ABSTRACT
When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.
Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer/methods , Health Plan Implementation/methods , Consensus , Delivery of Health Care , Developing Countries , Early Detection of Cancer/economics , Female , Global Health , Health Plan Implementation/economics , Humans , Practice Guidelines as Topic , Socioeconomic FactorsABSTRACT
PURPOSE: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type. METHODS: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. RESULTS: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001). CONCLUSIONS: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.
Subject(s)
Amazona , Breast Neoplasms , Animals , Brazil/epidemiology , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Female , Humans , Insurance Coverage , Insurance, Health , Prospective StudiesABSTRACT
Breast cancer (BC) risk assessment models base their estimations on different aspects of a woman's personal and familial history. The Gail and Tyrer-Cuzick models are the most commonly used, and BC risks assigned by them vary considerably especially concerning familial history. In this study, our aim was to compare the Gail and Tyrer-Cuzick models after initial screening for familial history of cancer in primary care using the FHS-7 questionnaire. We compared 846 unrelated women with at least one positive answer to any of the seven FHS-7 questions (positive group) and 892 unrelated women that answered negatively (negative group). Concordance between BC risk estimates was compared by Bland-Altman graphics. Mean BC risk estimates were higher using the Tyrer-Cuzick Model in women from the positive group, while women from the negative group had higher BC risk estimates using the Gail model. With increasing estimates, discordance also increased, mainly in the FHS-7 positive group. Our results show that in women with a familial history of cancer, the Gail model underestimates risk and the Tyrer-Cuzick seems to be more appropriate. FHS-7 can be a useful tool for the identification of women with higher breast cancer risks in the primary care setting.
ABSTRACT
PURPOSE: The aim of this study is to assess potential risk factors for breast cancer in a population in Southern Brazil and build a multivariate logistic model using these factors for breast cancer risk prediction. METHODS: A total of 4242 women between 40 and 69 years of age without a history of breast cancer were selected at primary healthcare facilities in Porto Alegre and submitted to mammographic screening. They were evaluated for potential risk factors. RESULTS: In all, 73 participants among the 4242 women had a breast cancer diagnosis during the follow-up of the project (10 years). The multivariate analysis considering all the patients aged 40-69 years showed that older age (OR 1.08, 95% CI 1.04-1.12), higher height (OR 1.04, 95% CI 1.01-1.09), and history of previous breast biopsy (OR 2.66, 95% CI 1.38-5.13) were associated with the development of breast cancer. Conversely, the number of pregnancies (OR 0.87, 95% CI 0.78-0.98) and use of hormone replacement therapy (OR 0.39, 95% CI 0.20-0.75) were considered a protective factor. Additionally, we performed an analysis separating the participants into groups of 40-49 and 50-69 years old, since a risk factor could have a specific behavior in these age groups. No additional risk factors were identified within these age brackets, and some factors lost statistical significance. CONCLUSION: The risk prediction model indicates that the following variables should be assessed in this specific population: age, height, having had previous breast biopsies, number of pregnancies, and use of hormone replacement therapy. These findings may help to better understand the causal model of breast cancer in Southern Brazil.
Subject(s)
Breast Neoplasms/epidemiology , Breast/diagnostic imaging , Carcinoma, Ductal, Breast/epidemiology , Early Detection of Cancer , Adult , Aged , Brazil , Breast/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/pathology , Female , Hormone Replacement Therapy/adverse effects , Humans , Mammography , Middle Aged , Risk Assessment , Risk FactorsABSTRACT
In Brazil, breast cancer is a public health care problem due to its high incidence and mortality rates. In this study, we investigated the prevalence of hereditary breast cancer syndromes (HBCS) in a population-based cohort in Brazils southernmost capital, Porto Alegre. All participants answered a questionnaire about family history (FH) of breast, ovarian and colorectal cancer and those with a positive FH were invited for genetic cancer risk assessment (GCRA). If pedigree analysis was suggestive of HBCS, genetic testing of the BRCA1, BRCA2, TP53, and CHEK2 genes was offered. Of 902 women submitted to GCRA, 214 had pedigrees suggestive of HBCS. Fifty of them underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 mutation screening, respectively, and 7 for CHEK2 1100delC testing. A deleterious BRCA2 mutation was identified in one of the HBOC probands and the CHEK2 1100delC mutation occurred in one of the HBCC families. No deleterious germline alterations were identified in BRCA1 or TP53. Although strict inclusion criteria and a comprehensive testing approach were used, the suspected genetic risk in these families remains unexplained. Further studies in a larger cohort are necessary to better understand the genetic component of hereditary breast cancer in Southern Brazil.
