Delayed diagnosis and increased mortality risk: Assessing the effects of the COVID-19 pandemic on breast cancer recurrence.

OBJECTIVES: The COVID-19 pandemic has had a significant global impact since its declaration in March 2020. The COVID-19 pandemic has disproportionately impacted cancer patients, particularly those with breast cancer. This study aims to analyze the effects of the pandemic on women diagnosed with breast cancer recurrence. METHODS: A cohort study was conducted at a tertiary public hospital in São Paulo State, Brazil. Data were collected from electronic records. Patients diagnosed with breast cancer and experiencing recurrence between January 2011 and March 2022 were included. Survival analysis was performed using the Kaplan-Meier estimator and Cox regression. RESULTS: The study included 187 patients, 45 in the pandemic group (recurrence after March 23, 2020) and 142 in the pre-pandemic group. Distant recurrences were more frequent in both groups (pre-pandemic: 62.7 %, pandemic: 75.5 %). Compared to the pre-pandemic group (1.8 years), the pandemic group experienced a longer mean time to recurrence detection (2.9 years) and significantly decreased median survival (9 months vs. 22 months). The Cox regression analysis confirmed an increased risk of death for women diagnosed with breast cancer recurrence during the pandemic period (HR = 1.92, 95 % CI 1.19‒3.12). CONCLUSION: The present study is among the first to investigate the pandemic's specific effects on breast cancer recurrence, revealing concerning delays in detection and a decrease in survival rates. Prompt diagnosis, timely treatment initiation, and comprehensive support are crucial during public health crises. These findings urge healthcare systems to prioritize tailored care for breast cancer patients during pandemics.

Converging and evolving immuno-genomic routes toward immune escape in breast cancer.

The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.

10-year opportunistic mammographic screening scenario in Brazil and its impact on breast cancer early detection: a nationwide population-based study.

Background: Mammographic screening has been used to reduce breast cancer mortality worldwide and remains the main modality for the early detection of this disease. Women from low- and middle-income countries still lack access to periodic mammograms and efficient health care. This cross-sectional study aimed to explore opportunistic mammographic coverage in Brazil, while considering the privately insured population and its association with early breast cancer (EBC) detection. Methods: Data on population, gross domestic product (GDP), number of mammograms performed under the Sistema Único de Saúde (SUS) public health system or private system, and women diagnosed with early-stage breast cancer from 2010 to 2019 were retrieved from publicly available databases. Results: A total of 39 555 636 mammograms with an average of 3 955 564 ± 395 704 mammograms were obtained per year from 2010 to 2019 in Brazil. Most examinations (58.6%) were performed in the target population (50-69 years old), while 32% were performed in women aged 40-49, and 9.4% were performed in women <40 years or >70 years of age. The 10-year mammogram coverage was 30.6% in the target population and 24.8% in the population aged 40-49 years, with significant variation across states and municipalities. The overall EBC detection rates in Brazil were 30.6% in populations aged 50-70 and 24.8% in those aged 40-50 years. We observed a positive correlation between coverage and EBC detection rate (r = 0.68; P = 0.0001 (50-70 years) and r = 0.75; P < 0.0001 (40-50 years)). According to the GDP, the municipalities with higher GDP per capita had higher mammogram coverage (P < 0.0001). Conclusions: The coverage of mammographic screening for women under the SUS is far below the international guidelines. Additionally, a significant number of mammograms have been performed in non-target populations. This scenario reflects the problematic screening programs in developing countries and reflects low rates of EBC diagnosis. As Brazil is a continental country with heterogeneous socioeconomic indicators, we observed significant variations in the number of mammograms performed by age groups when separated by states and municipalities. Even when considering supplemental health system coverage, municipalities with higher GDP per capita were associated with higher mammogram coverage.

