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

Toma de decisión en la prevención del cáncer de mama

Breast cancer is one of the most common cancers among women and the leading cause of death in women between the ages of 45-60 in most developed countries. The efficacy of prevention options has been established and includes lifestyle modifications, chemoprevention, and prophylactic surgery. Despite the efficacy of these options, breast cancer prevention remains underused, resulting in avoidable morbidity and mortality. Here, the main barriers to effective use of breast cancer prevention are outlined and a framework to facilitate patient-centered and evidence-based breast cancer prevention decision making is presented. The framework is intended to encourage a shared decision making approach to prevention decisions, within the context of a woman’s overall health. The inclusion of effective lifestyle interventions makes this framework relevant to most women, and is not exclusive to women at increased risk of developing breast cancer.El cáncer de mama es uno de los canceres más comunes y la causa principal de muerte entre las mujeres de las edades de 45 a 60 en la mayoría de los países desarrollados. La eficacia de las opciones preventivas están bien determinadas e incluyen modificaciones en el estilo de vida, quimioprevención y cirugía profiláctica. A pesar de la eficacia de estas opciones, los medios preventivos están infrautilizados, con resultados de morbilidad y mortalidad que podrían evitarse. En el presente trabajo, se exponen las barreras principales del uso efectivo de los medios de prevención del cáncer de mama y se presenta un encuadre para tomar decisiones en la prevención del cáncer de mama centradas en el paciente y basado en datos acerca de su eficacia. Este encuadre se propone para estimular una aproximación a la toma de decisiones compartida en el contexto de la salud global de la mujer. La inclusión de intervenciones efectivas sobre el estilo de vida hace que este encuadre sea relevante para la mayor parte de las mujeres y no sea exclusivo de las que tengan alto riesgo de cáncer de mama

Development of a Personalized Decision Aid for Breast Cancer Risk Reduction and Management

Background: Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Methods: Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Results: Overall, the evaluations were favorable. The patient focus group evaluations and usability testing (N = 34) provided qualitative feedback about format and design; 88% of these participants found the tool useful and 94% found it easy to use. 91% of the providers (N = 23) indicated that they would use the tool in their clinical setting. Conclusion: BreastHealthDecisions.org represents a new approach to breast cancer prevention care and a framework for high quality preventive healthcare. The ability to integrate risk assessment and decision support in real time will allow for informed, value-driven, and patient-centered breast cancer prevention decisions. The tool is being further evaluated in the clinical setting

A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel.

Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we report a case of severe drug-induced liver injury requiring liver transplantation due to vanishing bile duct syndrome (VBDS) after exposure to pexidartinib in the I-SPY 2 Trial, a phase 2 multicenter randomized neoadjuvant chemotherapy trial in patients with Stage II-III breast cancer. We also review the current literature on this rare, idiosyncratic, and potentially life-threatening entity

Decision making in breast cancer prevention

Breast cancer is one of the most common cancers among women and the leading cause of death in women between the ages of 45-60 in most developed countries. The efficacy of prevention options has been established and includes lifestyle modifications, chemoprevention, and prophylactic surgery. Despite the efficacy of these options, breast cancer prevention remains underused, resulting in avoidable morbidity and mortality. Here, the main barriers to effective use of breast cancer prevention are outlined and a framework to facilitate patient-centered and evidence-based breast cancer prevention decision making is presented. The framework is intended to encourage a shared decision making approach to prevention decisions, within the context of a woman’s overall health. The inclusion of effective lifestyle interventions makes this framework relevant to most women, and is not exclusive to women at increased risk of developing breast cancer

Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15-13.81, p = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p = 0.009), second surgeries (54.6% versus 20.2%, p < 0.001), and completion mastectomies (27.7% versus 4.5%, p < 0.001). In this large cohort of women with ILC, re-excision lumpectomy was highly successful at clearing positive margins. Additionally, positive margins and completion mastectomy rates significantly decreased over time. These findings highlight improvements in management of ILC, and suggest that completion mastectomy may not be required for those with positive margins after initial BCS

Training community resource center and clinic personnel to prompt patients in listing questions for doctors: Follow-up interviews about barriers and facilitators to the implementation of consultation planning

BackgroundVisit preparation interventions help patients prepare to meet with a medical provider. Systematic reviews have found some positive effects, but there are no reports describing implementation experiences. Consultation Planning (CP) is a visit preparation technique in which a trained coach or facilitator elicits and documents patient questions for an upcoming medical appointment. We integrated CP into a university breast cancer clinic beginning in 1998. Representatives of other organizations expressed interest in CP, so we invited them to training workshops in 2000, 2001, and 2002.ObjectivesIn order to learn from experience and generate hypotheses, we asked: 1) How many trainees implemented CP? 2) What facilitated implementation? 3) How have trainees, patients, physicians, and administrative leaders of implementing organizations reacted to CP? 4) What were the barriers to implementation?MethodsWe attempted to contact 32 trainees and scheduled follow-up, semi-structured, audio-recorded telephone interviews with 18. We analyzed quantitative data by tabulating frequencies and qualitative data by coding transcripts and identifying themes.ResultsTrainees came from two different types of organizations, clinics (which provide medical care) versus resource centers (which provide patient support services but not medical care). We found that: 1) Fourteen of 21 respondents, from five of eight resource centers, implemented CP. Four of the five implementing resource centers were rural. 2) Implementers identified the championing of CP by an internal staff member as a critical success factor. 3) Implementers reported that modified CP has been productive. 4) Four respondents, from two resource centers and two clinics, did not implement CP, reporting resource limitations or conflicting priorities as the critical barriers.ConclusionCP training workshops have been associated with subsequent CP implementations at resource centers but not clinics. We hypothesize that CP workshops combined with an internal champion and adequate program resources may be sufficient for some patient support organizations to implement CP

Tamoxifen may prevent both ER+ and ER- breast cancers and select for ER- carcinogenesis: an alternative hypothesis

Introduction: Breast Cancer Prevention Trial (BCPT) and Multiple Outcomes of Raloxifene (MORE) data have been interpreted to indicate that tamoxifen reduces the risk of ER+ but not ER- breast carcinogenesis. We explored whether these data also support an alternative hypothesis, that tamoxifen influences the natural history of both ER+ and ER- cancers, that it may be equally effective in abrogating or delaying ER- and ER+ carcinogenesis, and place selection pressure, in some cases, for the outgrowth of ER- cancers. Methods: BCPT and MORE data were used to investigate whether: first, tamoxifen could reduce equally the emergence of ER- and ER+ tumors; and second, tamoxifen could select a fraction of emerging ER+ cancers and promote their transformation to ER- cancers. Assuming that some proportion, Z, of ER+ tumors becomes ER- after tamoxifen exposure and that the risk reduction for both ER- and ER+ tumors is equal, we solved for both the transformation rate and the risk reduction rate. Results: If tamoxifen equally reduces the incidence of ER+ and ER- tumors by 60%, the BCPT results are achieved with a transformation of approximately Z = 20% of ER+ to ER- tumors. Validation with MORE data using an equal risk reduction of 60% associated with tamoxifen produces an almost identical transformation rate Z of 23%. Conclusion: Data support an alternative hypothesis that tamoxifen may promote ER- carcinogenesis from a precursor lesion that would otherwise have developed as ER+ without tamoxifen selection

Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted