Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV.

PURPOSE: Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS: Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS: We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION: This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

Gaps in completion and timeliness of breast surgery and adjuvant therapy: a retrospective cohort of Haitian patients with nonmetastatic breast cancer.

BACKGROUND: There are limited data on breast surgery completion rates and prevalence of care-continuum delays in breast cancer treatment programs in low-income countries. METHODS: This study analyzes treatment data in a retrospective cohort of 312 female patients with non-metastatic breast cancer in Haiti. Descriptive statistics were used to summarize patient characteristics; treatments received; and treatment delays of > 12 weeks. Multivariate logistic regressions were performed to identify factors associated with receiving surgery and with treatment delays. Exploratory multivariate survival analysis examined the association between surgery delays and disease-free survival (DFS). RESULTS: Of 312 patients, 249 (80%) completed breast surgery. The odds ratio (OR) for surgery completion for urban vs. rural dwellers was 2.15 (95% confidence interval [CI]: 1.19-3.88) and for those with locally advanced vs. early-stage disease was 0.34 (95%CI: 0.16-0.73). Among the 223 patients with evaluable surgery completion timelines, 96 (43%) experienced delays. Of the 221 patients eligible for adjuvant chemotherapy, 141 (64%) received adjuvant chemotherapy, 66 of whom (47%) experienced delays in chemotherapy initiation. Presentation in the later years of the cohort (2015-2016) was associated with lower rates of surgery completion (75% vs. 85%) and with delays in adjuvant chemotherapy initiation (OR [95%CI]: 3.25 [1.50-7.06]). Exploratory analysis revealed no association between surgical delays and DFS. CONCLUSION: While majority of patients obtained curative-intent surgery, nearly half experienced delays in surgery and adjuvant chemotherapy initiation. Although our study was not powered to identify an association between surgical delays and DFS, these delays may negatively impact long-term outcomes.

Body Mass Index, Chemotherapy-Related Weight Changes, and Disease-Free Survival in Haitian Women With Nonmetastatic Breast Cancer.

PURPOSE: Few studies have explored the relationship between body habitus and breast cancer outcomes in Caribbean women of African ancestry. This study evaluates the association between body mass index (BMI) and disease-free survival (DFS) in a retrospective cohort of 224 female Haitian patients with nonmetastatic breast cancer. PATIENTS AND METHODS: BMI was obtained from the medical records and categorized as normal weight (< 25 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). DFS was defined as time from surgical resection to disease recurrence, death, or censoring. Kaplan-Meier survival curves were generated, and the association between BMI and DFS was evaluated using Cox proportional hazard models to control for multiple confounders. Exploratory analyses were conducted on weight changes during adjuvant chemotherapy. RESULTS: Eighty-three patients (37.1%) were normal weight, 66 (29.5%) were overweight, and 75 (33.5%) were obese. There were no statistical differences in baseline characteristics or treatments received by BMI group. Twenty-six patients died and 73 had disease recurrence. Median DFS was 41.1 months. Kaplan-Meier estimates showed no significant DFS differences by BMI categories. After controlling for confounders, normal weight patients, when compared with overweight and obese patients, had adjusted hazard ratios of 0.85 (95% CI, 0.49 to 1.49) and 0.90 (95% CI, 0.52 to 1.55), respectively. Overall, mean weight loss of 2% of body weight was noted over the course of adjuvant chemotherapy. Patients who were postmenopausal (P = .007) and obese (P = .05) lost more weight than other groups. However, chemotherapy-related weight changes did not have an impact on DFS. CONCLUSION: Baseline BMI and weight changes during adjuvant chemotherapy did not have an impact on DFS in this cohort. Future prospective studies in similar Caribbean breast cancer cohorts are needed to verify study findings.

Diretrizes de rastreamento do câncer de mama com práticas personalizadas e baseadas em risco: estamos preparados? / Breast cancer screening guidelines with personalized, risk-based practices: are we ready?

