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 \u3c.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.

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Differences in breast cancer outcomes amongst Black United States-born and Caribbean-born immigrants

1088 Background: The Black population in the US constitutes of 4 million immigrants, with 50% from the Caribbean. It has been shown that breast cancer is responsible for 14%-30% of cancer deaths in the Caribbean; this is up to two times higher than the USA. Methods: Retrospective cohort of 1369 self-identified Black women with breast cancer. Data was obtained from Jackson Memorial Health Systems and University of Miami Health System Tumor Registry. Individual-level data from 1132 cases was used to estimate hazard rations (HRs) of women born in the Caribbean (CB) or in the USA (USB) using Cox proportional hazards regression analysis for overall survival. Median follow-up was 115 months (interquartile range, 91.9-138.1 months) per participant. Results: Data from 622 (54.9%) USB women and 507 (45%) CB women diagnosed with breast cancer between 2006-2017. 90% (n = 1232) of the cohort is of non-Hispanic ethnicity. Caribbean immigrants from Haiti (18.3%), Jamaica (6.5%), Bahamas (3.1%), Cuba and Dominica Republic (2.8% each), Trinidad and Tobago (1%) and other nationalities from the Organization of Eastern Caribbean States were included, mean age 55.7 [95% CI, 54.7-56.8]; USB mean age 57.6 [95% CI, 56.4-58.7] (P = 0.02). Compared to USB, CB had lower BMI at diagnosis 29.6 [95% CI, 28.9-30.3] versus 30.9 [95% CI, 30.1-31.7, P = 0.015]. Compared to CB patients, USB patients had more ER- [31.4% vs 39.1 %, P = 0.018] and triple negative breast cancers [19.6% vs 27.9%, P = 0.003]. Compared to USB patients, CB presented at more advanced stage, III and IV [44.2% vs 35.2%], p = 0.016. In spite of higher advanced stage at diagnoses, CB patients had a better breast cancer overall survival [HR = 0.75; 95%CI, 0.59-0.96; P = 0.024]. Black Hispanic patients had a better overall survival [HR = 0.51; 95%CI, 0.28-0.93; p = 0.028] compared to non-Hispanic Blacks. Compared to Hispanic Caribbean, non-Hispanic Caribbean had a worse overall survival [HR = 1.98; 95%CI, 1.00-3.94; P = 0.048]. The distribution of patients treated at the private cancer center and the safety net hospital were the same, differences in outcomes observed are due to intrinsic differences. Conclusions: This is the largest analysis to date of self-identified Black breast cancer patients in the context of nativity, race, ethnic identity and overall survival with clinico-pathologic characteristics. CB immigrants diagnosed with breast cancer have a better overall survival than US born Black patients. This finding suggests that within the African diaspora in the USA, additional factors beyond race contribute to the outcomes

Comparing breast cancer characteristics and outcomes between black U.S.-born patients and black immigrant patients from individual Caribbean islands

e13633 Background: Caribbean-born black immigrants (CBI) represent 57% of all black immigrants in the US; they come mainly from Haiti, Jamaica, Dominican Republic (DR), and Cuba. Breast cancer (BC) is the leading cause of cancer deaths in women living in the Caribbean, however, our previous retrospective cohort of 1131 black women with BC shows that CBI have a better overall survival compared with US-born black (USB). The Caribbean has a majority of African ancestry; nonetheless, different ancestral populations differ in genetic composition, making the Caribbean a distinct population with several health disparities within it. Therefore, we stratified our study by each Caribbean country compared to USB patients with the objective of further studying the difference in BC outcomes between USB patients and CBI. Methods: We identified BC patients through a Safety Net and Private Hospital Tumor Registries. We selected the most populace sites: Haiti, Jamaica, Bahamas, Cuba and DR; and used data from 1,082 patients to estimate hazard rations (HRs) using Cox proportional hazards regression and Kaplan Meier analysis for overall survival; Chi Squared and independent sample t-test to verify associations in categorical variables. Results: The study has 250 Haitian, 89 Jamaican, 43 Bahamian, 38 Dominican, 38 Cuban and 624 USB women. Haitians underwent less surgery (HB 61.2% vs USB 72.9%; P = 0.001) and had less triple negative BC (18% vs USB 27.8%; P = 0.006). Bahamians were the youngest at diagnosis (50.5 years vs. USB 57.6 P < 0.001) and presented at more advanced stages (stage 3/4, 54.3% vs USB 35.3%; P = 0.02). Jamaicans and DR underwent more radiation therapy (43.8%, P = 0.002 and 44.7%, P = 0.028 vs. USB 28%). Jamaican women had a better overall survival compared to USB patients (median of 154.93 months, 95% CI: 114.1-195.5 vs 98.63 months, 95% CI: 76.4-120.8; Log-Rank Mantel Cox P = 0.034). Favorable factors for survival were: radiation therapy in Haitian and USB (aHR = 0.45, 95% 0.27-0.77; P = 0.004); and surgery in USB (aHR = 0.26 (0.19-0.36), p < 0.001), Bahamians (aHR = 0.05 (0.01-0.47), p = 0.008) and Jamaicans (aHR = 0.08 (0.03-0.24), p < 0.001). Conclusions: This study underlines the vast heterogeneity in the Caribbean population and demonstrates that Jamaican immigrants with BC have a higher overall survival compared to USB patients, proposing that genetic and other cancer related factors inherent to country of origin impact survival within Caribbean immigrants and highlighting the need for further studies in this immigrant sub-group

Abstract 3343: The Florida women’s cancer study: Breast cancer presentation among African American and Afro Caribbean women in south Florida, a 10-year cohort

Abstract Introduction: The Black population in the US constitutes about 4 million immigrants. Of this, 50% is from the Caribbean region. Jamaica is the largest contributing country, followed by Haiti and Trinidad and Tobago. Florida has the second largest Caribbean population in the USA. Breast cancer is the main cause of cancer death among females responsible for 14%-30% of cancer deaths in the Caribbean; this is up to two times higher than the USA. Little is known about the molecular subtypes of breast cancer and the demographics of Black Caribbean Immigrants. Objectives: Study the demographics of BC patients in the African diaspora, determine similarities and differences in cause, subtype and outcome of women with breast cancers in African American (AA) and Afro-Caribbean (AC) immigrants. Methods: Approved by the Ethics Committee of the University of Miami IRB. Patients treated for breast cancer between 2006 to 2016 were included. Abstracted data included sociodemographic factors, genetic testing results, and treatment histories. Results: A retrospective US-based cohort of 1369 women (self-identified as black), diagnosed with BC - the Florida Women’s Cancer Study (FLWCS), at Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital in Florida. This cohort contains data from 624 (46%) African-American (AA) women and 507 (37%) AC women diagnosed with breast cancer between 2006-2016. Ninety per cent (n=1232) of the cohort is of non-Hispanic ethnicity.FLWCS country distribution includes is composed of Haiti (18.3%), Jamaica (6.5%), Bahamas (3.1%), Cuba and Dominica Republic (2.8% each), Trinidad and Tobago (1%) and other nationalities from the Organization of Eastern Caribbean States (Antigua, St. Kitts and Nevis, Anguilla, Dominica, St. Lucia and Grenada) at 2.5%. ACwomen living in Miami were diagnosed at a younger age (53.7 years versus 54.9 years), than AA women.Twenty-eight percent of the AA women were premenopausal compared with 32% of the AC women. The AA women had a higher BMI, 32.1 vs 29.8 (p=0.0001), a lower proportion of HER2 positive breast cancer of 17.6% versus 23% (p=0.027), and more children 3.1 versus 2.8 (p=0.023), than the AC women. The rate of HER2 overexpression in the Caucasian population is12% while HER2 positivity was seen in 26.2% Jamaican women, 25.8% in Haitian women and 26.5% in Cuban women (p=0.043) respectively. Less than 5% of the cohort underwent genetic testing with less than 1% having a pathogenic germline mutation. Conclusion: African American (AA) and AC women have many similarities there are significant differences in terms of ancestral diversity, inherited genetic mutations, environmental exposures and access to medical care. Thus, it is imperative to gain an understanding of the causes of cancer in AC women in their own countries in order to better serve those immigrant populations once they reach the US. Citation Format: Priscila Barreto Coelho, Matthew Schlumbrecht, Danielle Cerbon, Carlos Parra, Judith Hurley, Sophia George. The Florida women’s cancer study: Breast cancer presentation among African American and Afro Caribbean women in south Florida, a 10-year cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3343

Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST