This follows an earlier study of the same data set, which, through its findings, presented new questions that are investigated in this study. Both studies used a prospective controlled design, wherein women receiving genetic counseling for breast cancer risk were randomized into two groups. Subjects receiving an audiotaped recording of their genetic consultation (tape group) were compared to subjects who also had a genetic consultation but did not receive an audiotaped recording of it (no-tape group). Participants were drawn from attendees at the genetic clinics of two London hospitals and included 115 women with a family history of breast cancer. Cancer worry and psychological distress were assessed before genetic consultation (baseline), and at one- and six-month follow-ups by post. Objective risk was estimated by the geneticist during the consultation, and subjective risk was assessed at one month follow-up. The goals of the current study were to investigate relationships between cancer worry, psychological distress, and recall of genetic risk for breast cancer in a sample of women receiving genetic counseling for breast cancer risk, and to investigate the role sociodemographic variables on cancer worry, psychological distress, or risk recall for these women. Results for this sample of women with a family history of breast cancer found that there were consistent relationships between cancer worry, psychological distress, objective risk, and subjective risk before and after genetic consultation. This suggests that women=s psychological responses are appropriate to their level of cancer risk. There were no differences found between the tape and no-tape groups for objective or subjective risk, or for nearness of recall accuracy or degree of under-/over-estimation. Provision of an audiotaped recording of the genetic consultation did not appear to enhance recall of risk information. The role of sociodemographic variables on the psychological and risk variables assessed in this study was very minor. Age was mildly correlated with cancer worry, and employment was predictive of cancer worry only at baseline.

American Cancer Society estimates that in 2021 nearly 300,000 women in the United States will be diagnosed with invasive breast cancer, and about 43,600 women will die from breast cancer. While many have access to health care and cancer screening, women from rural or underdeveloped communities often have limited access. Therefore, there is a need for an inexpensive and easy-to-use breast cancer identification device, which can be employed in small clinics to provide support to primary care physicians. This work aims to develop a method to characterize breast tumors and tissue using non-invasive imaging modalities. The proposed bimodal imaging system has tactile and multispectral imaging capabilities. Tactile imaging modality characterizes tumors by esti-mating their depth, size, and stiffness, along with the Tactile Index. Multispectral imaging modality identifies breast asymmetry, texture, and inflammation changes, together with the Spectral Index. These indices are combined with the BCRAT Index, the risk score devel¬oped by the National Institute of Health, to form the Multimodal Index for personalized breast cancer risk assessment. In this study, we will describe the development of the bimodal imaging system. We will present the algorithms for tactile and multispectral modalities. Tactile and Multispec¬tral Profile Diagrams are developed to capture broad imaging signals in a compact and application-specific way. A Tactile Profile Diagram is a pictorial representation of the rel¬ative depth, size, and stiffness of the imaged tumor. A Multispectral Profile Diagram is a representative pattern image for breast tissue superficial optical properties. To classify the profile diagrams, we employ the Convolutional Neural Network deep learning method. We will describe the results of the experiments conducted using tissue-mimicking phan¬toms and human in-vivo experiments. The results demonstrate the ability of the method to classify and quantify tumor and tissue characteristics. Finally, we describe the method to calculate Multimodal Index for the malignancy risk assessment via tactile and multispectral imaging modalities and the risk probability based on the health records. / Electrical and Computer Engineering

