A Noninvasive Blood-based Combinatorial Proteomic Biomarker Assay to Detect Breast Cancer in Women over age 50 with BI-RADS 3, 4, or 5 Assessment.

PURPOSE: With improvements in breast cancer imaging, there has been a corresponding increase in false-positives and avoidable biopsies. There is a need to better differentiate when a breast biopsy is warranted and determine appropriate follow-up. This study describes the design and clinical performance of a combinatorial proteomic biomarker assay (CPBA), Videssa Breast, in women over age 50 years. EXPERIMENTAL DESIGN: A BI-RADS 3, 4, or 5 assessment was required for clinical trial enrollment. Serum was collected prior to breast biopsy and subjects were followed for 6-12 months and clinically relevant outcomes were recorded. Samples were split into training (70%) and validation (30%) cohorts with an approximate 1:4 case:control ratio in both arms. RESULTS: A CPBA that combines biomarker data with patient clinical data was developed using a training cohort (469 women, cancer incidence: 18.5%), resulting in 94% sensitivity and 97% negative predictive value (NPV). Independent validation of the final algorithm in 194 subjects (breast cancer incidence: 19.6%) demonstrated a sensitivity of 95% and a NPV of 97%. When combined with previously published data for women under age 50, Videssa Breast achieves a comprehensive 93% sensitivity and 98% NPV in a population of women ages 25-75. Had Videssa Breast results been incorporated into the clinical workflow, approximately 45% of biopsies might have been avoided. CONCLUSIONS: Videssa Breast combines serum biomarkers with clinical patient characteristics to provide clinicians with additional information for patients with indeterminate breast imaging results, potentially reducing false-positive breast biopsies.

Assessment of the accuracy of the Gail model in women with atypical hyperplasia.

PURPOSE: An accurate estimate of a woman's breast cancer risk is essential for optimal patient counseling and management. Women with biopsy-confirmed atypical hyperplasia of the breast (atypia) are at high risk for breast cancer. The Gail model is widely used in these women, but has not been validated in them. PATIENTS AND METHODS: Women with atypia were identified from the Mayo Benign Breast Disease (BBD) cohort (1967 to 1991). Their risk factors for breast cancer were obtained, and the Gail model was used to predict 5-year-and follow-up-specific risks for each woman. The predicted and observed numbers of breast cancers were compared, and the concordance between individual risk levels and outcomes was computed. RESULTS: Of the 9,376 women in the BBD cohort, 331 women had atypia (3.5%). At a mean follow-up of 13.7 years, 58 of 331 (17.5%) patients had developed invasive breast cancer, 1.66 times more than the 34.9 predicted by the Gail model (95% CI, 1.29 to 2.15; P < .001). For individual women, the concordance between predicted and observed outcomes was low, with a concordance statistic of 0.50 (95% CI, 0.44 to 0.55). CONCLUSION: The Gail model significantly underestimates the risk of breast cancer in women with atypia. Its ability to discriminate women with atypia into those who did and did not develop breast cancer is limited. Health care professionals should be cautious when using the Gail model to counsel individual patients with atypia.

Paget's disease of the breast: accuracy of preoperative assessment.

BACKGROUND: Routine preoperative assessment may not accurately assess the extent of underlying cancer in patients with Paget's disease (PD) of the breast. We performed this study to correlate findings on clinical examination and mammography with pathologic results and outcomes in women with PD. METHODS: An IRB-approved retrospective review identified all patients with PD between 1975 and 2000. Clinical exam and mammographic findings were recorded, and information on recurrence and survival was obtained from medical records. RESULTS: Univariate analyses identified palpable mass and suspicious mammogram as risk factors significantly associated with a worse outcome. Patients were therefore categorized by combinations of these two preoperative factors. All patients with a palpable mass and a suspicious mammogram had invasive cancer. In the subgroup of 40 women with a benign mammogram and no palpable mass, invasive cancer occurred in 5% and the majority (68%) had ductal carcinoma in situ which extended beyond the nipple. Women with a palpable mass and a suspicious mammogram had significantly worse survival compared to those with a benign mammogram and no palpable mass (P = 0.008). With a median follow-up of 6.4 years, five local recurrences occurred in patients with invasive cancer who underwent mastectomy. CONCLUSION: In women with PD, a palpable mass or suspicious mammogram portends a high likelihood of invasive cancer. Underlying cancer is common even in women with a benign mammogram and no palpable mass. Although breast conservation is an attractive option in patients with PD, mammography and physical exam may significantly underestimate the presence and extent of underlying disease.

Translating evidence-based information into effective risk communication: current challenges and opportunities.

Recent medical advances and the easy availability of evidence-based information at the point of care are believed to provide physicians with improved tools for risk communication. However, evidence indicates that physicians still display marked variability in ordering tests. Factors that determine a physician's test-ordering tendencies vary by specialization, practice, geographical location, defensive practice, and tolerance of uncertainty and are also modified by patient requests. Understanding of statistical terms on the part of both physicians and patients remains limited. Physicians may display limited ability to assess pretest and posttest probabilities, especially in low- and intermediate-risk patients, even after attending short courses in epidemiology, or may find the process impractical. Presentation of diagnostic-test results in a natural-frequency format might improve understanding. Both physicians and patients have difficulty grasping the term "number needed to treat" compared with "relative risk reduction" when comparing therapeutic options. Other patient-related factors that limit understanding include low literacy, individual risk tolerance, and framing patterns of the problem (potential gains vs losses). Despite numerous available modalities (quantitative and qualitative) of risk communication, consensus over the advantage of any single modality in translating evidence into risk communication is limited. It is essential that physicians remain patient-centered, generate trust, and build a partnership with the patient to achieve consensus for medical decision-making. Future studies are indicated to assess the effectiveness of novel risk-communication modalities based on patients' and physicians' characteristics and identify appropriate modality of translating evidence (quantitative or qualitative information).