Burden Of Breast Cancer Research Articles

Evaluation of lifestyle risk factor differences in global patterns of breast cancer mortality and DALYs during 1990-2017 using hierarchical age-period-cohort analysis.

Statistical evidence on breast cancer (BC) burden related to health and lifestyle risk factors are valuable for health policy-making. This study aimed to compare the trends in BC mortality and disability adjusted life years (DALYs) attributable to various health and life style risk factors among different world's regions according to sociodemographic index (SDI). We extracted the age-standardized and age-specific rate of mortality and DALYs of women BC during 1990-2017 using the comparative risk assessment framework of the 2017 global burden of disease (GBD) study. We performed hierarchical age-period-cohort analysis to estimate age- and time-related trends, and effect of interactions between different risk factors on BC risk. During 1990-2017, the age-standardized rate of mortality and DALYs of women BC was increasing in less developed and under developing regions. The risk factor alcohol use [RR 51.3(95%CI 17.6-149.7)] and smoking [5.9(2.0-17.3)] were significantly highly contributor to increased mortality risk in high SDI region. Whereas in the low-SDI region, the greater mortality risk was observed in alcohol use [6.9(2.4-17)] and high FPG [2.7(1.5-3.1)]-related deaths. The adjusting for individualage, period, and risk factor effects, the significant interaction effect between metabolic risk factors and older ages were observed in all SDI regions and globally as well. However, an increasing cohort effect of alcohol, high fasting plasma glucose (FPG) and smoking-related death, and DALYs was observed during 1960 to 1985 cohorts among low-SDI regions. The age-standardized rates of mortality and DALYs due to BC has been increasing in low-SDI region. Alcohol consumption, high body mass index (BMI), high FPG, and smoking are potential BC risk factors particularly in older ages that leading to adverse disease outcomes. Therefore, rapid aging and prevalence of these prospective risk factors may strengthen the increasing mortality and DALYs of BC in low-SDI region. Hence, preventive measure along with strict action against concerned BC risk factors should be taken to reduce the disease burden specifically among lower-SDI regions.

Net survival differences of breast cancer between stages at diagnosis and age groups in the east coast region of West Malaysia: a retrospective cohort study

ObjectiveEstimation of the net survival of breast cancer helps in assessing breast cancer burden at a population level. Thus, this study aims to estimate the net survival of breast cancer...

PREDICTORS OF CLINICAL BREAST EXAMINATION AND MAMMOGRAPHY SCREENING UPTAKE AMONG WOMEN AGED 20-79 YEARS IN MALE’ REGION, MALDIVES

Breast cancer is the most prevalent form of cancer among women. Breast cancer is identified as the second-highest cancer in the Maldives and the most common cancer among females. Early detection and diagnosis of breast cancer facilitate effective treatment and cure. The main objective of the study is to identify the factors that serve as potential predictors for breast cancer screening uptake (CBE and Mammography) among women in the Male’ region. The cross-sectional study was conducted among 600 women aged 20-79 years in the Male’ region. Stratified random sampling was used to select the study sample. Data was collected using an interviewer-administered questionnaire. About 41.40% and 34.40% of the respondents reported ever having a CBE and a mammogram done respectively. Significant predictors for CBE uptake were age [OR=1.045, 95% CI(1.019-1.072)], ever being diagnosed for any breast disease [OR=12.405, 95% CI(4.099-37.541)], having regular medical check-up [OR=2.156, 95% CI(1.301-3.573)], knowledge on early detection of BC [OR=1.108, 95% CI(1.030-1.193)], perceptions on the susceptibility to BC [OR=1.100, 95% CI(1.022-1.184)], perceptions on the benefits of CBE [OR=1.163, 95% CI(1.036-1.306)], perceptions on barriers towards CBE [OR=0.926, 95% CI(0.866-0.991)], self-efficacy [OR=0.960, 95% CI(0.925-0.996)] and ever performed BSE [OR=2.447, 95% CI(1.423-4.209)]. Significant predictors for mammography screening uptake were having regular medical check-up [OR=2.896, 95% CI(1.289-6.503)], benefits of mammography screening [OR=1.131, 95% CI(1.003-1.277)], and ever done CBE [OR=19.135, 95% CI(7.461-49.077)]. Breast cancer screening uptake rates among Maldivian women are found to be low. Focused and well-planned multiple strategies are needed to enhance the health-promoting and preventive behaviours among Maldivian women for better management of breast cancer burden in the country.