Breast cancer incidence, particularly late-stage disease, is increasing in U.S. women under 40 years of age, pointing to the importance of exposures acting early in the life course to increase breast cancer risk. Earlier onset of breast development has recently been identified as an independent risk factor for breast cancer. Thus, identifying modifiable factors that can delay the onset of breast development may provide an opportunity for breast cancer primary prevention starting early in life. This dissertation examined the influence of the early-life environment on the age at onset of breast development through: 1) a systematic review of the literature relating maternal pre-pregnancy body size, gestational weight gain (GWG), birth size, and infant growth to the timing of breast development and menarche; 2) analyses assessing the associations between these factors and the onset of breast development in a pubertal cohort enriched for breast cancer family history (BCFH); and 3) a pilot study assessing whether these factors are associated with serum levels of insulin-like growth factor(IGF)-1 and insulin-like growth factor binding protein(IGFBP)-3 during puberty. Our systematic review identified 96 studies, the majority of which examined the association between birthweight and age at menarche. Although low birthweight is often cited as a risk factor for early menarche, the majority of studies (40/73 total) that examined this association did not observe a statistically significant association. Differences in exposure assessment, inadequate control for confounders, and differences in postnatal growth across studies may drive inconsistencies in the birthweight literature. In contrast, higher maternal body mass index (BMI) prior to pregnancy, GWG in excess of recommended guidelines and faster rates of weight gain between birth and 2 years of age were consistently associated with earlier age at breast development and menarche. We used data from the LEGACY Girls Study, a prospective cohort of girls primarily ages 6-13 years at baseline in which approximately 50% of girls had a family history of breast cancer, to examine the relations between maternal factors, birth size and infant growth and the onset of breast development, defined as a maternal report of breast Tanner stage 2 or greater. Daughters of women with a pre-pregnancy BMI of 25 or greater and who gained 30lbs or more during pregnancy experienced breast development at an earlier age than daughters of women with a pre-pregnancy BMI less than 25 and who gained less than 30lbs. This association was similar in girls with and without a BCFH. Birthweight and birthlength were not associated with the timing of breast development. In a subset of LEGACY girls with height and weight data during infancy available from medical records, we examined the associations between changes in weight-for-age and length-for-age Z-scores from birth to 1 year of age and the onset of breast development. We observed a modest association between faster rates of weight gain from 0-12 months and earlier age at breast development. When we examined smaller age intervals within infancy, faster weight gain from 2-4 months and 6-9 months were each associated with an earlier age at breast development. A similar pattern was observed for growth in length, and these associations did not vary by BCFH. In our pilot study including 109 girls with available serum samples between 6-17 years of age at the LEGACY New York site, rapid weight gain from 0-12 months was associated with higher mean levels of IGF-1 relative to IGFBP-3. Although not statistically significant, girls with a maternal pre-pregnancy BMI≥25 and GWG≥30lbs also had higher mean levels of the IGF-1/IGFBP-3 ratio. Since serum IGF-1 and IGFBP-3 are objective measures that are known to increase rapidly during puberty, the results of our pilot study support that the maternal BMI, GWG and rapid infant weight gain are associated with biological changes in the girls. Our findings suggest that measurement error in outcome assessment or confounding did not drive the associations that we observed between these factors and earlier onset of breast development. In conclusion, we identified higher maternal pre-pregnancy BMI, excess GWG and rapid growth during infancy as modifiable factors associated with earlier onset of breast development in girls across the spectrum of familial risk for breast cancer. While this suggests that modifying these factors may decrease breast cancer risk later in life, further research should consider additional and potentially opposing pathways, such as childhood body size, through which the early-life environment affects breast cancer risk.

