Publications by authors named "Sophia George"

43 Publications

Was Sleep a Problem for the Elderly During COVID-19?

Sleep Vigil 2021 Sep 6:1-7. Epub 2021 Sep 6.

Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed to be University), Paneer, Deralakatte, Mangalore, Karnataka 575018 India.

Over the past few decades, the population of geriatrics has seen an exponential rise and it is well known that the prevalence of chronic diseases and other associated comorbidities is higher among them which in turn, has an established association with sleep disorders. During these unprecedented circumstances, geriatrics are predisposed to be at an increased risk of sleep disorders due to the social isolation and loneliness imposed on them by the lockdowns. The fact that older adults are at a greater risk of contracting the virus due to the presence of comorbidities and the high virulence adds on to the existing risk of sleep disturbances. A lack of sleep in these circumstances has the potential to add on to the vicious cycle of sleep disorders predisposed by chronic disease and vice versa. Mental health, sleep and the presence of comorbidities are closely interlinked and they often tend to overlap. Research in sleep has established insomnia to be the most commonly diagnosed sleep disorder affecting almost 50% of the older adults which can subsequently, elevate their risk of falls. This prevalence of sleep disorders is hypothesized to increase during the second wave of the COVID-19 pandemic and a good sleep routine needs to be advocated for to improve the quality of life of this population. However, scientific evidence concerning this is scarce and this review aims to highlight the significance of sleep and urges its readers to undertake studies that investigate the architecture of sleep amongst older adults during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s41782-021-00164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420144PMC
September 2021

Human Papilloma Virus Distribution Across the African Diaspora.

JCO Glob Oncol 2021 07;7:1206-1208

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, MI.

Purpose: Understanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora.

Methods: This study was approved by the African Caribbean Consortium (AC3). Six member institutions (Benin, Ethiopia, The Bahamas, Tobago, Curacao, and Jamaica) provided independently collected HPV data. Prevalence comparisons across for each nation were performed followed by an assessment of anticipated 9-valent vaccine coverage. Chi-square or Fisher's exact tests were used with significance at < .05.

Results: One thousand three hundred fifty high-risk (HR) and 584 low-risk (LR) HPV subtypes were identified in the entire cohort. The most common HR HPV subtype was HPV 16 (17.9%) of infections. The distribution of HR and LR subtypes varied by country. The proportion of HR-HPV subtypes covered by the current 9-valent vaccine was lower in African countries compared with the Caribbean countries (47.9% 67.9%; < .01). No significant difference was seen for LR subtypes (8.1% African continent 5.2% Caribbean; = .20). Marked variation in the proportion of infections covered by the 9-valent vaccine persisted in individual countries.

Conclusion: Significant variations in HPV prevalence were identified among African and Afro-Caribbean women. A large number of women in these regions are potentially uncovered by current vaccination formulation, particularly low-risk HPV infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/GO.21.00151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457790PMC
July 2021

Lost opportunities for mismatch repair (MMR) screening among minority women with endometrial cancer.

Sci Rep 2021 Jun 3;11(1):11712. Epub 2021 Jun 3.

Department of Pathology, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL, 33136, USA.

Lynch Syndrome (LS) prevalence in underrepresented minorities are lacking. The objective of this study was to assess the prevalence of LS in a minority patient population. Secondary objectives included identifying factors associated with successful LS screening and to characterize clinicopathologic features. Women with endometrial cancer treated within a university system from 2014 and 2016 were included. Immunohistochemistry (IHC) results of MLH1, PMS2, MSH2 and MSH6 were obtained from medical records and clinicopathologic factors abstracted. Patients not previously screened for LS were screened. 276 patients were evaluable. More minority women were screened as part of their routine cancer care (p = 0.005). Additionally, women 50 years or younger were more likely to be screened for LS compared to women older than 51(p = 0.009) and uninsured or reliant on Medicaid patients (p = 0.011) were more likely to be screened during routine care. Six patients received confirmatory germline testing for LS (4.3%), and another 8 patients had a staining pattern suggestive of LS. In an underrepresented population, the rate of LS in endometrial cancer is similar to previous reports. LS may be under diagnosed and opportunities missed when universal screening is not applied in minority women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91053-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175729PMC
June 2021

Black Is Diverse: The Untapped Beauty and Benefit of Cancer Genomics and Precision Medicine.

JCO Oncol Pract 2021 05;17(5):279-283

African Caribbean Cancer Consortium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/OP.21.00236DOI Listing
May 2021

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

JAMA Netw Open 2021 03 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.
View Article and Find Full Text PDF

Download full-text PDF

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

Effects of initiating physician-performed germline testing in safety net clinic patients with epithelial overian cancer.

Gynecol Oncol Rep 2020 Nov 28;34:100662. Epub 2020 Oct 28.

