Judy A. Tjoe

CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues

UNLABELLED Although high mammographic density is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high mammographic density share key histologic features with stromal components within malignant lesions of tumor tissues, specifically low adipocyte and high extracellular matrix (ECM) content. We show that CD36, a transmembrane receptor that coordinately modulates multiple protumorigenic phenotypes, including adipocyte differentiation, angiogenesis, cell-ECM interactions, and immune signaling, is greatly repressed in multiple cell types of disease-free stroma associated with high mammographic density and tumor stroma. Using both in vitro and in vivo assays, we show that CD36 repression is necessary and sufficient to recapitulate the above-mentioned phenotypes observed in high mammographic density and tumor tissues. Consistent with a functional role for this coordinated program in tumorigenesis, we observe that clinical outcomes are strongly associated with CD36 expression. SIGNIFICANCE CD36 simultaneously controls adipocyte content and matrix accumulation and is coordinately repressed in multiple cell types within tumor and high mammographic density stroma, suggesting that activation of this stromal program is an early event in tumorigenesis. Levels of CD36 and extent of mammographic density are both modifiable factors that provide potential for intervention.

Does breast tumor location influence success of sentinel lymph node biopsy

BACKGROUND Controversy exists regarding the influence of sentinel lymph node (SLN) mapping technique or patient variables on the success rate of SLN mapping. We undertook a prospective study in a single institution series to evaluate multiple variables that could adversely affect SLN identification rates. STUDY DESIGN Data were collected on 174 patients who underwent 177 SLN mapping procedures followed by axillary dissection from October 1996 through January 2000. Patient demographics, body mass index (BMI), biopsy method, tumor size, palpability, and location were recorded. SLNs were identified by blue dye only (n = 31), Tc-99m sulfur colloid only (n = 34), or combined techniques (n = 112). Data were analyzed by logistic regression analysis and expressed as the probability of failure to map the SLN. RESULTS SLNs were identified successfully in 150 of 177 procedures (85%) with a false negative rate of 3.7%. Mapping success reached 93% using combination blue dye and isotope. Variables found to adversely affect SLN mapping success and the odds ratio of failure (OR) included lower inner quadrant (LIQ) location (OR 35.6), blue dye only (OR 42.4), BMI >30 and upper outer quadrant (UOQ) location (OR 14.6), and nonpalpable UIQ location (OR 25). LIQ location adversely affects mapping success independent of technique, tumor size, or obesity. Obesity and nonpalpability were adverse factors when tumors were located in the UOQ and UIQ, respectively. Age, biopsy technique, and tumor diameter did not affect SLN mapping success. CONCLUSIONS SLN mapping success is influenced by technique and tumor location, with best results achieved using combined techniques and for lesions located in quadrants other than the LIQ. Obesity and tumor palpability influence success in the context of tumor location.

Measures of Appropriateness and Value for Breast Surgeons and Their Patients: The American Society of Breast Surgeons Choosing Wisely® Initiative

BackgroundCurrent breast cancer care is based on high-level evidence from randomized, controlled trials. Despite these data, there continues to be variability of breast cancer care, including overutilization of some tests and operations. To reduce overutilization, the American Board of Internal Medicine Choosing Wisely® Campaign recommends that professional organizations provide patients and providers with a list of care practices that may not be necessary. Shared decision making regarding these services is encouraged.MethodsThe Patient Safety and Quality Committee of the American Society of Breast Surgeons (ASBrS) solicited candidate measures for the Choosing Wisely® Campaign. The resulting list of “appropriateness” measures of care was ranked by a modified Delphi appropriateness methodology. The highest-ranked measures were submitted to and later approved by the ASBrS Board of Directors. They are listed below.Results(1) Don’t routinely order breast magnetic resonance imaging in new breast cancer patients. (2) Don’t routinely excise all the lymph nodes beneath the arm in patients having lumpectomy for breast cancer. (3) Don’t routinely order specialized tumor gene testing in all new breast cancer patients. (4) Don’t routinely reoperate on patients with invasive cancer if the cancer is close to the edge of the excised lumpectomy tissue. (5) Don’t routinely perform a double mastectomy in patients who have a single breast with cancer.ConclusionsThe ASBrS list for the Choosing Wisely® campaign is easily accessible to breast cancer patients online. These measures provide surgeons and their patients with a starting point for shared decision making regarding potentially unnecessary testing and operations.