Made available in DSpace on 2016-03-22T17:27:34Z (GMT). No. of bitstreams: 1 Rafaela Bulow Bergmann.pdf: 1551363 bytes, checksum: 5175c2d3946e786b40017d62f40a91c3 (MD5) Previous issue date: 2014-09-16 / This dissertation presents a study that aimed to evaluate for the first time the association between metabolic syndrome (MetS) and breast cancer (BC) in southern Brazil, using the definitions from the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) and International diabetes Federation (IDF) for the syndrome. It is a case-control study nested in a cohort, conducted between December 2013 and August 2014 in the oncology department of the Teaching Hospital of the Federal University of Pelotas (UFPel), the Radiotherapy and Oncology Center of Santa Casa de Misericordia of Pelotas and Gynecology Abulatory (UFPel), whose attendance is from the Unified Health System (SUS). For each newly diagnosed BC case, prior to treatment, a control matched for age (± 5 years) and menopausal status was included. Women who agreed to participate (n = 164) were interviewed and asked to make a blood test including fasting glucose, HDL-cholesterol and triglycerides. Participants were also evaluated for blood pressure and waist circumference (WC). According to the NCEP ATP III MetS was diagnosed in the presence of three of five factors: blood pressure &#8805; 130/85 mmHg (or hypertension), WC &#8805; 88 cm, HDL-cholesterol <50 mg/dl (or medication), triglycerides &#8805; 150 mg/dl (or medication), and fasting glucose > 110mg/dl (or type II diabetes). Considering the IDF consensus, MetS was identified by essential presence of abdominal obesity (WC &#8805; 80 cm), in addition of two other alterations: blood pressure &#8805; 130/85 mmHg (or hypertension), HDL-cholesterol <50 mg/dl (or medication ), triglycerides &#8805; 150 mg/dl (or medication) and fasting glucose > 100 mg/dl (or type II diabetes). Cases showed a larger number of altered components of the syndrome than wemen belonging to the control group, regardless of the criteria used, and the controls were more likely to have zero, one or two metabolic abnormalities (P <0.001). According to NCEP ATP III criteria, the presence of three altered components of MetS was associated with a 7.2 times greater risk of BC compared to no alterations (95% CI: 1.97, 26.11), while the odds ratio for the IDF criteria corresponded to 10:08 (95% CI: 1.82, 55.91). The odds for having BC was 4.7 times higher in women diagnosed with MetS, regardless of the definition used (NCEP ATP III: 95% CI: 2.14, 10.23; IDF: 95% CI: 2.13, 10.17 ). Low HDL-cholesterol was related to BC risk (OR = 2.88, 95% CI: 1:47, 5.67) as well as systolic blood pressure (OR = 7.3, 95% CI: 2:43; 21.91), diastolic blood pressure (OR = 4:56; 95% CI: 1.82; 11:44) and WC &#8805; 80cm (OR = 2.1 95% CI: 1.03; 4:42). The results indicated that there was a strong relationship between MetS and risk of BC among women from southern Brazil, through both NCEP ATP III and IDF criteria. Although more studies are needed, MetS may be a promising target for future interventions aiming BC prevention / Esta dissertação expõe um estudo que objetivou avaliar pela primeira vez a associação entre a síndrome metabólica (SM) e câncer de mama (CM) no Sul do Brasil, utilizando as definições do National Colesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) e International diabetes Federation (IDF) para a síndrome. Trata-se de um estudo do tipo caso-controle aninhado a uma coorte, realizado entre dezembro de 2013 e agosto de 2014 no setor de oncologia do Hospital Escola da Universidade Federal de Pelotas (UFPel), no Centro de Radioterapia e Oncologia da Santa Casa de Misericórdia de Pelotas e no Ambulatório de Ginecologia da UFPel, cujos atendimentos se dão através do Sistema Único de Saúde (SUS). Para cada caso recém diagnosticado de CM, prévio ao tratamento, um controle pareado em idade (± 5 anos) e fase da menopausa foi incluido. As mulheres que aceitaram participar (n=164) foram entrevistadas e convidadas a fazer um exame de sangue incluindo glicemia de jejum, HDL-colesterol e triglicerídeos. Participantes também foram avaliadas quanto aos níveis de pressão arterial e circunferência da cintura (CC). Segundo o critério NCEP ATP III, a SM foi diagnosticada na presença de três dos cinco fatores: pressão arterial &#8805; 130/85 mmHg (ou hipertensão), CC &#8805; 88 cm, HDL-colesterol < 50 mg/dl (ou medicação), triglicerideos &#8805; 150 mg/dl (ou medicação), e glicose de jejum > 110mg/dl (ou diabetes tipo II). Considerando o consenso IDF, a SM foi identificada pela presença essencial de obesidade abdominal (CC &#8805; 80 cm), em adição a duas outras alterações: pressão arterial &#8805; 130/85 mmHg (ou hipertensão), HDL-colesterol < 50 mg/dl (ou medicação), triglicerideos &#8805; 150 mg/dl (ou medicação) e glicemia de jejum > 100 mg/dl (ou diabetes tipo II). O grupo de casos demonstrou um maior número de componentes da síndrome alterados do que aquelas que pertenciam ao grupo controle, independentemente do critério utilizado, e os controles foram mais propensos a ter zero, uma ou duas alterações metabólicas (P < 0.001). De acordo com o critério NCEP ATP III, a presença de três componentes alterados da SM foi associado a um risco 7,2 vezes maior de CM em relação a ausência de alterações (IC95%: 1,97; 26,11), sendo que para o critério IDF a razão de chances correspondeu a 10.08 (IC95%:1.82; 55.91). A probabilidade de ter CM foi 4,7 vezes maior em mulheres com diagnóstico de SM, independentemente da definição utilizada (NCEP ATP III: IC95%: 2,14; 10,23; IDF: IC95%: 2,13; 10,17). Baixo HDL-colesterol foi relacionado ao risco de CM (OR=2.88; 95%CI: 1.47; 5.67), bem como a pressão arterial sistólica (OR=7.3; 95%CI: 2.43; 21.91), diastólica (OR=4.56; 95%CI: 1.82; 11.44) e CC &#8805; 80cm (OR=2.1 95%CI: 1.03; 4.42). Os resultados obtidos indicaram que houve uma forte relação entre SM e risco de CM entre as mulheres do Sul do Brasil, tanto através do critério NCEP ATP III quanto IDF. Apesar de mais estudos serem necessários, a SM pode ser um alvo promissor para futuras intervenções almejando a prevenção do CM

