Prevention Of Breast Cancer In Women Research Articles

Antiprogestins for breast cancer treatment: We are almost ready

The development of antiprogestins was initially a gynecological purpose. However, since mifepristone was developed, its application for breast cancer treatment was immediately proposed. Later, new compounds with lower antiglucocorticoid and antiandrogenic effects were developed to be applied to different pathologies, including breast cancer. We describe herein the studies performed in the breast cancer field with special focus on those reported in recent years, ranging from preclinical biological models to those carried out in patients. We highlight the potential use of antiprogestins in breast cancer prevention in women with BRCA1 mutations, and their use for breast cancer treatment, emphasizing the need to elucidate which patients will respond. In this sense, the PR isoform ratio has emerged as a possible tool to predict antiprogestin responsiveness. The effects of combined treatments of antiprogestins together with other drugs currently used in the clinic, such as tamoxifen, CDK4/CDK6 inhibitors or pembrolizumab in preclinical models is discussed since it is in this scenario that antiprogestins will be probably introduced. Finally, we explain how transcriptomic or proteomic studies, that were carried out in different luminal breast cancer models and in breast cancer samples that responded or were predicted to respond to the antiprogestin therapy, show a decrease in proliferative pathways. Deregulated pathways intrinsic of each model are discussed, as well as how these analyses may contribute to a better understanding of the mechanisms involved.

Identify risk factors affecting participation of Turkish women in mammography screening for breast cancer prevention

PurposeCancer screening is a public health intervention aiming to reduce cancer-caused deaths. This study aims to determine the factors affecting the mammography screening time among women aged 40–69.MethodsThe micro dataset obtained from the Türkiye Health Survey conducted by the Turkish Statistical Institute (TurkStat) in 2019 and 2022 was used in the present study. Stereotype logistic regression was used to determine the variables affecting mammography screening and period for breast cancer prevention in women in Türkiye.ResultsGiven the results achieved from the analysis, it was found that factors such as age, marital status, general health condition, comorbidity, receiving psychosocial support, high blood lipid levels, and performing breast self-examinations affected women’s adherence to cancer screening programs.ConclusionSince adherence to mammography increases with age, it is recommended to pay importance to education for women approaching the age of mammography screening. Educated individuals are expected to have access to multiple sources of information as to cancer and to access this information more easily. In order to gain more insight into the recommended preventive measures and outcomes related to cancer, it is suggested to review policies, which will increase the educational level of women, and provide privileges in the field of education.

Increases in BMI contribute to worsening inflammatory biomarkers related to breast cancer risk in women: a longitudinal study.

Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.

Abstract P2-07-01: Hydroxytyrosol, a Component of Olive Oil for Breast Cancer Prevention in Women at High Risk