ABSTRACT
BACKGROUND: One of the hallmarks of cancer is the occurrence of high levels of chromosomal rearrangements as a result of inaccurate repair of double-strand breaks (DSB). Germline mutations in BRCA and RAD51 genes, involved in DSB repair, are strongly associated with hereditary breast cancer. Pol θ, a translesional DNA polymerase specialized in the replication of damaged DNA, has been also shown to contribute to DNA synthesis associated to DSB repair. It is noteworthy that POLQ is highly expressed in breast tumors and this expression is able to predict patient outcome. The objective of this study was to analyze genetic variants related to POLQ as new population biomarkers of risk in hereditary (HBC) and sporadic (SBC) breast cancer. METHODS: We analyzed through case-control study nine SNPs of POLQ in hereditary (HBC) and sporadic (SBC) breast cancer patients using Taqman Real Time PCR assays. Polymorphisms were systematically identified through the NCBI database and are located within exons or promoter regions. We recruited 204 breast cancer patients (101 SBC and 103 HBC) and 212 unaffected controls residing in Southern Brazil. RESULTS: The rs581553 SNP located in the promoter region was strongly associated with HBC (c.-1060A > G; HBC GG = 15, Control TT = 8; OR = 5.67, CI95% = 2.26-14.20; p < 0.0001). Interestingly, 11 of 15 homozygotes for this polymorphism fulfilled criteria for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Furthermore, 12 of them developed bilateral breast cancer and one had a familial history of bilateral breast cancer. This polymorphism was also associated with bilateral breast cancer in 67 patients (OR = 9.86, CI95% = 3.81-25.54). There was no statistically significant difference of age at breast cancer diagnosis between SNP carriers and non-carriers. CONCLUSIONS: Considering that Pol θ is involved in DBS repair, our results suggest that this polymorphism may contribute to the etiology of HBC, particularly in patients with bilateral breast cancer.
Subject(s)
DNA Repair , DNA-Directed DNA Polymerase/genetics , Genetic Predisposition to Disease , Genetic Variation , Alleles , Amino Acid Substitution , Breast Neoplasms/genetics , Case-Control Studies , Female , Gene Frequency , Genotype , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Humans , Odds Ratio , Polymorphism, Single Nucleotide , DNA Polymerase thetaABSTRACT
Background: An increased number of breast cancer patients are challenged by acute and persistent treatment side effects. Oncology guidelines have been establishing physical exercise to counteract several treatment-related toxicities throughout cancer care. However, evidence regarding the optimal dose-response, feasibility, and the minimal resistance exercise volume and/or intensity remains unclear. The ABRACE Study will assess the impact of different resistance training volumes (i.e., single or multiple sets) combined with aerobic exercise on physical and psychological outcomes of breast cancer patients undergoing primary treatment. Methods: This study is a randomized, controlled, three-armed parallel trial. A total of 84 participants, aged ≥18 years, with breast cancer stages I-III, initiating adjuvant or neoadjuvant chemotherapy (≤50% of sessions completed) will be randomized to multiple sets resistance training plus aerobic training group, single set resistance training plus aerobic training group or control group. Neuromuscular and cancer-related fatigue (primary outcomes), muscle strength, muscle thickness, muscle quality by echo intensity, body composition, cardiorespiratory capacity, functional performance, upper-body endurance and quality of life will be measured before and after the 12-week intervention. Our analysis will follow the intention-to-treat approach and per-protocol criteria, with additional sub-group analysis. Discussion: Findings support prescribing exercise during chemotherapy for breast cancer and elucidate the potential role of different resistance training volumes as a management strategy for physical and psychological impairments in women with early-stage breast cancer. Our main hypothesis is for superiority in physical and psychological outcomes for both training groups compared to the control group, with no difference between single or multiple sets groups. Trial registration: Clinical trials NCT03314168.
ABSTRACT
Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.
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PURPOSE: The objective of this review is to address the barriers limiting access to treatment of advanced metastatic breast cancer (mBC) in Brazil, specifically for patients in the public health care system, arguably those with the least access to innovation. MATERIALS AND METHODS: A selected panel of Brazilian experts in BC were provided with a series of relevant questions to address in a multiday conference. During the conference, responses were discussed and edited by the entire group through numerous drafts and rounds of discussion until a consensus was achieved. RESULTS: The authors propose specific and realistic recommendations for implementing access to new drugs in cancer care in Brazil. Moreover, in creating these recommendations and framework, the authors strive to address the most important barriers and impediments for technology incorporation. A feasible and specific multidisciplinary process is proposed, which is based on the collective participation of all involved stakeholders. CONCLUSION: Given the current benefits and likely future developments, there is a great need to expand treatments for mBC not only in Brazil but also in most other countries in the world where access issues remain an unresolved demand. Adapting the current framework is essential for accomplishing this goal. The recommendations in this review can serve as a framework for adoption of new technologies in countries with limited resources.