Mammographic density, the amount of radiodense tissue on a mammogram, is a strong risk factor for breast cancer, with properties that could be an asset in screening and prevention programmes. Its use in risk prediction contexts is currently limited, however, mainly due to di culties in measuring and interpreting density. This research investigates rstly, the properties of density as an independent marker of breast cancer risk and secondly, how density should be measured. The rst question was addressed by analysing data from a chemoprevention trial, a trial of hormonal treatment, and a cohort study of women with a family history of breast cancer . Tamoxifen-induced density reduction was observed to be a good predictor of breast cancer risk reduction in high-risk una ected subjects. Density and its changes did not predict risk or treatment outcome in subjects with a primary invasive breast tumour. Finally absolute density predicted risk better than percent density and showed a potential to improve existing risk-prediction models, even in a population at enhanced familial risk of breast cancer. The second part of thesis focuses on density measurement and in particular evaluates two fully-automated volumetric methods, Quantra and Volpara. These two methods are highly correlated and in both cases absolute density (cm3) discriminated cases from controls better than percent density. Finally, we evaluated and compared di erent measurement methods. Our ndings suggested good reliability of the Cumulus and visual assessments. Quantra volumetric estimates appeared negligibly a ected by measurement error, but were less variable than visual bi-dimensional ones, a ecting their ability to discriminate cases from controls. Overall, visual assessments showed the strongest association with breast cancer risk in comparison to computerised methods. Our research supports the hypothesis that density should have a role in personalising screening programs and risk management. Volumetric density measuring methods, though promising, could be improved.

Background: Estrogen receptor (ER)- and progesterone receptor (PR)-negative (ER-PR-) breast cancer is associated with higher grade and poorer prognosis compared with other breast cancer subtypes. High parity, coupled with lack of breastfeeding, has been associated with an increased risk of ER-PR- cancer. The mechanism of this etiology is unclear, and may be obfuscated by ER and PR correlation with each other as well as other prognostic tumor characteristics. Methods: Using population-based and clinic-based ascertained cases and controls from the Breast Cancer Family Registry, I examined reproductive risk factors, including parity, breastfeeding, and oral contraceptive (OC) use, in relation to ER and PR status, using polytomous logistic regression (for the population-based data) and the method of generalized estimating equations (GEE) (for the clinic-based data) as well as the pseudo-conditional likelihood approach, which accounts for correlated outcome variables. Results: High parity (≥ 3 live births) combined with lack of breastfeeding, was positively associated with ER-PR- tumors (odds ratio [OR]=1.57, 95% confidence interval [CI] 1.10-2.24, population-based cases vs. controls) relative to nulliparity. There was no association with ER-PR- tumors and parity in women who breastfed (OR=0.93, 95%CI 0.71-1.22) relative to nulliparous women. Associations with ER-PR- cancer were higher across all races/ethnicities among women who did not breastfeed compared with women who did. Population-based and clinic-based data were generally in agreement (OR=2.07, 95% CI 1.09-3.91, clinic-based cases vs. controls, relative to nulliparity). When adjusted for the correlation of PR-status and grade, to ER-status, the association between high parity +lack of breastfeeding and ER- status, was maintained. OC use before year 1975 was associated with an increased risk of ER-PR- tumors (OR=1.32, 95% CI 1.04-1.67, population-based data, cases vs. controls) relative to never use of OCs. For women who began OC use in 1975 or later there was no increased risk. Analysis of OC use in clinic-based data agreed with the findings of the population-based data. Conclusions: My findings support that there are modifiable factors for ER-PR- breast cancer, and that breastfeeding in particular may mitigate the increased risk of ER-PR-cancers seen from multiparity. The mechanism of both risk and risk mitigation may operate primarily through the estrogen, rather than progesterone, pathway.

While sisters of breast cancer patients are at increased risk for developing breast cancer due to their family cancer history and age, little research with first-degree relatives of cancer patients has focused solely on sisters. To address this issue, the current study examined sisters screening and health behaviors and the predictors of these behaviors. In accordance with the Parallel Processing Theory, the current study assessed the relationship of cognitive and emotional factors to screening and health-promoting behaviors among sisters of breast cancer patients. In addition, this study expanded upon the Parallel Processing Theory by also examining the relationship of interpersonal factors to screening and health-promoting behaviors. One-hundred-twenty sisters of breast cancer patients from 89 different families completed questionnaires assessing perceived risk of breast cancer, perceived response efficacy of mammography, diet, and exercise, breast cancer worry, trait anxiety, involvement in sister's cancer care, satisfaction with the sister relationship, mammography screenings, physical activity, and amount of fruits and vegetables consumed. Findings indicated that cognitive, emotional, and relational factors were significantly related to mammography screenings, but not to diet or exercise. Specifically, response efficacy for mammography screening was positively related to mammography screening; while trait anxiety and involvement in sister's care were negatively related to mammography screening. Additional analyses indicated that breast cancer worry had a curvilinear relationship with mammography screenings, such that no relationship was seen for women with lower breast cancer worry; for women with higher levels of worry, the greater their worry, the less likely they were to obtain mammography screenings. Breast cancer worry was also found to interact with involvement in care, such that among women less involved in their sister's care, greater breast cancer worry was associated with having fewer mammography screenings. However, for women more involved in their sister's care, greater breast cancer worry was associated with having more mammography screenings. Future research should further assess whether a teachable moment exists related to the family member's cancer diagnosis and treatment during which to encourage the FDR to engage in screening health-promoting behaviors.

