Rozprawy doktorskie na temat „Breast Cancer Screening Policies”

Ces travaux de thèse sont motivés par le développement de techniques d’imagerie alternatives pour le diagnostic précoce du cancer du sein. Parmi celles-ci, l’imagerie photoacoustique couple potentiellement les avantages de deux modalités d’imagerie non-invasives, à savoir la quantification de contrastes physiologiques du fait de l’excitation optique et la haute résolution du fait d’un sondage acoustique.Le but de ces travaux est de proposer une modélisation multiondes du phénomène photoacoustique, et d’incorporer ce modèle dans un algorithme de reconstruction efficace pour résoudre le problème inverse. Celui-ci se rapporte à la reconstruction de cartes de propriétés physiques (optique et/ou acoustiques) de l’intérieur du sein. La Méthode des Eléments Finis (MEF) a été retenue pour résoudre l’équation de propagation optique. Pour la résolution de l’équation de propagation acoustique, une méthode semi-analytique, basée sur des calculs par transformées de Fourier (méthod k-space), a été choisie. Pour la résolution du problème inverse, deux approches ont été étudiées : i) un sondage passif, permettant de remonter à la distribution de pression initiale, à l’aide de la méthode de retournement temporel ; ii) un sondage actif, où l’on interroge le milieu sélectivement sous différentes excitations, permettant de remonter quantitativement aux propriétés optiques du milieu. On appelle cette dernière approche Tomographie PhotoAcoustique Quantitative (TPAQ). Une étude spécifique sur le protocole d’illumination/détection a été conduite, prenant également en compte les contraintes expérimentales
The present work was motivated by the development of alternative imaging techniques for breast cancer early diagnosis, that is photoacoustic imaging, which potentially couples the merits of optical imaging and ultrasound imaging, that is high optical functional contrasts brought by optical probing and high spatial resolution by ultrasound detection. Our work aims at modeling the photoacoustic multiwave phenomenon and incorporate it in an efficient reconstruction algorithm to solve the inverse problem. The inverse problem consists in the recovery of interior maps of physical properties of the breast. The forward model couples optical and acoustic propagations. The Finite Element Method (FEM) was chosen for solving the optical propagation equation, while a semi-analytical method based on Fourier transforms calculations (k-space method) was preferred for solving the acoustic propagation equation. For the inverse model, time reversal method was adopted to reconstruct the initial pressure distribution, an active approach of the inverse problem was also achieved, which decoupled the optical properties from measured photoacoustic pressure, this approach is called quantitative photoacoustic tomography (QPAT), in this approach, illumination/detection protocol was studied, and the experimental set up is also take into consideration. In the last step, photoacoustic pressure measurements obtained from experiment and simulation are studied and compared

Les cancers du sein peuvent être classifiés selon le statut de récepteur d’estrogène (RE), de récepteur de progestérone (RP), de récepteur HER2, ou selon quatre sous-types (Luminal A, Luminal B, HER2-enrichi, Triple-négatif) ayant des propriétés biologiques et cliniques différentes. La sensibilité du dépistage par mammographie pourrait varier selon ces types de cancers mais ceci n’est pas encore clair. L’agressivité de la tumeur, mesurée par le grade histologique pourrait expliquer cette association. Les types de cancers d’intervalle ont été comparés à ceux de cancers détectés par dépistage parmi 1536 cas infiltrants provenant d’un centre de référence de Québec. Les tumeurs RE-négatif, RP-négatif, HER2-positif, Luminal B, HER2-enrichi et TPN étaient tous plus fréquentes chez les femmes avec cancers d’intervalle que chez celles avec cancers détectés par dépistage. À l’exception des tumeurs HER2-positif et HER2-enrichi, le grade histologique expliquait en grande partie la variabilité observée entre les types de cancer et la sensibilité.
Breast cancers can be classified according to tumour estrogen (ER) and progesterone (PR) receptors, human epidermal growth factor receptor 2 (HER2), and according to four subtypes (Luminal A, Luminal B, HER2-enriched, Triple-negative), each with different biological and clinical profiles. These tumour types may also influence screening mammography sensitivity but this is still not clear. Tumour aggressiveness, measured by the histological grade, may also play a role in explaining this association. Interval cancer types were compared to screen-detected cancer types in 1536 invasive cases obtained from a reference center in Quebec. ER-negative, PR-negative and HER2-positive, Luminal B, HER2-enriched and TPN tumours were all more frequent in women with interval cancers than in women with screen-detected cancers. Except for HER2-positive and HER2-enriched tumours, histological grade explained most of the variability observed between tumour receptor status, subtypes and sensitivity.

The aim of this thesis is to carry out an in-depth study of various aspects of breast cancer epidemiology. Firstly, we have confirmed that DCIS incidence in Girona has increased over recent decades. Proportions of screen-detected cancers, interval cancers and non-screen-detected cancers during the start-up phase of the mammographic screening programme were found to be 42.2%, 5.8% and 52.2%, respectively. Secondly, we have found that luminal A-like was the most frequent subtype associated with the best survival rate, while triple-negative breast cancer was related to the lowest survival rate. Importantly, we have concluded that breast cancer molecular subtype defined by IHC biomarkers provides prognostic value, regardless of age, tumour size, histological grade, lymph node involvement and method of detection. Finally, we have demonstrated that method of detection also provides prognostic value regardless of age, tumour size, histological grade, lymph node involvement and breast cancer molecular subtype defined by IHC biomarkers.
L’objectiu d’aquesta tesi és realitzar aprofundir en diversos aspectes de l'epidemiologia del càncer de mama. Hem confirmat que la incidència del DCIS a Girona ha augmentat en les últimes dècades. Les proporcions dels càncers detectats mitjançant el programa de cribratge, fora d’aquest i els càncers d'interval van ser del 42,2%, 52,2% i 5,8%, respectivament. Per altra banda, el subtipus amb la supervivència més elevada i més baixa van ser el luminal A-like i el triple negatiu, respectivament. És important destacar que el subtipus molecular de càncer de mama definit per biomarcadors determinats amb tècniques d’IHC proporciona valor pronòstic, independentment de l'edat, la mida, el grau histològic, l’afectació dels ganglis i el mètode de detecció. Finalment, hem demostrat que el mètode de detecció del càncer també proporciona valor pronòstic independentment de l'edat, la mida, el grau histològic, l'afectació dels ganglis i el subtipus molecular.

Thesis (M.Eng. and S.B.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2001.
Includes bibliographical references (leaf 72).
by Natalia V. Iliouchina.
M.Eng.and S.B.

Health beliefs of 221 postmenopausal women were assessed to predict the Breast Cancer Screening Behaviors of breast self-examination (BSE) and utilization of mammography. Champion's (1991) revised Health Belief Model (HBM) instrument for BSE, which assesses the HBM constructs of Seriousness, Susceptibility, Benefits, Barriers, Confidence and Health Motivation, was utilized along with her Barriers and Benefits instrument for mammography usage. Ronis' and Harel's (1989) constructs of Severity-Late and Severity-Early were evaluated along with Cuing and demographic variables. These exogenous latent constructs were utilized in a LISREL path model to predict Breast Cancer Screening Behavior.

Cette thèse étudie les facteurs d’offre et de demande associés au recours au dépistage du cancer du sein. Parmi les facteurs d’offre, j’examine comment la coexistence du dépistage organisé au côté du dépistage individuel influence le contenu de l’examen de dépistage ainsi que le recours régulier au dépistage. En plus des facteurs de demande tels les caractéristiques socioéconomiques, une attention particulière est portée à la possibilité d’expliquer le recours régulier au dépistage par les préférences face au risque et temporelles ainsi que les perceptions. À partir de régularités psychologiques identifiées dans les travaux d’économie comportementale et de psychologie, trois interventions de type nudge sont testées dans le cadre d’une expérience randomisée sur le terrain visant à augmenter le taux de dépistage dans le programme national
This thesis explores supply and demand factors associated with the use of breast cancer screening. Among the supply factors, I examine how the coexistence of organized and opportunistic screenings influences the content of the screening exam and screening regularity. Besides the usual demand factors such as socioeconomic characteristics, a special attention is being given to the possibility of explaining screening regularly by individuals’ risk and time preferences and perceptions. Based on psychological patterns identified in the literature in behavioral economics and psychology, three nudge interventions are tested in a randomized field experiment to increase the national program uptake rate

Despite multiple campaigns by the American Cancer Society, reports indicate that Latinas living in the United States who contract breast cancer are more likely than Anglos to die. These findings correlate with low participation in breast cancer screenings among Latinas. The objective of this study was to identify key obstacles that influence Latinas' low participation in breast cancer screenings, based on their health beliefs, knowledge of screenings, acculturation, and socio-economic factors.The study was a face-to-face informal interview, combined with a survey questionnaire conducted at churches, social clubs and/or at the participants' homes in a southwest Florida urban community. The sample consisted of a total of 50 women: all of the participants were Latinas 40 years of age and over; they had to be fluent in Spanish or English or both. A Spanish-English bilingual individual conducted a personal interview in the preferred language of each participant. The first part of the interview was to identify barriers that affect screenings. The second part used a survey to weigh the identified factors in order to determine their importance to the participants' health decisions. This study used a health belief model scale to evaluate women's beliefs about breast cancer, and the benefits of screenings.The research results revealed that Latinas who participated in this study were acculturated to the United States culture; the largest group of participants reported being from Colombia, followed by Cuba and Puerto Rico; only two of the participants were Mexican. Seventy-eight percent of the participants self- reported having yearly mammograms, and 74% performed monthly breast self examination BSE; 60% were bilingual; 68% had some kind of health insurance. These results differ from earlier studies from the western United States where the majority of Latinas were of Mexican or Central American origin. This suggested that Latinas from Southwest Florida are different from Latinas in other areas of the United States. A weak but significant correlation was found between acculturation and perceived barriers to breast cancer screenings, (r = 0.45, p = .01); Latinas who are more acculturated perceived more barriers than those who are less acculturated. There was not significant difference between participants who had health insurance and those who did not (t = 0.96, p = .35). The results of this study are significant for nurses and especially for advanced practice nurses, who can assess patients' knowledge about cancer in general, and breast cancer in particular when caring for Latinas; of particular concern should be the evaluation of patients' levels of acculturation, health beliefs, and understanding of the English language. Still the fundamental barrier to Latinas not bilingual in Spanish and English may be the lack of resources and information in Spanish.

The aim of the study is to assess the connection between women’s participation in breast cancer screening and beliefs towards breast cancer, breast self-examination and mammography. The objectives of the study: 1. To assess validity and reliability of Champion Health Belief Model Scale for beliefs towards breast cancer, breast self-examination and mammography screening for Lithuanian women. 2. To estimate perceived susceptibility, perceived severity, perceived benefits, perceived barriers, confidence and health motivation. 3. To compare beliefs towards breast cancer, breast self-examination and mammography screening of participant and non-participant women in the screening program. 4. To assess perceived barriers towards mammography screening. 5. To investigate the role of information about breast cancer and mammography screening for women‘s beliefs towards breast cancer, breast self-examination and mammography screening. CONCLUSIONS 1. Champion Health Belief Model Scale is a valid and reliable to assess beliefs towards breast cancer, breast self- examination and mammography. The barriers- mammography item “Regular mammography screening would make me worry about breast cancer” was inappropriate to the scale and expunged from the questionnaire. 2. Surveyed women did not feel much threat to get breast cancer. They overvalued benefits of breast self-examination and positively rated mammography screening. However, confidence to perform breast self-examination was properly low... [to full text]
Šio darbo tikslas buvo įvertinti atvykusių ir neatvykusių tikrintis mamografiškai moterų nuostatų į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą skirtumus. Tikslui pasiekti iškelti tokie uždaviniai: 1. Įvertinti Champion VL sveikatos įsitikinimų modelio klausimyno tinkamumą tirti Lietuvos moterų nuostatoms į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą. 2. Nustatyti moterų suvoktą krūties vėžio grėsmę, apsaugančios nuo krūties vėžio pasekmių elgsenos naudą ir kliūtis šiai veiklai, sveikos gyvensenos motyvaciją. 3. Palyginti atvykusių ir neatvykusių tirtis mamografiškai dėl krūties vėžio moterų nuostatas į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą. 4. Įvertinti dalyvavusių atrankinėje mamografinėje patikroje dėl krūties vėžio moterų kliūtis tirtis mamografiškai. 5. Ištirti papildomos informacijos apie krūties vėžį, mamografinę patikrą įtaką moterų nuostatoms į krūties vėžį, savityrą bei atrankinę mamografinę patikrą ir moterų dalyvavimui atrankinės patikros programoje. Išvados: 1. Patikrintas ir įteisintas VL Champion sveikatos įsitikinimų modelio skalės klausimynas yra tinkamas Lietuvos moterų nuostatoms į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą tirti. Sveikos gyvensenos motyvacijos skalė turi būti padalinta į požiūrio į sveiką gyvenseną ir veiklos sveikatos labui subskales. Kliūčių tirtis mamografiškai teiginys “reguliarus mamografinis ištyrimas verstų mane nerimauti dėl krūties vėžio” išbrauktas... [toliau žr. visą tekstą]

Background: Behavioral interventions and evidence based guidelines along the cancer control continuum can reduce the burden of cancer. Objectives: This dissertation aims to increase our understanding of colorectal cancer screening (CRCS) decisional conflict and breast cancer survivorship care. This project: 1) assesses CRCS decisional conflict in a general population, 2) uses the Theory of Triadic Influence to model and evaluate direct and indirect associations between CRCS decisional conflict and colonoscopy adherence, 3) assesses post-treatment breast cancer care. Methods: Data from a questionnaire administered to randomly selected adults, 50-75 years, living in six MN communities (N=1,268) and the 2010 Behavioral Risk Factor Surveillance System (BRFSS) (N=1,024, women ages 27-99) were used. Multivariable logistic regression was used to identify characteristics associated with high CRCS decisional conflict; then structural equation modelling (SEM) was performed to assess direct and indirect associations of CRCS decisional conflict and colonoscopy adherence. Using BRFSS data, multivariable logistic regression was performed to assess the association between years since diagnosis and the type of clinician providing the majority of care for breast cancer survivors after treatment completion. Results: Greater colonoscopy barriers (OR=1.04; 95% CI: 1.02-1.05) and CRCS-specific confusion (OR=1.12; 95% CI: 1.10-1.15) as well as a healthcare provider not discussing CRCS options (OR=1.67; 95% CI: 1.18-2.37) were associated with increased odds of high CRCS decisional conflict. A similar relationship was found in the SEM analyses: both greater levels of perceived colonoscopy barriers and CRCS confusion were associated with higher decisional conflict (standardized total effects=0.42 and 0.39, respectively, p-values < 0.01). CRCS decisional conflict was associated with increased non-adherence to colonoscopy. This relationship was mediated by CRCS-specific self-efficacy and intention (standardized total effect=0.14, p-value <0.01). Among breast cancer survivors, women 0–1 and 2–3 years since diagnosis were 2.1-2.6 times more likely to have a cancer-related clinician providing the majority of care compared to women 6+ years since diagnosis (95% CIs: 1.0-4.3; 1.4-4.6). Conclusions: Decreasing colonoscopy barriers and CRCS-specific confusion could decrease CRCS decisional conflict and ultimately increase CRCS uptake. National policies to move breast cancer follow-up care to a primary care provider might be well-received by cancer survivors.

Morbidity and mortality from breast cancer can be reduced by early detection through screening. Despite recommended guidelines for breast screening since 1988, participation rates have been suboptimal. The objectives of the current study were to describe: (1) changes in breast cancer screening knowledge, attitudes, decisional conflict, intentions and practices among women aged 50-69 years since initiation of a regional mass screening program in Ottawa-Carleton in 1991; and (2) breast cancer screening knowledge attitudes, intentions, and practices among women aged 40-49 years compared to women aged 50-69 years. Among women aged 50-69 years, the percentage ever having had a mammogram increased from 60% in 1991 to 83% in 1994. There were commensurate increases in the percentage reporting mammography within two years from 47% to 74%. There was an insignificant improvement in the annual professional breast examination (PBE) rate from 57% to 59%. A small, but statistically significant increase occurred in monthly breast self-examination (BSE) rate from 46% to 54%. Women in their forties continue to overutilize screening mammography; 63% reported ever having had a mammogram and 44% reported having had a mammogram within the past two years. Reported annual PBE and monthly BSE rates of women aged 40-49 years were comparable to the rates of women aged 50-69 years; 63% versus 59% and 48% versus 54% respectively. Intentions to have mammography every two years once they are 50 years and to have annual PBE were similar to those of women 50-69 years, however, they were more likely to accept an invitation to screening (71% versus 56%). Women 40-49 years were more knowledgeable than women 50-69 years while they had similar concerns about future mammography as the women over 50 years. (Abstract shortened by UMI.)

In the US, breast cancer is one of the most common forms of cancer and the most lethal. There are many decisions that must be made by the doctor and/or the patient when dealing with a potential breast cancer. Many of these decisions are made under uncertainty, whether it is the uncertainty related to the progression of the patient's health, or that related to the accuracy of the doctor's tests. Each possible action under consideration can have positive effects, such as a surgery successfully removing a tumour, and negative effects: a post-surgery infection for example. The human mind simply cannot take into account all the variables involved and possible outcomes when making these decisions. In this report, a detailed Partially Observable Markov Decision Process (POMDP) for breast cancer screening decisions is presented. It includes 151 states, covering 144 different cancer states, and 2 competing screening methods. The necessary parameters were first set up using relevant medical literature and a patient history simulator. Then the POMDP was solved optimally for an infinite horizon, using the Perseus algorithm. The resulting policy provided several recommendations for breast cancer screening. The results indicated that clinical breast examinations are important for screening younger women. Regarding the decision to operate on a woman with breast cancer, the policy showed that invasive cancers with either a tumour size above 1.5 cm or which are in metastasis, should be surgically removed as soon as possible. However, the policy also recommended that patients who are certain to be healthy should have a breast biopsy. The cause of this error was explored further and the conclusion was reached that a finite horizon may be more appropriate for this application.

Breast screening is controversial. Despite many supporters and a large evidence base, some experienced breast screening experts disagree with selected policies and practices. I sought to examine the reasoning of people who have influenced breast screening in Australia. I used an empirical ethics approach, combining empirical study with theoretical analysis. I interviewed Australians with expertise and influence in breast screening across a range of professional roles. I found that participants drew on values as well as evidence when talking and reasoning about breast screening. Participants expressed a range of interpretations and prioritisations for each value and experts’ disagreements were based, at least in part, on these differences. Experts did not always acknowledge the role of values in shaping their views or recognise different ways of conceptualising or prioritising values. I recommend including values in decision making for breast screening policy and practice. I provide guidance about formats for values based discussions. I conclude that values play an important but often unrecognised role in shaping breast screening policy and practice, and propose regular review of values to deliver breast screening in the most ethically sound manner.

The introduction of screening mammography in Australia has been associated with an increase in the incidence of early-stage breast cancer. Concern is growing about the problems caused when women are diagnosed with breast cancer and undergo treatments that do not benefit them because their cancer would not progress, or would progress, but would not become symptomatic within the remaining lifetime of the patient. This is known as overdiagnosis. Screening mammography aims to decrease breast cancer morbidity and mortality by advancing in time the diagnosis and thereby increasing the chance of successful treatment. But overdiagnosis and the consequent overtreatment can cause serious lifelong harm and are therefore considered the major downsides of breast screening. Mounting evidence of the extent of overdiagnosis has led to the recognition that the benefits and harms of breast screening are finely balanced, and women need to know the magnitude of the trade-offs. The extent of overdiagnosis due to breast screening is contested, with published estimates ranging from 1% to 57%. There is a critical need for research investigating the harm to benefit ratio in Australia and quantification of the effects of screening mammography on the incidence of stage-specific breast cancer and overdiagnosis. Individual women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. A challenge to estimating this in a randomised controlled trial is nonadherence to the trial protocol. Previous systematic reviews have provided estimates of the effect of receiving an invitation to screening on the risk of dying due to breast cancer. Chapter 2 presents a meta-analysis of the screening mammography trials using a simple adjustment that estimates the probability of a reduction in breast cancer mortality and risk of overdiagnosis due to the effect of receiving screening by regularly participating in a breast screening program. Adjustment for nonadherence increased the size of the size of the effect by up to 50%. The prevented fraction of breast cancer mortality at 13-year follow-up increased from 0.22 to 0.30 with deattenuation. The percentage risk of overdiagnosis during the screening period in women invited to screening increased from 19.0% to 29.7%. From 2013 through 2017, the Australian national breast cancer screening programme gradually invited women aged 70 to 74 years to attend screening, following a policy decision to extend invitations to older women. Yet no formal evaluation of the effects of the change in policy on outcomes for women was undertaken. Building on my meta-analysis, in Chapter 3 I used a Markov model and applied the breast cancer mortality reduction and overdiagnosis estimates reported in Chapter 2 to Australian breast cancer incidence and mortality data to estimate the benefits and harms of the new package of biennial screening from age 50 to 74 compared with the previous programme of screening from age 50 to 69. I found that the extra five years of screening results in approximately seven more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. To identify temporal trends in stage-specific breast cancer in Australia, I used an observational study design to analyse data on women who received a diagnosis of breast cancer from 1972 to 2012 as recorded in the New South Wales Cancer Registry (Chapter 4). I explored trends in stage-specific incidence before screening and compared them to periods after screening began. I found that screening was not associated with lower incidence of late-stage breast cancer at diagnosis and incidence for all stages remained higher than prescreening levels. In women aged 50 to 69 years, the incidence of carcinoma in situ, localised and regional breast cancer has more than doubled compared to the prescreening era. The data presented in Chapter 4 indicate that excess detection of breast cancer is a problem in New South Wales. Thus I designed an ecological study to quantify overdiagnosis. I estimated the background trend of increasing incidence using two approaches, the first based on the prescreening trend in women of screening age (50 years and older), and the second based on the contemporary trend in women too young to be screened (40 to 44 years of age). From these trends, I estimated the expected age-standardised incidence of breast cancer, by stage at diagnosis, in the absence of screening, for women aged 50 years and over in the years since the national screening mammography program, BreastScreen, was introduced (1988 to 2012). I then calculated the difference in observed and expected incidence rates to determine the excess incidence of early-stage breast cancer and reduction in the incidence of late-stage disease. I found that screening mammography has resulted in overdiagnosis of early-stage and regional breast cancer. I estimate that around six additional cases of early and regional breast cancer are detected for every distant metastatic breast cancer prevented. Due to the substantial increase in detection of carcinoma in situ of the breast observed in Chapter 4, I explored sub-types and causes of this. Chapter 6 presents a descriptive analysis of temporal trends in the incidence of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) in women who received a diagnosis from 1972 to 2012, recorded in the NSW Cancer Registry. Carcinoma in situ as a proportion of all breast cancer increased dramatically, and incidence of DCIS across all ages rose from 0.15 per 100,000 during 1972 to 1983 to 16.81 per 100,000 over 2006 to 2012, with the greatest increase seen among women in the target age group for screening (50 to 69 years). DCIS incidence has not stabilized despite screening being well established for over 20 years, and participation rates in the target age range remaining stable. Our observational estimate of overdiagnosis from Chapter 5 is different to those from meta-analyses of randomised controlled trials of screening mammography and some other observational studies. Thus the final paper in this thesis presents a Cochrane Protocol on Overdiagnosis due to screening mammography for women aged 40 years and older (Chapter 7). We present methodology to identify and evaluate all primary epidemiological studies that have quantified overdiagnosis resulting from screening mammography and provide estimates of its frequency (including randomised and observational studies). An approach to assessing the risk of bias due to lead time is also discussed. Trying to quantify the benefits and harms of screening mammography and present them to women using natural frequencies should better enable informed choice, and is consistent with the international shift towards promoting and supporting shared decision making for screening. This thesis provides valuable new evidence about the trade-offs of screening mammography in Australia. The finding that risk of harm is greater than the chance of benefit is consistent with international studies of breast screening and demonstrates the importance of continuing this work to better quantify overdiagnosis for women, clinicians, and policymakers.

Breast cancer is a serious illness that often has fatal consequences. Adherence to the recommendations for breast cancer surveillance is poorly practiced among African American women. The purpose of this phenomenological study was to seek individual professed barriers to breast cancer screening among African American women to better understand why breast cancer continues to be one of the principal basis of mortality among African American women. The theoretical framework for this study was the behavioral model of health services use. Purposeful selection was used to invite 14 African American women to participate in the in-depth interview process. Interview data were transcribed and then coded for recurring themes and meaning. The findings of this study demonstrate that these women's perceived barriers to breast cancer screening were lack of information, a belief that genetics dictates who gets breast cancer, embarrassment, a norm of people not going for health checkups, the procedure of breast cancer screening, and fear. Participants noted that the improved method of mammography may promote utilization within the population. Breast cancer disparities among African American women may decline if healthcare providers promote awareness of the availability and accessibility of breast cancer prevention resources and if African American women understand the barriers to breast cancer prevention and change their own screening practices.

Purpose: This study assessed effectiveness of five tools recommended by the US Preventive Services Task Force (USPSTF), designed to help primary care clinicians determine which unaffected patients to refer to genetics specialists for breast cancer risk assessment based on concerning family history. Design: This descriptive secondary analysis included 85 women aged 40-74. All participants had a first-degree female relative previously diagnosed with breast cancer who also had uninformative negative BRCA1/2 tests. Methods: Each pedigree was evaluated using the five tools including the Family History Screen-7 (FHS-7), Pedigree Assessment Tool (PAT), Manchester Scoring System, Referral Screening Tool (RST), and Ontario-Family History Assessment Tool (Ontario-FHAT). All five tools were applied to each study participant. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to describe each tool’s ability to identify women with elevated risk as calculated by the Claus model. Receiver operating curves (ROC) were also plotted. Differences between areas under the curve (AUCs) for all possible pairs of tools were estimated through logistic regression to assess for differences in tool performance. Results: Claus calculations identified 14 women out of 85 whose lifetime risk of breast cancer was elevated at > 15%. Only two tools, the Ontario-FHAT and FHS-7, identified all 14 women with elevated risk, a sensitivity of 100%. The FHS-7 tool flagged all 85 participants, meaning its specificity was zero. The Ontario-FHAT flagged 59 participants as needing referral (specificity 36.2%) and had a negative predictive value (NPV) of 100%, indicating that if a woman was not found to need a referral to a genetics professional, it is likely she did not have an elevated lifetime risk of developing breast cancer. AUC values were not significantly different between tools (all p values > .05), and thus were not helpful in discriminating between the tools. Conclusion: In this population, the Ontario-FHAT out-performed other tools in terms of sensitivity and negative predictive value; however, low specificity and positive predictive value must be balanced against these findings. Thus, the Ontario-FHAT can help determine which women would benefit from referral to a genetics specialist.

Although the incidence of breast cancer is almost the same for middle-aged African American and Caucasian women, the rate of patients' following breast cancer screening and following up recommendations differs. African American women are less likely to follow recommendations and have higher mortality rates when compared to Caucasian women. One factor thought to affect compliance with breast cancer screening and follow up is culturally sensitive communication. This purpose of this quantitative correlational study was to determine if the culturally sensitive communication of a medical center influenced compliance with breast cancer screening and follow up and if compliance has an effect on the stage of breast cancer when diagnosed for African American women between the ages of 50 and 74. The research questions were aligned with the theoretical pathways of the Patient-Centered Culturally Sensitive Healthcare Model. This quantitative cross-sectional study was based on secondary data of African American women aged 50-74 from electronic systems for each Southern California location of a national health maintenance organization between the years 2012-2016. The results of the regression analysis from averages of the scores from the Member Appraisal of Physician/Provider Services questionnaire, determined associations between the cultural sensitivity scores of the African American woman's medical center and their compliance with recommendations for breast cancer screening and follow up after screening. However, no association between the stage of cancer and medical center's cultural sensitivity was found. Results can be used to develop cultural sensitivity interventions at medical centers aimed to enhance African American women's compliance with breast cancer screening and follow-up recommendations.

In 2009, 713,220 new cases of cancer were diagnosed for women in the United States with more than a quarter million deaths. African American women and lesbians exhibit behavioral risk factors as well as diminished access to and utilization of breast cancer screening that reduces opportunities for early detection. This secondary analysis of a national convenience-based study examined screening compliance among 647 African American lesbian and bisexual women. Barriers to accessing screening represented the theoretical framework for this study. Bivariate chi square analysis was used to assess the association between independent variables: sociodemographic characteristics; participation in wellness activities; sexual orientation/gender identity; and experience with health care providers and the three dependent breast cancer screening compliance variables: breast self-examination (BSE), clinical breast examination (CBE), and mammography screening. Statistically significant associations between dependent and independent variables at the .05 level were further analyzed with logistic regression. Results of the ten regression models found that BSE was predicted by socioeconomic characteristics and participation in wellness activities. Compliance with CBE guidelines was predicted by sociodemographic characteristics, wellness activities, sexual orientation/gender identity and provider experience. Sociodemographic variables and provider experience also predicted mammography screening. Overall compliance was predicted by sociodemographic characteristics, namely insurance status. The social change implications of this research are an improved understanding of African American lesbian and bisexual women's screening behavior and guidance toward interventions that can improve and breast cancer screening compliance with guidelines.

Background: In Lebanon, breast cancer (BC) is the most common cancer among females. Previous studies around the world have shown that early detection through screening can reduce BC mortality and increases the treatment choices. Aim: This thesis explores barriers and facilitators to Lebanese women’s participation in BC screening services. Methods: This aim was achieved by using a mix of qualitative and quantitative methods. A knowledge, attitudes and practices survey was administered with 231 Lebanese women and 17 focus groups discussions were facilitated with 163 women living in eight governorates across Lebanon. 12 interviews were also conducted with key informants, in addition to six women survivors of BC. The health belief model was utilized to structure, guide and explain the thesis findings and analysis. Results: From the different methods used, I obtained some reliable findings regarding Lebanese women’s perceptions, knowledge and beliefs of the barriers and facilitators in accessing BC screening services. Barriers to BC screening include family, knowledge and awareness, perceived susceptibility, healthcare system and experience, self-efficacy, psychological, social, cultural, economic, geographical, as well as religious and fear related factors. Facilitators to screening were related to family, self-motivation and practices, awareness campaigns and knowledge about BC, physicians and healthcare professionals, as well as economic, religious and social factors. Residing in urban areas and being employed, educated or insured influences also women’s participation in BC. Conclusion: There are multiple intertwined factors and identified barriers that simultaneously influence Lebanese women’s decision making process to seek screening. A woman would weigh the different factors, fears and expected outcomes, rather than each element separately. Even when the levels of “ever conducting a mammography test” were relatively high in certain occasions this behavior is not maintained but rather conducted intermittently or on one single occasion in a lifetime. Religion, age, geographical locations and health coverage also play a significant role in influencing women’s decision towards screening. Recommendations: In order to increase women’s participation in BC screening, tackle the identified barriers and capitalize on the facilitators, policies, campaigns and programs can work towards tailoring awareness raising campaigns and adopting more personalized communication and messaging with women, increasing engagement of family members and community-based organizations, placing more attention on women in rural areas, providing psycho-social support for patients and women seeking screening, working on prevention in addition to early detection, encouraging breast self-examination and improving the comfort of mammography experience.

Breast cancer is the second leading cause of cancer death among women in the United States. Nonadherence to recommended screening guidelines and lack of screening contribute to late stage diagnosis and increased morbidity and mortality among racial and ethnic women in the United States. The purpose of this study was to assess breast cancer screening practices, knowledge, and beliefs among Cameroonian immigrant women who were 40 years and older living in the metropolitan Washington, D.C. region. This quantitative cross-sectional study was guided by the health belief model and used the revised version of Champion's health belief model scale. A convenience sample (N=267) responded to a 60-item self-administered online survey that assessed knowledge of breast cancer screening, demographic variables, constructs of the health belief model and adherence (defined as obtaining a mammogram within two years). Data analyses performed included descriptive analysis, correlational and multiple linear regression. Results of this study revealed that increased level of education and self-efficacy were associated with greater knowledge of the benefits of mammography. Additionally, women who had more self-efficacy in obtaining a mammogram, perceived less cultural barriers, lived longer in the United States, and who had a regular healthcare provider were more likely to be adherent. Study findings suggest that positive social change can be achieved by empowering women to take control of their health. Efforts promoting awareness of breast cancer screening guidelines and facilitating access to a regular healthcare provider could significantly increase uptake of screening services and lead to better health outcomes and reduced mortality.

Breast cancer is a leading cause of cancer death in Africa. Hsp90 has been identified as a target for anti-cancer treatments as its inhibition results in the disruption and ubiquitin–proteasome degradation of activated oncoproteins. Currently, there are no US Food and Drug Administration approved Hsp90 inhibitor drugs and existing Hsp90 inhibitors such as geldanamycin and novobiocin are hepatotoxic and display a low affinity for Hsp90, respectively. Therefore, there is a need for the development of Hsp90 inhibitors with improved inhibitory properties. In this study twelve natural compounds bearing a quinone nucleus were screened and characterised for the modulation of Hsp90. The compounds analysed formed three series; the sargaquinoic acid (SQA), naphthoquinone, and pyrroloiminoquinone alkaloid series. Certain compounds exhibited half maximal inhibitory concentrations of between 3.32 μM and 12.4 μM, while others showed no antiproliferative activity at concentrations of up to 500 μM in the MDA-MB-231 breast adenocarcinoma cell line. Immunofluorescence and Western analyses indicated that the modulation of Hsp90 and partner proteins by SQA was more similar to that of novobiocin. Isothermal titration calorimetry analyses suggested that SQA interacted with Hsp90β with a low affinity, and saturation-transfer difference nuclear magnetic resonance confirmed that this interaction with Hsp90β occurred through the methyl moiety bound to 1, 4 benzoquinone of SQA. Pulldown assays indicated SQA disrupted the association between Hsp90 and Hop dose-dependently, more similarly to novobiocin. Immunofluorescence and Western analyses performed on naphthoquinone and pyrroloiminoquinone alkaloid compounds indicated modulation of Hsp90 and Hsp90 partner proteins by the compounds. Naphthoquinone compounds were prioritised for analysis for binding to Hsp90β over the pyrroloiminoquinone alkaloid compounds. Lapachol interacted with Hsp90β with a low affinity however; this interaction was thought to be too weak to disrupt the association of Hsp90 and Hop. The remaining naphthoquinone compounds showed no interaction with Hsp90β, thus allowing the determination of a preliminary structure-activity relationship for these compounds. To the best of our knowledge, this is the first study to describe a systematic subcellular analysis of the effects of geldanamycin and novobiocin in comparison to sargaquinoic acid and compounds of the naphthoquinone and pyrroloquinoline scaffold on Hsp90 and its partner proteins.
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Cancer is the second leading cause of death among the world and it has an increasing share among all causes of death. Economical burden of cancer is increasing especially in high and middle-income countries. Leaving cancer in competitive markets would lead to inefficiencies
hence governments should intervene in the market and make public decisions in struggling cancer. Among all cancer types breast cancer has the highest incidence and mortality rates in females. Causes of breast cancer still remains indeterminate and only way to cope with breast cancer are by early diagnoses. Early diagnoses can best be achieved by regular mammography screenings. This study analyzes the possible outcomes of implementing regular breast cancer mammography screening program in Turkey. A simulation model is constructed and run for 10 years, to obtain the costs and benefits of such a screening program. Costs of such a program include the screening costs and costs due to abnormal mammograms. Benefits, on the other hand are reduced treatment costs due to early diagnosis, reduced mortality and morbidity. Simulation model is run for 11 different screening strategies for determining the optimal screening strategy in terms of screening interval and minimum age to screen. The necessary data is obtained from hospital records, Cancer Early Diagnosis and Treatment Center records, IMF, WHO and TUIK databases and literature. Results of the simulation suggest that women over 40 in Turkey should be screened biennially for economical efficiency.

