Karen T. Lane

Association of Hypertension, Diabetes, Dyslipidemia, and Metabolic Syndrome with Obesity: Findings from the National Health and Nutrition Examination Survey, 1999 to 2004

BACKGROUND Hypertension, diabetes, and dyslipidemia are common conditions associated with obesity. This study provides current estimates of the prevalence of hypertension, diabetes, dyslipidemia, and metabolic syndrome according to the severity of obesity in men and women participating in the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES). STUDY DESIGN Data from a representative sample of 13,745 US men and women who participated in the NHANES between 1999 and 2004 were reviewed. Overweight and obesity classes 1, 2, and 3 were defined as a body mass index of 25.0 to 29.9, 30.0 to 34.9, 35.0 to 39.9, and> or =40.0 kg/m(2), respectively. Metabolic syndrome was defined according to the 2004 National Heart, Lung and Blood Institute/American Heart Association conference proceedings. RESULTS With increasing overweight and obesity class, there is an increase in the prevalence of hypertension (18.1% for normal weight to 52.3% for obesity class 3), diabetes (2.4% for normal weight to 14.2% for obesity class 3), dyslipidemia (8.9% for normal weight to 19.0% for obesity class 3), and metabolic syndrome (13.6% for normal weight to 39.2% for obesity class 3). With normal weight individuals as a reference, individuals with obesity class 3 had an adjusted odds ratio of 4.8 (95% CI 3.8 to 5.9) for hypertension, 5.1 (95% CI 3.7 to 7.0) for diabetes, 2.2 (95% CI 1.7 to 2.4) for dyslipidemia, and 2.0 (95% CI 1.4 to 2.8) for metabolic syndrome. CONCLUSIONS The prevalence of hypertension, diabetes, dyslipidemia, and metabolic syndrome substantially increases with increasing body mass index. These findings have important public health implications for the prevention and treatments (surgical and nonsurgical) of obesity.

Nutrition impacts the prevalence of peripheral arterial disease in the United States

OBJECTIVE Traditional recommendations for peripheral arterial disease (PAD) risk factor reduction include smoking cessation, low-fat/low-salt diet, exercise, and optimal medical management of chronic disease. Little attention has been paid to the role of dietary supplementation of specific nutrients in the prevention of PAD. METHODS This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES) to determine specific nutrients that are associated with prevalent PAD in the United States (US) population. NHANES data include nationwide sampling of the US population, using physical examination, questionnaire, and laboratory testing. PAD status was defined by an ankle-brachial index (ABI) of <0.9. Nutritional information was collected by 24-hour dietary recall using the US Department of Agriculture dietary collection instrument. Data were linked to a database of foods and their nutrient composition. Univariate and multivariate logistic regression analyses were performed to evaluate associations between specific nutrient intake and the presence of PAD. Multivariate models adjusted for the effects of age, gender, hypertension, coronary vascular disease, diabetes, and smoking. RESULTS NHANES data for 1999 to 2004 included 7203 lower extremity examinations, of which 422 individuals had prevalent PAD (5.9%). Examinees with PAD had significantly higher rates of hypertension, coronary artery disease, diabetes, and smoking than those without PAD. Univariate analysis revealed that consumption of all nutrients considered were associated with lower odds of PAD, including antioxidants (vitamins A, C, and E), folate, other B vitamins (B(6), B(12)), fiber, and polyunsaturated and saturated fatty acids. After adjustment for traditional risk factors, nutrients associated with reduced prevalence of PAD were vitamin A (odds ratio [OR], 0.79; P = .036), vitamin C (OR, 0.84; P < .001), vitamin E (OR, 0.78; P = .011), vitamin B(6) (OR, 0.71; P = .023), fiber (OR, 0.65; P < .001), folate (OR, 0.67; P = .006), and omega-3 (alpha-linolenic) fatty acid (OR, 0.79; P = .028). CONCLUSIONS Improved nutrition is associated with a reduced prevalence of PAD in the US population. Higher consumption of specific nutrients, including antioxidants (vitamin A, C, and E), vitamin B(6), fiber, folate, and omega-3 fatty acids have a significant protective effect, irrespective of traditional cardiovascular risk factors. These findings suggest specific dietary supplementation may afford additional protection, above traditional risk factor modification, for the prevention of PAD.