O estudo averiguou se a literatura atual pode ajudar na orientação de sistemas e profissionais de saúde para a promoção de rastreamento personalizado centrado no perfil de risco das mulheres. Revisamos artigos publicados entre 2010 e 2015, indexados no banco de dados Medline. Os artigos foram selecionados com base em conteúdo tratando de métodos de rastreamento, diretrizes e fatores de risco levados em consideração no processo de tomada de decisão. Os descritores de busca foram câncer de mama, rastreamento, diretrizes e avaliação de qualidade. Os 40 artigos selecionados para leitura completa foram organizados em ordem cronológica segundo a data de publicação. Dos 40 artigos, 32 se referem a diretrizes nacionais ou internacionais já existentes sobre rastreamento do câncer de mama. Vários fatores de risco relevantes para estratégias de rastreamento, incluindo os modelos de avaliação de risco cumulativo, são considerados em todos os 40 artigos, sendo os mais comuns idade, histórico familiar e densidade do tecido da mama. Contudo, não há consenso explícito sobre se o rastreamento do câncer de mama deve ser visto como uma escolha da paciente ou se é um imperativo das políticas de saúde pública. As evidências sugerem que os sistemas de saúde e os médicos deveriam considerar a mudança do paradigma de rastreamento rotineiro de mulheres de 50 a 69 anos para o rastreamento personalizado do câncer de mama baseado em avaliação de risco nos países em que isso é factível.(AU)

The study ascertained whether the current literature may be helpful in guiding health systems and healthcare providers to promote personalized screening centered on women's risk profiles. We reviewed Medline database indexed articles published between 2010 and 2015, indexed in the Medline databased. Articles were selected based on their content dealing with screening methods, guidelines, and risk factors considered in the decision-making process. The descriptors used for the search were breast cancer, screening, guidelines, and quality assessment. The 40 articles selected for full text reading were organized in chronological order by date of publishing. Of the 40 articles, 32 refer to the existing national or international breast cancer screening guidelines. Various risk factors relevant to screening strategies, including the cumulative risk assessment models, are considered in all 40 articles, with the most common being age, family history, and breast tissue density. However, there is no explicit consensus on whether to view breast cancer screening as a patient choice or as an imperative of public health policies. The evidences suggest that health systems and physicians should consider switching from the routine screening paradigm for women aged 50-69 to personalized risk-assessment-based screening for breast cancer in countries where this is feasible. (AU)

Patient Characteristics and Outcomes of Nonmetastatic Breast Cancer in Haiti: Results from a Retrospective Cohort.

BACKGROUND: There are few studies on breast cancer outcomes in the Caribbean region. This study identified a retrospective cohort of female patients with nonmetastatic breast cancer in Haiti and conducted survival analyses to identify prognostic factors that may affect patient outcomes. METHODS: The cohort included 341 patients presenting between June 2012 and December 2016. The primary endpoint was event-free survival (EFS), defined as time to disease progression, recurrence, or death. Descriptive summaries of patient characteristics and treatments were reported. Survival curves were plotted using Kaplan-Meier estimation. Multivariate survival analyses were performed using Cox proportional hazards regression. RESULTS: Median age at diagnosis was 49 years, with 64.2% being premenopausal. Most patients (55.1%) were staged as locally advanced. One hundred and sixty patients received neoadjuvant therapy: 33.3% of patients with early stage disease and 61.2% of those with locally advanced stage disease. Curative-intent surgery was performed in 278 (81.5%) patients, and 225 patients received adjuvant therapy. Adjuvant endocrine therapy was used in 82.0% of patients with estrogen receptor-positive disease. During the follow-up period, 28 patients died, 77 had disease recurrence, and 10 had progressive disease. EFS rates at 2 years and 3 years were 80.9% and 63.4%, respectively. After controlling for multiple confounders, the locally advanced stage group had a statistically significant adjusted hazard ratio for EFS of 3.27 compared with early stage. CONCLUSION: Patients with nonmetastatic breast cancer in Haiti have more advanced disease, poorer prognostic factors, and worse outcomes compared with patients in high-income countries. Despite several limitations, curative treatment is possible in Haiti. IMPLICATIONS FOR PRACTICE: Patients with breast cancer in Haiti have poor outcomes. Prior studies show that most Haitian patients are diagnosed at later stages. However, there are no rigorous studies describing how late-stage diagnosis and other prognostic factors affect outcomes in this population. This study presents a detailed analysis of survival outcomes and assessment of prognostic factors in patients with nonmetastatic breast cancer treated in Haiti. In addition to late-stage diagnosis, other unfavorable prognostic factors identified were young age and estrogen receptor-negative disease. The study also highlights that the availability of basic breast cancer treatment in Haiti can lead to promising early patient outcomes.