Abstract Background Breast cancer is the most frequently diagnosed cancer in women in developed countries with increased incidence in women at high risk such as those with strong family history, BRCA mutations, atypical hyperplasia etc. Chemoprevention with drugs like tamoxifen and aromatase inhibitors come with challenges of intolerance and limited efficacy in estrogen receptor negative breast cancers. The purpose of our study was to evaluate the effects of hydroxytyrosol (HT), a component of olive oil on mammographic breast density reduction, which is a validated surrogate biomarker for breast cancer prevention as well as to explore on-target effects on Wingless-related integration site (Wnt) pathway, and alterations in key pathways of proliferation, DNA damage repair and stem cell function. Methods This study was conducted using 25mg/day oral dose of HT for 12 months in both pre- and post-menopausal women who are at increased risk of breast cancer with Gail 5-year risk score ≥ 1.67 and/or > 10% probability of BRCA mutation and had declined standard chemoprevention. These women underwent annual mammograms as well as had the option to have a biopsy of normal breast tissue before and after HT. Maximum volumetric breast density (Max VBD%) was assessed quantitatively using Volpara software (VIS 3.2) and the annualized percent decrease in max VBD% between baseline (BL) and end of treatment (EOT) with HT was analyzed in the study. RNA was extracted from the breast biopsies and RNA sequencing (RNA-Seq) and multiplex analysis of 28 proteins using NanoString nCounter analysis was performed to compare the BL with EOT samples. Results A total of 61 women were screened for the trial, 51 were enrolled and 41 patients completed the study. Median age for the study population was 54 years (range 35-76 years). There were 26 patients with paired BL and EOT mammograms. There were 14 patients with paired BL and EOT breast biopsies and seven patients with only BL and seven with only EOT biopsies. Mammographic density as measured by max VBD% showed a non-significant change of -0.038%, p = 0.49. However, on subgroup analysis in women 60-years or older, the mean decrease in max VBD% was - 3.7% (p = 0.0391), especially in those with high baseline mammographic density (> 10% baseline max VBD%). RNAseq data was generated from 15 BL and 17 EOT samples and pathways were confirmed by NanoString. Our bioinformatics pipeline identified 190 transcripts that were upregulated and 90 that were downregulated in EOT vs. BL by at least 1.5 fold. Reactome pathway R-HSA-195721 (Signaling by WNT) is identified as the top pathway enriched with EOT downregulated genes. On further review of the expression profiles, 82 of 261 member genes had p-value < 0.05 for EOT vs. BL, among which only 4 were upregulated and 78 were downregulated in EOT samples. These 82 genes were highly interactive with each other, with 379 high confidence protein-protein interactions (PPIs) (confidence score > 0.7 from STRING database) involving 81 out of 82 genes. In addition, mitotic telophase/cytokinesis (p = 0.004), ATM signaling (p = 0.007) were some pathways that were upregulated whereas, NOTCH signaling (p = 0.007), oxidative stress induced senescence (p = 0.0001) pathways were downregulated in EOT vs. BL. Conclusions Hydroxytyrosol, a component of olive oil did not show a decrease in breast density in the intention to treat population but showed some reduction in breast density in women 60-years of age and above, especially in those with high baseline breast density. HT showed on target effects by affecting Wnt signaling pathway, as well as decrease in proliferation. This study lays the foundation for future larger studies in exploring a natural compound such as HT for chemoprevention of breast cancer. Citation Format: Akshjot Puri, Zheng Yin, Sergio Granados-Principal, Joe Ensor, Liliana Guzman, Roberto Rosato, Hong Zhao, Stephen Wong, Tejal Patel, Jenny Chang. Hydroxytyrosol, a Component of Olive Oil for Breast Cancer Prevention in Women at High Risk [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-07-01.

Abstract P037: Association between circulating osteoprotegerin levels and estimated risk of BRCA1-associated breast cancer

Abstract Purpose: Dysregulation of the receptor activator of nuclear factor κB (RANK) pathway may contribute to the pathogenesis of BRCA1-associated breast cancer. Specifically, lower levels of osteoprotegerin (OPG), an endogenous inhibitor of RANK-ligand (RANKL) that competes with RANK for RANKL binding, have been reported among women with pathogenic or likely pathogenic variant (mutation) in the BRCA1 gene. It has been suggested that lower OPG levels may be associated with an increased risk of breast cancer, proposing that OPG may serve as a biomarker for breast cancer risk. Whether OPG is associated with estimated breast cancer risk remains unknown. The goal of this study was to evaluate the relationship between OPG and the estimated risk of breast cancer in women with a BRCA1 mutation. Methods: Women were eligible for inclusion if they had a BRCA1 mutation, were between ages 18 and 79, had a pedigree, had no prior history of cancer, had not undergone prophylactic bilateral mastectomy and provided a blood sample available for OPG analysis. Detailed information on various risk factors (i.e., reproductive, hormonal, family history) was collected using biennial questionnaires. An enzyme-linked immunosorbent assay was used to quantify serum OPG levels (pg/mL). Risk of breast cancer was estimated using Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 6 incorporated in the CanRisk tool. The relationship between OPG and estimated lifetime (up to age 80) and ten-year (age 40–50) risks of breast cancer was evaluated using quantile regression analyses. Analyses were further stratified by age (≤50 vs >50 years). Results: A total of 539 women were included in the analysis. The median age at blood collection was 39 years (18–77 years). For lifetime breast cancer risk, a 1 standard deviation (SD; 38.40 pg/ml) increase in OPG level was associated with a 5.4% lower risk at the 25th percentile (P ≤ 0.001), a 4.2% lower risk at the 50th percentile (P ≤ 0.001), and a 1.5% lower risk at the 75th percentile (P ≤ 0.001). For ten-year breast cancer risk, a 1 SD increase in OPG level was associated with a 1.2% lower risk at the 25th percentile (P ≤ 0.001), a 0.8% lower risk at the 50th percentile (P ≤ 0.001), and a 0.8% lower risk at the 75th percentile (P = 0.005). The association between OPG and both estimated risks did not vary in the analysis stratified by age (≤50 vs >50 years). Conclusion: Higher circulating OPG levels were associated with significantly lower estimated lifetime and ten-year risks of BRCA1-associated breast cancer. These associations were stronger for women at a lower risk of developing lifetime breast cancer. Further research is needed to determine whether integrating circulating OPG levels can improve existing risk prediction models. These data contribute to ongoing interest in the role of RANK signaling in mammary tumorigenesis. Inhibiting RANK signaling may therefore be a potential target for breast cancer prevention in women with a BRCA1 mutation and other high-risk populations. Citation Format: Sarah S. Park, Tasnim Zaman, Shana J. Kim, Jennifer D. Brooks, Andy K. O. Wong, Jan Lubiński, Steven A. Narod, Leonardo Salmena, Joanne Kotsopoulos. Association between circulating osteoprotegerin levels and estimated risk of BRCA1-associated breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P037.

Recombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers.

Strategies for breast cancer prevention in women with germline BRCA1/2 mutations are limited. We previously showed that recombinant human chorionic gonadotropin (r-hCG) induces mammary gland differentiation and inhibits mammary tumorigenesis in rats. The present study investigated hCG-induced signaling pathways in the breast of young nulliparous women carrying germline BRCA1/2 mutations. We performed RNA-sequencing on breast tissues from 25 BRCA1/2 mutation carriers who received r-hCG treatment for 3 months in a phase II clinical trial, we analyzed the biological processes, reactome pathways, canonical pathways, and upstream regulators associated with genes differentially expressed after r-hCG treatment, and validated genes of interest. We observed that r-hCG induces remarkable transcriptomic changes in the breast of BRCA1/2 carriers, especially in genes related to cell development, cell differentiation, cell cycle, apoptosis, DNA repair, chromatin remodeling, and G protein-coupled receptor signaling. We revealed that r-hCG inhibits Wnt/β-catenin signaling, MYC, HMGA1 , and HOTAIR , whereas activates TGFB/TGFBR-SMAD2/3/4, BRCA1, TP53, and upregulates BRCA1 protein. Our data suggest that the use of r-hCG at young age may reduce the risk of breast cancer in BRCA1/2 carriers by inhibiting pathways associated with stem/progenitor cell maintenance and neoplastic transformation, whereas activating genes crucial for breast epithelial differentiation and lineage commitment, and DNA repair.

Mammographic density, endocrine therapy and breast cancer risk: a prognostic and predictive biomarker review.

Mammographic density, endocrine therapy and breast cancer risk: a prognostic and predictive biomarker review.

Pengaruh Edukasi Informasi Berbasis Media Sosial Terhadap Pengetahuan Kanker Payudara Pada Wanita Usia Subur

Breast cancer is a type of malignant tumor which is still the number one killer for women. In Indonesia, it is estimated that 51,136 women were diagnosed with breast cancer in 2015. The limited knowledge of women of childbearing age about what breast cancer is and how to detect it is one of the reasons why breast cancer continues to increase. Knowledge is very important in the prevention of breast cancer. With good knowledge, it is expected that women of childbearing age are able to motivate themselves and even those around them to do breast self-examination. One way to increase knowledge is by providing education. Providing education can be done by utilizing social media, namely Instagram. Instagram has a strong appeal to share information resources with all people. Through Instagram, respondents not only hear the material delivered but can also see posts in the form of attractive and effective images and videos. This study aims to determine the effect of social media-based information education on breast cancer knowledge in women of childbearing age. Methods: This research is a quantitative research with Pre-Experimental design with Two Group Pre-Posttest Design, the sampling technique is convenience sampling. conducted in May-July 2021, the research sample was 60 women of childbearing age. Data analysis using Paired Sample T-test and ANCOVA. There is a significant difference between the knowledge scores of breast cancer prevention in women of childbearing age. who received social media-based information education intervention compared to the group that did not get the intervention with p-value = 0.000 (p < ? 0,05). This intervention regarding social media-based information education has an effect on increasing knowledge of breast cancer in women of childbearing age.