Suppression of genes involved in DNA repair, tumor suppression and detoxification through epigenetic modifications has been implicated in the etiology of cancer. As such analysis of promoter methylation patterns in genes frequently down regulated in breast cancer in non-cancerous subjects may serve as an indicator of breast cancer risk. CpG-island hypermethylation of single genes has been detected in cells isolated from nipple aspirate and ductal lavage, yet both isolation methods yield insufficient cells to complete an extensive analysis on any one donor sample. As an alternative we have turned to magnetic separation of human mammary epithelial cells from breast milk. Initial studies with these cells, which are detailed in chapter one, show that a breast milk sample provides sufficient epithelial cells to isolate high quality RNA for gene expression analyses or genomic DNA for methylation analysis of multiple genes. Using quantitative RT-PCR of RNA collected from these samples we detected differences in the mRNA levels for six genes known to be down regulated in breast cancers: BRCA1, p16, CDH1, TMS-1, GSTPi, and SFRP1. Additionally using methyl-specific PCR (MSP) we assayed for a small panel of genes frequently methylated in cancer and found them to be unmethylated in the few breast milk samples examined. However, given the small number of CpG sites which can be assayed by the MSP technique it is not surprising that methylation was not detected in disease-free subjects. With methods for collecting breast milk samples and processing them for genetic material established we turned to a more comprehensive study of DNA methylation in larger population of donors which is detailed in chapter two. Utilizing a highly sensitive and highly quantitative methylation analysis technique known as Pyrosequencing we examined age-related methylation patterns for RASSF1A, TMS-1, CDH1, SFRP1, GSTPi, and CRBP1 in genomic DNA purified from exfoliated epithelial cells magnetically enriched from breast milk (n=111) and whether the protective effects conveyed by early pregnancy could be partly due to decreases in DNA hypermethylation. Although firm answers about early pregnancy were inconclusive based on our sample pool, this body of work lays down a solid foundation for future studies.

Indiana University-Purdue University Indianapolis (IUPUI) / Hispanics are more likely to die from breast cancer compared to non - Hispanic whites matched on stage and age at diagnosis. Higher mortality rates among Hispanics are attributed to cancer - related disparities across the cancer continuum including later - stage detection. While research has shown that socioeconomic factors play a significant role in the development and maintenance of cancer - related disparities, differences persist when these factors are controlled. Thus far, research on cultural factors and cognitions surrounding cancer is limited. The current study investigated illness representations of cancer and their determinants among Hispanic men and women (N = 120) using a cross - sectional survey approach. The study sample was comprised of predominantly first generation, employed Hispanic women in their early - thirties from Mexico. Most had not resided in the U.S. for more than 5 - 9 years. Half of the sample reported an annual income of $20,001 - $30,000 and completing at least a middle school education. While the majority indicated that they did not have health insurance, most indicated that they did have a regular source of health care. Additionally, while most had not been diagnosed with cancer, nearly half of the sample knew of someone diagnosed with cancer. Descriptive data regarding illness identity, illness coherence, timeline, causes, consequences, and controllability are provided. Results suggest that demographic factors (i.e. acculturation, education, and income), cultural constructs (i.e. fatalism and familism), intrapersonal factors (state and trait anxiety), and previous experience with cancer were associated with illness representations of breast cancer. The study adds to theliterature by systematically investigate illness representations of breast cancer and their determinants among a diverse sample of Hispanic men and women. This is a significant first step that can be used to guide and develop effective and culturally appropriate interventions that ultimately reduce disparities across the cancer continuum.

This study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and combination treatments induced dose- and time-dependent apoptotic cell death in MCF-7 cells. The percentage of apoptosis was higher in combination treatments than single treatments with either phytochemical, although the difference was not statistically significant. The combination of genistein and anthocyanin extract peaked in efficacy at 48 hours of treatment, to exhibit significantly greater (P<. O5) dose- and time-dependent cell cytotoxicity than single treatments. This study reveals potential chemopreventive implications for the complementary effects of genistein and anthocyanin extract. / by Corine M. Stinson. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.