University of Miami Sylvester Comprehensive Cancer Center Division of Gynecologic Oncology, United States.

Germline genetic mutations occur in approximately 25% of women with epithelial ovarian cancers (EOC). We sought to determine whether newly initiated in-office oncologist-led germline testing improved time to testing and dissemination of results compared with historical controls. Patients with epithelial ovarian cancer seen between 4/1/2018 and 12/31/2019 were identified. Patients treated before genetic testing kits were made available in the gynecologic oncology clinics were compared to those treated after. Categorical variables were compared using Chi Squared and Fisher's Exact test. Cox proportional hazards model was used to compare elapsed time from testing to results. 73 patients were identified, and 502 clinic visits were analyzed. 56 (76.7%) patients were White Hispanic, 15 (20.5%) were Black, and 2 (2.7%) were White non-Hispanic. 55 (75.7%) underwent germline testing. Median time to genetic testing in the intervention group was shorter than in the control group (5, vs 24.3 weeks, 95% CI = 0-10.8 vs 14.9-33.7, p < 0.001). Among the 51 patients with genetic tests completed; results were recorded in a clinic note at 14 weeks (95% CI = 0-28.1) from first visit in the intervention group compared with 47 weeks (95% CI = 30.7-63.3) in the control group (p < 0.001). The majority of patients tested had county charity care insurance or were uninsured. Genetic testing in a safety net gynecologic oncology clinic is feasible. By initiating in-office testing, time to testing and receipt of results were meaningfully shortened. This allowed for timely identification of patients who would most benefit from PARP inhibitor maintenance therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gore.2020.100662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644881PMC
November 2020

mRNA expression in low grade serous ovarian cancer: Results of a nanoString assay in a diverse population.

Gynecol Oncol 2020 11 18;159(2):554-562. Epub 2020 Sep 18.

Sylvester Comprehensive Cancer Center, University of Miami, Division of Gynecologic Oncology, USA. Electronic address:

Objective: Mutations in the MAP kinase pathway (KRAS, NRAS, BRAF) are common in low grade serous ovarian carcinoma (LGSOC). The effect of these and other mutations on RNA transcription in this disease is poorly understood. Our objective was to describe patterns of somatic mutations and gene transcription in a racially diverse population with LGSOC.

Methods: Utilizing an institutional tumor registry, patients with LGSOC were identified and charts were reviewed. RNA was extracted from available tumor tissue. Commercial tumor profiling results were analyzed with PanCancer pathway nanoString mRNA expression data. Along with nanoString n-Solver software, Chi-squared, Fishers Exact, and Cox proportional hazards models were used for statistical analysis, with significance set at p < 0.05.

Results: 39 patients were identified-20% Black, 43% Hispanic, and 36% non-Hispanic White. 18 patients had commercial somatic DNA test results, and 23 had available tumor tissue for RNA extraction and nanoString analysis. The most common somatic alterations identified was KRAS (11 patients, 61%), followed by ERCC1 and TUBB3 (9 each, 50%). KRAS mutations were less common in smokers (14.3% vs 90.9%, p = 0.002). RNA expression analysis demonstrated a greater than two-fold decrease in expression of HRAS in tumors from older patients (p = 0.04), and a greater than two-fold decrease in the expression of HRAS in recurrent tumors (p = 0.007). No significant differences were seen in somatic testing results, RNA expression analysis, or progression free survival between different racial and ethnic cohorts.

Conclusions: Somatic deficiencies in ERCC1, TUBB3, and KRAS are common in LGSOC in a population of minority patients. HRAS demonstrates decreased expression in tumors from older patients and recurrent tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054444PMC
November 2020

Thrombocytosis as a Biomarker in Type II, Non-Endometrioid Endometrial Cancer.

Cancers (Basel) 2020 Aug 22;12(9). Epub 2020 Aug 22.

Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.

Thrombocytosis (platelets ≥ 400K) is a common hematologic finding in gynecologic malignancies and associated with worse outcomes. Limited data exist on the prognostic capability of thrombocytosis in women with high-grade endometrial cancer (EC). Our objective was to describe the associations between elevated platelets at diagnosis, clinicopathologic features, and survival outcomes among women with high-grade, non-endometrioid EC. A review of the institutional cancer registry was performed to identify these women treated between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were performed using chi-square tests, Cox proportional hazards models, and the Kaplan-Meier method. A total of 271 women were included in the analysis. A total of 19.3% of women had thrombocytosis at diagnosis. Thrombocytosis was associated with reduced median overall survival (OS) compared with those not displaying thrombocytosis (29.4 months vs. 60 months, < 0.01). This finding was most pronounced in uterine serous carcinoma (16.4 months with thrombocytosis vs. 34.4 months without, < 0.01). While non-White women had shorter median OS for the whole cohort in the setting of thrombocytosis (29.4 months vs. 39.6 months, < 0.01), among those with uterine serous carcinoma (USC), this finding was reversed, with decreased median OS in White women (22.1 vs. 16.4 months, = 0.01). Thrombocytosis is concluded to have negative associations with OS and patient race.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563482PMC
August 2020

Race and Ethnicity Influence Survival Outcomes in Women of Caribbean Nativity With Epithelial Ovarian Cancer.