Endocrine prevention of breast cancer

Breast cancer (BC) is the most common non-cutaneous malignancy among women worldwide and is a significant cause of morbidity, mortality, and national health care expenditure. Unfortunately, with few exceptions like alcohol consumption, obesity, and physical activity, most BC risk factors are unmodifiable. Antiestrogen endocrine therapy, commonly known as BC chemoprevention, is an effective method of BC prevention. In multiple randomized trials, two selective estrogen receptor modulators — tamoxifen and raloxifene, and two aromatase inhibitors — exemestane and anastrozole have reduced BC incidence by 50%–65% in high-risk women. An estimated 15% of the US women between 35 and 79 years of age may qualify as high risk for BC, yet a small percentage of these women will ever have a formal BC risk assessment or a discussion of endocrine prevention options. The etiology of underutilization of endocrine prevention of BC is multifactorial — infrequent use of BC risk assessment tools in the primary care settings, insufficient knowledge of BC risk assessment tools and antiestrogen agents among primary care providers, concerns of side effects, inadequate time for counseling during primary care visit, and lack of predictive biomarkers may play significant roles. Many small studies incorporating risk assessment tools and decision-making aids showed minimal success in enhancing endocrine prevention. One critical factor for underutilization of endocrine prevention is low uptake of endocrine prevention by high-risk women even when appropriately recommended. Furthermore, adherence to BC endocrine prevention is unsatisfactorily low. Despite the current infrequent usage, endocrine prevention has the potential to reduce the public health burden of BC significantly. Innovative approaches like finding new agents, alternative dosing and schedule of currently available agents, transdermal medication delivery, increased public and professional awareness, and policymakers' commitments may bring the desired changes.

Mapping evidence on the distribution of the costs associated with cancer of prostate, cervix, and female breast in the sub-Saharan Africa: protocol for a scoping review

BackgroundDespite the well-documented information on cancer prevention and management, among noncommunicable diseases (NCDs), globally, cancer continues to be the second leading cause of morbidity and mortality with devastating economic consequences. The burden is disproportionately more among developing countries and the extent of evidence available on the economic consequences (direct and indirect costs) of cancer remains unknown in low-income countries particularly in the sub-Saharan region. Understanding the costs of illness is important to inform decision-making on setting up health care policies and informing economic evaluation of interventions.This study aims to map evidence on the distribution of the economic burden (direct and indirect costs) associated with prevention, diagnosis, and treatment of three predominant cancers: prostate, cervix, and female breast in the sub-Saharan Africa.MethodsThis scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR), and will be conducted following Arksey and O’Malley’s framework. We will search PubMed/MEDLINE, Web of Science, CINHAL (via EBSCOhost platform), Science Direct, Cochrane Database of Systematic Reviews, Africa-Wide Information, Google Scholar, and WHO Library. We will perform hand-searching of the reference lists of included studies and other relevant documents.Two reviewers will independently screen all citations, full-text articles, and abstract data.We will include primary studies from all study designs reporting costs associated with prevention, diagnosis and treatment of prostate, cervical, and breast cancers in the sub-Saharan region. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., thematic analysis) methods. A narrative summary of findings will be presented.DiscussionThis review will map the extent of information available on the economic burden (direct and indirect costs) of prostate, cervical, and breast cancers in the sub-Saharan region. Further guidance for future research in the subject area will be discussed.Systematic review registrationOpen Science Framework

Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020.

Background:Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions.Methods:We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths.Results:Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes.Conclusions:The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.

Locally Advanced Breast Cancer—A Narrative Review of Management in the Indian Scenario

AbstractLocally advanced breast cancer (LABC) forms a significant proportion of the total breast cancer (BC) burden in the country. It is a heterogeneous entity, encompassing a variety of presentations indicative of advanced disease. The standard of care for the treatment of LABC is multimodal, involving chemotherapy, surgery, radiation, and/or hormonal therapy. With improved understanding of the biology of BC, addition of newer agents of systemic therapy to our armamentarium, advances in surgical techniques and radiation delivery, clinicians are now able to tailor treatment according to the individual and consider a more conservative approach to management (in contrast to a mandatory radical mastectomy, decades ago), disease biology, and stage permitting with better survival outcomes. Here, we review all the treatment modalities and options available to aid a clinician in formulating an optimal treatment plan for a patient presenting with LABC and also how best to tailor the treatment to enable cost effectiveness in the Indian setting.