Subject(s)
Breast Neoplasms , Pharmaceutical Preparations , Brazil , Breast Neoplasms/drug therapy , Consensus , Female , Humans , Therapies, InvestigationalABSTRACT
BACKGROUND: Breast cancer has a high incidence and increasing mortality in Southern Brazil. The present study evaluated clinical and sociodemographic characteristics, and their association with overall survival in a private cancer center. METHODS: 1113 breast cancer patients were included in this study. The association between survival and clinicopathological and sociodemographic characteristics was analyzed using Cox regression and Kaplan-Meyer curves. RESULTS: Median age at diagnosis was 52 years (SD 13.5). Most patients were diagnosed in stages 0 and I (62.7%), while only 1.3% had stage IV disease. Five- and 10-year overall survival were 93.5% and 83.8%, respectively. According to multivariate analysis, age at diagnosis (HR 1.05; CI95 1.03-1.06), staging (stage III: HR 4.04; CI95 1.34-12.19; stage IV: HR 9.61; CI95 2.17-42.50), high KI67 (HR 5.46; CI95 1.27-23.32) and distant recurrence (HR 7.28; CI95 4.79-11.06) were significantly associated with survival. Smoking status, years of education, BMI, and tumor biological status were not significantly associated with mortality. CONCLUSIONS: This cohort of Brazilian patients, who received timely and appropriate treatment, achieved outcomes that are comparable to those from high income countries. Breast cancer mortality seems dependent on the quality of health care available to patients.
Subject(s)
Breast Neoplasms/mortality , Health Services Accessibility/statistics & numerical data , Adult , Brazil/epidemiology , Breast Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Socioeconomic Factors , Time-to-Treatment/statistics & numerical dataABSTRACT
PURPOSE: The objective of this review was to address the barriers limiting access to genetic cancer risk assessment and genetic testing for individuals with suspected hereditary breast and ovarian cancer (HBOC) through a review of the diagnosis and management steps of HBOC. METHODS: A selected panel of Brazilian experts in fields related to HBOC was provided with a series of relevant questions to address before the multiday conference. During this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion, until a consensus was achieved. RESULTS: The authors propose specific and realistic recommendations for improving access to early diagnosis, risk management, and cancer care of HBOC specific to Brazil. Moreover, in creating these recommendations, the authors strived to address all the barriers and impediments mentioned in this article. CONCLUSION: There is a great need to expand hereditary cancer testing and counseling in Brazil, and changing current policies is essential to accomplishing this goal. Increased knowledge and awareness, together with regulatory actions to increase access to this technology, have the potential to improve patient care and prevention and treatment efforts for patients with cancer across the country.
Subject(s)
Breast Neoplasms , Ovarian Neoplasms , Brazil , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Carcinoma, Ovarian Epithelial , Female , Genetic Testing , Humans , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/geneticsABSTRACT
BACKGROUND: Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. METHODS: A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. RESULTS: Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5-26.2) had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65). CONCLUSION: A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations.
Subject(s)
Breast Neoplasms/epidemiology , Data Collection/methods , Genetic Diseases, Inborn/epidemiology , Primary Health Care/methods , Adult , Brazil/epidemiology , Breast Neoplasms/congenital , Breast Neoplasms/diagnosis , Cohort Studies , Female , Genetic Diseases, Inborn/diagnosis , Humans , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Breast cancer (BC) is a major public health problem, with rising incidence in many regions of the globe. Although mortality has recently dropped in developed countries, death rates are still increasing in some developing countries, as seen in Brazil. Among the reasons for this phenomenon are the lack of structured screening programs, a long waiting period between diagnosis and treatment, and lack of access to health services for a large proportion of the Brazilian population. METHODS AND DESIGN: Since 2004, an intervention study in a cohort of women in Southern Brazil, denominated Porto Alegre Breast Health Intervention Cohort, is being conducted in order to test the effectiveness and cost-effectiveness of a model for BC early detection and treatment. In this study, over 4,000 women from underserved communities aged 40 to 69 years are being screened annually with mammography and clinical breast examination performed by a multidisciplinary team, which also involves nutritional counseling and genetic cancer risk assessment. Risk factors for BC development are also being evaluated. Active search of participants by lay community health workers is one of the major features of our program. The accrual of new participants was concluded in 2006 and the study will last for 10 years. The main goal of the study is to demonstrate significant downstaging of BC in an underserved population through proper screening, attaining a higher rate of early-stage BC diagnoses than usually seen in women diagnosed in the Brazilian Public Health System. Preliminary results show a very high BC incidence in this population (117 cases per 100,000 women per year), despite a low prevalence of classical risk factors. DISCUSSION: This study will allow us to test a model of BC early diagnosis and treatment and evaluate its cost-effectiveness in a developing country where the mortality associated with this disease is very high. Also, it might contribute to the evaluation of risk factors in a population with a different ethnic background from that studied in developed countries. If our model is proven effective, it may be replicated in other parts of the globe where BC is also a major public health problem.
