Angélica Nogueira-Rodrigues

Breast and gynecologic cancers as a Brazilian health priority

Cancer imposes a profound burden on low- and middle-income countries where 65% of the global cancer deaths occurred in 2020. The objective of the present review was to describe female cancer epidemiology in Brazil, barriers to prevention, screening, and treatment, and to propose strategies to a better control. For the process of literature search and scientific acquisition, we have utilized the terms "female cancer" AND "breast cancer," AND "cervical cancer" AND "endometrial cancer" AND "ovarian cancer" AND "Brazil" in PubMed. References of the articles included in this review were manually searched in order to identify relevant studies on the topic. The official Brazilian epidemiology data were extensively analyzed at the governmental site www.inca.gov.br. Considering cases of breast and gynecologic cancers together, 105,770 new cases are expected to be diagnosed yearly, positioning female cancer as the highest cancer incidence in Brazil. Female breast cancer is the most common and the leading cause of death from cancer in the female population in all regions of Brazil, except in the North, where cervical cancer ranks first. Cervical cancer, a preventable disease, corresponds to the third-most common neoplasia in women, with higher incidences in the North and Northeast regions of Brazil. An upward trend has been observed in endometrial cancer incidence, a tendency that follows the increase of its two most common risk factors: population aging and obesity. Ovarian cancer currently occupies the eighth position among female cancers in Brazil, but it is the most lethal gynecologic cancer. The main strategies to reduce female cancer mortality rates are the reduction of inequalities in healthcare services and the early diagnosis of cases. The lack of a specific national cancer program results in a reactive and unplanned approach to healthcare provision, ultimately leading to suboptimal resource utilization and higher expenditure. Analyzed together, breast and gynecologic cancers correspond to the leading cause of cancer in Brazil. A heterogeneous group, female cancer includes diseases with a high primary and secondary prevention potential. The organization of a female cancer program in Brazil prioritizing primary and secondary prevention strategies, such as adequate mammography screening and human papillomavirus vaccination coverage, could significantly improve female cancer control in the country.

Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment

Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.

Management of endometrial cancer in Latin America: raising the standard of care and optimizing outcomes

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network—that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions.

Exploring cervical cancer mortality in Brazil: an ecological study on socioeconomic and healthcare factors

To evaluate the correlation between socioeconomic and healthcare factors and cervical cancer mortality rates, as well as the accessibility to prevention and treatment across Brazilian states and macroregions. The aim is to highlight the multifaceted challenge of addressing cervical cancer mortality, particularly in low-and middle-income countries. This ecological study analyzed public data from the Brazilian National Institute of Cancer (INCA), the National Institute of Geography and Statistics (IBGE), and the Brazilian Ministry of Health. Data were collected on indicators such as the Human Development Index (HDI), physician density, average household income, human papillomavirus (HPV) vaccine coverage, Pap smear screening rates, radiotherapy machine density, and non-White population rates by state and macroregion across Brazil. Spearman's rank correlation test and simple linear regression analysis were employed. Cervical cancer mortality rates are statistically lower in women with health insurance, positive self-perception of health, located in states with a higher HDI, higher per capita household income, greater density of physicians, and higher availability of radiotherapy machines. In contrast, mortality rates proportionally increase according to poverty levels, as expected, and rates of non-White population. Considering public health, HDI scores significantly affected Pap smear test coverage, the number of radiotherapy machines, and HPV vaccine uptake. The North and the Southeast regions have, respectively, the lowest and the highest socioeconomic indicators, proportional to their mortality rates. No significant correlation was found between mortality rates and HPV vaccine or Pap smear coverage. Cervical cancer mortality in Brazil is significantly influenced by socioeconomic and healthcare disparities. This study provides a data-driven basis for public health strategies that address both medical and social determinants of health.