Automatic patient search for breast cancer clinical trials using free-text medical reports

The purpose of this work is to develop algorithms to automatically identify qualified patients for breast cancer clinical trials from free-text medical reports. Specifically, we developed an algorithm, called subtree match, that achieves this by finding structural patterns in free-text patient report sentences that are consistent with given trial criteria. Experimental results indicate that this technique is effective and performs better than several competing techniques. Our work is useful in two respects. First, it can potentially increase the efficiency and reduce the cost of the patient enrollment process. Second, it can be extended/adapted to the clinical trials of other diseases

Survivors speak: a qualitative analysis of motivational factors influencing breast cancer survivors' participation in a sprint distance triathlon.

AIMS AND OBJECTIVES To examine motivational factors influencing breast cancer survivors to participate in triathlon training, complete a triathlon and maintain an exercise thereafter. BACKGROUND Routine exercise has been shown to improve quality of life and reduce recurrence for breast cancer survivors. Yet physical and psychological factors present barriers for initiating and maintaining an exercise routine. Research is limited in exploring factors of exercise motivation from the survivors perspective. DESIGN Qualitative design using focus groups and individual follow-up phone interviews to explore motivation for exercise initiation and maintenance. METHODS One to two weeks after completing a triathlon, 11 breast cancer survivors who trained together participated in one of three focus groups to discuss their experience. Five months post triathlon 6 of the 11 participants were successfully contacted and phone interviews were conducted to explore exercise maintenance. Focus groups and interviews were analysed using content and thematic analysis. RESULTS Five themes emerged (1) Champion for Exercise, (2) Part of a Team, (3) Everyone Had a Story, (4) Not Really Exercise and (5) What Do We Do Now? Overall, survivors recognised their need for lifestyle change (e.g. moving from a sedentary lifestyle to a more active one). More importantly, they identified the team approach to exercise initiation was crucial in their success in sustaining a behavioural change. CONCLUSIONS Emphasis needed on developing team exercise training programmes for survivors. Nurses can play a critical role in discussing with survivors, the benefits of exercise initiation and maintenance. RELEVANCE TO CLINICAL PRACTICE Breast cancer survivors are hesitant to initiate routine exercise. Training with women who share a common lived experience increases the likelihood of success. Nurses are in a position to encourage breast cancer survivors to participate in group exercise programmes as a way to improve quality of life.

The American Society of Breast Surgeons and Quality Payment Programs: Ranking, Defining, and Benchmarking More Than 1 Million Patient Quality Measure Encounters

BackgroundTo identify and remediate gaps in the quality of surgical care, the American Society of Breast Surgeons (ASBrS) developed surgeon-specific quality measures (QMs), built a patient registry, and nominated itself to become a Center for Medicare and Medicaid Services (CMS) Qualified Clinical Data Registry (QCDR), thereby linking surgical performance to potential reimbursement and public reporting. This report provides a summary of the program development.MethodsUsing a modified Delphi process, more than 100 measures of care quality were ranked. In compliance with CMS rules, selected QMs were specified with inclusion, exclusion, and exception criteria, then incorporated into an electronic patient registry. After surgeons entered QM data into the registry, the ASBrS provided real-time peer performance comparisons.ResultsAfter ranking, 9 of 144 measures of quality were chosen, submitted, and subsequently accepted by CMS as a QCDR in 2014. The measures selected were diagnosis of cancer by needle biopsy, surgical-site infection, mastectomy reoperation rate, and appropriateness of specimen imaging, intraoperative specimen orientation, sentinel node use, hereditary assessment, antibiotic choice, and antibiotic duration. More than 1 million patient-measure encounters were captured from 2010 to 2015. Benchmarking functionality with peer performance comparison was successful. In 2016, the ASBrS provided public transparency on its website for the 2015 performance reported by our surgeon participants.ConclusionsIn an effort to improve quality of care and to participate in CMS quality payment programs, the ASBrS defined QMs, tracked compliance, provided benchmarking, and reported breast-specific QMs to the public.

Automatic Patient Search Using Bernoulli Model

Objective: Develop algorithms to automatically identify qualified patients for breast cancer clinical trials from free-text medical reports. Design: The Bernoulli model was trained to search for a qualified patient based on criterion. Measurement: The performance of the Bernoulli model was evaluated by the Precision-Recall curve and F-score. Results: The Single-word Bernoulli model trained in a two-class mode has greater performance than the model trained in a one-class mode. The performance of the model was also compared with some other techniques. Conclusions: The Bernoulli model method is easier to implement and performs better than several competing techniques.