The Untapped Social Impact of Artificial Intelligence for Breast Cancer Screening in Developing Countries: A Critical Commentary of DeepMind

The Untapped Social Impact of Artificial Intelligence for Breast Cancer Screening in Developing Countries: A Critical Commentary of DeepMind

Trends in breast-conserving surgery in Mexico after the implementation of a public health insurance system

Although breast conserving surgery is the standard of care for patients with localized breast cancer in high-income countries, little is known about its use in developing countries, where disparities in access to treatment may lead to an increased use of mastectomy. We examined the use of breast conserving surgery at a Mexican cancer center after the implementation of a public insurance program aimed at providing coverage for previously uninsured patients. Between 2006 and 2016, 4519 women received surgical treatment for breast cancer, of which 39% had early-stage disease. The proportion of patients treated with breast conserving surgery increased from 10% in the 2006–2009 period to 33% in the 2013–2016 period, with most of this increase occurring among women with early-stage disease (17–52%). Improving access to care and reducing the financial burden of breast cancer in developing countries may lead to an increased use of breast conserving surgery.

Tackling Immune Targets for Breast Cancer: Beyond PD-1/PD-L1 Axis.

The burden of breast cancer is imposing a huge global problem. Drug discovery research and novel approaches to treat breast cancer have been carried out extensively over the last decades. Although immune checkpoint inhibitors are showing promising preclinical and clinical results in treating breast cancer, they are facing multiple limitations. From an immunological perspective, a recent report highlighted breast cancer as an “inflamed tumor” with an immunosuppressive microenvironment. Consequently, researchers have been focusing on identifying novel immunological targets that can tune up the tumor immune microenvironment. In this context, several novel non-classical immune targets have been targeted to determine their ability to uncouple immunoregulatory pathways at play in the tumor microenvironment. This article will highlight strategies designed to increase the immunogenicity of the breast tumor microenvironment. It also addresses the latest studies on targets which can enhance immune responses to breast cancer and discusses examples of preclinical and clinical trial landscapes that utilize these targets.

Estimating the Breast Cancer Burden in Germany and Implications for Risk-based Screening.

In Germany, it is currently recommended that women start mammographic breast cancer screening at age 50. However, recently updated guidelines state that for women younger than 50 and older than 70 years of age, screening decisions should be based on individual risk. International clinical guidelines recommend starting screening when a woman's 5-year risk of breast cancer exceeds 1.7%. We thus compared the performance of the current age-based screening practice with an alternative risk-adapted approach using data from a German population representative survey. We found that 10,498,000 German women ages 50-69 years are eligible for mammographic screening based on age alone. Applying the 5-year risk threshold of 1.7% to individual breast cancer risk estimated from a model that considers a woman's reproductive and personal characteristics, 39,000 German women ages 40-49 years would additionally be eligible. Among those women, the number needed to screen to detect one breast cancer case, NNS, was 282, which was close to the NNS = 292 among all 50- to 69-year-old women. In contrast, NNS = 703 for the 113,000 German women ages 50-69 years old with 5-year breast cancer risk <0.8%, the median 5-year breast cancer risk for German women ages 45-49 years, which we used as a low-risk threshold. For these low-risk women, longer screening intervals might be considered to avoid unnecessary diagnostic procedures. In conclusion, we show that risk-adapted mammographic screening could benefit German women ages 40-49 years who are at elevated breast cancer risk and reduce cost and burden among low-risk women ages 50-69 years. PREVENTION RELEVANCE: We show that a risk-based approach to mammography screening for German women can help detect breast cancer in women ages 40-49 years with increased risk and reduce screening costs and burdens for low-risk women ages 50-69 years. However, before recommending a particular implementation of a risk-based mammographic screening approach, further investigations of models and thresholds used are needed.

Abstract LT021: Targeting AXL favors an anti-tumorigenic tumor microenvironment that enhances immunotherapy responses by decreasing HIF-1a levels in cancer cells

Abstract Breast cancer-related deaths are predominantly associated to complications arising from metastases. Hypoxia is an important biological process that fuels metastasis and contributes to deregulate the tumor microenvironment (TME) of solid tumors. Hypoxia also promotes resistance to therapies by a plethora of mechanisms including enhancing tumoral angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition (EMT) and immune evasion. The expression of the receptor tyrosine kinase AXL, a hypoxia-induced gene, is associated with poor clinical prognosis and metastasis in various cancers, including breast cancer. Here, we hypothesize that genetic or pharmacological interference of AXL may alter hypoxic responses and associated modulation of the TME offering an ideal setting for immunotherapy. In a HER2 mouse model of breast cancer (MMTV-NIC), we found that the mammary gland epithelial cells specific deletion of AXL led to a reduction of lung metastases and improved the TME by reducing the hypoxic response in tumor cells. When breast cancer cells were subjected to hypoxic conditions, we found that AXL inhibition reduced the levels of the hypoxia transcription factor HIF-1a which resulted in an altered hypoxic response. Specifically, AXL deletion led to a reduction of hypoxia-induced EMT and invasion, and a reduction of the secretion of key cytokines for macrophages recruitment and polarization. We demonstrate in vivo that AXL pharmacological inhibition in the MMTV-NIC breast cancer model generated an anti-inflammatory TME that enhanced an anti-PD-1 immune checkpoint blockade response and decreased the metastatic burden. Collectively, these results suggest that targeting AXL could be a powerful approach to improve immunotherapy response by generating an anti-tumoral microenvironment therefore limiting the metastatic burden of breast cancer. Citation Format: Marie-Anne Goyette, Jean-Philippe Gratton, Jean-François Côté. Targeting AXL favors an anti-tumorigenic tumor microenvironment that enhances immunotherapy responses by decreasing HIF-1a levels in cancer cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT021.

Global incidence and mortality of breast cancer: a trend analysis.

This study aimed to evaluate the global incidence and mortality trends of breast cancer among females by region and age in the past decade. We retrieved country-specific incidence and mortality data from the Global Cancer Observatory up to 2018 and Cancer Incidence in Five Continents volumes I-XI, the Nordic Cancer Registries, the Surveillance, Epidemiology, and End Results, and WHO mortality database up to 2016. The temporal patterns were using Average Annual Percent Change (AAPC) with the 95% confidence interval (CI) by joinpoint regression analysis. Most countries showed an increasing trend in incidence. For the older population aged ≥ 50 years, Japan (5.63, 4.90-6.36), Slovakia (3.63, 3.03-4.22), China (2.86, 2.00-3.72) reported the most prominent increase. For young females (<50 years), Japan (AAPC=3.81, 95% CI=2.71-4.93), Germany (AAPC=2.60, 95% CI=1.41-3.81) and Slovakia (1.91, 1.13-2.69) reported the most drastic rise. Similarly, 12 countries showed an incidence increase among women aged <40 years. As for mortality, the Philippines (4.36, 3.65-5.07), Thailand (4.35, 3.12-5.59), Colombia (0.75, 0.08-1.42), and Brazil (0.44, 0.19-0.68) reported a significant increase. The disease burden of breast cancer showed an increasing trend in a large number of populations. More preventive efforts are recommended for these countries. Further research should explore the underlying reasons for these epidemiological trends.

Trends in breast cancer incidence in Ho Chi Minh City 1996-2015: A registry-based study.

The burden of breast cancer in Vietnam has not been documented. This study sought to estimate the incidence of breast cancer in Ho Chi Minh City, the largest economic center of Vietnam, from 1996 to 2015. This was a population-based study using the Ho Chi Minh City Cancer Registry as a source of data (coverage period: 1996-2015). The Registry adopted the International Classification of Diseases for Oncology, 3rd Edition for the classification of primary sites and morphology, and guidelines from the International Agency for Research on Cancer and the International Association of Cancer Registries. Using the population statistics from census data of Ho Chi Minh City, the point incidence of breast cancer for 5-year period was estimated. Based on the national population, we calculated the age-standardized rate (ASR) of breast cancer between 1996 and 2015. Overall 14,222 new cases of breast cancer (13,948 women, or 98%) had been registered during the 1996-2015 period; among whom, just over half (52%) were in the 2nd stage and 26% in the 3rd and 4th stages. In women, the median age at diagnosis was 50 years and there was a slight increase over time. The ASR of breast cancer during the 2011-2015 period was 107.4 cases per 100,000 women, representing an increase of 70% compared to the rate during the 1996-2000 period. In men, there was also a significant increase in the ASR: from 1.13 during the 1996-2001 period to 2.32 per 100,000 men during the 2011-2015 period. These very first data from Vietnam suggest that although the incidence of breast cancer in Vietnam remains relatively low, it has increased over time.

A retrospective evaluation of clinicalopathologic characteristics and prognostic factors for synchronous bilateral breast cancer in a single center

Objective: To investigate the clinicopathologic features of synchronous bilateral breast cancer (SBBC) and prognostic factors. Methods: The clinicopathologic features of patients with SBBC treated in Peking University First Hospital from January 2008 to March 2019 were retrospectively analyzed. Results: Of all 4 111 patients diagnosed with breast cancer, 57(1.4%) cases were diagnosed with SBBC.Forty-three (75.4%) patients were treated with bilateral mastectomy. The median follow-up time was 58 months. The 5-year disease-free survival of SBBC was 80.7% and 5-year overall survival was 84.1%. The N stage and HER2 status of second primary breast cancer were associated with prognosis by univariated analysis (Z=5.866 and 4.231, both P<0.05). Conclusion: Majority of patients with SBBC were treated with bilateral mastectomy. While therapeutic strategy of SBBC should take both tumor burden and biomarker status of bilateral breast cancer into consideration.

Five-Year Cancer Epidemiology at the National Referral Hospital: Hospital-Based Cancer Registry Data in Indonesia.

PURPOSEIn 2016, there were 1,308,061 cases of cancer being treated in Indonesia, with 2.2 trillion rupiahs spent, amounting to $486,960,633 in US dollars (purchasing power parity 2016). The high burden of cancers in Indonesia requires a valid data collection to inform future cancer-related policies. The purpose of this study is to report cancer epidemiological data from 2008 to 2012 based on Hospital-Based Cancer Registry (HBCR) data from Cipto Mangunkusumo Hospital, Indonesia.METHODSThis was a descriptive study with cross-sectional design. Data were collected from Cipto Mangunkusumo Hospital HBCR 2008-2012. Demographical, diagnostic, stages of cancer, and histopathological types of cancer data were extracted.RESULTSAfter screening, 18,216 cases were included. A total of 12,438 patients were older than 39 years of age (68.3%), with a female-to-male ratio of 9:5. Most patients have cancers at advanced stages (stages III and IV, 10.2%). The most common sites of cancer were cervix uteri (2,878 cases, 15.8%), breast (2,459 cases, 13.5%), hematopoietic and reticuloendothelial systems (1,422 cases, 7.8%), nasopharynx (1,338 cases, 7.4%), and lymph nodes (1,104 cases, 6.1%).CONCLUSIONFrom this HBCR, cancer incidence in female was almost twice the incidence in male, largely because of the burden of cervical and breast cancers. The cervix uteri as one of the top five cancer sites based on this HBCR, 2008-2012, are still approximately consistent with Global Cancer Incidence, Mortality and Prevalence 2018, which portrayed that Indonesia has been severely afflicted by cervical cancer cases more than any other Association of Southeast Asian Nations countries. The HBCR could serve as a robust database of epidemiological data for cancer cases in Indonesia.

Isolation and morphology of circulating tumor cells by cell block technique in breast cancer.

Circulating tumor cells (CTCs) are cells present in the blood stream that are antigenically or genetically similar to a specific tumor type and are markers of tumor diagnosis, prognosis, residual disease and metastasis. The ever-increasing burden of breast cancer globally warrants the incorporation of this all-inclusive marker in the diagnostic repertoire using the simplest of techniques. To identify CTCs in peripheral blood by cell block (CB) technique in cases of breast cancer diagnosed on fine-needle aspiration (FNA) or core needle biopsy (CNB) and to correlate their presence with nodal metastasis. This study was conducted in the Department of Pathology, at a tertiary care hospital. Peripheral blood samples from a total of 30 cases of primary breast carcinoma diagnosed on FNA or CNB without prior neoadjuvant chemotherapy were analyzed using the CB technique. The age ranged between 29-74 years with the most common presenting complaint being a palpable, single, unilateral breast lump. CTCs were detected in 2 (6.7%) cases with a <5 cell cluster with both the cases being grade I breast carcinomas and also displaying nodal metastasis.

Global, regional, national burden of breast cancer in 185 countries: evidence from GLOBOCAN 2018.

This study aims to examine the burden of breast cancer in 185 countries in 2018. The estimates of incidence, mortality, and prevalence of breast cancer were drawn from GLOBOCAN 2018. The overall burden of breast cancer was gauged using breast cancer burden index (BRCBI)-a novel index comprising age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), mortality-to-incidence ratio (MIR), prevalence-to-incidence ratio (PIR), and prevalence-to-mortality ratio (PMR). The socioeconomic status of countries was measured using human development index (HDI) RESULTS: Globally, breast cancer was responsible for an estimated 626,679 deaths at age-standardized rate of 13/100,000; there were 2.1 million cases diagnosed in 2018 at age-standardized rate of 46.3/100,000. The ASIR varied 22-fold from 5/100,000 (Bhutan) to 113.2/100,000 (Belgium). The ASMR varied 13-fold from 2.7/100,000 (Bhutan) to 36.9/100,000 (Fiji). The HDI exhibited a positive gradient with ASIR (r = 0.73), PIR (r = 0.98), and PMR (r = 0.85); with MIR, however, it exhibited a negative association (r = -0.83). The BRCBI spanned from 0.70 in Somalia to 78.92 in South Korea and exhibited a positive association with HDI (r = 0.76). An additional 46,823 female lives in 2018 and a cumulative total of 333,304 lives could have been saved over 2013-2018, had countries performed as per their HDI. The substantial burden of breast cancer in developing and low-resource economies calls for a holistic approach to cancer management and control that includes oncologic infrastructure to provide cost-effective screening, diagnostic, therapeutic, and palliative services, greater breast cancer awareness, and mitigation of risk factors.

The Role of Forkhead Box Q1 Transcription Factor in Anticancer Effects of Withaferin A in Breast Cancer.

Elimination of both rapidly dividing epithelial mammary cancer cells as well as breast cancer stem-like cells (bCSC) is essential for maximizing antitumor response. Withaferin A (WA), a small molecule derived from a medicinal plant (Withania somnifera), is highly effective in reducing burden and/or incidence of breast cancer in vivo in various preclinical models. We have shown previously that suppression of breast cancer incidence by WA administration in a rat model is associated with a decrease in self-renewal of bCSC but the underlying mechanism is still elusive. This study investigated the role of forkhead box Q1 (FoxQ1) transcription factor in antitumor responses to WA. Exposure of MDA-MB-231 and SUM159 cells to WA resulted in downregulation of protein and mRNA levels of FoxQ1 as well as inhibition of its transcriptional activity. FoxQ1 overexpression in SUM159 and MCF-7 cells resulted in a marked protection against WA-mediated inhibition of bCSC as judged by flow cytometric analysis of CD49fhigh population and mammosphere assay. RNA-sequencing analysis revealed upregulation of many bCSC-associated genes by FoxQ1 overexpression in SUM159 cells, including IL8 whose expression was decreased by WA treatment in SUM159 and MCF-7 cells. FoxQ1 was recruited to the promoter of IL8 that was inhibited significantly by WA treatment. On the other hand, WA-mediated inhibition of cell proliferation or migration was not affected by FoxQ1 overexpression. The FoxQ1 overexpression partially attenuated WA-mediated G2-M phase cell cycle arrest in SUM159 cells only. These results indicate that FoxQ1 is a target of WA for inhibition of bCSC fraction. PREVENTION RELEVANCE: Withaferin A (WA) is highly effective in reducing burden and/or incidence of breast cancer in various preclinical models. However, the mechanism underlying breast cancer prevention by WA is not fully understood. This study shows a role for FoxQ1 in antitumor response to WA.

Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening.

BackgroundBreast and ovarian cancers are the most prevalent cancers and one of the leading causes of death in Indian women. The healthcare burden of breast and ovarian cancers and the rise in mortality rate are worrying and stress the need for early detection and treatment.MethodsWe performed amplicon sequencing of 144 cases who had breast/ovarian cancer disease (total 137 cases are patients and seven are tested for BRCA1/2 carrier) Using our custom designed gene panel consisting of 14 genes, that are associated with high to moderate risk of breast and ovarian cancers. Variants were called using Torrent Variant Caller and were annotated using ThermoFisher’s Ion Reporter software. Classification of variants and their clinical significance were identified by searching the variants against ClinVar database.ResultsFrom a total of 144 cases, we were able to detect 42 pathogenic mutations in [40/144] cases. Majority of pathogenic mutations (30/41) were detected in BRCA1 gene, while (7/41) pathogenic mutations were detected in BRCA2 gene, whereas, (2/41) pathogenic mutations were detected in TP53 gene and BRIP1, PALB2, and ATM genes respectively. So, BRCA genes contributed 88.09% of pathogenic mutations, whereas non-BRCA genes contributed 11.91% of pathogenic mutations. We were also able to detect 25 VUS which were predicted to be damaging by in silico prediction tools.ConclusionEarly detection of cancers in the Indian population can be done by genetic screening using customized multi-gene panels. Indications of our findings show that in the Indian population, apart from the common BRCA genes, there are other genes that are also responsible for the disease. High frequency mutations detected in the study and variants of uncertain significance predicted to be damaging by in silico pathogenicity prediction tools can be potential biomarkers of hereditary breast and ovarian cancer in Indian HBOC patients.