Mastalgia in medical students: a prospective and multicentric study

Introduction: Mastalgia or breast pain affects most women, especially those of reproductive age. Of organic or nonorganic cause and variable intensity, it is related to factors such as hormonal, dietary, metabolic, and emotional changes, making it difficult to understand its pathophysiology and the definition of care conduct. It can influence the quality of life. The aim of this study was to identify, classify, and know the treatments and their effectiveness for breast pain in university students, relating their interference in the quality of life. Methods: A total of 1,064 students from two medical schools in the interior of São Paulo were interviewed and evaluated using a standardized and specific questionnaire with the aim of characterizing breast pain. Results: Mastalgia was reported in 1,034 students (p=0.0003), body mass index >25 increased breast tenderness by 4.3 times (RR=4.3; p=0.001; 95%CI 2.5­6.73), and sedentary lifestyle increased by 10.82 times (p=0.02). It was more common in the premenstrual cycle (p=0.002), and the greater the intensity, the smaller the number of students who performed the self-examination (p=0.02). The greater the pain, the greater the chance of being absent from classes (RR=15.82; p=0.0003; 95%CI 13.23­17.3). Drug treatment was applied in 15.54% of the cases, with satisfactory results in 92.16% of them (p=0.000004). Conclusions: The study showed a high incidence of breast pain in medical students, impairing their academic activities, making it clear the importance of investigating any symptom related to the hormonal axis and showing significant efficiency of the pharmacological treatment.

Axillary ultrasound and fine-needle aspiration cytology to predict clinically relevant nodal burden in breast cancer patients.

BACKGROUND: Axillary lymph node involvement is one important prognostic factor in breast cancer, but the way to access this information has been modified over the years. This study evaluated if axillary ultrasound (US) coupled with fine-needle aspiration cytology (FNAC) can accurately predict clinically relevant node metastasis in patients with breast cancer, and thus assist clinical decisions METHODS: This is a cross-sectional study with retrospective data collection of 241 individuals (239 women and 2 men) with unilateral operable breast cancer who were submitted to preoperative axillary assessment by physical exam, US and FNAC if suspicious nodes by imaging. We calculated sensitivity, specificity, and accuracy of the methods. We compared the patient's characteristics using chi-square test, parametrics and non-parametrics statistics according to the variable. RESULTS: The most sensible method was US (0.59; 95% CI, 0.50-0.69), and the most specific was US coupled with FNAC (0.97; 95% CI, 0.92-0.99). Only 2.7% of the patients with normal axillary US had more than 2 metastatic nodes in the axillary lymph node dissection, against 50% of the patients with suspicious lymph nodes in the US and positive FNAC. CONCLUSIONS: Axillary US coupled with FNAC can sort patients who have a few metastatic nodes at most from those with heavy axillary burden and could be one more tool to initially evaluate patients and define treatment strategies.

A propensity score-matched case-control study of laparoscopy and laparotomy for endometrial cancer.

OBJECTIVE: A surgery is essential for the management of early endometrial carcinoma. Due to the comorbidities associated with the disease, the complications of surgery are common. Laparoscopic surgery may reduce surgical complications but also have oncological risks. We aimed to compare recurrence and overall survival (OS) associated with laparoscopy and laparotomy for early endometrial cancer. METHODS: We included women treated for presumed early endometrial carcinoma at the Clinics Hospital of Ribeirão Preto Medical School from January 1998 to December 2017. We designed a 1:2 propensity score-matched case-control and compared the patients' characteristics, short-term outcomes, recurrence, and OS. RESULTS: A total of 252 women were included in this study, 168 underwent laparotomy, and 84 underwent laparoscopy. The two groups were well balanced according to most of the variables, and obesity was a characteristic of patients in both groups. Laparoscopy was associated with increased surgical time (194.7 min vesus 165.6 min; p<0.001) and reduced rate of surgical complications (6.5% versus 0; p=0.038). Laparoscopic surgery was not associated with the risk of tumor recurrence (HR: 0.41, 95%CI 0.14-1.19, p=0.100) or all-cause mortality (HR: 0.49, 95%CI 0.18-1.35, p=0.170). CONCLUSION: Laparoscopy was safe in terms of oncological outcomes and was associated with a lower rate of surgical complications. Our data support the use of minimally invasive surgery as the preferential approach in the management of early endometrial carcinoma.

