and show cancer profiles that are unique to the region. Providing comprehensive and locally responsive cancer care is particularly challenging in the Caribbean because of the geographical spread of the islands, the frequently under-resourced health-care systems, and the absence of a cohesive approach to cancer control. In many Caribbean countries and territories, cancer surveillance systems are poorly developed, advanced disease presentations are commonplace, and access to cancer screening, diagnostics, and treatment is often suboptimal, with many patients with cancer seeking treatment abroad. Capacity building across the cancer-control continuum in the region is urgently needed and can be accomplished through collaborative efforts and increased investment in health care and cancer control.
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http://dx.doi.org/10.1016/S1470-2045(19)30512-1DOI Listing
September 2019

Impact of prophylaxis on health-related quality of life of boys with hemophilia: An analysis of pooled data from 9 countries.

Res Pract Thromb Haemost 2019 Jul 23;3(3):397-404. Epub 2019 Apr 23.

Child Health Evaluative Sciences Program, Research Institute The Hospital for Sick Children (SickKids) Toronto Ontario Canada.

Background: Prophylaxis reduces the frequency of bleeds in boys with severe hemophilia and is the standard care for their management in resource-abundant countries. The effect of prophylaxis on Health-Related Quality of Life (HRQoL) has not been established, because the sample sizes of most studies are too small to explore the relationship of multiple factors that influence HRQoL.

Methods: The aim of this study was to assess the impact of hemophilia severity and treatment regimen on HRQoL and to establish the minimum important difference (MID) using the international level of score distributions. HRQoL data were pooled from 7 studies across 9 countries. HRQoL was measured using the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT). A mixed-effect linear regression analysis was employed to assess the impact of prophylaxis on the CHO-KLAT score.

Results: Data from 401 boys with hemophilia were analyzed (57.6% severe hemophilia and 57.6% receiving prophylaxis). The model revealed that receiving prophylaxis was significantly associated with higher HRQoL (regression coefficient 8.5, 95% confidence interval [CI] 3.9-13.1). Boys with severe hemophilia had a significantly lower HRQoL as compared to boys with moderate and mild hemophilia whose CHO-KLAT scores were 7.0 and 6.6 points higher, respectively. There was a significant interaction between treatment and disease severity (=0.023), indicating prophylaxis has the most significant impact in boys with severe hemophilia. Based on these pooled data, the MID of the CHO-KLAT was established at 6.5.

Conclusions: This study confirms the positive effect of prophylaxis on HRQoL in boys with hemophilia in a real-world setting and provides initial benchmarks for interpreting HRQoL scores based on use of the CHO-KLAT instrument.
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http://dx.doi.org/10.1002/rth2.12202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611476PMC
July 2019

A high frequency of PALB2 mutations in Jamaican patients with breast cancer.

Breast Cancer Res Treat 2017 04 13;162(3):591-596. Epub 2017 Feb 13.

Women's College Research Institute, Women's College Hospital, 76 Grenville St.Room 6421, Toronto, ON, M5S 1B2, Canada.

Purpose: Jamaica is an island nation with one of the highest breast cancer incidence rates in the Caribbean (40/100,000 per year). The contribution of cancer susceptibility gene mutations to the burden of breast cancer in Jamaica has not yet been explored. We sought to determine the prevalence of germline mutations in BRCA1, BRCA2, and PALB2 in 179 unselected Jamaican women with breast cancer.

Methods: We sequenced the entire coding regions of BRCA1, BRCA2, and PALB2 for all the study subjects.

Results: Overall, 8 of 179 patients (4.5%) had a mutation in one of the three genes: one in BRCA1, two in BRCA2, and five in PALB2.

Conclusions: These data suggest that in addition to BRCA1 and BRCA2, PALB2 should be included in genetic testing for breast cancer patients in Jamaica.
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http://dx.doi.org/10.1007/s10549-017-4148-1DOI Listing
April 2017

Bridging the Distance in the Caribbean: Telemedicine as a means to build capacity for care in paediatric cancer and blood disorders.

Stud Health Technol Inform 2015 ;209:1-8

Centre for Global Child Health, The Hospital for Sick Children, Toronto, Canada.

