Comprehensive diagnostic program for medically underserved women with abnormal breast screening evaluations in an urban population.

OBJECTIVE: To institute a patient navigator program for underinsured women to eliminate delays in diagnostic resolution of abnormal screening mammograms, provide services for abnormalities noted during breast cancer screening, describe demographic and clinical characteristics of enrollees, and assess postscreening follow-up care. PATIENTS AND METHODS: Coordinators from area health departments worked with a navigator nurse at Mayo Clinic Cancer Center in Jacksonville, FL, to refer patients for additional diagnostic services, including diagnostic mammography, ultrasonography, ultrasonography-guided biopsy, stereotactic biopsy, breast magnetic resonance imaging, and biopsy guided by magnetic resonance imaging. Women with abnormal screening mammograms (Breast Imaging Reporting and Data System [BI-RADS] category 4 or 5) or palpable suspect breast masses were eligible. Data were extracted from clinical service records. Timeliness of postscreening follow-up was assessed. RESULTS: The study enrolled 447 women from June 30, 2000, to December 29, 2006. Data on the time from screening to diagnosis were available for 399 women, and median time from detection of screening abnormality to diagnosis was 37 days. Time between screening and diagnosis was 60 days or less for 325 (81%) of the 399 women for whom data were available and for 60 (82%) of the 73 women with BI-RADS category 4 or 5 assessments. Both of these percentages exceeded the Centers for Disease Control and Prevention quality benchmark of 75%. Mean time from study enrollment to diagnosis was 2 days for women with BI-RADS category 3 or 4 assessments and 7 days for women with BI-RADS category 5 assessments. CONCLUSION: This program demonstrated a successful collaboration between an academic medical center and community health centers. Most women with BI-RADS category 4 or 5 assessments received a diagnosis within 60 days of screening.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models.

CONTEXT: Models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is unclear. OBJECTIVE: To compare the performance characteristics of four BRCA1/BRCA2 gene mutation prediction models: LAMBDA, based on a checklist and scores developed from data on Ashkenazi Jewish (AJ) women; BRCAPRO, a Bayesian computer program; modified Couch tables based on regression analyses; and Myriad II tables collated by Myriad Genetics Laboratories. DESIGN AND SETTING: Family cancer history data were analyzed from 200 probands from the Mayo Clinic Familial Cancer Program, in a multispecialty tertiary care group practice. All probands had clinical testing for BRCA1 and BRCA2 mutations conducted in a single laboratory. MAIN OUTCOMES MEASURES: For each model, performance was assessed by the area under the receiver operator characteristic curve (ROC) and by tests of accuracy and dispersion. Cases "missed" by one or more models (model predicted less than 10% probability of mutation when a mutation was actually found) were compared across models. RESULTS: All models gave similar areas under the ROC curve of 0.71 to 0.76. All models except LAMBDA substantially under-predicted the numbers of carriers. All models were too dispersed. CONCLUSIONS: In terms of ranking, all prediction models performed reasonably well with similar performance characteristics. Model predictions were widely discrepant for some families. Review of cancer family histories by an experienced clinician continues to be vital to ensure that critical elements are not missed and that the most appropriate risk prediction figures are provided.

Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients with breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed-care population of women with breast cancer. PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tamoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an AI (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7% in the AI group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the AI group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the AI group than in the non-AI group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. CONCLUSION: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an AI for breast cancer.

Pilot evaluation of citalopram for the treatment of hot flashes in women with inadequate benefit from venlafaxine.

BACKGROUND: While newer antidepressants, such as venlafaxine and paroxetine, substantially decrease hot flashes, there is no published information with regards to whether a different antidepressant will be effective when one antidepressant does not adequately relieve hot flashes. OBJECTIVE: The objective of this trial was to provide pilot information with regards to whether citalopram would effectively reduce hot flashes in patients who did not receive adequate enough hot flash reduction with venlafaxine. DESIGN: This was a prospective pilot trial. MEASUREMENTS: Validated patient-completed hot flash diary questionnaires were utilized for measuring hot flashes. SUBJECTS: Thirty patients were recruited to this trial, 22 of whom were fully evaluable. RESULTS: Compared to a baseline week, hot flash scores were reduced by 53% 4 weeks later. The citalopram appeared to be well tolerated with many quality-of-life and potential toxicity symptoms much improved compared to the baseline week. At the end of the 4-week treatment, 19 patients (63% of patients entering the study and 86% of the patient completing the study treatment) chose to continue to use citalopram. CONCLUSION: This pilot information supports the hypothesis that citalopram will reduce hot flashes in patients with inadequate hot flash relief while taking venlafaxine.

Advances in screening, diagnosis, and treatment of breast cancer.