Epidemiological Analyses Reveal a High Incidence of Breast Cancer in Young Women in Brazil.

PURPOSE: Breast cancer screening is not recommended for young women (< 40 years old); therefore, those diagnosed are more likely to have advanced and metastatic disease, reducing treatment outcomes. This study aimed to investigate breast cancer epidemiology among young women in Brazil. METHODS: Data from three publicly available databases and a cohort from a university hospital in Brazil were analyzed in a retrospective study. Descriptive statistics was performed on disease prevalence and stage distribution across age groups. Incidence was estimated using age-standardized incidence ratio. The impact of age in disease-specific survival was also analyzed. RESULTS: Invasive breast cancer prevalence data by age group revealed that 4.4% and 20.6% of patients were < 35 and < 45 years old, respectively. In the United States, this prevalence was 1.85% and 11.5%, respectively (odds ratio [OR], 2.2; P < .0001). The percentage of regional and metastatic diseases were higher in São Paulo State (Fundação Oncocentro de São Paulo [FOSP]) compared with the United States (45% and 9.8% v 29% and 5.7%, respectively; P < .0001). In FOSP, regional and metastatic disease prevalence were higher among young patients (53.5% and 11.3%, respectively). The median tumor size in patients < 40 years old was higher (25.0 mm × 20.9 mm; P < .0001), and young patients have higher risk to be diagnosed with positive lymph nodes (OR, 1.5; P = .004) and higher proportion of luminal-B and triple-negative (TNBC) tumors. Young patients have a poor disease-specific survival because of late-stage diagnosis and more aggressive breast cancer subtypes (human epidermal growth factor receptor 2-enriched and TNBC) (P < .0001). CONCLUSION: In Brazil, breast cancer prevalence among young patients and late-stage incidence during this age span is higher. Advanced disease and more aggressive subtypes lead to a significant impact on breast cancer-specific survival in young patients.

Analysis of the relationship between hospital characteristics and survival in ovarian cancer: A historical cohort.

BACKGROUND AND OBJECTIVES: The management of ovarian cancer requires complex surgical and medical interventions. Specialized care is associated with superior outcomes in early and advanced stages. This study aimed to estimate the effect of hospital characteristics on the overall survival of women with epithelial ovarian cancer. METHODS: We established a cohort with data recorded by the Fundação Oncocentro de São Paulo cancer registry. We included 6111 women treated for ovarian cancer in the state of Sao Paulo from January 2000 to December 2018. From 76 hospitals analyzed, 7 were high volume (20 or more cases a year) and 69 low volume. Twenty-nine were teaching and 47 community hospitals. A 10-year survival was analyzed using the Kaplan-Meyer estimator and the Cox model. RESULTS: Fifty-two percent of the epithelial ovarian cancer patients were treated in high-volume hospitals. High-volume - (HR, 0.86; 95% CI, 0.8-0.92; P < .001) and teaching - (HR, 0.91; 95% CI, 0.85-0.99; P = .019) were hospital characteristics associated with low risk of death in 10 years. CONCLUSIONS: High-volume and teaching hospitals are associated with better overall survival in ovarian cancer. Our data suggest that both hospital characteristics are important indicators of good quality of care in ovarian cancer treatment.

Mammography Coverage and Tumor Stage in the Opportunistic Screening Context.