Front Oncol 2020 29;10:880. Epub 2020 May 29.

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, Miami, FL, United States.

Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures. A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at < 0.05. 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, = 0.009) and be treated at a public facility (62.5 vs. 33.5%, < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39-0.95], = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank = 0.04). Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273510PMC
May 2020

Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla-Site of Origin of Serous Carcinoma of the Ovary.

Cancers (Basel) 2020 Apr 27;12(5). Epub 2020 Apr 27.

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, Leonard Miller School of Medicine, University of Miami, 1550 NW 10th Ave, Miami, 33134 FL, USA.

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12051090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281286PMC
April 2020

The Moore Criteria: Applicability in a diverse, non-trial, recurrent cervical cancer population.

Gynecol Oncol 2020 04 23;157(1):167-172. Epub 2020 Jan 23.

Sylvester Comprehensive Cancer Center, University of Miami, Division of Gynecologic Oncology, United States of America. Electronic address:

Objective: The Moore Criteria is a prognostic index for recurrent or metastatic cervical cancer based on five factors. The criteria were developed retrospectively and validated prospectively in clinical trial populations receiving systemic chemotherapy (C). Our objective was to evaluate the prognostic value of the Moore Criteria in a largely minority, non-trial population at first recurrence.

Methods: Patients treated for recurrent cervical cancer diagnosed between 2012 and 2017 were analyzed retrospectively. Progression free survival (PFS) was defined from the date of recurrence to date of second recurrence. Overall survival (OS) was defined from the date of recurrence to date of death.

Results: Of 274 patients identified, 78 were treated in the second line. 48 (61.5%) were Hispanic, 22 (28.2%) were black, and 7 (9%) were white non-Hispanic. By Moore criteria, 9 patients (11.5%) were classified as low-risk, 48 (61.5%) as moderate risk, and 21 (26.9%) as high-risk. 53 patients (67.9%) received C, and 25 (32.1%) received other treatment modalities without C. The high-risk category carried a significantly higher hazard ratio for both PFS (5.24, p < .001) and OS (3.15, p = .002) compared with the low- and intermediate-risk combined group. The low- and intermediate-risk groups demonstrated 78.9% response rate, compared with 33.3% in the high-risk category (p = .001). Black race did not affect survival or response rate.

Conclusion: The Moore Criteria carries prognostic value across a diverse recurrent cervical cancer population outside of the clinical trial setting. Our data suggest that in a non-trial population, black race is not predictive of worse OS or PFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.01.001DOI Listing
April 2020

Cancer Risks Associated With Germline Pathogenic Variants: An International Study of 524 Families.

J Clin Oncol 2020 03 16;38(7):674-685. Epub 2019 Dec 16.

Biopathologie, Centre Léon Bérard, Lyon, France.

Purpose: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline pathogenic variants (PVs) because these risks have not been extensively characterized.

Methods: We analyzed data from 524 families with PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.

Results: We found associations between PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; = 6.5 × 10), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; = 4.1 × 10), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; = 8.7 × 10), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; = 2.6 × 10). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( for trend = 2.0 × 10). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.

Conclusion: These results confirm as a major breast cancer susceptibility gene and establish substantial associations between germline PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of into risk prediction models and optimize the clinical cancer risk management of PV carriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.01907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049229PMC
March 2020

Endometrial cancer among a cohort of urban Haitian immigrants.

World J Clin Oncol 2019 Oct;10(10):340-349

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer center, University of Miami Miller School of Medicine, Miami, FL 33139, United States.

Background: Black women are known to have a higher risk of aggressive endometrial cancers. Little data exist about the role of nativity as a determinant of survival outcomes in women with this disease.

Aim: Our objective was to evaluate a population of Haitian immigrants with endometrial cancer in an urban setting using the Florida Cancer Data System (FCDS).

Methods: A search of FCDS identified 107 women born in Haiti and who received treatment for invasive endometrial cancer in Miami-Dade County between 1989 and 2013. Clinicopathologic data were extracted to describe the cohort and assess associations with overall survival. Statistical analyses were performed using Cox proportional hazards models, the log-rank test, and the Kaplan-Meier method, with significance set at ≤ 0.05.

