Stochastic Decision Modeling to Improve Breast Cancer Preventive Care

Breast cancer is a leading cause of premature mortality among women in the United States. Breast cancer screening tests can help with detecting breast cancer in early stages and thereby reducing the breast cancer mortality risk. However, due to the imperfect nature of screening tests, there is always some associated overdiagnosis, false positives, and false negatives risks. Therefore, to improve breast cancer preventive care, we defined the focus of this dissertation on modeling breast cancer screening decisions.Breast cancer overdiagnosis is the first issue that is addressed in this dissertation. Although overdiagnosis is known to be the major risk inherent in mammography screening; currently there is no way to distinguish between overdiagnosed cancers and the ones that would cause problems over a patient’s lifetime. Overdiagnosis risk significantly depends on a patient’s compliance with screening recommendations. In Chapter 2, we use a stochastic framework to perform a harm-benefit analysis to compare the overdiagnosis risk with the benefits that breast cancer screening provides. In addition, we estimate the lifetime mortality risk of breast cancer while considering the overdiagnosis risk and the uncertainty in a patient’s adherence behavior. Our results show that, although overdiagnosis rate is relatively high in breast cancer screening, the benefits of breast cancer mammography screening outweigh the overdiagnosis risk.The second issue that is addressed in this dissertation is false negative results caused by density of breast tissue. Breast density is known to increase breast cancer risk and decrease mammography screening sensitivity. Breast density notification laws, require physicians to inform women with high breast density of these potential risks. The laws usually require healthcare providers to notify patients of the possibility of using more sensitive supplemental screening tests (e.g., ultrasound). Since the enactment of the laws, there have been controversial debates over i) their implementations due to the potential radiologists bias in breast density classification of mammogram images and ii) the necessity of supplemental screenings for all patients with high breast density. Breast density is a dynamic risk factor. Therefore, in the third chapter, we apply a hidden Markov model (HMM) on a sparse unbalanced longitudinal data to quantify the yearly progression of breast density based on Breast Imaging Reporting and Data System (BI-RADs) classifications.In Chapter 4, we use the results from previous chapter to investigate the effectiveness of supplemental screening and the impact of radiologists’ bias on patients’ outcomes under the breast density notification law. We consider the conditional probability of eventually detecting breast cancer in early states given that the patient develops breast cancer in her lifetime and the expected number of supplemental tests as patient’s outcome. Our results indicate that referring patients to a supplemental test solely based on their breast density may not necessarily improve their health outcomes and other risk factors need to be considered when making such referrals. Additionally, average-skilled radiologists’ performances are shown to be comparable with the performance of a perfect radiologist

Defining and Estimating Intervention Effects for Groups that will Develop an Auxiliary Outcome

It has recently become popular to define treatment effects for subsets of the target population characterized by variables not observable at the time a treatment decision is made. Characterizing and estimating such treatment effects is tricky; the most popular but naive approach inappropriately adjusts for variables affected by treatment and so is biased. We consider several appropriate ways to formalize the effects: principal stratification, stratification on a single potential auxiliary variable, stratification on an observed auxiliary variable and stratification on expected levels of auxiliary variables. We then outline identifying assumptions for each type of estimand. We evaluate the utility of these estimands and estimation procedures for decision making and understanding causal processes, contrasting them with the concepts of direct and indirect effects. We motivate our development with examples from nephrology and cancer screening, and use simulated data and real data on cancer screening to illustrate the estimation methods.Comment: Published at http://dx.doi.org/10.1214/088342306000000655 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

The WISDOM Study: breaking the deadlock in the breast cancer screening debate.

There are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions-whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age-have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman's specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy makers, technology companies and payers to help break the deadlock in this debate and advance towards a new, dynamic approach to breast cancer screening

EPMA position paper in cancer:current overview and future perspectives

At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision

Overdiagnosis due to screening mammography for women aged 40 years and over

This is a protocol for a Cochrane Review. The objective was to assess the effect of screening mammography for breast cancer on overdiagnosis in women aged 40 years and older at average risk of breast cancer

Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases

Background: Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening. Methods: Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy. Results: In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7%; 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade. Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions. Conclusion: The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into groups with significantly different risks of malignancy. Biopsy assessment of appropriately selected microcalcifications is an effective method of detecting invasive breast cancer and DCIS, particularly of non-low-grade subtypes.G Farshid, T Sullivan, P Downey, P G Gill, and S Pieters

Changes over time in socioeconomic inequalities in breast and rectal cancer survival in England and Wales during a 32-year period (1973-2004): the potential role of health care.

BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but they vary for different cancers and over time. Reasons for these differences are poorly understood. PATIENTS AND METHODS: For England and Wales, we examined trends in socioeconomic survival inequalities for breast cancer in women and rectal cancer in men during the 32-year period 1973-2004. We used a theoretical framework based on Victora's 'inverse equity' law, under which survival inequalities could change with the advent of successive new treatments, of varying effectiveness, which are disseminated with different speed among patients of different socioeconomic groups. We estimated 5-year relative survival for patients of different deprivation quintiles and examined trends in survival inequalities in light of major treatment innovations. RESULTS: Inequalities in breast cancer survival (921,611 cases) narrowed steadily during the study (from -10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases) widened overall (form -5% to -11%) with fluctuating periods of narrowing inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient factors are unlikely explanations of observed changes over time in survival inequalities. The sequential introduction into clinical practice of new treatments of progressively smaller incremental benefit may partly explain the reduction in inequality in breast cancer survival

Estimating The Costs And Cost-effectiveness Of Promoting Mammography Screening Among US-based Latinas

Purpose: We characterize the costs and cost-effectiveness of a community health worker (CHW)-based intervention to promote screening mammography among US-based non-adherent Latinas. Methods: The parent study was a randomized controlled trial for 536 Latinas aged 42-74 years old who had sought care within a safety net health center in Western Washington. Participants were block-randomized within clinic to the control arm (usual care) or intervention arm (CHW-led motivational interviewing intervention). We used the perspective of the organization implementing promotional activities to characterize costs and cost-effectiveness. Cost data were categorized as program set-up and maintenance (initial training, booster/annual training) program implementation (administrative activities, intervention delivery); and, overhead/miscellaneous expenses. Cost-effectiveness was calculated as the incremental cost of screening for each additional woman screened between the intervention and control arms. Results: The respective costs per participant for standard care and the intervention arm were $69.96 and$300.99. There were no study arm differences in 1-year QALYs among women who completed a 12-month follow-up survey (intervention= 0.8827, standard care = 0.8841). Most costs pertained to program implementation and administrative activities specifically. The incremental cost per additional woman screened was $2,595.32. Conclusions: Our findings are within the ranges of costs and cost-effectiveness for other CHW programs to promote screening mammography among underserved populations. Our strong study design and focus on non-adherent women provides important strengths to this body of work, especially give implementation and dissemination science efforts regarding CHW-based health promotion for health disparity populations

Feasibility Pilot Outcomes of a Mammography Decision Support and Navigation Intervention for Women With Serious Mental Illness Living in Supportive Housing Settings.

Objective: People with serious mental illness (SMI) experience significant disparities in morbidity and mortality from preventable and treatable medical conditions. Women with SMI have low mammography screening rates. SMI, poverty, and poor access to care can have a significant effect on a woman’s opportunity to learn about and discuss breast cancer screening with health care providers. This study examines the feasibility pilot outcomes of mammography decision support and patient navigation intervention (DSNI) for women with SMI living in supportive housing settings. The primary research question was: Does the DSNI increase knowledge, promote favorable attitudes, and decrease decisional conflict relating to screening mammography? Methods: We developed the intervention with the community using participatory methods. Women (n = 21) with SMI who had not undergone screening mammography in the past year participated in an educational module and decision counseling session and received patient navigation over a 6-month period. We conducted surveys and interviews at baseline and follow-ups to assess mammography decisional conflict. Results: Among study participants, 67% received a mammogram. The mammogram DSNI was feasible and acceptable to women with SMI living in supportive housing settings. From baseline to 1-month follow-up, decisional conflict decreased significantly (P= .01). The patient navigation process resulted in 270 attempted contacts (M= 12.86, SD = 10.61) by study staff (phone calls and emails with patient and/or case manager) and 165 navigation conversations (M= 7.86, SD = 4.84). A barrier to navigation was phone communication, with in-person navigation being more successful. Participants reported they found the intervention helpful and made suggestions for further improvement. Conclusions: The process and outcomes evaluation support the feasibility and acceptability of the mammography DSNI. This project provides initial evidence that an intervention developed with participatory methods can improve cancer screening outcomes in supportive housing programs for people with SMI