Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2–4 N0–1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P<0.0001). Higher Ki-67 proliferation indices were associated with PgR− tumours (median 28.3%, PgR+ 22.9%; P=0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P=0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P=0.004)

Application of ecological momentary assessment in stress-related diseases

Many physical diseases have been reported to be associated with psychosocial factors. In these diseases, assessment relies mainly on subjective symptoms in natural settings. Therefore, it is important to assess symptoms and/or relationships between psychosocial factors and symptoms in natural settings. Symptoms are usually assessed by self-report when patients visit their doctors. However, self-report by recall has an intrinsic problem; "recall bias". Recently, ecological momentary assessment (EMA) has been proposed as a reliable method to assess and record events and subjective symptoms as well as physiological and behavioral variables in natural settings. Although EMA is a useful method to assess stress-related diseases, it has not been fully acknowledged, especially by clinicians. Therefore, the present brief review introduces the application and future direction of EMA for the assessment and intervention for stress-related diseases

A general solution for optimal egg size during external fertilization, extended scope for intermediate optimal egg size and the introduction of Don Ottavio 'tango'

Egg sizes of marine invertebrates vary greatly, both within and between species. Among the proposed causes of this are a trade-off between egg size, egg number and survival probability of offspring, and a selection pressure exerted by sperm limitation during external fertilization. Although larger eggs are indeed a larger target for sperm, producing larger eggs also implies making fewer of them. There has been discussion about whether sperm limitation can (theoretically) and does (in nature) select for larger egg size than under ad libitum sperm. In one specific model, based on a particular fertilization kinetics model and an empirically derived mortality function. the theoretical possibility of a negative shift in optimal egg size with sperm concentration was demonstrated. Here we present a generalized analytical model to explore the effects of survival and fertilization probabilities on optimal egg size. It is demonstrated that incorporating fertilization kinetics greatly increases the scope for intermediate optimal egg size, as opposed to eggs of minimal or maximal size. Second, we present a general analytical qualitative solution to the question whether optimal egg size depends on sperm concentration. It is shown that, under the condition that an intermediate optimal egg size exists, this qualitative outcome of the model (positive, negative or no relation between optimal egg size and sperm limitation) depends on the structure of the fertilization kinetics part of the model. Finally, we evaluate fertilization kinetics models with respect to the general solution, using two previously published kinetics models ('Don Giovanni' and 'Don Ottavio') and a novel alteration of one of them in which sperm concentration covaries with egg concentration (Don Ottavio 'tango'). For all three models the relationship between optimal egg size and sperm concentration is shown to be always negative. This paper thus shows how biologically realistic relationships between egg size on the one hand and survival and fertilization probability on the other hand predict optimal egg size to be intermediate. and that this optimum is in general expected to increase when sperm become more limiting. (C) 2004 Elsevier Ltd. All rights reserved