Subject(s)
Breast Neoplasms/diagnosis , Mass Screening/economics , Adult , Brazil/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/ethnology , Cohort Studies , Cost-Benefit Analysis , Early Diagnosis , Female , Humans , Mammography/economics , Middle Aged , Models, Economic , Risk Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND & AIMS: A better understanding of the factors that affect self-perception of body characteristics may play an important role in weight control practices. The objective of this study was to analyze body weight perception and body image satisfaction in low-income adult women in Southern Brazil. METHODS: This was a cross-sectional survey study in a cohort of women recruited from areas of social vulnerability in the city of Porto Alegre, RS. A random sample (n = 218) of women was interviewed, and socioeconomic and lifestyle factors, body image perception using the Stunkard Scale, body weight estimation, weight concern and duplicate anthropometric measurements were obtained. RESULTS: The average age of the low-income women was 56.3 ± 9.5 years. The prevalences of overweight and obese individuals were 34.1% and 52.5%, respectively. Among all women, 83.0% were dissatisfied with their body image, and 68.9% of the women estimated their body weight correctly. In addition to BMI (body mass index), the proportions of women with a higher income (p = 0.05), smoking history (p < 0.01) and history of hypertension (p = 0.04) were significantly different between groups according to body image satisfaction. Multivariate analyses using Poisson regression showed that black/mixed race, higher income, and underweight and obese women were more likely to be dissatisfied with their body image. CONCLUSIONS: The majority of women know their body weight and have body image dissatisfaction. Skin color, higher income and BMI were significantly associated with dissatisfaction. In addition, these women consider the "healthiest" body image to be thinner than the "ideal" body image, and the "ideal" image is one of normal weight and not too thin.
Subject(s)
Body Image/psychology , Body Weight , Personal Satisfaction , Poverty/statistics & numerical data , Self Concept , Body Mass Index , Brazil , Cohort Studies , Cross-Sectional Studies , Female , Humans , Middle AgedABSTRACT
Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mutation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS.
Subject(s)
Genes, p53 , Genetic Predisposition to Disease , Germ-Line Mutation , Neoplasms/genetics , Adult , Aged , Brazil , Breast Neoplasms/diagnosis , Female , Genetic Testing , Humans , Li-Fraumeni Syndrome/genetics , Middle Aged , PedigreeABSTRACT
BACKGROUND: Current studies have shown that fast weight gain may be more important than body mass index on the incidence of breast cancer. The aim of this study was to evaluate the association between body weight and breast cancer. PATIENTS AND METHODS: This was a case-control study nested in a cohort of a breast cancer mammography screening program in Southern Brazil. A trained investigator administered a standardized interview to collect sociodemographic and clinical data, and body weight history (weight at menarche, at marriage, at first and last pregnancy, and at menopause). Current anthropometric measurements were also made. RESULTS: Fifty-seven women with cancer (66.7% postmenopausal) and 159 controls were included. Current age (60.3 ± 10.4 vs. 55.8 ± 8.4 years, P < .01), marital status (49.1% vs. 64.8% with a partner, P = .03), and physical activity (48.2% vs. 32.3% sedentary, P = .01) were significantly different between cases and controls, respectively. Odds ratio showed that age and current waist circumference were associated with postmenopausal cancer. No difference was found in relation to body weight at different stages of life. CONCLUSION: Women with social vulnerability recruited at a mammography screening program in Southern Brazil showed a large weight gain during life, but no significant differences were found in body weight between women with or without breast cancer.