Over the past 50 years, survival for children in high-income countries has increased from 30% to over 80%, compared to 10-30% in low and middle income countries (LMIC). Given this gap in survival, established paediatric cancer treatment centres, such as The Hospital for Sick Children (SickKids) are well positioned to share clinical expertise. Through the SickKids Centre for Global Child Health, the SickKids-Caribbean Initiative (SCI) was launched in March 2013 to improve the outcomes and quality of life for children with cancer and blood disorders in the Caribbean. The six participating Caribbean countries are among those defined by the United Nations as Small Island Developing States, due to their small size, remote location and limited accessibility. Telemedicine presents an opportunity to increase their accessibility to health care services and has been used by SCI to facilitate two series of interprofessional rounds. Case Consultation Review Rounds are a forum for learning about diagnostic work-up, management challenges and treatment recommendations for these diseases. To date, 54 cases have been reviewed by SickKids staff, of which 35 have been presented in monthly rounds. Patient Care Education Rounds provide nurses and other staff with the knowledge base needed to safely care for children and adolescents receiving treatment. Five of these rounds have taken place to date, with over 200 attendees. Utilized by SCI for both clinical and non-clinical meetings, telemedicine has enhanced opportunities for collaboration within the Caribbean region. By building capacity and nurturing expert knowledge through education, SCI hopes to contribute to closing the gap in childhood survival between high and low-resource settings.
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October 2016

Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma.

Clin Immunol 2014 Dec 28;155(2):176-87. Epub 2014 Sep 28.

Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8 mg/kg. Up to 8 mg/kg of daclizumab administered every 3 weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.
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http://dx.doi.org/10.1016/j.clim.2014.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306230PMC
December 2014

Locally advanced breast cancer in Jamaica: prevalence, disease characteristics and response to preoperative therapy.

Asian Pac J Cancer Prev 2014 ;15(7):3323-6

Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona, Jamaica E-mail :

Breast cancer is the most common cancer in Jamaican women. Locally advanced breast cancer (LABC) is associated with aggressive biology and poor prognosis, and has a predilection for African-American women. In this retrospective review, we assessed the prevalence of LABC as a breast cancer presentation in a population of mainly Afro-centric ethnicity, and determined disease characteristics and response to pre-operative chemotherapy. LABC was prevalent (20%), and had a low pathological response rate to pre-operative chemotherapy, with a high risk of disease recurrence. Increased utilization of breast cancer screening may help detect cancer at less advanced stages, and optimizing pre-operative chemotherapy is recommended to improve response rates and ultimately survival.
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http://dx.doi.org/10.7314/apjcp.2014.15.7.3323DOI Listing
January 2015

Clinicopathologic characteristics of breast cancer in Jamaica.

Asian Pac J Cancer Prev 2014 ;15(7):3319-22

Department of Medicine, Faculty of Medical Sciences, University of the West Indies, Mona, Jamaica E-mail :

Breast cancer is the most common cancer in Jamaican women. This study assessed the clinicopathologic features of cases in a hospital-based specialist clinic in Kingston, Jamaica. A retrospective chart review was performed for the 2-year study period and relevant clinical and surgico-pathologic data were recorded and analyzed. Median age of the 121 breast cancer patients was 52 years (range 22-84, IQR 20) and there was 1 case of male breast cancer. Most patients (65%) were referred from the surgical service after definitive breast cancer surgery, 20% were referred for pre-operative systemic therapy, and 15% had a diagnosis of metastatic disease. The surgico-pathologic group comprised 78 women who were referred for adjuvant therapy. The majority had presented with a palpable breast lump (91%), with median tumour size 3.5cm (range 0.4-13, IQR 4). Most tumours were node positive (56%). Approximately one-third of patients had stage III disease (33%). Most women presented with large palpable tumours and had lymph node involvement confirmed on surgicopathological evaluation, indicative of limited early breast cancer detection. A national screening mammography programme is recommended for detection of earlier lesions. Pre-operative systemic therapy should be considered as an option for eligible patients.
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http://dx.doi.org/10.7314/apjcp.2014.15.7.3319DOI Listing
January 2015

Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma.

Blood 2012 Aug 22;120(9):1816-9. Epub 2012 Jun 22.

Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs. cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.
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http://dx.doi.org/10.1182/blood-2012-01-401349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433088PMC
August 2012

A woman with diabetes presenting with pyomyoma and treated with subtotal hysterectomy: a case report.

J Med Case Rep 2009 Sep 8;3:7439. Epub 2009 Sep 8.

Introduction: Pyomyoma (suppurative leiomyoma of the uterus) is a rare condition resulting from infarction and infection of a leiomyoma. It is more usual in pregnant women or postmenopausal women who have vascular disease. The condition is usually fatal unless treated with appropriate antibiotics and surgical intervention.

Case Presentation: We report a case of a 44-year-old Afro-Caribbean woman with diabetes who presented with recurrent episodes of abdominal pain and fever over a period of five months. Her problem proved to be a diagnostic dilemma mimicking cholecystitis, pyelonephritis and ovarian cancer. Her blood cultures were positive on one occasion for methicillin-resistant Staphylococcus epidermidis. An ultrasound scan suggested uterine fibroids but a computed tomography scan suggested an ovarian malignancy because the mass appeared heterogeneous with fluid filled areas. She was treated with several courses of antibiotics and eventually at laparotomy, she was found to have a large pyomyoma which was successfully removed by subtotal hysterectomy with immediate and complete resolution of her symptoms.

Conclusion: The diagnosis of pyomyoma should be considered in perimenopausal women with large fibroids and pyrexia of unknown origin.
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http://dx.doi.org/10.4076/1752-1947-3-7439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767137PMC
September 2009

Multiple metachronous malignancies, one patient with three primary malignancies: a case report.

J Med Case Rep 2007 May 2;1:15. Epub 2007 May 2.

Department of Obstetrics and Gynaecology, University of the West Indies, Mona, Kingston, Jamaica.

We present a 61 year old Para 4 woman who presented with stage II Infiltrating lobular carcinoma of the breast after modified radical mastectomy. She was treated with Tamoxifen for seven years. She was diagnosed with multiple myeloma during year seven post mastectomy because of wrist pain. She was treated with melphalan, prednisone and allopurinol which she tolerated well and the pain in the wrist improved. Tamoxifen was also stopped. Ten months later she presented with vaginal bleeding and was diagnosed with a poorly differentiated endometrial adenocarcinoma at hysteroscopic suction curettage and had an abdominal hysterectomy. Two years later the patient succumbed to metastatic endometrial cancer.
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http://dx.doi.org/10.1186/1752-1947-1-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871600PMC
May 2007

Treatment of intractable vaginal bleeding with formaldehyde soaked packs.

J Obstet Gynaecol 2002 Sep;22(5):570-1

Department of Obstetrics and Gynaecology, University of the West Indies, Mona, Kingston, Jamaica.

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http://dx.doi.org/10.1080/014436102760298999DOI Listing
September 2002

Seroprevalence of hepatitis C virus in haemophiliacs in Jamaica.

Hum Antibodies 2002 ;11(3):61-4

Department of Pathology, The University of the West Indies, Mona, Kingston 7, Jamaica, West Indies.

Haemophilic patients (n = 90) and household contacts (n = 40) were tested for serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV) and elevated serum aminotransferases using commercially prepared reagents. Of the haemophiliacs 41% (37/90) tested positive for antibodies to HCV (anti-HCV); 36% (32/90) antibodies to hepatitis B core antigen (anti-HBc); 54% (49/90) antibodies to hepatitis B surface antigen (anti-HBs) and 2% (2/90) hepatitis B surface antigen. On the other hand, 29% (26/90) of the patients and 90% (36/40) of the household contacts tested negative for all of the viral markers. Anti-HCV positivity in the haemophilic patients correlated positively with anti-HBc (p < 0.025). Increasing age (odds ratio 2.09; p < 0.01), severity of disease (odds ratio 6.2; p < 0.05) and the requirement for transfusion (odds ratio 3.2; p < 0.05) were risk factors for anti-HCV positivity. The presence of anti-HBc (odds ratio 3.8; p < 0.01) and coinfection with HCV and HBV also correlated positively with age (odds ratio 2.5; p < 0.01). The provision of anti-HCV screened donor blood and virally inactivated blood products for treatment of all haemophilic patients are goals that must be achieved.
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May 2003