TOX3 mutations in breast cancer.

TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs) in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe) was identified in one tumour (genomic DNA and cDNA). Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.

Maternal and neonatal outcomes of spontaneously conceived pregnancies in mothers over 45 years: a review of the literature.

PURPOSE: There is little published data on pregnancy outcomes in women who had conceived spontaneously after age 45 years. The aim of this review is to provide accurate information on the risks and probable outcomes of spontaneously conceived pregnancies in women over the age of 45 years, which will enable clinicians to counsel such women appropriately, carry out adequate risk assessment, and ensure better care for pregnancies in this population. DESIGN: A literature search was performed using EmBase and PubMed for English language articles published between 1970 and 2011, with extractable data on mothers aged ≥45 at the time of delivery and with ≥95% spontaneous conception in the study population. RESULTS: Six such studies with a total pooled number of 505 women were identified. Overall, there is increased maternal morbidity and rates of caesarean section, as well as higher incidence of premature births and admission to special care baby unit. Contrary to popular belief, career is not always an important factor in delaying childbearing, especially in developing countries. Other factors may include cultural acceptance of large families and lack of contraception, although more research may be carried out in order to explain these hypotheses. CONCLUSION: Pooled retrospective data suggest that women who conceived spontaneously after the age of 45 years have increased maternal morbidity and rates of caesarean section, as well as higher incidence of premature births and admission to special care baby unit.