The impact of chemotherapy dose density and dose intensity on breast cancer outcome: what have we learned?

Optimising chemotherapy dose density and dose intensity are strategies aimed at improving outcomes in adjuvant therapy for patients with breast cancer. There are, in theory, at least five models allowing the delivery of a higher overall drug dose intensity. These are reviewed in this article and vary according to three main variables: the dose per course, the interval between doses and the total cumulative dose. Cyclophosphamide, anthracyclines and taxanes are among the most active agents for the treatment of breast cancer and, as such, they have been or are currently the focus of prospective, randomised clinical trials testing some of these dose-intensity models in the adjuvant setting. The results of recent trials suggest that anthracyclines, but not cyclophosphamide, are associated with better outcomes if used at higher doses per course and at higher cumulative doses. However, care has to be taken with premenopausal women where an increased dose of anthracycline per course but a reduced cumulative dose appears to produce a worse outcome. Moreover, decreasing the interval between doses, for anthracyclines and cyclophosphamide, does not seem to provide, so far, additional benefits for women with locally advanced breast cancer. This approach is not feasible with docetaxel, since an increase in dose density induces unwanted side-effects. These results represent our current state of knowledge, but clinical trials are being performed to evaluate further the effect of dose intensity, dose density and cumulative dose of key therapeutic agents on patient outcomes.

Impact of various endocrine and paracrine factors on in vitro culture of preantral follicles in rodents

Folliculogenesis is a complex process regulated by various paracrine and autocrine factors. In vitro growth systems of primordial and preantral follicles have been developed for future use of immature oocytes, as sources of fertilizable oocytes and for studying follicular growth and oocyte maturation mechanisms. Rodents were often chosen for in vitro follicular culture research and a lot of factors implicated in folliculogenesis have been identified using this model. To date, the mouse is the only species in which the whole process of follicular growth, oocyte maturation, fertilization and embryo transfer into recipient females was successfully performed. However, the efficiency of in vitro culture systems must still be considerably improved. Within the follicle, numerous events affect cell proliferation and the acquisition of oocyte developmental competency in vitro, including interactions between the follicular cells and the oocyte, and the composition of the culture medium. Effects of the acting factors depend on the stage of follicle development, the culture system used and the species. This paper reviews the action of endocrine, paracrine factors and other components of culture medium on in vitro growth of preantral follicles in rodents.