Breast Cancer: Evaluation of Response to Neoadjuvant Chemotherapy with 3.0-T MR Imaging

PURPOSE To assess how the molecular biomarker status of a breast cancer, including human epidermal growth factor receptor 2 (HER2), hormone receptors, and the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant. Fifty patients (age range, 28-82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored with 3.0-T MR imaging. The longest dimension of the residual cancer was measured at MR imaging and correlated with pathologic findings. Patients were further divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status. Pathologic complete response (pCR) was defined as when there were no residual invasive cancer cells. The Pearson correlation was used to correlate MR imaging-determined and pathologic tumor size, and the unpaired t test was used to compare MR imaging-pathologic size discrepancies. RESULTS Of the 50 women, 14 achieved pCR. There were seven false-negative diagnoses at MR imaging. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging-pathologic size discrepancy was 0.5 cm ± 0.9 (standard deviation) for HER2-positive cancer and 2.3 cm ± 3.5 for HER2-negative cancer (P = .009). In the HER2-negative group, the size discrepancy was smaller for hormone receptor-negative than for hormone receptor-positive cancers (1.0 cm ± 1.1 vs 3.0 cm ± 4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater Ki-67 expression (0.8 cm ± 1.1) than in patients with 10% or less Ki-67 expression (3.9 cm ± 5.1, P = .06). CONCLUSION The diagnostic accuracy of breast MR imaging is better in more aggressive than in less aggressive cancers. When MR imaging is used for surgical planning, caution should be taken with HER2-negative hormone receptor-positive cancers.

Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile.

BACKGROUND This study aimed to evaluate the influence of hormone receptor (HR) and Ki-67 proliferation markers in predicting the accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in patients with HER2-negative (HER2(-)) breast cancer receiving neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS Fifty-four women were studied. Patients received AC (doxorubicin (Adriamycin)/cyclophosphamide) and/or taxane-based regimens. The accuracy of MR-determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathologically diagnosed tumor size using the Pearson correlation. RESULTS MRI correctly diagnosed 16 of the 17 cases of pCR. There were 8 false-negative diagnoses: 7 HR(+) and 1 HR(-). The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI vs. pathologically determined tumor size correlation, HR(-) cancers showed a higher correlation (R = 0.79) than did HR(+) cancers (R = 0.58). A worse MRI/pathology size discrepancy was found in HR(+) cancer than in HR(-)cancer (1.6 ± 2.8 cm vs. 0.56 ± 0.9 cm; P = .05). Tumors with low Ki-67 proliferation (< 40%) showed a larger size discrepancy than did those with high Ki-67 proliferation (≥ 40%) (1.2 ± 2.0 cm vs. 0.4 ± 0.8 cm; P = .05). CONCLUSIONS The results showed that the diagnostic performance of MRI for patients with breast cancer undergoing NAC is associated with a molecular biomarker profile. Among HER2(-)tumors, the accuracy of MRI was worse in HR(+)cancers than in HR(-)cancers and was also worse in low-proliferation tumors than in high-proliferation tumors. These findings may help in surgical planning.

Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology

To investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC).

Provider perceptions and expectations of breast cancer posttreatment care: a University of California Athena Breast Health Network project

PurposeThe Athena Breast Health Network collaboration is a University of California system-wide project initiated with the intent to drive innovation in breast cancer prevention, screening, and treatment. This qualitative research examines provider perceptions and expectations of posttreatment breast cancer care across five network sites with the goal of better understanding provider behavior during the posttreatment phase of the cancer care trajectory.MethodsInvestigators at each site conducted semi-structured interviews with oncology specialists and primary care providers (PCPs). Interviews used case study examples and open- and closed-ended questions on the delivery of posttreatment breast cancer care. Informant responses were manually recorded by the interviewer, compiled in a database, then coded and analyzed using NVivo 9 software.ResultsThere were 39 key informants across the sites: 14 medical oncologists, 7 radiation oncologists, 11 surgeons, 3 oncology nurses, and 4 PCPs. Care coordination was a major unprompted theme identified in the interviews. There was a perceived need for greater care coordination across institutions in order to improve delivery of posttreatment health care services and a need for greater care coordination within oncology, particularly to help avoid duplication of follow-up care and services. Participants expect frequent follow-up visits and to use biomarker tests and advanced imaging services as part of routine surveillance care. Implementing survivorship care programs was perceived as a way to improve care delivery.ConclusionsThese results identify a need for increased focus on care coordination during the posttreatment phase of breast cancer care within the University of California system and the potential for system and provider-level interventions that could help increase coordination of posttreatment care.Implications for Cancer SurvivorsBreast cancer survivors do not always receive evidence-based care. This research helps to better understand what motivates provider behavior during the posttreatment phase and lays a foundation for targeted interventions to increase adherence to evidence-based recommendations.

Quality of care among breast cancer (BC) survivors in the University of California (UC) Athena Breast Health Network.

164 Background: Post-treatment cancer care needs improvement (IOM 2006), including use of treatment summaries (TS) and survivorship care plans (SCP). ASCO BC surveillance guidelines (2006) suggest only 1 provider needs to see patients 3 to 4 times a year in first 2 years, and every 6 to 12 months thereafter. Athena is a collaborative project designed to drive innovation in BC care among the five UC cancer centers. Interviews with Athena MDs and RNs noted visit redundancy and poor guideline adherence (Hahn ASCO Breast 2011). METHODS BC patients diagnosed in 2008-09 were recruited from UC hospital tumor registries. With UC-wide IRB approval, patients were invited to participate in a mailed survey on post-treatment care starting September 2011. A 30-page survey collected information on post treatment care including number and type of provider visits, discussion of key topics, satisfaction with care, and quality of life. We targeted 100 completed questionnaires from each site. RESULTS Data from the first 194 respondents are reported. Most were white, college graduates, with mean age 61 yrs, and mean time from diagnosis 3.2 ± 0.6 years. TREATMENTS surgery (S) only=33; S and radiation (XRT)=66; S and chemotherapy (C)=25; S, C, XRT=70. Mean number of BC follow-up care providers (2.3±1) was not related to treatment received (p=0.3). S-only treatment resulted in fewer BC specific clinic visits than C-treatment (33% vs. 45% to 58%). Of 80% who attended UC clinics, most received follow-up care every 3 to 4 months. The providers seen were: oncologists (66%), surgeon (38%), radiation oncologist (47%), primary care (40%). There were no differences in visit frequency by <3 or >=3 years since diagnosis. 68% had copies of medical records; 40% had received a TS; 57% had a SCP (61% at UC vs. 41% not at UC, p=0.03). The presentation will update data with a larger sample and multivariable models. CONCLUSIONS Patient reports confirm that multiple providers are delivering BC specific follow-up care. Visit frequency may exceed guideline recommendations, and does not reflect risk of recurrence or treatment intensity. Less than half of patients received TS, but more than half had SCP. There is room to improve the coordination of post-treatment BC care.

