Prognostic Value of MammaPrint® in Invasive Lobular Breast Cancer.

BACKGROUND: MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup. STUDY AIM: The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. MATERIALS AND METHODS: Univariate and multivariate survival associations for overall survival (OS), distant metastasis-free interval (DMFI), and distant metastasis-free survival (DMFS) were studied in a study population of 217 early-stage ILC breast cancer patients from five different clinical studies. RESULTS AND DISCUSSION: A significant association between MammaPrint High Risk and poor clinical outcome was shown for OS, DMFI, and DMFS. A subanalysis was performed on the lymph node-negative study population. In the lymph node-negative study population, we report an up to 11 times higher change in the diagnosis of an event in the MammaPrint High Risk group. For DMFI, the reported hazard ratio is 11.1 (95% confidence interval = 2.3-53.0). CONCLUSION: Study results validate MammaPrint as an independent factor for breast cancer patients with early-stage invasive lobular breast cancer. Hazard ratios up to 11 in multivariate analyses emphasize the independent value of MammaPrint, specifically in lymph node-negative ILC breast cancers.

Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart.

Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions. Two NER subpathways have been identified, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Little is known about the expression of NER pathways in differentiated cells. We assessed the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4 PP) in terminally differentiated myocytes and proliferating fibroblasts isolated from the hearts of neonatal rats. Myocytes and fibroblasts were found to carry out efficient removal of 6-4 PP but display poor repair of CPD by GGR. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. The inefficient repair of CPD at the genome overall level occurs in the absence of massive apoptosis, but goes along with an undetectable level of transcription of the p48 gene, known to be mutated in xeroderma pigmentosum group E (XP-E) patients and recently proposed to be essential for repair of CPD in nonexpressed DNA. Taken together, the results suggest that primary non-dividing cardiac myocytes and proliferating fibroblasts from rat heart selectively remove CPD from the transcribed strand of transcriptionally active genes. GGR of CPD is poor due to the absence of p48 expression.

A titanium plasma-sprayed cup with and without hydroxyapatite-coating: a randomised radiostereometric study of stability and osseointegration.

We present a prospective, two-centre radiostereometric analysis (RSA) regarding the stability of a flattened pole titanium press-fit cup (EP-FIT PLUS), and whether additional hydroxyapatite coating leads to faster bone ingrowth into the porous coating. Forty-two postmenopausal female patients (44 hips) undergoing total hip arthroplasty for primary osteoarthritis, selected to avoid hormonal factors influencing bone metabolism, were randomised to receive this cup with a titanium-plasma-sprayed surface with or without an additional hydroxyapatite coating. RSA was used to measure cup translation and rotation along three cardinal axes with respect to the host bone at the following time points: immediately postoperatively, at 6 weeks, and at 3, 6, 12, and 24 months. The most pronounced translation was proximal (0.11 mm) and posterior tilt (-0.27°). No difference in translation and rotation could be detected between the two groups. With the exception of one cup with an isolated radiolucent line <2 mm in zone 1, all cups showed complete osseointegration on conventional radiographs. The flattened pole cup provided excellent early stability and no advantage could be detected with additional hydroxyapatite coating.