Cancer incidence and mortality rates and trends in Trinidad and Tobago.

BACKGROUND: Cancer is the second leading cause of death in the Caribbean, including the islands of Trinidad and Tobago (TT). The population of TT consists of over 1.3 million people with diverse ancestral and sociocultural backgrounds, both of which may influence cancer incidence and mortality. The objective of this study was to examine incidence and mortality patterns and trends in TT. METHODS: Cancer surveillance data on 29,512 incident cancer cases reported to the Dr. Elizabeth Quamina Cancer Registry (population-based cancer registry of TT) between 1995 and 2009 were analyzed. Age-standardized rates, overall and by sex, ancestry, and geography, were reported. RESULTS: The highest incidence and mortality rates were observed for cancers related to reproductive organs in women, namely, breast, cervical, and uterine cancers, and prostate, lung and colorectal cancers among men. Average incidence rates were highest in areas covered by the Tobago Regional Health Authority (TRHA) (188 per 100,000), while average mortality rates were highest in areas covered by the North West Regional Health Authority (108 per 100,000). Nationals of African ancestry exhibited the highest rates of cancer incidence (243 per 100,000) and mortality (156 per 100,000) compared to their counterparts who were of East Indian (incidence, 125 per 100,000; mortality, 66 per 100,000) or mixed ancestry (incidence, 119 per 100,000; mortality, 66 per 100,000). CONCLUSIONS: Our findings highlight the need for national investment to improve the understanding of the epidemiology of cancer in Trinidad and Tobago, and to ultimately guide much needed cancer prevention and control initiatives in the near future.

The burden of prostate cancer in Trinidad and Tobago: one of the highest mortality rates in the world.

PURPOSE: In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world. METHODS: 6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography. RESULTS: The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively). CONCLUSIONS: Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report.

Cancer Genomics: Diversity and Disparity Across Ethnicity and Geography.

Ethnic and geographic differences in cancer incidence, prognosis, and treatment outcomes can be attributed to diversity in the inherited (germline) and somatic genome. Although international large-scale sequencing efforts are beginning to unravel the genomic underpinnings of cancer traits, much remains to be known about the underlying mechanisms and determinants of genomic diversity. Carcinogenesis is a dynamic, complex phenomenon representing the interplay between genetic and environmental factors that results in divergent phenotypes across ethnicities and geography. For example, compared with whites, there is a higher incidence of prostate cancer among Africans and African Americans, and the disease is generally more aggressive and fatal. Genome-wide association studies have identified germline susceptibility loci that may account for differences between the African and non-African patients, but the lack of availability of appropriate cohorts for replication studies and the incomplete understanding of genomic architecture across populations pose major limitations. We further discuss the transformative potential of routine diagnostic evaluation for actionable somatic alterations, using lung cancer as an example, highlighting implications of population disparities, current hurdles in implementation, and the far-reaching potential of clinical genomics in enhancing cancer prevention, diagnosis, and treatment. As we enter the era of precision cancer medicine, a concerted multinational effort is key to addressing population and genomic diversity as well as overcoming barriers and geographical disparities in research and health care delivery.

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

OBJECTIVE: This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. METHODS: Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. RESULTS: Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. CONCLUSIONS: Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.