Association between pathologic complete response and survival in patients treated with sequential anthracyclines and concomitant taxanes and trastuzumab in HER2-positive breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3141 Background: We reported high pathologic complete response (pCR) rates in patients with AC-sensitive and AC-resistant breast cancer (BC) who received trastuzumab-based chemotherapy regimens (SABCS 2004-2007). Following standard chemotherapy, pCR in 33% patients with HER2-positive breast cancer (BC) predicts 5-year DFS of 94% compared to 69% in 67% of patients with residual disease (RD)-a 25% difference (MD Anderson data). However, a similar association of DFS with pCR following trastuzumab has yet to be demonstrated. Material and Methods: A retrospective analysis of 40 patients with stage I-IIIC (6T4a-c, 9T4d, 8T3, 11T2, 6TX-1, 7 LN-negative, 33 LN-positive) HER2-positive (IHC2+ and FISH+ or IHC3+) BC treated preoperatively on and off institutional trials with trastuzumab-based regimens between 11/2002 and 10/2007 was conducted. Generally, patients received in vivo chemosensitivity-adjusted dose-dense doxorubicin and cyclophosphamide (2-4 cycles) followed by paclitaxel (cremophor or albumin-bound), carboplatin and trastuzumab for 12-16 weeks. Median age was 51 (range 26-71), and 16 (40%) had HR-positive BC. Postoperative treatment included radiation based on pretreatment stage, hormonal modulation for HR-positive BC, and additional trastuzumab was optional. Results: Twenty-six (65%, 95% CI 48-79%) patients achieved pCR in breast and axilla. pCR rate was 30%, 67% and 90% (p=0.02) with increasing HER2 FISH ratio of 1-4 (n=10), >4 (n=18), and >7 (n=10), respectively. pCR was demonstrated in 50% HR-positive and in 75% HR-negative BC (p=0.17). DFS and OS of 40 patients at a median follow-up of 28 months (range 2-56) of live patients is 88% (95% CI: 73-96) and 93% (95% CI: 80-98). DFS was 95% for patients who achieved pCR and 69% for patients with RD (Hazard ratio 0.12; 95% CI: 0.02 to 0.72, p=0.022). Age, grade, tumor size, preoperative lymph node and hormone receptor status were not prognostically significant in this small series. DFS was 94% for HER2+/HR+ and 83% for HER2+/HR- BC. Of the 5 relapses, 3 patients had inflammatory (2 had brain relapse as first site), one IIIB and one IIB BC. Discussion: This is the first demonstration of statistically significant difference in DFS of 95% in 65% achieving pCR versus 69% in 35% with RD treated preoperatively with trastuzumab-taxanes following anthracyclines. The strength of association between pCR and DFS is same as that following non-trastuzumab chemotherapy. In contrast, the 2-3 times higher pCR following trastuzumab is associated with a higher DFS of 88% for overall HER+ BC despite inclusion of inflammatory and locally advanced BC, and compares favorably with adjuvant trastuzumab studies of operable BC. The association between pCR and longer-term outcome also underscores the adequacy of in vivo chemosensitivity-adjusted 12-16 weeks (short course) of trastuzumab-taxanes combination sequenced following 2-4 cycles of anthracyclines in the neoadjuvant setting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3141.

Orbital Metastases from Breast Cancer with BRCA2 Mutation: A Case Report and Literature Review

Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Of these women, 5–10% have an inherited form of breast cancer with a mutation in a major gene, such as the breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Triple negative (the most common subtype of BRCA1-associated breast cancers) and Her2-positive breast cancer patients have more frequently been observed to develop central nervous system (CNS) metastases compared to other molecular subtypes of breast cancers. However, it remains an open question if BRCA2-associated breast cancers also have a higher propensity to develop CNS metastases. Here we report a rare case of recurrent BRCA2-associated breast cancer which manifested as orbital metastases. At the time of this publication, this is one of the first cases of BRCA2-associated breast cancer to present with orbital metastases. In this article, we discuss the diagnostic challenges and review the literature regarding this rare presentation.

Intraoperative margin assessment with the MarginProbe at different mammographic breast densities.

47 Background: Mammographic breast density (BD) is known to affect breast imaging. MarginProbe is an RF Spectroscopy intraoperative margin assessment tool. We looked at the effect of mammographic breast density (BD) on the performance of the device. Mammographic density was assigned by Breast Imaging-Reporting and Data System (BI-RADS) classification prior to breast conserving surgery with the MarginProbe. METHODS For the current study we analyzed MarginProbe device arm data from the MarginProbe Pivotal Trial for which BD data was available. Clear margins of the main specimen, which is where the MarginProbe was applied, were defined as no tumor on ink. Clinical benefit was defined as clearing positive main specimen margins or cancer in the shaving. Analysis was performed based on logistic and linear regression, with univariate analysis. RESULTS The dataset for the analysis included 196 patients for which preoperative BD data was available. With higher BD, there was an increase in the rate of main lumpectomy specimen with positive margins (OR 1.65 per change in density category, p=0.025). The rate of shavings with clinical benefit showed an upward trend, with increasing BD. The number of shavings per patient increased with BD, however the overall volume of shavings did not increase. There was an increase in the per patient relative clinical benefit as BD increased (OR 1.6 per change in density category, p=0.024). CONCLUSIONS With higher breast density patients and surgeons face an increase in risk for main specimen positive margins. With the increased BD and main specimen positivity more shavings were removed, but shavings volume did not increase as average shaving volume decreased with higher BD. Higher level of patient clinical benefit was observed with higher BD.