"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1(st )line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2(nd )line), 46.1% (on 3(rd )line) and 20% (on 4(th )line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7%) patients had de novo resistance on 1(st )line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2(nd )line) and 22.2% (on 3(rd )line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4(th )line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1(st )line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances

The Effect of Gender Policies on Fertility: The Moderating Role of Education and Normative Context

In this paper, we aim to assess the extent to which individual-level completed fertility varies across contexts characterized by policies supporting different gender division of labor models. We examine key labor market and care policies that shape gender relations in households and in the public domain. We also consider the role of gender norms, which can act as both a moderator and a confounding factor for policy effects. We hypothesize that, by facilitating role compatibility and reducing the gendered costs of childrearing, policies that support gender equality lead to an increase in fertility levels and to a reduction in fertility differentials by the level of education. Using individual-level data from the European Union Survey on Income and Living Conditions for 16 countries, combined with country-level data, we analyze completed fertility through multilevel Poisson’s models. We find that the national level of childcare coverage is positively associated with fertility. Family allowances, prevalence of women’s part-time employment and length of paid leaves were also found to be positively associated with completed fertility, though the associations were not statistically significant. These variables show a significant positive pattern according to education. A high number of average working hours for men are negatively associated with completed fertility and show a strong negative pattern by educational level. The prevalence of gender-egalitarian norms is highly predictive of fertility levels, yet we found no consistent evidence of a weaker association of gender-equality policies in countries where egalitarian values are less prevalent

Measuring proliferation in breast cancer: practicalities and applications

Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy

MMP Activity Detection in Zymograms

Matrix metalloproteinases (MMP) belong to a distinguished class of zinc-depending endopeptidases. Zymography is a semi-quantitative tool for determining the activity of different MMP isoenzymes in a variety of biological samples. In substrate gel zymography, protein samples of different origin (tissue, cell lysates, plasma/serum, perfusates, other liquids) are separated in sodium dodecyl sulfate (SDS) polyacrylamide gels containing co-polymerized substrate (gelatin, casein, elastin, etc.), and after incubation enabling substrate cleavage by MMPs, MMP activities are detected after the gel staining as transparent bands against a dark-blue background. In situ zymography is a histological modification of substrate zymography in frozen sections, allowing detection of the localization of the MMP activities within the tissue. Here we describe detailed experimental protocols of all abovementioned techniques and provide examples of several sample measurements

Renewed interest in the progesterone receptor in breast cancer

Elgene Lim, Carlo Palmieri, and Wayne D Tille