Breast cancer is the most common cancer in women in the United States; this year, approximately 215,900 new cases will be diagnosed. Mammography remains the cornerstone of screening, with technologies such as ultrasonography and magnetic resonance imaging having an increasingly defined role. Improved risk assessment and prevention strategies have been implemented, and current research in these areas includes better identification of patients at risk, the use of aromatase inhibitors and other agents to reduce risk, and the use of surrogate markers. Breast cancer staging has been optimized recently; also, local management of breast cancer, adjuvant systemic therapies, and treatment of patients with advanced disease have been evolving. Advances in screening, diagnosis, and treatment of breast cancer continue to influence our approach to patients with this disease. Many improvements have been made as well in supportive care, including increased tolerability of therapy and notable amelioration of disease symptoms.

The role of positron emission tomographic imaging in breast cancer.

Studies have shown that deoxy-2-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) has limited value in detecting primary tumors and axillary lymph node involvement in breast cancer. PET is most successful when it is used to evaluate locally advanced breast tumors. Identification of smaller, earlier-stage tumors and noninvasive or lobular tumors has been suboptimal. Because of several factors, PET should not replace standard techniques for evaluation of breast cancer, especially for micrometastasis. However, PET can provide invaluable information about disease extent, recurrent disease, and distant metastases, and this information can affect treatment decisions. (18)FDG PET can also facilitate the differentiation of therapy responders from nonresponders, allowing treatment regimen changes at an earlier stage.

The management of bone loss in patients with breast or prostate cancer.

Osteoporosis is a disease that is associated with significant morbidity and mortality, much of which can be prevented with available therapy. The risk for osteoporosis is increased in individuals with some types of cancer, especially in women with breast cancer and men with prostate cancer. This is caused by several factors, including premature ovarian failure and systemic antihormonal therapy in women, androgen ablation therapy in men, and potential direct effects of chemotherapy and of cancer on bone metabolism. With continual increases in the incidence of breast cancer, earlier detection and treatment, and improvements in survival for both patients with breast and prostate cancer, the importance of appropriate screening for and management of osteoporosis is evident. We review the evidence supporting an increased risk for development of osteoporosis in individuals with breast or prostate cancer, and strategies for prevention and treatment of osteoporosis in these patients.

Genetics and the management of women at high risk for breast cancer.

It is estimated that 5%-10% of all breast cancers in women are associated with hereditary susceptibility due to mutations in autosomal dominant genes, such as BRCA1 and BRCA2, p53, pTEN, and STK11/LKB1. Another 15%-20% of female breast cancers occur in women with a family history but without an apparent autosomal dominant inheritance pattern, and are probably due to other genetic factors with environmental influence. Approximately 7%-10% of ovarian cancers occur in women with hereditary susceptibility, primarily secondary to mutations in BRCA1 and BRCA2, with smaller contributions from mutations in mismatch repair genes associated with the hereditary nonpolyposis colorectal cancer and other, as yet undiscovered, genes.

Inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura.

We report an unusual case of a 51-year-old woman with inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura. We propose that the presence of all three disorders together suggests that they may share an interrelated immune mechanism.

Osteoporosis in women with breast cancer.

Osteoporosis is a disease that causes substantial morbidity and mortality for which preventive therapy is available. Women with breast cancer are at increased risk for osteoporosis for several reasons, including premature ovarian failure as a result of treatment, direct effects of chemotherapy, and effects of the breast cancer itself. As the incidence of breast cancer continues to increase and survival rates continue to improve, the importance of appropriate screening for and management of osteoporosis becomes more apparent. This article reviews the evidence supporting an increased risk for development of osteoporosis in women with breast cancer and summarizes strategies for prevention and treatment of osteoporosis in this population.

Adjuvant therapy for breast cancer: recommendations for management based on consensus review and recent clinical trials.

Determining the optimal individual adjuvant systemic therapy for breast cancer patients is a challenging undertaking because it requires translating data from clinical trials that have involved thousands of patients into a highly individualized, risk-adjusted approach for the patient at hand. Choosing adjuvant therapy for women with breast cancer includes consideration of four issues: A) evaluation of risk of relapse; B) extrapolation of results from clinical trials; C) therapeutic ratio, and D) the patient's preferences following a thorough discussion with her physician. Data from recently completed phase III adjuvant trials and worldwide consensus conferences document the benefits of adjuvant therapy in improving disease-free survival and overall survival for patients diagnosed with invasive breast cancer >1.0 cm in size. The benefits of hormonal therapy are clear, but limited to patients with estrogen receptor-positive breast cancer. Anthracyclines lead to improved outcomes compared with nonanthracycline regimens. Taxanes appear to improve disease-free survival in patients with node-positive disease, although longer follow-up is required to assess their impact on overall survival. Some countries have reported a reduction in the mortality rate from breast cancer over the past several years. The improved survival rate is due, at least in part, to the use of adjuvant systemic therapy. Ongoing studies are evaluating targeted therapies, with the potential of remarkably improving patient outcome.