Results: Median age at diagnosis was 65 years. 63.9% of the patients had a type II, high-grade, histology, and 52.6% presented with extrauterine metastatic disease. Nearly three quarters had health insurance. Within the entire cohort, only presence of extrauterine disease was associated with worse overall survival [Hazard ratio (HR) = 2.70, 95% confidence interval (CI): 1.31-5.57, = 0.007]. However, after stratification by histologic grade, both age (HR = 0.88, 95%CI: 0.81-0.96, = 0.002) and extrauterine disease (HR = 2.49, 95%CI: 1.01-6.21, = 0.049) were independently associated with worse survival, but only in women with type II malignancies.

Conclusion: Urban Haitian women with endometrial cancer have a high burden of aggressive histologies. Additional investigation to explain the etiology of these findings is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5306/wjco.v10.i10.340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885451PMC
October 2019

Pressing Need to Dig Deeper Into Female Cancer Health Disparities.

J Clin Oncol 2019 12 2;37(35):3464-3465. Epub 2019 Oct 2.

Matthew Schlumbrecht, MD, MPH, Sylvester Comprehensive Cancer Center, Miami, FL; Camille Ragin, PhD, Fox Chase Cancer Center, Philadelphia, PA; Laura Kohn-Wood, PhD, University of Miami, Coral Gables, FL; and Sophia George, PhD, Sylvester Comprehensive Cancer Center, Miami, FL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.01720DOI Listing
December 2019

Meeting report from the 2018 12th Biennial Ovarian Cancer Research Symposium detection and prevention of ovarian cancer.

Int J Gynecol Cancer 2019 08;29(Suppl 2):s2-s6

Sylvester Comprehensive Cancer Center, Miami, Florida, USA.

The objective of this review is to summarize recent research advances in the detection and prevention of ovarian cancer and discuss the experts' opinions of future directions. The 12th Biennial Ovarian Cancer Research Symposium was held in Seattle, Washington, in September 2018. At this meeting, experts in ovarian cancer research gathered to present and discuss recent breakthroughs and their visions of future ovarian cancer research. Session 1 of the symposium focused on the detection and prevention of ovarian cancer. It included two invited oral presentations from Ranjit Manchanda, MD, PhD (Barts Cancer Institute) and Rosana Risques, PhD (University of Washington). Another eight oral presentations were selected from abstract submissions. Fifteen abstracts were presented in poster format. These presentations covered topics including cellular origin of high-grade serous cancer, risk factors for ovarian cancer, new methods for early detection of ovarian cancer, mechanisms underlying ovarian cancer development, and new therapeutic approaches for preventing ovarian cancer from forming or progressing. In conclusion, a clear understanding of the cellular origin and molecular mechanisms underlying the initiation of high-grade serous cancer is essential for developing effective means for early detection and prevention of this most devastating type of ovarian cancer. Recognizing the complexity of ovarian cancer and appreciating that ovarian cancer is not a single disease will help us to generate proper models, design rational experiments, and collect and analyze patient data in a meaningful way. A concerted effort in the field will help to bridge the basic science and clinical applications and lead to more precise and effective detection and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ijgc-2019-000454DOI Listing
August 2019

Differences in breast cancer outcomes amongst Black US-born and Caribbean-born immigrants.

Breast Cancer Res Treat 2019 Nov 14;178(2):433-440. Epub 2019 Aug 14.

Sylvester Comprehensive Cancer Center, Miami, FL, USA.

Background: There are few studies that directly investigate disparities in outcome within the African diaspora in the US. We investigated the association between nativity of Black women diagnosed with breast cancer (Caribbean or USA place of birth) and ethnicity, age at diagnosis, treatment, tumor characteristics and outcome.

Methods: The data were obtained from the University of Miami Health System, and Jackson Health System. Individual-level data from 1132 cases was used to estimate hazard rations (HRs) of women born in the Caribbean (Caribbean Blacks, CB) or in the USA (US Black, USB) using Cox proportional hazards regression analysis for overall survival.

Results: The cohort contains data from 624 (54.9%) USB women and 507 (45%) CB women diagnosed with breast cancer between 2006 and 2017. Compared to CB patients, USB patients had more Estrogen Receptor negative (31.4% vs. 39.1%, P = 0.018) and triple negative breast cancers (19.6% vs. 27.9%, P = 0.003). CB women presented at more advanced stages III/IV (44.2% vs. 35.2%; P = 0.016). CB patients showed a better overall survival (hazard ratio, HR = 0.75; 95% CI 0.59-0.96; P = 0.024). Overall Black Hispanic patients had a better overall survival (HR = 0.51; 95% CI 0.28-0.93; P = 0.028) compared to non-Hispanic Black patients.