Subject(s)
Body Weight , Breast Neoplasms/epidemiology , Aged , Body Size , Brazil/epidemiology , Case-Control Studies , Cohort Studies , Female , Humans , Incidence , Mammography/statistics & numerical data , Menopause , Middle Aged , Odds Ratio , Risk Factors , Vulnerable Populations , Weight GainABSTRACT
Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous cancer predisposition syndromes characterized by diagnosis of early-onset and often multiple cancers with variable tumor patterns and incomplete penetrance. To date, the genetic modifiers described in LFS/LFL have been shown to map to either TP53 or its main negative regulator, MDM2. Additionally, all studies were focused on families with different TP53 germline mutations. Hence, in this study we explored the effect of the most studied polymorphisms of p53 pathway genes on clinical manifestations of individuals carrying the founder TP53 mutation R337H (n = 136) and controls (n = 186). Cancer-affected carriers had been diagnosed either with adrenocortical carcinoma (ACC, n = 29) or breast cancer (BC, n = 43). Allelic discrimation using TaqMan assay was used for genotyping MDM2 SNP 309 (rs2279744) as well as MDM4 (rs1563828) and USP7 (rs1529916) polymorphisms. We found significantly higher MDM2 SNP 309 GG genotype and G allele frequencies in the LFS cohort than in controls. Furthermore, median age at first diagnosis was earlier in MDM2 SNP309 GG carriers when compared to other genotypes for both cancers (ACC: age 1 vs. 2 years; BC: age 35 vs. 43 years, respectively), although not statistically different. The allelic and genotypic frequencies for all SNPs did not differ between cancer affected and unaffected carriers, neither between patients with ACC or BC. In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation.
Subject(s)
Genetic Predisposition to Disease , Li-Fraumeni Syndrome/genetics , Proto-Oncogene Proteins c-mdm2/genetics , Signal Transduction/genetics , Tumor Suppressor Protein p53/metabolism , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , Adult , Age of Onset , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Case-Control Studies , Child , Child, Preschool , Female , Gene Frequency , Humans , Infant , Li-Fraumeni Syndrome/pathology , Male , Middle Aged , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/geneticsABSTRACT
PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic tumors treated in the public health system in Brazil do not have access to trastuzumab. This study aimed to estimate the impact of the lack of access to anti-HER2 therapies on the mortality of these patients. METHODS: On the basis of published data, the number of patients with HER2-positive advanced breast cancer in 2016 who should receive anti-HER2 targeted therapy was estimated. Three different treatment groups were considered for this hypothetical cohort: chemotherapy alone, chemotherapy plus trastuzumab, and chemotherapy plus trastuzumab and pertuzumab. The number of patients alive after 2 years of follow-up was estimated on the basis of the efficacy results of the pivotal trials considering these interventions. RESULTS: It was calculated that 2,008 women will be diagnosed with advanced HER2-positive breast cancer in Brazil in 2016. It was estimated that only 808 women would be alive in 2018 if they receive only chemotherapy (which is the treatment offered by the public health system). On the other hand, the bar rises to 1,408 women alive in 2018 if they receive chemotherapy plus trastuzumab and 1,576 women alive in 2018 if they receive the gold standard of chemotherapy plus trastuzumab and pertuzumab. CONCLUSION: Trastuzumab is included in the WHO's list of essential medications, but the Brazilian public health system does not yet provide this treatment to its population with advanced disease. The introduction of trastuzumab and pertuzumab would have a positive effect, preventing premature deaths in women with metastatic HER2-positive breast cancer in Brazil.
Subject(s)
Neoplasms , Brazil/epidemiology , Humans , Medical Oncology , Neoplasms/therapy , Societies, MedicalABSTRACT
Germline mutations in TP53 are the underlying defects in Li-Fraumeni syndrome (LFS) and its variant, Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders that are characterized by predisposition to multiple early onset cancers. Here, we identified rs78378222 (A > C), a rare variant that is located in the 3' untranslated region (3' UTR) of TP53, in 7 probands (5.4%) of a cohort from LFS/LFL patients without TP53 germline mutations in the coding regions. To support its association with the LFS/LFL phenotype, we assessed p53 expression in tumor specimens and fibroblasts from rs78378222[C] carriers. Additionally, we investigated using in silico tools the evolutionary conservation and whether rs78378222[C] affects microRNA (miRNA) binding sites in the 3' UTR of TP53 mRNA. We found lower p53 protein levels in biological samples from rs78378222[C] carriers. Additionally, we showed that rs78378222[C] could interfere with a putative target site of miR-545-3p, a novel miRNA that is predicted to directly target the 3' UTR TP53. To our knowledge, this is the first description of rs78378222[C] in LFS/LFL patients. Moreover, these findings suggest that rs78378222[C] lead to haploinsufficiency of p53, a new mechanism of carcinogenesis in LFS/LFL.