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Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex- and age-matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.

Chronic pain was more prevalent in BCS compared to the general population. Significant predictors for sequelae related to breast cancer were radiotherapy and younger age. Future research should therefore prioritize sequelae prevention.

SUMMARY Much preclinical and epidemiologic evidence supports anticancer effects of HMG-CoA reductase inhibitors (statins). Epidemiologic evidence does not support an association between statin use and reduced breast cancer incidence, but does support a protective effect of statins—particularly simvastatin—on breast cancer prognosis. We argue that the current evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins. We advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence, then the indications for a safe, well-tolerated, and in expensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several design opportunities—including candidate predictive biomarkers of statin safety and efficacy—and offer solutions to key challenges to enrolment, follow-up, and analysis of such a trial.

The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.

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Genome-wide association studies recently linked the locus for Na 1 ,HCO 3 2 -cotransporter NBCn1 (SLC4A7) to breast cancer susceptibility, yet functional insights have been lacking. To determine whether NBCn1, by transporting HCO 3 2 into cells, may dispose of acid produced during high metabolic activity, we studied the expression of NBCn1 and the functional impact of Na 1 ,HCO 3 2 -cotransport in human breast cancer. We found that the plasmalemmal density of NBCn1 was 20-30% higher in primary breast carcinomas and metastases compared to matched normal breast tissue. The increase in NBCn1 density was similar in magnitude to that observed for Na 1 /H 1 -exchanger NHE1 (SLC9A1), a transporter previously implicated in cell migration, proliferation and malignancy. In primary breast carcinomas, the apparent molecular weight for NBCn1 was increased compared to normal tissue. Using pH-sensitive fluorophores, we showed that Na 1 ,HCO 3 2 -cotransport is the predominant mechanism of acid extrusion and is inhibited 34 6 9% by 200 lM 4,4 0 -diisothiocyanatostilbene-2,2 0 -disulfonic acid in human primary breast carcinomas. At intracellular pH (pH i ) levels >6.6, CO 2 /HCO 3 2 -dependent mechanisms accounted for >90% of total net acid extrusion. Na 1 /H 1 -exchange activity was prominent only at lower pH i -values. Furthermore, steadystate pH i was 0.35 6 0.06 units lower in the absence than in the presence of CO 2 /HCO 3 2 . In conclusion, expression of NBCn1 is upregulated in human primary breast carcinomas and metastases compared to normal breast tissue. Na 1 ,HCO 3 2 -cotransport is a major determinant of pH i in breast cancer and the modest DIDS-sensitivity is consistent with NBCn1 being predominantly responsible. Hence, our results suggest a major pathophysiological role for NBCn1 that may be clinically relevant.

Background:We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries.Methods:We analysed the data on 257 362 women diagnosed with breast cancer during 2000–7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis.Results:Age-standardised 3-year net survival was 87–89% in the UK and Denmark, and 91–94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42–45% elsewhere. Women in the UK had low survival for TNM stage III–IV disease compared with other countries.Conclusion:International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.