Conclusion: In conclusion the study found that CB immigrants diagnosed with breast cancer have an improved overall survival when compared with USB patients. This finding suggests that within the African diaspora in the USA, additional factors beyond race contribute to worse outcomes in African Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-019-05403-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039732PMC
November 2019

Corrigendum to "Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain" [Int. J. Biochem. Cell Biol. 114 (September 2019) 105558].

Int J Biochem Cell Biol 2019 Sep 5;114:105577. Epub 2019 Aug 5.

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India. Electronic address:

Cancer pathogenesis has been attributed to the minor and major disruptions in the cell cycle, with a key role being played by several of the recently discovered epigenetic factors. Lately, UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic regulator has been shown to be evidently over expressed in numerous malignancies through an in-depth review of literature. Molecular docking studies have found that existing drugs such as propranolol, naphthazarin and thymoquinone have favourable interactions with specific domains of UHRF1. However, these findings would need large scale clinical trials to confirm their potency and safety during chemotherapy. UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic factor, plays a crucial role as an important checkpoint in the cell machinery. Basic science continues to unravel multiple facets of this five domain protein which includes a detailed elucidation of its roles and mechanisms of interaction with various enzymes during DNA replication. The gene has recently begun to be also termed as the "Universal Oncogene" in response to the results of research conducted in heterogenous populations and in over 17 cancers displaying heightened mRNA and protein expression in breast, liver, lung, head and neck cancers and many more. This gene could therefore, be a potential biomarker for diagnosis and for the prediction of the prognosis and survival of the diseased. A scientifically established solution in the form of targeted treatment must follow such a discovery and therefore, several natural and synthetic compounds such as thymoquinone and the well-known antihypertensive, propranolol have been docked and reported to have favourable interactions with the SRA (Set and Ring Associated) domain of UHRF1 in this review. This comprehensive review is thus, a brief synopsis of details regarding the structure and heightened levels of UHRF1 in several malignancies. Furthermore, pharmacogenomic research revolving around this oncogene is a potential sphere for clinical studies to be conducted in much larger and heterogenous populations to not only validate these therapeutic docking results but to also to bring personalised medicine to the bedside for the benefit of the patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocel.2019.105577DOI Listing
September 2019

Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain.

Int J Biochem Cell Biol 2019 09 22;114:105558. Epub 2019 Jun 22.

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India. Electronic address:

The figure describes the location of UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1) gene, mRNA and protein synthesis in the tumor cell and its structural domains with a focus on the docking of Naphthazarin on the SRA domain of UHRF1, resulting in reduction of tumor size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocel.2019.06.006DOI Listing
September 2019

CCAAT/enhancer binding protein delta (C/EBPδ) demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinoma.

EBioMedicine 2019 Jun 9;44:261-274. Epub 2019 May 9.

Sylvester Comprehensive Cancer Center, Miami, Florida, United States; Department of Obstetrics and Gynecology and Reproductive Sciences, Division of Gynecology Oncology, Miami, Florida, United States; University of Miami, Leonard Miller School of Medicine, Miami, Florida, United States. Electronic address:

Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors.

Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition.

Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells.

Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. FUND: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer - The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603855PMC
June 2019

Endometrial cancer outcomes among non-Hispanic US born and Caribbean born black women.

Int J Gynecol Cancer 2019 May 3. Epub 2019 May 3.

Sylvester Comprehensive Cancer Center, Miami, Florida, USA.

Purpose: Data on endometrial cancer outcomes among immigrant women in the USA are lacking. The objective was to determine the effect of Caribbean nativity on outcomes in black women with endometrial cancer compared with women born in the USA, with attention paid to the effects of tumor grade, sociodemographic factors, and treatment approaches.

Methods: A review of the institutional cancer registry was performed to identify black, non-Hispanic women with known nativity and treated for endometrial cancer between 2001 and 2017. Sociodemographic, treatment, and outcomes data were collected. Analyses were done using the χ test, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at P<0.05.

Results: 195 women were included in the analysis. High grade histologies were present in a large proportion of both US born (64.5%) and Caribbean born (72.2%) patients. Compared with US born women, those of Caribbean nativity were more likely to be non-smokers (P=0.01) and be uninsured (P=0.03). Caribbean born women had more cases of stage III disease (27.8% versus 12.5%, P<0.01), while carcinosarcoma was more common in US born black women (23.6% versus 10.6%, P=0.05). Caribbean nativity trended towards improvement in overall survival (hazard ratio (HR) 0.65 (0.40-1.07)). Radiation (HR 0.53 (0.29-1.00)) was associated with improved survival while advanced stage (HR 3.81 (2.20-6.57)) and high grade histology (HR 2.34 (1.17-4.72)) were predictive of worse survival.

