Differential impact of body mass index on absolute and percent breast density: implications regarding their use as breast cancer risk biomarkers.

Percent breast density (PBD), a commonly used biomarker of breast cancer risk (BCR), is confounded by the influence of non-dense breast tissue on its measurement and factors, such as BMI, which have an impact on non-dense tissue. Consequently, BMI, a potent BCR factor, is, paradoxically, negatively correlated with PBD. We propose that absolute breast density (ABD) is a more accurate biomarker of BCR. We used a volumetric method to compare the correlation between PBD and ABD with baseline demographics and dietary and physical activity variables in a group of 169 postmenopausal women enrolled in a clinical trial prior to any intervention. As expected, a strong negative correlation between PBD and BMI was observed (Rho = -0.5, p < 5e(-12)). In contrast, we observed a strong, previously not well established, positive correlation of BMI with ABD (Rho = 0.41, p < 2.5e(-8)), which supports the use of ABD as a more accurate indicator of BCR. Correction of PBD by BMI did not frequently provide the same information as ABD. In addition, because of the strong influence of BMI on ABD, many correlations between dietary variables and ABD did not emerge, until adjustment was made for BMI. ABD corrected by BMI should be the gold standard BD measurement. These findings identify the optimal measurement of BD when testing the influence of an intervention on BD as a biomarker of BCR.

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.

Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration.

Lenalidomide-associated hepatotoxicity--a case report and literature review.

BACKGROUND: Lenalidomide is an immunomodulatory drug frequently used for treatment of patients with multiple myeloma and myelodysplastic syndromes. This report presents a rare case of lenalidomide-associated hepatotoxicity and reviews the available literature. CASE REPORT: A 67-year-old male with multiple myeloma was hospitalized with nausea, vomiting and jaundice, while treated with a second three-week course of lenalidomide. The patient was found to have acutely elevated bilirubin, alkaline phosphatase, AST and ALT. He also had acute on chronic renal function impairment. Serology for viral hepatitis, abdominal ultrasound, magnetic resonance cholangiopancreatography and hepatobiliary scan revealed no abnormalities. Lenalidomide was stopped, resulting in subsequent (8 days) clinical improvement and normalization of the liver abnormalities. The RUCAM causality assessment score was 8, consistent with probable lenalidomide-associated hepatotoxicity. Literature review revealed four other published cases of lenalidomide-associated hepatotoxicity with clinical presentation varying between cholestatic-, hepatocellular- or mixed-pattern of liver injury. All patients had clinical and laboratory improvement soon after lenalidomide discontinuation. Renal function impairment was present in 3 of the 5 reported cases. The exact mechanism of lenalidomide-associated liver injury remains unclear as only 2 patients had liver biopsies without specific findings. CONCLUSION: Physicians should be aware of the potential for lenalidomide-associated hepatotoxicity, particularly in patients with underlying renal insufficiency.

Chemoprevention of breast cancer by fish oil in preclinical models: trials and tribulations.

Despite the perception that omega-3 fatty acids (n-3 FA) protect against breast cancer, epidemiologic studies have yielded inconsistent results. Although preclinical data have been, in general, more supportive of a protective effect of n-3 FA on breast cancer, inconsistencies still remain, which preclude definite conclusions or in-depth mechanistic investigations despite 30 years of research in this area. In this review, we discuss key variables that may account for inconsistencies of results across preclinical studies and provide recommendations for future experiments testing the chemopreventive effect of n-3 FAs in breast cancer, as part of a multiagent approach under rigorously controlled conditions.

Effect of gastric bypass on vitamin D and secondary hyperparathyroidism.

Obesity as well as bariatric surgery may increase the risk for vitamin D deficiency. We retrospectively compared vitamin D levels in obese patients (n = 123) prior to bariatric surgery and 1 year postoperatively. We also evaluated parathyroid hormone levels (PTH) 1 year after surgery. A higher percentage of patients had baseline vitamin D deficiency (86%), defined as 25-hydroxy vitamin D <32 ng/mL, compared with the 1-year (post-surgical) levels, (70%; p < 0.001). Body mass index (BMI) inversely correlated with vitamin D deficiency at baseline (r = -0.3, p = 0.06) and at the postoperative follow-up (r = -0.2, p = 0.013). One third of the postoperative population had secondary hyperparathyroidism, defined by a serum PTH level >62 pg/mL; however, postoperative PTH and vitamin D levels were unrelated (r = -0.001, p = 0.994). Pre- and postoperative vitamin D levels were inversely correlated with BMI. Secondary hyperparathyroidism was observed in 33% of patients postoperatively; however, this did not correlate with vitamin D.