Dealing with cancer screening in the COVID-19 era

This article aims to alert health professionals for cancer screening in the face of the possibility of new waves of disease. A narrative review was conducted through a search in MEDLINE, Lilacs, Chinese Biomedical Literature Database, and international medical societies publications. Breast cancer: in high-risk patients (confirmed familial cancer syndrome or with high-risk tools scores), clinicians should act according to usual recommendations; in average-risk individuals, consider screening with mammography with a longer time span (maximum of two years). Cervical cancer: women turning 25 years old who have already been immunized and with no previous Pap test can have the test postponed during the pandemic; if there is no previous dose of Human Papillomavirus vaccination, initiation of screening should be recommended following a more rigid approach for COVID prevention; in women over 30 years of age who have never participated in cervical screening, the first screening exam is also essential. Colorectal cancer: if the individual is at elevated risk for familial cancer, the screening with colonoscopy according to usual recommendations should be supported; if at average risk consider screening with Fecal Occult Blood Test. Prostate cancer: there is a trend to postpone routine prostate cancer screening until the pandemic subsides. The decision to keep cancer screening must be discussed and individualized, considering the possibility of new waves of COVID-19.

The utility of pretreatment systemic inflammatory response biomarkers on overall survival of cervical cancer patients stratified by clinical staging

Inflammation plays a crucial role in the initiation and progression of many cancers. This study aimed to investigate the utility of pretreatmentneutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), derived neutrophil-lymphocyte ratio (dNLR), and a combination of PLR and NLR in predicting the risk of death according to clinical staging in cervical cancer (CC) patients. A cohort study of women with CC, diagnosed and treated at a single cancer referral center in Brazil, from 2006 to 2009. A multivariate Cox regression analysis and ROC curve analysis accessed the predictive value of inflammatory response biomarkers in overall survival (OS). The median values of the biomarkers were used as cut-off points. A total of 1,266 patients were included in the study, 76.0% with locally advanced disease. After adjusting for clinical variables, NLR > 2.57, PLR ≥ 146.70, dNLR ≥ 1.778 and PLR + NLR in combination had equivalent performance in predicting worse OS, but only among patients with locally advanced disease (adjusted Hazard Ratio [aHR] = 1.453, 95% Confidence Interval [CI] = 1.227-1.722; p < 0.001; aHR = 1.429; 95% CI = 1.209-1.688; p < 0.001; aHR = 1.486, 95% CI = 1.257-1.756, p < 0.001, aHR = 1.731; 95% CI = 1.411-2.123; p < 0.001, respectively). In conclusion, PLR, NLR, dNLR and PLR + NLR in combination presented equivalent performance in predicting OS in locally advanced CC patients. They are simple and readily available from routine blood tests, not entailing additional costs. PLR, NLR, dNLR and PLR + NLR in combination are strong prognostic biomarkers candidates in locally advanced CC and should be further explored in prospective trials.

Comprehensive management of vulvovaginal cancers

AbstractVulvar and vaginal cancers represent rare malignancies, with an incidence of 2.7 per 100,000 women for vulvar cancer, predominantly affecting women older than 60 years, although rising rates are observed in younger demographics. Approximately 90% of vulvar cancers are squamous cell carcinoma and frequently are associated with human papillomavirus (HPV) infection. Vaginal cancer, constituting less than 1% of all female cancers, similarly exhibit HPV‐related trends. This review delineates the etiology, histopathology, and treatment strategies for carcinomas and vulvovaginal melanomas and sarcomas. Surgical intervention remains the primary treatment modality for vulvar cancer, involving tumor resection and inguinofemoral lymph node staging. For locally advanced vulvar carcinoma, chemoradiation is advised when exenterative surgery would be indicated. Recurrence rates within 2 years after diagnosis range from 12% to 37%. Unfortunately, systemic treatments for recurrent or metastatic disease are limited, with 5‐year survival rates at approximately 20%. Current evidence primarily derives from retrospective studies or small phase 2 trials or otherwise is extrapolated from the treatment of cervical cancer. Enrollment in clinical trials is strongly advocated, along with prompt access to best supportive care to mitigate the effect of locoregional progression on quality of life. Moreover, the psychosocial implications of treatment on body image and sexuality necessitate careful consideration. Future HPV vaccination initiatives may reduce cancer incidence, although significant effects of such vaccination will manifest over decades, underscoring the urgent need to enhance treatment efficacy and minimize morbidity in vulvar and vaginal cancers.

Clinical Trial Protocol for ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in advanced platinum-resistant ovarian cancer

Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinum-resistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol's antiapoptotic effects, enhancing chemotherapy's efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nab-paclitaxel or nab-paclitaxel monotherapy. The study's primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes. ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18.