Background The debate regarding the lower age limit for mammography service screening is old and lively; a product in part of the lower breast cancer risk in younger ages as well as the limited data available for studies of the younger age group. Recently the idea of inviting only high risk groups has gained momentum, however high risk might not be equivalent to greater benefit from screening. Therefore, there is a need for information on effectiveness of screening as it relates to young women and to specific risk groups. To this end, this thesis evaluates mammography screening for the age group – 40 to 49 year old women – in terms of breast cancer mortality reduction in total and in subgroups based on breast cancer risk factors. Overdiagnosis of mammography screening is also evaluated for women 40 to 49 years old. In addition, this thesis presents a statistical method to estimate this effectiveness and to test for differences in effectiveness between subgroups adjusted for non-compliance and contamination. Methods The studies of this thesis are based on data from the Screening of Young Women (SCRY) database. The SCRY database consists of detailed information on diagnosis, death, screening exposure and risk factors for breast cancer cases and population size by year (between 1986 and 2005) and municipality for women in Sweden between 40 and 49 years old. The material was divided into a study group consisting of the counties that invited women in the age group 40-49 years to mammography screening, and a contemporaneous control group consisting of the counties that did not. Effectiveness was estimated in terms of rate ratios for two different exposures (invitation to and participation in screening), and overdiagnosis for subsequent screening was estimated adjusting for lead time bias. Defining a reference period enabled adjustment for possible underlying differences in breast cancer mortality and incidence. A statistical model for adjusting for non-compliance and contamination in randomised controlled trials was further developed to allow for adjustment in cohort studies using a Poisson model with log-linear structure for exposure and background risk. Results During the study period (1986-2005), there were 619 and 1205 breast cancer deaths and 6047 and 7790 breast cancer cases in the study group and the control groups, respectively. For women between 40 and 49 years old, the breast cancer mortality reduction was estimated at 26% [95% CI, 17 to 34%] for invited to screening and 29% [95% CI, 20 to 38%] for attending screening. The RR estimates for the high-risk groups based on the risk factors parity, age at birth of first child, and socio-economic status were equal to or higher than that of the low risk groups. The new statistical method showed that the decrease in effectiveness with parity was not a statistically significant trend. The overdiagnosis from subsequent screening for 40 to 49 year old women was estimated at 1% [95 % CI, -6 to 8 %] (i.e., not statistically significant). Conclusion Subgroup specific effectiveness was also estimated. The relative effectiveness of screening for breast cancer with mammography for women age 40 to 49 years appears to be comparable to that for older women. These findings and the fact that there was no statistically significant overdiagnosis from subsequent screening speak for inviting women 40 to 49 years old to screening. High-risk screening for nulliparous women aged 40 to 49 years, for example, might be an alternative in countries where population-based screening for all women between 40 and 49 years old is not possible. However, the matter of risk factors and the effect of their combinations is complex and risk group screening presents ethical and practical difficulties. The new statistical model is a useful tool for analysing cohorts with exposed and non-exposed populations where non-compliance and contamination is a potential source of bias.

Introducció: S'ha demostrat que el cribratge mamogràfic redueix la mortalitat per càncer de mama. Seguint les recomanacions de la Comissió Europea, els països europeus han establert programes poblacionals de cribratge que ofereixen mamografies biennals a dones d'entre 50 i 69 anys d'edat. No obstant això, el cribratge de càncer de mama no està lliure de controvèrsia ja que existeix un debat en relació a l'equilibri entre la reducció de la mortalitat i els efectes adversos. Per a millorar aquest equilibri, l'evidència científica actual dóna suport al cribratge personalitzat. Els estudis de modelització han demostrat que modificar l'interval de cribratge, la prova de cribratge o el rang d'edat de la població objectiu en funció del risc individual de les dones produeix un major benefici que les estratègies convencionals. Per tant, és necessari ampliar la informació actual sobre els factors de risc d'aquesta malaltia i crear models de predicció del risc individual mitjançant l'anàlisi de grans bases de dades poblacionals. Objectiu: L'objectiu general d'aquesta tesi és aprofundir en l'anàlisi del cribratge poblacional del càncer de mama. En concret, aquesta tesi pretén avaluar diferents factors de risc de càncer de mama per a desenvolupar i validar un model de predicció de risc individual d'aquesta malaltia. Es va analitzar com la densitat mamària afecta als diferents indicadors del cribratge en el context de la mamografia digital. A continuació, es van avaluar les diferències en el risc de càncer de mama en funció de si una lesió benigna de mama es va diagnosticar en un cribratge prevalent o un cribratge incident. També es va analitzar la interacció entre la densitat mamària i les lesions benignes en el risc de desenvolupar càncer de mama. Posteriorment, es va realitzar una revisió sistemàtica per a actualitzar l'evidència existent, dur a terme una valoració crítica i una avaluació del risc de biaix i resumir els resultats dels models de risc individualitzats que s'utilitzen per a estimar el risc de càncer de mama en les dones de la població general. Finalment, es va dissenyar un model de predicció individual del risc de càncer de mama i es va validar internament, a partir d'informació fàcilment accessible en un episodi de cribratge. Conclusions: i) Els diferents indicadors de cribratge es veuen afectats negativament per la densitat mamària, disminuint la sensibilitat i el valor predictiu positiu de la prova a mesura que augmenta la densitat mamària. ii) El risc de càncer de mama conferit per una lesió benigna difereix segons la mena de cribratge (prevalent o incident). Fins on sabem, aquest és el primer estudi que analitza l'impacte del tipus de cribratge en el pronòstic de la lesió benigna. iii) El risc de càncer de mama augmenta de manera independent amb la presència d'una lesió benigna i amb una major densitat mamària i es manté elevat durant més de 15 anys. iv) Els models de predicció són eines prometedores per a implementar polítiques de cribratge basades en el risc individualitzat. No obstant això, és un repte recomanar qualsevol d'ells per a la personalització del cribratge ja que necessiten millorar la seva qualitat i capacitat discriminatòria. v) Es va dissenyar i validar internament un model de predicció de risc capaç d'estimar el risc de càncer de mama a curt i llarg termini utilitzant la informació recollida de manera rutinària en el cribratge mamogràfic. El model inclou edat, antecedents familiars de càncer de mama, antecedents de lesió benigna i patrons mamogràfics previs, que van resultar estar relacionats amb un augment del risc de càncer de mama. El model ha de ser validat externament i actualitzat amb noves variables.
Introducción: Se ha demostrado que el cribado mamográfico reduce la mortalidad por cáncer de mama. Siguiendo las recomendaciones de la Comisión Europea, los países europeos han establecido programas poblacionales de cribado que ofrecen mamografías bienales a mujeres de entre 50 y 69 años de edad. Sin embargo, el cribado de cáncer de mama no está libre de controversia ya que existe un debate en cuanto al equilibrio entre la reducción de la mortalidad y los efectos adversos. Para mejorar este equilibrio, la evidencia científica actual apoya el cribado personalizado. Los estudios de modelización han demostrado que modificar el intervalo de cribado, la prueba de cribado o el rango de edad de la población objetivo en función del riesgo individual de las mujeres produce un mayor beneficio que las estrategias convencionales. Por lo tanto, es necesario ampliar la información actual sobre los factores de riesgo de esta enfermedad y crear modelos de predicción del riesgo individual mediante el análisis de grandes bases de datos poblacionales. Objetivo: El objetivo general de esta tesis es profundizar en el análisis del cribado poblacional del cáncer de mama. En concreto, esta tesis pretende evaluar diferentes factores de riesgo de cáncer de mama para desarrollar y validar un modelo de predicción de riesgo individual de esta enfermedad. Se analizó cómo la densidad mamaria afecta a los distintos indicadores de cribado en el contexto de la mamografía digital. A continuación, se evaluaron las diferencias en el riesgo de cáncer de mama en función de si una lesión benigna de mama se diagnosticó en un cribado prevalente o un cribado incidente. También se analizó la interacción entre la densidad mamaria y las lesiones benignas en el riesgo de cáncer de mama. Posteriormente, se realizó una revisión sistemática para actualizar la evidencia existente, llevar a cabo una valoración crítica y una evaluación del riesgo de sesgo y resumir los resultados de los modelos de riesgo individualizados que se utilizan para estimar el riesgo de cáncer de mama en las mujeres de la población general. Por último, se diseñó un modelo de predicción individual del riesgo de cáncer de mama y se validó internamente, basado en información fácilmente accesible en un episodio de cribado. Conclusiones: i) Los distintos indicadores de cribado se ven afectados negativamente por la densidad mamaria, disminuyendo la sensibilidad y el valor predictivo positivo de la prueba a medida que aumenta la densidad mamaria. ii) El riesgo de cáncer de mama conferido por una lesión benigna difiere según el tipo de cribado (prevalente o incidente). Hasta donde sabemos, este es el primer estudio que analiza el impacto del tipo de cribado en el pronóstico de la lesión benigna. iii) El riesgo de cáncer de mama aumenta de forma independiente con la presencia de una lesión benigna y con una mayor densidad mamaria y se mantiene elevado durante más de 15 años. iv) Los modelos de predicción son herramientas prometedoras para implementar políticas de cribado basadas en el riesgo individualizado. Sin embargo, es un reto recomendar cualquiera de ellos para la personalización del cribado ya que necesitan mejorar su calidad y capacidad discriminatoria. v) Diseñamos y validamos internamente un modelo de predicción de riesgo capaz de estimar el riesgo de cáncer de mama a corto y largo plazo utilizando la información recogida de forma rutinaria en el cribado mamográfico. El modelo incluye edad, antecedentes familiares de cáncer de mama, antecedentes de lesión benigna y patrones mamográficos previos, que resultaron estar relacionados con un aumento del riesgo de cáncer de mama. El modelo debe ser validado externamente y actualizado con nuevas variables.
Background: Mammographic screening has been shown to reduce mortality from breast cancer. Following the recommendations of the European Council, European countries have started population-based screening programs that offer biennial mammograms to women aged between 50 and 69 years. The results of the effectiveness of population-based screening are controversial in terms of the balance between mortality reduction and adverse effects. To improve this balance, current evidence supports personalized screening. Modeling studies have shown that modifying the screening interval, screening modality, or age range of the target population based on women's individual risk yields a greater benefit than conventional standard strategies. Several risk models have been designed to estimate women's individual breast cancer risk based on their personal characteristics. However, most of these models have not been specifically developed to estimate the risk of women targeted for breast cancer screening. There is therefore a need to broaden current information on risk factors for breast cancer and the estimation of individual risk prediction models through the analysis of large population-based databases. Aims: The general objective of the thesis is to deepen the analysis of population-based breast cancer screening. Specifically, the aim of this thesis is to assess different breast cancer risk factors in order to develop and validate an individualized breast cancer risk prediction model. We evaluated how breast density affects screening performance indicators in a digital mammography context. Then, we assessed differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens. To our knowledge, this is the first time that such an approach has been used. We also evaluated the interaction between breast density and benign breast disease. Subsequently, we performed a systematic review to update the existing evidence, conduct a critical appraisal and risk of bias assessment and summarize the results of the individualized risk models that are used to estimate the risk of breast cancer in women in the general population. Finally, a breast cancer risk prediction model was designed and internally validated, based on information easily accessible at screening. Conclusions: i) Performance screening measures are negatively affected by breast density, with sensitivity and positive predictive value decreasing as breast density increases. ii) The risk of breast cancer conferred by benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyze the impact of screening type on the prognosis of benign breast disease. iii) The risk of breast cancer independently increased with the presence of benign breast disease and with greater breast density and remained elevated for over 15 years. iv) Individualized risk prediction models are promising tools for implementing risk-based screening policies. However, it is a challenge to recommend any of them since they need further improvement in their quality and discriminatory capacity. v) We designed and internally validated a risk prediction model able to estimate short- and long-term breast cancer risk using information routinely reported at screening participation. The model included age, family history of breast cancer, benign breast disease and previous mammographic findings, which were found to be related to an increase in breast cancer risk. The model should be externally validated and updated with new variables.
Universitat Autònoma de Barcelona. Programa de Doctorat en Metodologia de la Recerca Biomèdica i Salut Pública

