Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study

Estrogen may have opposing effects on health, namely increasing the risk of breast cancer and improving bone health by increasing bone mineral density (BMD). The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) BMD between women newly diagnosed with breast cancer and matched controls without breast cancer. Women newly diagnosed with breast cancer treated between April 2012 and October 2017 were prospectively enrolled. A control group was established of women with negative mammography or breast ultrasound, matched 1:1 by age, body mass index, parity, and the use of hormone replacement therapy. All those included had DXA BMD, and lab assessments at enrollment. Of 869 women with newly diagnosed breast cancer, 464 signed informed consent. Of the 344 who completed the study protocol, 284 were matched to controls. Overall, the mean age was 58 years. Compared to the control group, for the breast cancer group, the mean vitamin D level was lower (48.9 ± 19.0 vs. 53.8 ± 28.8 nmol/L, p = 0.022); and mean values were higher of total hip BMD (0.95 ± 0.14 vs. 0.92 ± 0.12 g/cm2, p = 0.002), T score (-0.38 ± 1.17 vs. -0.68 ± 0.98, p = 0.002), and Z score (0.32 ± 1.09 vs. 0.01 ± 0.88, p < 0.001). Among the women with breast cancer, no correlations were found of baseline BMD with tumor size or grade, nodal involvement, or breast cancer stage. We concluded that women with newly diagnosed breast cancer tend to have higher BMD than women with similar characteristics but without breast cancer. This implies that BMD might be considered a biomarker for breast cancer risk

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

Epidemiology of Neuroendocrine Tumors

Formerly named carcinoids, neuroendocrine tumors originate from diffuse endocrine cells, can involve any part of the gastrointestinal tract, endocrine pancreas and bronchopulmonary (BP) tree, and have a wide range of malignant potential. This chapter summarizes the data available on the epidemiology of neuroendocrine neoplasia (NEN) from around the world, including the relative frequency according to organ of origin, annual incidence rates (IR) and trends in IR at the various anatomic sites, age and stage at presentation, racial and gender differences in IR and 5-year survival rates. Over time, changes have been made in the classification and registration of NEN, both in the same registry and across the globe, thus confounding the possibility to draw conclusions as to the true rise in IR of NEN that is observed all over the world. BP NEN has become the most common site in many western countries, while NEN of the rectum is more common in the Far East. In some countries, appendiceal NEN is the most common site in females. When compared to adenocarcinoma of the same location, the prognosis of NEN patients is better. Five-year survival rates are highest for NEN originating in the rectum and appendix, but lower in small intestinal and pancreatic NEN. Future research is needed to understand the contribution of genetic and environmental factors to NEN epidemiology. (C) 2015 S. Karger AG, Base

A rare cause of postpartum acute hyponatremia

A previously healthy 24-year-old female underwent an emergent caesarean section without a major bleeding described. During the first post-operative days (POD) she complained of fatigue, headache and a failure to lactate with no specific and conclusive findings on head CT. On the following days, fever rose with a suspicion of an obstetric surgery-related infection, again with no evidence to support the diagnosis. On POD5 a new-onset hyponatremia was documented. The urine analysis suggested SIADH, and following a treatment failure, further investigation was performed and demonstrated both central hypothyroidism and adrenal insufficiency. The patient was immediately treated with hydrocortisone followed by levothyroxine with a rapid resolution of symptoms and hyponatremia. Further laboratory investigation demonstrated anterior hypopituitarism. The main differential diagnosis was Sheehan’s syndrome vs lymphocytic hypophysitis. Brain MRI was performed as soon as it was available and findings consistent with Sheehan’s syndrome confirmed the diagnosis. Lifelong hormonal replacement therapy was initiated. Further complaints on polyuria and polydipsia have led to a water deprivation testing and the diagnosis of partial central insipidus and appropriate treatment with DDAVP

Novel Susceptibility Genes Drive Familial Non-Medullary Thyroid Cancer in a Large Consanguineous Kindred

Familial non-medullary thyroid cancer (FNMTC) is a well-differentiated thyroid cancer (DTC) of follicular cell origin in two or more first-degree relatives. Patients typically demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. While known genes and chromosomal loci account for some FNMTC, the molecular basis for most FNMTC remains elusive. To identify the variation(s) causing FNMTC in an extended consanguineous family consisting of 16 papillary thyroid carcinoma (PTC) cases, we performed whole exome sequence (WES) analysis of six family patients. We demonstrated an association of ARHGEF28, FBXW10, and SLC47A1 genes with FNMTC. The variations in these genes may affect the structures of their encoded proteins and, thus, their function. The most promising causative gene is ARHGEF28, which has high expression in the thyroid, and its protein-protein interactions (PPIs) suggest predisposition of PTC through ARHGEF28-SQSTM1-TP53 or ARHGEF28-PTCSC2-FOXE1-TP53 associations. Using DNA from a patient’s thyroid malignant tissue, we analyzed the possible cooperation of somatic variations with these genes. We revealed two somatic heterozygote variations in XRCC1 and HRAS genes known to implicate thyroid cancer. Thus, the predisposition by the germline variations and a second hit by somatic variations could lead to the progression to PTC

Association between bone mineral density and incidence of breast cancer.

INTRODUCTION: Previous studies have suggested an inverse relationship between bone mineral density (BMD) and breast cancer incidence. The primary objective of this study was to assess whether BMD is associated with risk of subsequent breast cancer occurrence in the female population of southern Israel. METHODS: The electronic medical charts of women who underwent BMD at the Soroka Medical Center (SMC) between February 2003 and March 2011 were screened for subsequent breast cancer diagnoses. Women were divided by tertiles of BMD at 3 skeletal sites: lumbar spine (LS, L1-4), total hip (TH) and femoral neck (FN). The incidence of breast cancer was calculated. RESULTS: Of 15268 women who underwent BMD testing, 86 were subsequently diagnosed with breast cancer. Most women in the study were older than 50 years (94.2% and 92.7%, respectively; p = 0.597). Women who subsequently developed breast cancer had a higher mean body-mass index (BMI) (30.9 ± 5.5 vs. 29.1 ± 5.7 p = 0.004) and the mean BMD Z-score was significantly higher than in those without breast cancer for all 3 skeletal sites (LS: 0.36 ± 1.58 vs. -0.12 ± 1.42, p = 0.002; TH: 0.37 ± 1.08 vs. 0.03 ± 1.02, p = 0.002; FN: 0.04 ± 0.99 vs. -0.18 ± 0.94; p = 0.026). Women in the highest Z-score tertiles at the FN and TH had a higher chance of developing breast cancer compared to the lowest tertile; odds ratio of 2.15, 2.02, respectively (P = 0.004 and 0.01 respectively). No association was found between the BMD Z-score and the stage, histology, grade or survival from breast cancer. CONCLUSIONS: This study provides additional support for an inverse association between BMD and the risk of breast cancer

Time to diagnosis of breast cancer following BMD measurement in tertiles of BMD Z score at three skeletal sites.

<p>A. Femoral neck, B. Total hip, C. Lumbar spine.</p

Breast cancer characteristics according to femur neck BMD Z score tertiles (N = 86).

<p>This paper was presented in part at the annual meeting of the Endocrine Society, Houston Texas USA Jun 2012.</p

Tested population characteristics at the time of BMD measurement. Age, BMI25(OH)D and PTH are presented as mean ± SD.

*<p>Data was available fort 40% of the women.</p>**<p>Data was available for 15% of the women.</p