Does expression of estrogen receptor, progesterone receptor, and HER2 in atypical breast lesions predict a subsequent clinically significant event?

34 Background: Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) increase breast cancer risk 3-5 fold. Risk reduction strategies include intense radiographic surveillance, medical, or surgical prophylaxis, all with associated side effects. Thus, identifying predictors of future breast cancer associated with atypia would limit aggressive treatment to only those patients at highest risk for disease progression. Given that lifetime estrogen exposure is a risk factor for breast cancer, and human epidermal growth factor receptor-2 (HER2) gene amplification is linked to breast pathogenesis, we tested whether expression patterns of estrogen receptor (ER), progesterone receptor (PR), and HER2 at initial diagnosis of atypia predicted a subsequent clinically significant event (SCSE), defined as another occurrence of atypia, in situ, or invasive carcinoma. METHODS Patients with an initial diagnosis of ADH and/or ALH were retrospectively identified. 19 women who developed a SCSE (cases) were matched to 45 women with no SCSE for at least 5 years after the diagnosis of atypia (controls). Archived tissue from cases and controls were subjected to ER, PR, and HER2 immunohistochemistry. ER and PR were reported using Allred score (0 to 8). HER2 was reported as negative (0-1+), equivocal (2+) or positive (3+). Atypia with HER2 (2+) or (3+) scores were subject to SISH to confirm gene amplification. RESULTS There was no significant difference in expression of ER (mean Allred: cases = 7.26 ± 0.35; controls = 6.91 ± 0.43) or PR (mean Allred: cases = 6.95 ± 0.43; controls = 6.57 ± 0.34). >90% of both cases and controls were HER2 negative (0-1+). Longitudinal assessment of ER, PR, and HER2 in patients who developed a SCSE revealed that three of 19 cases presented with HER2 overexpression; however SISH analysis revealed no gene amplification. Interestingly, ER/PR expression decreased in three of seven patients with atypia who later developed an invasive malignancy. CONCLUSIONS ER and PR expression do not predict a SCSE after an initial diagnosis of breast atypia. HER2 does not appear to be a useful marker for risk prediction of a SCSE, as HER2 overexpression was not identified in any of our cases.

Erratum to: NK cell-mediated antibody-dependent cellular cytotoxicity is enhanced by tamoxifen in HER2/neu non-amplified, but not HER2/neu-amplified, breast cancer cells

Tumor-targeting antibodies have been successful in the treatment of various types of cancers. Antibodies engage the immune system with their Fc, stimulating immune cell effector function. In the clinic, FcγRIIIa polymorphisms with higher affinity for the Fc of antibodies were shown to improve response rates and overall survival. Efforts have been made to modify the Fc to enhance affinity to Fc receptors and thereby improve effector function. An alternative for improving immune effector function may be to increase the level of tumor antigen expression. In this study, tamoxifen was used to increase HER2/neu protein level to determine whether increased tumor antigen expression could enhance NK cell-mediated antibody-dependent cytotoxicity (ADCC). Tamoxifen was found to increase HER2/neu 1.5-fold to threefold in breast cancer cell lines that were HER2/neu non-amplified. Using flow cytometry to simultaneously evaluate NK cell degranulation and tumor cell death, the increase in HER2/neu enhanced NK cell-mediated ADCC. However, in cells that had HER2/neu gene amplification and estrogen receptor expression, tamoxifen elevated HER2/neu but failed to improve NK cell function. The quantity of HER2/neu on the tumor cell surface was approximately double that of the number of Fc receptors found on NK cells. This appears to reflect a ceiling at which increasing antigen expression fails to improve NK cell effector function. This has clinical implications as trying to increase antigen expression to enhance NK cell function may be useful for patients with antigen-low tumors, but not in those whose tumors have gene amplification or high levels of antigen expression.

Automated search for patient records: classification of free-text medical reports using conditional random fields

The purpose of this research is to develop a classifier to automatically identify qualified patients for breast cancer clinical trials from free-text medical reports. Specifically, we trained a conditional random field based classifier to identify patterns in sentences from free-text reports that are consistent with trial criteria. Experimental results indicate that this method works well, outperforming several competing techniques. Our work is important in two ways. First, it could be used to increase efficiency and decrease the cost of the patient enrollment process for clinical trials. Second, it could be extended and adapted to other patient identification problems.