In 2014, breast cancer was the second leading cause of death among Canadian women, with women over age 50 years making up 82% of the identified cases. To address this issue, the Ontario Breast Screening Program developed a media campaign that promoted the benefits of mammogram screening, but not the associated risks (i.e., false-positive, false-negative, radiation exposure, and overdiagnosis). This study was designed to determine whether there was a statistically significant relationship between knowledge of overdiagnosis and participation in mammogram screening. This cross-sectional, correlational study used schema theory supported by the effective health communication model. Forty-one women were invited to listen to a brief presentation on the benefits and risks of screening mammograms and then completed a modified Champion Health Belief Model Scale survey. Two sample t tests and logistic regression analyses of the survey scores showed that the data did not support any correlations with education and screening, but did indicate a correlation between overdiagnosis and participation. The less a participant felt that overdiagnosis was a negative consequence, the more likely they were to participate in breast screening. Survey participants also stated that promotions of mammograms should present balanced information about the benefits and risks of screening. The positive social change and policy implications of this study include providing women aged 50-69 years more information on overdiagnosis in mammograms so they are more informed participants in the decision-making process, and educating Ontario government policymakers with information about the barriers that women aged 50-69 years face in getting balanced information on mammography programs.

Breast cancer is one of the most widespread chronic diseases and a major cause of death among women in the United States. African American women have a higher incidence of breast cancer than their counterparts from other ethnic/racial groups. The purpose of this cross-sectional survey of 126 African American females from the western US metropolitan area was to assess knowledge, attitudes, and behavior with respect to breast cancer manifestation, detection services, and the role of mammography in breast cancer prevention and control. The health belief model guided this study. A 41-item, ethnically sensitive, self-administered, and gender-specific instrument, the Champion Revised Susceptibility, Benefits, and Barriers Scale for Mammography Screening, was used in this study. Analysis of variance, the Scheffe post hoc tests, and Fisher's exact test were used to analyze the data. The results showed that all but three participants (97.6%) reported having had breast cancer screening; almost all of the participants were compliant and answered the knowledge question. The findings also showed that the women with high levels of education reported lower benefits of mammography scores and lower barriers to mammography scores; and higher cues to action scores. Income was not significantly related to attitude toward breast cancer screening. The implication for positive social change is that these results may help to facilitate continued development of intervention strategies to encourage African American women to utilize early breast cancer detection services.

Background: Indigenous Australians have lower breast cancer rates but higher mortality rates compared with other women. With evidence of ethnic variations in MD globally, investigating MD in Indigenous women may provide insight into optimising diagnosis and care for an underserved population. Aims: To investigate the MD and BreastScreen attendance of Indigenous and non-Indigenous women in the NT and assess the diagnostic efficacy of radiologists in cases with varying breast densities. Methods: Indigenous status, age, postcode, HRT, family history of breast cancer, symptoms and language spoken at home from self-reported 857 Indigenous and 3236 non-Indigenous women were analysed for associations with MD (study 1) and screening attendance (study 2). ROC analyses were used to determine cut-off points for age and numbers of screening visits. Logistic regression analyses were used to determine odds ratios and p≤0.05 were considered significant. In study 3, mammography test scores of 273 radiologists were assessed on low MD (LMD) vs high MD (HMD) cases. Sensitivity, lesion sensitivity, specificity, ROC and JAFROC FOM were compared using Mann-Whitney U or unpaired t-tests. Results: MD was lower for Indigenous women. For non-Indigenous women, HMD was associated with ≤55 years of age, no family history of breast cancer, speaking mainly English, and living remotely. For Indigenous women, HMD was associated with younger age. Indigenous women have fewer visits to screening and non-English speaking was mainly associated for Indigenous women only. Remoteness was associated with fewer visits for non-Indigenous women only. Shared predictors were ≤55 years and no family history of breast cancer. Radiologists had better lesion sensitivity and specificity in LMD vs HMD cases in 3 of 5 tests. ROC and JAFROC were better in LMD vs HMD cases for 1 of 5 tests. Conclusions: Indigenous women have lower MD and lower attendance to BreastScreen than non-Indigenous women. Breast cancer detection is more effective in LMD cases indicating that Indigenous women would benefit from better program engagement given their density profile and high death rates from breast cancer.