INTRODUCTION: The increment of breast cancer screening coverage should lead to an increase in the proportion of early tumors diagnosed and the decrease of the cancer-related mortality. However, the effectiveness of opportunistic mammography screening is not well documented for public health systems in middle-income countries. PATIENTS AND METHODS: We conducted an ecologic study to evaluate the association of mammography coverage with trends in breast cancer stage distribution. We used data from a total of 42,850 breast cancer patients, diagnosed between 2000 and 2016, combined with estimated mammography coverage from 3 surveys (2003, 2008, and 2013). RESULTS: Biannual mammography coverage increased from 62.4% in 2003 to 73.9% in 2013. From 2000 to 2016, the proportion of in situ tumors increased 6.9%, the proportion of localized tumors increased 3.9%, the proportion of regional tumors decreased 6.9% and the frequency of distant tumors decreased 4% (P < .00001). CONCLUSION: Mammography coverage in the context of opportunistic breast cancer screening was associated with the increase of in situ and localized tumors and decrease of regional and distant tumors.

Development of New Formulations of Biologics: Expectations, Immunogenicity, and Safety for Subcutaneous Trastuzumab.

Subcutaneous (SC) trastuzumab has long been approved as a cancer treatment for early and advanced HER2-positive (HER2+) breast cancer by both the European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA), the Brazilian National Health Surveillance Agency. A pivotal non-inferiority phase III trial, which aimed to provide a more convenient and cost-effective treatment in the HER2+ breast cancer neoadjuvant setting, showed that the SC group met prespecified efficacy endpoints and the SC formulation was considered as safe as the intravenous (IV) formulation. Considering the recent approval of several biosimilars, new SC formulations are also an interesting manufacturer strategy as these drugs can obtain patent protection. Despite being considered non-inferior to the IV formulation of trastuzumab, in clinical development, the SC formulation elicited higher immunogenicity, mainly related to overall anti-drug antibodies (ADAs); however, this finding was classified as clinically non-significant. In this article, we explore different aspects of the benefits and risks of the SC trastuzumab formulation according to published data.

Identification of a Subtype of Poorly Differentiated Invasive Ductal Carcinoma of the Breast Based on Vimentin and E-cadherin Expression.

OBJECTIVE: The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). METHODS: We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. RESULTS: We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). CONCLUSION: Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

OBJETIVO: O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. MéTODOS: Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). RESULTADOS: Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença de metástase linfonodal foi menor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2 ; p = 0,01). CONCLUSãO: Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

Distinct subtypes of genomic PTEN deletion size influence the landscape of aneuploidy and outcome in prostate cancer.

BACKGROUND: Inactivation of the PTEN tumor suppressor gene by deletion occurs in 20-30% of prostate cancer tumors and loss strongly correlates with a worse outcome. PTEN loss of function not only leads to activation of the PI3K/AKT pathway, but is also thought to affect genome stability and increase levels of tumor aneuploidy. We performed an in silico integrative genomic and transcriptomic analysis of 491 TCGA prostate cancer tumors. These data were used to map the genomic sizes of PTEN gene deletions and to characterize levels of instability and patterns of aneuploidy acquisition. RESULTS: PTEN homozygous deletions had a significant increase in aneuploidy compared to PTEN tumors without an apparent deletion, and hemizygous deletions showed an intermediate aneuploidy profile. A supervised clustering of somatic copy number alterations (SCNA) demonstrated that the size of PTEN deletions was not random, but comprised five distinct subtypes: (1) "Small Interstitial" (70 bp-789Kb); (2) "Large Interstitial" (1-7 MB); (3) "Large Proximal" (3-65 MB); (4) "Large Terminal" (8-64 MB), and (5) "Extensive" (71-132 MB). Many of the deleted fragments in each subtype were flanked by low copy repetitive (LCR) sequences. SCNAs such as gain at 3q21.1-3q29 and deletions at 8p, RB1, TP53 and TMPRSS2-ERG were variably present in all subtypes. Other SCNAs appeared to be recurrent in some deletion subtypes, but absent from others. To determine how the aneuploidy influenced global levels of gene expression, we performed a comparative transcriptome analysis. One deletion subtype (Large Interstitial) was characterized by gene expression changes associated with angiogenesis and cell adhesion, structure, and metabolism. Logistic regression demonstrated that this deletion subtype was associated with a high Gleason score (HR = 2.386; 95% C.I. 1.245-4.572), extraprostatic extension (HR = 2.423, 95% C.I. 1.157-5.075), and metastasis (HR = 7.135; 95% C.I. 1.540-33.044). Univariate and multivariate Cox Regression showed that presence of this deletion subtype was also strongly predictive of disease recurrence. CONCLUSIONS: Our findings indicate that genomic deletions of PTEN fall into five different size distributions, with breakpoints that often occur close LCR regions, and that each subtype is associated with a characteristic aneuploidy signature. The Large Interstitial deletion had a distinct gene expression signature that was related to cancer progression and was also predictive of a worse prognosis.