Conclusions: The prevalence of high grade endometrial cancer histologies among black women of Caribbean nativity is higher than previously reported. Caribbean nativity may be associated with improved overall survival although additional study is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ijgc-2019-000347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039733PMC
May 2019

Polypharmacy in Patients with Ovarian Cancer.

Oncologist 2019 09 5;24(9):1201-1208. Epub 2019 Apr 5.

Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA

Objective: Polypharmacy has been associated with morbidity and mortality in patients with cancer. Data about polypharmacy among patients with ovarian cancer are limited. The primary objective of this study was to evaluate polypharmacy in a cohort of patients with ovarian cancer and to assess the evolution of polypharmacy from initial presentation to 2 years posttreatment. A secondary objective was to evaluate differences in polypharmacy between a subset of patients primarily treated in our comprehensive cancer center (CCC) and our safety net hospital (SNH).

Methods: Women treated for ovarian cancer between January 1, 2011, and December 31, 2016, were included. Data were abstracted from the electronic medical record. Medication safety was assessed using the established Anticholinergic Burden (ACB) scale and the Beers criteria. Statistical analyses were performed using paired tests and Cox proportional hazards models, with significance set at < .05.

Results: The study included 152 patients. The majority of patients had high-grade serous carcinoma. Hypertension was the most common medical problem. The mean number of medications at the time of diagnosis was 3.72. Paired testing demonstrated significant patient-level increases in the number medications at 2 years following initial diagnosis (4.16 vs. 7.01, < .001). At the CCC, 47.4% of patients met criteria for polypharmacy at diagnosis compared with 19.4% at the SNH ( < .001). By 2 years postdiagnosis, 77.6% of patients at the CCC met criteria for polypharmacy compared with 43.3% at the SNH ( = .001). The use of any medications on the ACB scale ( < .001) increased significantly between initial diagnosis and 2 years for the entire population. Polypharmacy was not a significant predictor of overall survival.

Conclusion: Polypharmacy worsens as women go through ovarian cancer treatment. Both at initial presentation and at 2 years postdiagnosis, rates of polypharmacy were higher at the CCC. Polypharmacy did not have an effect on survival in this cohort.

Implications For Practice: Awareness of escalating numbers of medications and potentially adverse interactions is crucial among women with ovarian cancer, who are at high risk for polypharmacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2018-0807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738286PMC
September 2019

Identifying disparities in germline and somatic testing for ovarian cancer.

Gynecol Oncol 2019 05 16;153(2):297-303. Epub 2019 Mar 16.

Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, United States of America.

Objective: Germline mutations occur in approximately 25% of patients with epithelial ovarian cancers while somatic BRCA mutations are estimated at 5-7%. The objectives of this study were to determine the rate of germline and somatic testing in women with ovarian cancer and to identify disparities in testing at a comprehensive cancer center (CCC) and a safety net hospital (SNH).

Methods: Patients treated for ovarian cancer from 2011 to 2016 were included. Clinicopathologic data were abstracted from the electronic medical records. Logistic regression modeling were performed to calculate odds ratios (OR) and corresponding 95% confidence intervals (95%CI).

Results: Out of 367 women, 55.3% completed germline testing; 27.0% received somatic testing. Women at the CCC were more likely to be tested for germline (60.4% vs 38.1%, p ≤ 0.001) and somatic (34.3% vs 2.4%, p ≤ 0.001) mutations than those at the SNH. Patients with Medicare (aOR = 0.51, 95%CI 0.28-0.94, p = 0.032) or Medicaid (aOR = 0.42, 95%CI 0.18-0.99, p = 0.048) were less likely to receive germline testing than those privately insured. Patients with Medicaid were less likely to receive somatic testing (aOR = 0.15, 95%CI 0.04-0.62, p = 0.009) than those privately insured. Women with disease recurrence had a higher likelihood of being tested for germline (OR = 3.64, 95%CI 1.94-6.83, P < 0.001) and somatic (OR = 7.89, 95%CI 3.41-18.23, p < 0.001) mutations. There was no difference in germline or somatic testing by race/ethnicity.

Conclusions: Disparities in both germline and somatic testing exist. Understanding and overcoming barriers to testing may improve cancer-related mortality by allowing for more tailored treatments as well as for improved cascade testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2019.03.007DOI Listing
May 2019

A clinically structured and partnered approach to genetic testing in Trinidadian women with breast cancer and their families.

Breast Cancer Res Treat 2019 Apr 4;174(2):469-477. Epub 2018 Dec 4.

Sylvester Comprehensive Cancer Center, Miami, FL, USA.