In Australia, early detection plays a leading role in reducing mortality from breast cancer. Little is known about how Chinese-Australian women engage in breast cancer screenings. This study aimed to investigate breast cancer screening practices and the associated factors amongst Chinese-Australian women. A cross-sectional quantitative method including convenient and snowball sampling was used to recruit 115 Chinese-Australian women living in Sydney (aged 35 years and older). The data was collected by self-administered questionnaires between July and September 2016. The results showed that the majority of participants performed breast self-examinations (78.1%), clinical breast examinations (69.8%) and mammograms (73.3%). Educational level was positively associated with having a breast self-examination. Age, religion, employment status and length of residence were significantly associated with performing a clinical breast examination. Income was related to having a mammogram. Significant associations between knowledge of breast cancer, cancer-related beliefs, and screening participation were also found. The length of residence was the strongest predictor of having a clinical breast examination and mammogram. The most common barrier to mammography screening was that doctors did not recommend it to participants. These findings can be used to develop tailored programs to promote the early detection of breast cancer among Chinese–Australian women.

Despite the existence of breast cancer screening that could promote early diagnosis and survival of breast cancer, high mortality rates of breast cancer persist among Filipino women. The purpose of the qualitative study was to describe the perceptions, beliefs, and behaviors of Filipino women working as Overseas Filipino Workers (OFWs) in Saudi Arabia. Face-to-face interviews were conducted with 20 Filipino women between the ages of 40 to 60 years who were recruited voluntarily using purposeful sampling technique. Guided by the structures of health belief model (HBM), the study used an inductive coding technique to elicit common themes from the raw data. The study established that the participants' screening behaviors were influenced by family history of breast cancer, the financial and emotional burden of the disease and its treatment, the benefit of early detection, mobility to participate, culture and language barriers, and the social media. The study also demonstrated that the desire to participate in breast cancer screening is influenced by the participants' perception of susceptibility and perception of severity to breast cancer. The findings of the study could create a positive social change as it may inform the practice of public health providers, influence the drafting of informed policies for comprehensive breast health care, and improve access to preventive health services for Filipino women OFWs. Furthermore, the study could empower Filipino women in their personal health decision making, especially when working in other countries where good health is the working capital and a precondition for survival.

Breast cancer, the most common malignancy diagnosed in women, is one of the leading causes of death in women worldwide. In South Africa only 32% of women diagnosed with advanced breast cancer survive more than five years. The search for new chemotherapeutic agents capable of effectively treating breast cancer is therefore essential. Recent evidence supporting the cancer stem cell theory of cancer development for breast cancer challenges the current theories of cancer development and hence treatment. Cancer stem cells are a small subpopulation of tumour cells that possess properties of both cancer cells and stem cells and are believed to be the tumour-initiating population of many cancers. Cancer stem cells are inherently resistant to many chemotherapeutic agents and in this way have been associated with repopulation of tumours after chemotherapy. This phenomenon is proposed as a possible mechanism for cancer relapse after treatment. Cancer stem cells have also been implicated in metastasis, the major cause of mortality in cancer patients. Therefore, any treatment that is capable of targeting and removing breast cancer stem cells may have the theoretical potential to effectively treat breast cancer. However, there are currently no such treatments available for clinical use. We were provided access to a library of novel indigenous small molecules isolated from red and brown algae found off the Eastern Cape of South Africa. The aim of this project was to analyse the anti-cancer and anti-cancer stem cell properties of the compounds in this library and to identify „hit‟ compounds which could form the basis for future development into new anti-cancer drugs. Ten novel compounds of algal origin were tested for cytotoxicity, by determining their ability to inhibit the growth of MCF12A breast epithelial cells and MCF7 breast cancer cells using the colorimetric MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assay. All but one of the compounds tested exhibited cytotoxicity towards the MCF7 cancer cell line, with IC50 values (the concentration of the compound that leads to a 50% inhibition in cell growth) of between 3 μM and 90 μM. The chemotherapeutic drug paclitaxel was used as a positive control. Four of the compounds (RUMB-001, RUMB-002, RUMB-007 and RUMB-010/saragaquinoic acid) were significantly more toxic to the MCF7 cancer cell line, than the „normal‟ MCF12A breast cells and were selected as priority compounds for further analyses. In addition, two other compounds were selected as priority compounds, one highly cytotoxic towards both MCF12A and MCF7 cell lines (RUMB-015) and one which was non toxic to either cell line (RUMB-017/018). Preliminary studies into the mechanism of cytotoxicity using Western blot analysis for poly (ADP-ribose) polymerase (PARP) cleavage and Hoechst 33342 immunostaining in MCF-7 cells were largely unsuccessful. The Hoechst 33342 immunostaining assay did provide tentative evidence that selected priority compounds were capable of inducing apoptosis, although these assays will need to be repeated using a less subjective assay to confirm the results. The priority compounds were subsequently investigated for their cytotoxic effect on the cancer stem cell-enriched side population in MCF7 cells. The ability of the priority compounds to selectively target the cancer stem cell containing side population was assessed using two complementary flow cytometry-based techniques – namely the Hoechst 33342-exclusion assay, and fluorescent immunostaining for the expression of the putative cancer stem cell marker, ABCG2+. The ABCG2+ staining assay was a novel technique developed during the course of this study. It remains to be fully validated, but it may provide a new and reliable way to identify and analyse cancer stem cell containing side population cells. The MCF7 cells were treated with the compounds and the proportion of putative cancer stem cells compared with the size of the population in untreated cells was assessed. Three compounds (RUMB-010, RUMB-015 and RUMB-017/018) capable of reducing the proportion of side population cells within the MCF7 cell line were identified. Taking these data together, we identified two potential „hit‟ compounds which should be prioritised for future research. These are compounds RUMB-010/sargaquinoic acid and RUMB-017/018. RUMB-010 is of interest as it was shown to target the putative cancer stem cell population, in addition to the bulk MCF7 tumour line, but was relatively less toxic to the „normal‟ MCF12A cell line. RUMB-017/018 is of interest due to the ability to selectively target the cancer stem cell enriched side population, while having little effect on the normal (MCF12A) or bulk tumour (MCF7) cell lines tested. These compounds will be important as „hit‟ compounds for drug development and as tool compounds to study cancer and cancer stem cell biology.

Autophagy is one of the major responses to stress in eukaryotic cells and is implicated in several pathological conditions such as infections, neurodegenerative diseases and cancer. Interestingly, cancer cells take full advantage of autophagy both to support tumor growth in adverse microenvironments and to oppose damages induced by anti-neoplastic therapies. Importantly, different human oncogenes are able to modulate this survival mechanism to support the transformation process, ultimately leading to “autophagy addiction”. Still, oncogenic signaling events, impinging on the control of autophagy, are poorly characterized, limiting our possibilities to take advantage of these mechanisms for therapeutic purposes. Here, we screened a library of activated kinases for their ability to stimulate autophagy. By this approach, we identified novel potential regulators of the autophagic process and, among them, the IKBKE oncogene. Specifically, we demonstrate that this oncoprotein is able to stimulate autophagy when overexpressed, an event frequently found in breast tumors, and that its activity is strictly required for breast cancer cells to support the autophagic process. Interestingly, different oncogenic pathways typically involved in breast cancer, namely ERBB2 and PI3K-AKT-MTOR, also rely on IKBKE to control this process. Ultimately, we show that IKBKE-dependent autophagy is necessary for breast cancer cell proliferation, suggesting an important supporting role for this oncogene and autophagy in these tumors.