Validity and Reliability Study of the Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors

Validity and Reliability Study of the Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors

Risk of invasive breast cancer in relatives of patients with breast carcinoma in situ: a prospective cohort study

BackgroundWide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer.MethodsWe analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer.ResultsHaving one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4–1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7–1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9–3.9%) and was not significantly different from 3.7% (3.6–3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped).ConclusionsThe risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.

Cytogenetic differences in blood and cancer tissue samples of the same patient group

Breast cancer (BC) is the most prevalent malignant disease in females worldwide. Genomic instability in tumor tissue has been associated with tumor progression. These genetic changes may take a variety of forms, including numerical and structural chromosomal abnormalities (CAs), epigenetic changes, and gene expression alterations. Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity play a central role in cancer research. In this study, CAs in blood and cancer tissues of patients with sporadic BC were examined. Our findings shows that the increase in numerical sex aneuploidy in BC tissues is significantly higher than in blood tissue. These aneuploidy increases in cancer tissues seem to be compatible with the development and increase of cancer, and can play a role in the pathogenesis of cancers. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. These findings should clarify our understanding of breast carcinogenesis in breast tissues and promote development of improved methods for risk assessment and BC prevention in women.

Breast Cancer Risk Perception and Mammography Screening Behavior of Women in Northeast Brazil

Background: Previous studies suggest that education and income affect Brazilian women's breast cancer prevention behavior. The present study focused on the impact of perceived and estimated risk on mammography screening (MS) behavior.Materials and Methods: Information regarding socioeconomic variables and risk perception was obtained from 396 healthy women aged 40–79 years. Perceived comparative risk was measured on a seven-point Likert scale. A Breast Cancer Risk Assessment Tool of 5-year risk to develop breast cancer was used to determine objective risk. Estimated comparative risk was determined as categories of perceived risk relative to the objective risk. Regression analysis was applied to determine odds ratios (ORs) and confidence intervals (95% CIs) of variables.Results: Asked about the potential of MS to lower risk of death because of breast cancer, 215 (54.29%) responded that it does not lower risk. Women with low perceived comparative risk had a twofold (OR = 0.493; 95% CI: 0.24–1.00) decreased chance to participate in MS annually, compared with women with high-perceived comparative risk (p = 0.020). Women without family history had a 7.6-fold (OR = 0.132; 95% CI: 0.07–0.25) decreased chance of having a high-perceived comparative risk (p = 0.000). If compared with underestimation, the overestimation and accurate estimation of comparative risk tended to be associated with a decreased chance of MS attendance (p = 0.017). Regression modeling indicated that low educational level, no occupation, and no family history decreased the chance of women having MS (p = 0.040; p = 0.010; p = 0.022).Conclusions: Risk perception depended on family history. Present data did not indicate that overestimation, or accurate estimation of comparative risk, increased chance of MS attendance. Educational level, occupation status, and family history, instead, determined MS performance.

Increased Extracellular Osteopontin Levels in Normal Human Breast Tissue at High Risk of Developing Cancer and Its Association With Inflammatory Biomarkers in situ

Mammographic breast density is a strong independent risk factor for breast cancer (BC), but the molecular mechanisms behind this risk is yet undetermined and prevention strategies for these women are lacking. The anti-estrogen tamoxifen may reduce the risk of BC but this treatment is associated with severe side effects. Thus, other means for BC prevention, such as diet interventions, need to be developed. Osteopontin (OPN) is a major mediator of inflammation which is key in carcinogenesis. OPN may be cleaved by proteases in the tissue and cleaved OPN may in turn induce an inflammatory cascade in the extracellular microenvironment. We aimed to determine if extracellular OPN was altered in BC and in normal breast tissue with different densities and if tamoxifen or a diet of flaxseed could modify OPN levels. The study comprised 103 women; 13 diagnosed with BC, 42 healthy post-menopausal women with different breast densities at their mammography screen, and 34 post-menopausal women who added 25 g of ground flaxseed/day or were treated with tamoxifen 20 mg/day and were investigated before and after 6 weeks of exposure. Additionally, 10 premenopausal women who added flaxseed for one menstrual cycle and four who were investigated in two unexposed consecutive luteal phases of the menstrual cycle. Microdialysis was used to sample extracellular proteins in vivo in breast tissue and proteins were quantified using a multiplex proximity extension assay. We found that, similar to BC, extracellular in vivo OPN levels were significantly increased in dense breast tissue. Additionally, significant correlations were found between OPN and chemokine (C-X-C motif) ligand (CXCL)-1, −8, −9, −10, and −11, interleukin-6, vascular endothelial growth factor, matrix metalloproteinase (MMP)-1, −2, −3, 7, and −12 and urokinase-type plasminogen activator whereas no correlations were found with MMP-9, chemokine (C-C motif) ligand (CCL)-2, and −5. Estradiol did not affect OPN levels in breast tissue. None of the interventions altered OPN levels. The pro-tumorigenic protein OPN may indeed be a molecular target for BC prevention in women with increased breast density but other means than tamoxifen or flaxseed i.e., more potent anti-inflammatory approaches, need to be evaluated for this purpose.

Some causes that hinder the prophylaxis of breast cancer

Introduction: Prophylaxis of breast cancer is one of the most important measures to limit this disease. Finding and eliminating the reasons, leading to its deterioration ensures its success. Purpose: To identify some of the reasons that lead to difficulties in breast cancer prevention in women. Material and methods: 1102 women aged 20-65 live in the regions - Varna, Dobrich, Silistra and Shumen. The survey covers the period January 2013 - March 2015. Sociological methods - document analysis, survey method; statistical methods. A personal (questionnaire) is used for conducting the survey. The data were statistically processed through SPSS v. 20.0 and are represented graphically. Results and Discussion: The study shows that only 47.50% of the respondents had been involved in breast cancer prevention. There is a difference in the proportion of prophylactic examinations in different age groups (I‡2 = 37,38; p<0,001). The results show that women above 46 years are more often involved in breast prophylaxis. It was found that women with a lower level of education were seen much less often than those with college and university education. Another significant cause of the prophylaxis of this type of cancer is the place of residence, with roughly half (49.10%) of the respondents in rural areas not conducting such examinations. Nearly half (49.60%) of women said they had difficulty performing prophylactic breast examinations that prevented them from participating in prevention. Nonetheless, respondents stated serious readiness to participate in the ongoing breast cancer prevention.

Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial.

Women with a BRCA1 or BRCA2 mutation are at high risk for breast cancer and must make important decisions about breast cancer prevention and screening. In the current study, we report a multisite, randomized, controlled trial evaluating the effectiveness of a decision aid for breast cancer prevention in women with a BRCA mutation with no previous diagnosis of cancer. Within 1 month of receiving a positive BRCA result, women were randomized to receive either usual care (control group) or decision aid (intervention group). Participants were followed at 3, 6, and 12 months; were asked about preventive measures; and completed standardized questionnaires assessing decision making and psychosocial functioning. One hundred fifty women were randomized. Mean cancer-related distress scores were significantly lower in the intervention group compared with the control group at 6 months (P = 0.01) and at 12 months postrandomization (P = 0.05). Decisional conflict scores declined over time for both groups and at no time were there statistical differences between the two groups. The decision aid for breast cancer prevention in women with a BRCA1 or BRCA2 mutation is effective in significantly decreasing cancer-related distress within the year following receipt of positive genetic test results.Genet Med 19 3, 330-336.

Development and psychometric testing of a new instrument to measure factors influencing women's breast cancer prevention behaviors (ASSISTS).