Introduction: Breast cancer (BC) is the leading cause of cancer death in Caribbean women. Across the Caribbean islands, the prevalence of hereditary breast cancer among unselected breast cancer patients ranges from 5 to 25%. Moreover, the prevalence of BC among younger women and the high mortality in the Caribbean region are notable. This BC burden presents an opportunity for cancer prevention and control that begins with genetic testing among high-risk women. Measured response to positive genetic test results includes the number of preventive procedures and cascade testing in family members. We previously reported data on an active approach to promote cascade testing in the Bahamas and report on preventive procedures showing moderate uptake. Here, we describe a clinically structured and community-partnered approach to the dissemination and follow-up of genetic test results including family counseling for the promotion of risk mitigation strategies and cascade testing in our Trinidadian cohort of patients tested positive for BC predisposition genes.

Methods: As a part of our initial study of BC genetic testing in Trinidad and Tobago, all participants received pre-test counseling including three-generation pedigree and genetic testing for BRCA1/2, PALB2, and RAD51C. The study was approved by the University of Miami IRB and the Ethics Committee of the Ministry of Health, Trinidad and Tobago. We prospectively evaluated a clinically structured approach to genetic counseling and follow-up of BC mutation carriers in Trinidad and Tobago in 2015. The intervention consisted of (1) engaging twenty-nine BC patients with a deleterious gene mutation (probands), and (2) invitation of their at-risk relatives to attend to a family counseling session. The session included information on the meaning of their results, risk of inheritance, risk of cancer, risk-reduction options, offering of cascade testing to family members, and follow-up of proband decision-making over two years.

Results: Twenty-four of twenty-nine mutation carriers (82.8%) consented to enroll in the study. At initial pedigree review, we identified 125 at-risk relatives (ARR). Seventy-seven ARR (62%) attended the family counseling sessions; of these, 76 ARR (99%) consented to be tested for their family gene mutation. Genetic sequencing revealed that of the 76 tested, 35 (46%) ARR were carriers of their family mutation. The ARR received their results and were urged to take preventative measures at post-test counseling. At 2-year follow-up, 6 of 21 probands with intact breasts elected to pursue preventive mastectomy (28.5%) and 4 of 20 women with intact ovaries underwent RRSO (20%).

Conclusions: In Trinidad and Tobago, a clinically structured and partnered approach to our testing program led to a significant rate of proband response by completing the intervention counseling session, executing risk-reducing procedures as well as informing and motivating at-risk relatives, thereby demonstrating the utility and efficacy of this BC control program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-018-5045-yDOI Listing
April 2019

New biological research and understanding of Papanicolaou's test.

Diagn Cytopathol 2018 Jun 16;46(6):507-515. Epub 2018 Apr 16.

Department of Cell Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, 33136.

The development of the Papanicolaou smear test by Dr. George Nicholas Papanicolaou (1883-1962) is one of the most significant achievements in screening for disease and cancer prevention in history. The Papanicolaou smear has been used for screening of cervical cancer since the 1950s. The test is technically straightforward and practical and based on a simple scientific observation: malignant cells have an aberrant nuclear morphology that can be distinguished from benign cells. Here, we review the scientific understanding that has been achieved and continues to be made on the causes and consequences of abnormal nuclear morphology, the basis of Dr. Papanicolaou's invention. The deformed nuclear shape is caused by the loss of lamina and nuclear envelope structural proteins. The consequences of a nuclear envelope defect include chromosomal numerical instability, altered chromatin organization and gene expression, and increased cell mobility because of a malleable nuclear envelope. HPV (Human Papilloma Virus) infection is recognized as the key etiology in the development of cervical cancer. Persistent HPV infection causes disruption of the nuclear lamina, which presents as a change in nuclear morphology detectable by a Papanicolaou smear. Thus, the causes and consequences of nuclear deformation are now linked to the mechanisms of viral carcinogenesis, and are still undergoing active investigation to reveal the details. Recently a statue was installed in front of the Papanicolaou's Cancer Research Building to honor the inventor. Remarkably, the invention nearly 60 years ago by Dr. Papanicolaou still exerts clinical impacts and inspires scientific inquiries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.23941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949091PMC
June 2018

Presentation, Treatment, and Outcomes of Haitian Women With Breast Cancer in Miami and Haiti: Disparities in Breast Cancer-A Retrospective Cohort Study.

J Glob Oncol 2017 Aug 2;3(4):389-399. Epub 2016 Nov 2.

, , and , University of Miami/Jackson Memorial Hospital; , Sylvester Comprehensive Cancer Center, University of Miami; , Sylvester Biostatistics and Bioinformatics Core Resource, University of Miami, Miami; and , University of Florida College of Medicine, Gainesville, FL; and and , Innovating Health International, Port-au-Prince, Haiti.

Purpose: We compared a cohort of Haitian immigrants with residents in Haiti with breast cancer (BC) to evaluate the effects of location on presentation, treatment, and outcomes.

Patients And Methods: Participants were Haitian women with BC living in Miami who presented to the University of Miami/Jackson Memorial Hospital and women with BC living in Haiti who presented to the Innovating Health International Women's Cancer Center. The primary outcome was the relationship between location, cancer characteristics, and survival. The secondary objective was to compare our results with data extracted from the SEER database. Cox regression was used to compare survival.

Results: One hundred two patients from University of Miami/Jackson Memorial Hospital and 94 patients from Innovating Health International were included. The patients in Haiti, compared with the patients in Miami, were younger (mean age, 50.2 53.7 years, respectively; = .042), presented after a longer duration of symptoms (median, 20 3 months, respectively; < .001), had more advanced stage (44.7% 25.5% with stage III and 27.6% 18.6% with stage IV BC, respectively), and had more estrogen receptor (ER) -negative tumors (44.9% 26.5%, respectively; = .024). The percentage of women who died was 31.9% in Haiti died compared with 17.6% in Miami. Median survival time was 53.7 months for women in Haiti and was not reached in Miami. The risk of death was higher for women in Haiti versus women in Miami (adjusted hazard ratio, 3.09; = .0024).

Conclusion: Women with BC in Haiti experience a significantly worse outcome than immigrants in Miami, which seems to be related to a more advanced stage and younger age at diagnosis, more ER-negative tumors, and lack of timely effective treatments. The differences in age and ER status are not a result of access to care and are unexplained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JGO.2016.005975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560455PMC
August 2017

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-017-4148-1DOI Listing
April 2017

Primary Peritoneal Carcinoma in a BRCA1/2-negative, PALB2-positive patient.

Gynecol Oncol Rep 2016 Aug 2;17:93-5. Epub 2016 Aug 2.

University of Miami, Miller School of Medicine, United States; Department of Obstetrics and Gynecology, Division of Gynecology Oncology, University of Miami, United States; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, United States.

•First reported case of PPC after BSO in a BRCA1/2-negative, PALB2-positive patient•The PALB2 mutation and genetic counseling is discussed•Multi-gene panel testing can benefit prognostic factors and targeted therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gore.2016.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983106PMC
August 2016

A Survey of BRCA1, BRCA2, and PALB2 mutations in women with breast cancer in Trinidad and Tobago.

Breast Cancer Res Treat 2016 08 28;159(1):131-8. Epub 2016 Jul 28.

Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Avenue, D8-4, Miami, FL, 33136, USA.

The mortality rate from breast cancer in the nation of Trinidad and Tobago is among the highest of any country in the Caribbean region. The contribution of inherited gene mutations to the burden of breast cancer in Trinidad and Tobago has not been studied. We examined the prevalence of mutations in three susceptibility genes (BRCA1, BRCA2, and PALB2) in breast cancer patients in Trinidad and Tobago. We studied 268 unselected breast cancer patients from Trinidad and Tobago and looked for mutations across the entire coding sequences of BRCA1, BRCA2, and PALB2. Overall, 28 of 268 patients (10.4 %) had a mutation in one of the three genes, including 15 in BRCA1, ten in BRCA2, two in PALB2, and one in both BRCA2 and PALB2. There were 25 different mutations identified; of these, four mutations were seen in two patients each. Given the high prevalence of mutations, it is reasonable to offer genetic testing for these three genes to all breast cancer patients in Trinidad and Tobago.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-016-3870-4DOI Listing
August 2016

Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for Prevention.

Front Oncol 2016 2;6:108. Epub 2016 May 2.

Department of Obstetrics and Gynecology, Division of Gynecology Oncology, Miller School of Medicine, University of Miami, Miami, FL, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.

High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of EOC, the rationale for risk-reducing salpingectomy in the high-risk population, and opportunities for salpingectomy in the low-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2016.00108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852190PMC
May 2016

In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose.

J Vis Exp 2015 Oct 14(105):e52721. Epub 2015 Oct 14.

Section of Urology, Department of Surgery, The University of Chicago;

High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the contribution of omental adipose tissue to ovarian cancer progression remains understudied. Omental adipose is unusual in that it contains structures known as milky spots, which are comprised of B, T, and NK cells, macrophages, and progenitor cells surrounding dense nests of vasculature. Milky spots play a key role in the physiologic functions of the omentum, which are required for peritoneal homeostasis. We have shown that milky spots also promote ovarian cancer metastatic colonization of peritoneal adipose, a key step in the development of peritoneal metastases. Here we describe the approaches we developed to evaluate and quantify milky spots in peritoneal adipose and study their functional contribution to ovarian cancer cell metastatic colonization of omental tissues both in vivo and ex vivo. These approaches are generalizable to additional mouse models and cell lines, thus enabling the study of ovarian cancer metastasis formation from initial localization of cells to milky spot structures to the development of widespread peritoneal metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/52721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692646PMC
October 2015
-->