Background Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis. Methods VDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality. Results We found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34–0.91) and 0.59 (0.30–1.16) respectively. Conclusions This study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor. Electronic supplementary material The online version of this article (10.1186/s13058-019-1169-1) contains supplementary material, which is available to authorized users.

BackgroundIt has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels.MethodsThe Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer.ResultsThe majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68–0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52–1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low.ConclusionsSNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0925-3) contains supplementary material, which is available to authorized users.

PurposeVitamin D, parathyroid hormone (PTH) and calcium in blood are correlated with each other. Previous studies have suggested vitamin D to have anti-proliferative effects on tumor cells, whereas PTH may have carcinogenic effects. A cancer disease may influence calcium levels in blood, but less is known about calcium and its potential effect on cancer risk and survival. The aim of this study was to examine pre-diagnostic levels of vitamin D (25OHD), PTH and calcium in relation to survival after breast cancer.MethodsThe Malmö Diet and Cancer Study enrolled 17,035 women between 1991 and 1996. 672 patients developed incident invasive breast cancer up until 31 December 2006. Serum samples collected at baseline were analyzed for 25OHD, PTH and calcium. All patients were followed until 31 December 2010 using the Swedish Cause of Death Registry. The analytes were divided into tertiles and the risk of death from breast cancer was analyzed using an adjusted Cox proportional hazards analysis, yielding hazard ratios with 95 % confidence intervals.ResultsLevels of 25OHD and breast cancer mortality were associated in a u-shaped manner with the highest mortality among patients in the first (2.46: 1.38–4.37) and third tertiles (1.99: 1.14–3.49), as compared to the second. An inverse relation was found between calcium levels and breast cancer mortality, with the lowest mortality in the third tertile, (0.53: 0.30–0.92) as compared to the first. There was no clear association between PTH and breast cancer mortality.ConclusionsThis study shows that pre-diagnostic 25OHD and calcium may affect survival following breast cancer.

Purpose The need for sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) patients is currently questioned. Our objective was to investigate the cost-effectiveness of a preoperative noninvasive lymph node staging (NILS) model (an artificial neural network model) for predicting pathological nodal status in patients with cN0 breast cancer (BC). Methods A health-economic decision-analytic model was developed to evaluate the utility of the NILS model in reducing the proportion of cN0 patients with low predicted risk undergoing SLNB. The model used information from a national registry and published studies, and three sensitivity/specificity scenarios of the NILS model were evaluated. Subgroup analysis explored the outcomes of breast-conserving surgery (BCS) or mastectomy. The results are presented as cost (€) and quality-adjusted life years (QALYs) per 1000 patients. Results All three scenarios of the NILS model reduced total costs (–€93,244 to –€398,941 per 1000 patients). The overall health benefit allowing for the impact of SLNB complications was a net health gain (7.0–26.9 QALYs per 1000 patients). Sensitivity analyses disregarding reduced quality of life from lymphedema showed a small loss in total health benefits (0.4–4.0 QALYs per 1000 patients) because of the reduction in total life years (0.6–6.5 life years per 1000 patients) after reduced adjuvant treatment. Subgroup analyses showed greater cost reductions and QALY gains in patients undergoing BCS. Conclusion Implementing the NILS model to identify patients with low risk for nodal metastases was associated with substantial cost reductions and likely overall health gains, especially in patients undergoing BCS.

Newly diagnosed breast cancer (BC) patients with clinical T1–T2 N0 disease undergo sentinel-lymph-node (SLN) biopsy, although most of them have a benign SLN. The pilot noninvasive lymph node staging (NILS) artificial neural network (ANN) model to predict nodal status was published in 2019, showing the potential to identify patients with a low risk of SLN metastasis. The aim of this study is to assess the performance measures of the model after a web-based implementation for the prediction of a healthy SLN in clinically N0 BC patients. This retrospective study was designed to validate the NILS prediction model for SLN status using preoperatively available clinicopathological and radiological data. The model results in an estimated probability of a healthy SLN for each study participant. Our primary endpoint is to report on the performance of the NILS prediction model to distinguish between healthy and metastatic SLNs (N0 vs. N+) and compare the observed and predicted event rates of benign SLNs. After validation, the prediction model may assist medical professionals and BC patients in shared decision making on omitting SLN biopsies in patients predicted to be node-negative by the NILS model. This study was prospectively registered in the ISRCTN registry (identification number: 14341750).

Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.

Previous research suggests associations between low systemic levels of vitamin D and poor breast cancer prognosis and between expression of the vitamin D receptor (VDR) in breast cancers and survival. This study aimed to study associations between pre-diagnostic systemic levels of vitamin D and expression of VDR in subsequent breast tumors, and interactions between vitamin D and VDR on breast cancer mortality. Systemic vitamin D levels were measured in women within the Malmö Diet and Cancer Study. The expression of VDR was evaluated immunohistochemically in a tissue microarray of subsequent breast cancers. Statistical analyses followed. Women with high levels of vitamin D had a smaller proportion of VDR negative breast tumors compared to women with low levels of vitamin D (odds ratio: 0.68; 95% confidence interval: 0.41–1.13). Vitamin D levels were not found to modify the association between low VDR expression and high breast cancer mortality. To conclude, there was no statistical evidence for an association between pre-diagnostic levels of vitamin D and the expression of VDRs in breast cancer, nor did vitamin D levels influence the association between VDR expression and breast cancer mortality. Further studies are needed in order to establish the effects of vitamin D on breast cancer.

Background Axillary staging via sentinel lymph node biopsy (SLNB) is performed for clinically node-negative (N0) breast cancer patients. The Skåne University Hospital (SUS) nomogram was developed to assess the possibility of omitting SLNB for patients with a low risk of nodal metastasis. Area under the receiver operating characteristic curve (AUC) was 0.74. The aim was to validate the SUS nomogram using only routinely collected data from the Swedish National Quality Registry for Breast Cancer at two breast cancer centres during different time periods. Method This retrospective study included patients with primary breast cancer who were treated at centres in Lund and Malmö during 2008–2013. Clinicopathological predictors in the SUS nomogram were age, mode of detection, tumour size, multifocality, lymphovascular invasion and surrogate molecular subtype. Multiple imputation was used for missing data. Validation performance was assessed using AUC and calibration. Results The study included 2939 patients (1318 patients treated in Lund and 1621 treated in Malmö). Node-positive disease was detected in 1008 patients. The overall validation AUC was 0.74 (Lund cohort AUC: 0.75, Malmö cohort AUC: 0.73), and the calibration was satisfactory. Accepting a false-negative rate of 5 per cent for predicting N0, a possible SLNB reduction rate of 15 per cent was obtained in the overall cohort. Conclusion The SUS nomogram provided acceptable power for predicting a disease-free axilla in the validation cohort. This tool may assist surgeons in identifying and counselling patients with a low risk of nodal metastasis on the omission of SLNB staging.