BackgroundBreast cancer preventive behaviors have an extreme effect on women’s health. Despite the benefits of preventive behaviors regarding breast cancer, they have not been implemented as routine care for healthy women. To assess this health issue, a reliable and valid scale is needed. The aim of the present study is to develop and examine the psychometric properties of a new scale, called the ASSISTS, in order to identify factors that affect women’s breast cancer prevention behaviors.MethodsA multi-phase instrument development method was performed to develop the questionnaire from February 2012 to September 2014. The item pool was generated based on secondary analyses of previous qualitative data. Then, content and face validity were applied to provide a pre-final version of the scale. The scale validation was conducted with a sample of women recruited from health centers affiliated with Tehran University of Medical Sciences. The construct validity (both exploratory and confirmatory), convergent validity, discriminate validity, internal consistency reliability and test-retest analysis of the questionnaire were tested.ResultsFifty-eight items were initially extracted from the secondary analysis of previous qualitative data. After content validity, this was reduced to 49 items. The exploratory factor analysis revealed seven factors (Attitude, supportive systems, self-efficacy, information seeking, stress management, stimulant and self-care) containing 33 items that jointly accounted for 60.62 % of the observed variance. The confirmatory factor analysis showed a model with appropriate fitness for the data. The Cronbach’s alpha coefficient for the subscales ranged from 0.68 to 0.85, and the Intraclass Correlation Coefficient (ICC) ranged from 0.71 to 0.98; which is well above the acceptable thresholds.ConclusionThe findings showed that the designed questionnaire was a valid and reliable instrument for assessing factors affecting women’s breast cancer prevention behaviors that can be used both in practice and in future studies.

Towards research-tested smartphone applications for preventing breast cancer.

Efforts to prevent breast cancer and other chronic illnesses have focused on promoting physical activity, healthy diet and nutrition, and avoidance of excessive alcohol consumption. Smartphone applications (apps) offer a low-cost, effective strategy for breast cancer prevention in women through behavioral change. However, there are currently no research-tested smartphone apps for breast cancer prevention that are suitable for women with varying levels of health literacy and eHealth literacy. In this perspective, we consider modifiable risk factors for breast cancer in women in relation to the development of smartphone apps to promote healthy behaviors associated with breast cancer-risk reduction. First, we provide a summary of breast cancer risk factors that are modifiable through behavioral change including their corresponding relative risk. Second, we discuss scientific issues related to the development of smartphone apps for the primary prevention of breast cancer and offer suggestions for further research. Smartphone apps for preventing breast cancer should be tailored for women at different life stages (e.g., young women, women who are post-menopausal, and older women). Topics such as breastfeeding and oral contraceptives are appropriate for younger women. Weight management, physical activity, avoiding cigarette smoking, and dispelling breast cancer myths are appropriate for women of all ages. As women age, topics such as hormone replacement therapy or comorbid health conditions become more important to address. Apps for breast cancer prevention should be grounded in a behavioral theory or framework and should be suitable for people with varying levels of health literacy. Future developments in smartphone apps for breast cancer prevention should include apps that are tailored for specific cultural, racial, and ethnic groups.

Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women.

Abstract A16: Molecular tracking of metformin chemoprevention in a 300-person ALLIANCE randomized placebo controlled trial in women at high risk for triple-negative breast cancer

Abstract Background: Metformin (1,1-dimethylbiguanide hydrochloride) is a well-tolerated biguanide currently undergoing testing for secondary breast cancer prevention in women with prior breast cancer. Recently published population studies suggest that metformin decreases the incidence of cancer and cancer-related mortality in diabetic patients. While metformin is one of the most extensively studied drugs in vitro and in vivo, many pre-clinical studies use concentrations of metformin that are &amp;gt;1,000 times what is clinically achievable in humans and would be rapidly fatal if achieved. As a result, the molecular action of metformin in the breast tissue of women at high-risk who take metformin chemoprevention is poorly understood. Methods/Results: Here we use combined proteomic profiling, breast tissue cytokine analysis, and in vivo analysis of live mammary epithelial cells for mitochondrial membrane and glucose uptake to track the molecular action of metformin chemoprevention in overweight and obese women at high-risk for triple-negative breast cancer. Women are enrolled in a 300 person ALLIANCE randomized, placebo controlled chemoprevention trial. Our studies to date have shown that overweight and obese women have activation of Akt/mTOR and IL6 /Stat3 epithelial activation, epithelial glucose uptake and increased mitochondrial membrane potential, and increased mammary tissue IL6/insulin. Conclusion: These studies show our ability to directly track the molecular response to metformin chemoprevention. Note: This abstract was not presented at the conference. Citation Format: Victoria Seewaldt, James Marshall. Molecular tracking of metformin chemoprevention in a 300-person ALLIANCE randomized placebo controlled trial in women at high risk for triple-negative breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A16.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4–5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer.Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts.Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts.