Breast cancer electron intraoperative radiotherapy: assessment of preoperative selection factors from a retrospective analysis of 758 patients and review of literature.

PURPOSE: To report our experience with full-dose 21 Gy IORT in early breast cancer patients after breast-conserving surgery to define most important selection factors. METHODS: Seven hundred and fifty eight patients, subjected to conserving surgery and IORT, were retrospectively analyzed evaluating most important clinical outcomes. RESULTS: Median follow up was 5.2 years. Results from Cox analyses defined 2 groups of patients, "suitable" (age > 50 years, non lobular histology, tumour size ≤ 2 cm, pN0 or pNmic, ki67 ≤ 20%, non triple negative receptor status and G1-G2) and "unsuitable" for IORT, with a higher rate of breast related events moving from "suitable" to "unsuitable" group. The 5 year rate of IBR is 1.8% in suitable group with significant differences versus unsuitable (1.8 vs. 11.6%, p < 0.005). Same differences between two groups were evidenced in true local relapse (0.6 vs. 6.9%, p < 0.005) and in new ipsilateral BC (1.1 vs. 4.7%, p < 0.015). CONCLUSIONS: In our current practice we consider the following preoperative factors to select patients suitable for IORT: age > 50 years, absence of lobular histology, tumor size ≤ 2 cm, pN0 or pNmic, according to APBI consensus statement, including also ki67 ≤ 20%, non triple negative receptor status and G1-G2.

Maternal hypothyroidism selectively affects the expression of neuroendocrine-specific protein A messenger ribonucleic acid in the proliferative zone of the fetal rat brain cortex.

Thyroid hormone is essential for mammalian brain development, but the mechanisms by which thyroid hormone exerts its effects, the developmental processes affected, and the timing of thyroid hormone effects are poorly understood. An important question is whether thyroid hormone of maternal origin is essential in guiding fetal brain development. In both humans and rats, thyroid hormone of maternal origin reaches the fetus before the onset of fetal thyroid function. Moreover, receptors for thyroid hormone (TRs) are present in the fetal brain and are occupied by thyroid hormone. Finally, a recent report strongly indicates that transient undiagnosed maternal hypothyroidism can lead to measurable neurological deficits in the offspring despite the lack of neonatal hypothyroidism. Considering that TRs are ligand-activated transcription factors, we recently initiated a project to identify thyroid hormone-responsive genes in the fetal cortex before the onset of fetal thyroid function. One of the thyroid hormone-responsive genes we identified, neuroendocrine-specific protein (NSP), is expressed as two separate transcripts, NSP-A and NSP-C. Only NSP-A is affected by maternal thyroid hormone. We now demonstrate that the messenger RNA encoding NSP-A is expressed exclusively in the proliferative zone of the fetal cortex, and that its expression is affected by maternal hypothyroidism. Moreover, as development proceeds, NSP-A becomes selectively expressed in Purkinje cells of the cerebellum, a well known thyroid hormone-responsive cell. These findings strongly support the concept that thyroid hormone of maternal origin exerts specific receptor-mediated effects on fetal brain development.