Increased STAT1 Expression in High Grade Serous Ovarian Cancer Is Associated With a Better Outcome.

OBJECTIVE: Recently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America. METHODS: We evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox). RESULTS: High expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469). CONCLUSIONS: These findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.

Quality of Life in Women With Breast Cancer Treated With or Without Chemotherapy.

BACKGROUND: The diagnosis and treatment of breast cancer may negatively affect the quality of life (QOL) of women. OBJECTIVES: The aim of this study is to assess QOL in women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improved or worsening QOL in these women. METHODS: This cross-sectional study enrolled 112 women who were treated with chemotherapy (CTX group, with 85 [75.9%] women) or without chemotherapy (non-CTX group, with 27 [24.1%] women) for breast cancer. The Short-Form Health Survey (SF-36) assessed QOL and the Hospital Anxiety and Depression scale assessed anxiety and depression. RESULTS: The overall mean SF-36 score was below 50 in all domains. Relative to CTX women, non-CTX women were significantly older (P = .001) and more likely to engage in physical exercise (P = .002). The non-CTX group had higher scores in the Physical Functioning (P = .001) and Role-Physical (P = .0009) domains of the SF-36 relative to the CTX group, and the fluoruracil + epirubicin + cyclophosphamide group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02). CONCLUSION: Chemotherapy treatment for breast cancer worsens QOL in the Physical Functioning and the Role-Physical domains of the SF-36 relative to women treated without chemotherapy. IMPLICATIONS FOR PRACTICE: Nurses should assess Physical Functioning and the Role-Physical before treatment, as a woman who was not physically active before breast cancer is not likely to become physically active after treatment. Establishing support groups and providing educational sessions about the disease and its management, supportive care can improve the QOL of this population.

IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.

ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2(+) cells in breast carcinomas is a marker of resistance to chemotherapy, and based on in vitro assays and the genetic profile, we show, for the first time, that ABCG2 protein can be used as an independent marker for TIC identification in breast cancer.

Oral health after breast cancer treatment in postmenopausal women.

OBJECTIVE: Oral health can affect a patient's general health and quality of life. Given the increase in breast cancer survival rates, investigations of factors influencing the quality of life of survivors have gained importance. Therefore, the objective of our study was to characterize oral health in postmenopausal breast cancer survivors. METHODS: We conducted a matched case-control study. Forty-eight women who survived breast cancer (age 62.1±9.1 years) and 48 healthy controls (age 61.8±8.6 years) were included. For each case and control, a complete oral evaluation chart was completed. RESULTS: The prevalence of chronic periodontal disease was 98% in breast cancer survivors and 87% in controls. The breast cancer survivors had a median of 16 remaining teeth, whereas controls had a median of 22 remaining teeth (p = 0.03). The percentage of sites with gingival bleeding was 16.05% (0-100%) in breast cancer survivors and 0% (0-72%) in controls (p = 0.04). CONCLUSION: Chronic periodontal disease and tooth loss were highly prevalent in postmenopausal breast cancer survivors. To improve survivors' quality of life, a preventive oral health evaluation should be available prior to cancer treatment.