Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor‐positive breast cancer

Abstract

Although oxytocin (OT) and oxytocin receptor (OTR) are known for roles in parturition and milk let‐down, they are not hypothalamus‐restricted. OT is important in nurturing and opposition to stress. Transcripts encoding OT and OTR have been reported in adult human gut, and OT affects intestinal motility. We tested the hypotheses that OT is endogenous to the enteric nervous system (ENS) and that OTR signaling may participate in enteric neurophysiology. Reverse transcriptase polymerase chain reaction confirmed OT and OTR transcripts in adult mouse and rat gut and in precursors of enteric neurons immunoselected from fetal rats. Enteric OT and OTR expression continued through adulthood but was developmentally regulated, peaking at postnatal day 7. Coincidence of the immunoreactivities of OTR and the neural marker Hu was 100% in the P3 and 71% in the adult myenteric plexus, when submucosal neurons were also OTR‐immunoreactive. Co‐localization with NeuN established that intrinsic primary afferent neurons are OTR‐expressing. Because OTR transcripts and protein were detected in the nodose ganglia, OT signaling might also affect extrinsic primary afferent neurons. Although OT immunoreactivity was found only in ∼1% of myenteric neurons, extensive OT‐immunoreactive varicosities surrounded many others. Villus enterocytes were OTR‐immunoreactive through postnatal day 17; however, by postnatal day 19, immunoreactivity waned to become restricted to crypts and concentrated at crypt‐villus junctions. Immunoelectron microscopy revealed plasmalemmal OTR at enterocyte adherens junctions. We suggest that OT and OTR signaling might be important in ENS development and function and might play roles in visceral sensory perception and neural modulation of epithelial biology. J. Comp. Neurol. 512:256–270, 2009. © 2008 Wiley‐Liss, Inc.

Neoadjuvant endocrine treatment for breast cancer: from bedside to bench and back again?

“…The proact trial was a multicentre, double-blind study in 451 postmenopausal women with er-positive invasive cancer randomized to 3 months of preoperative anastrozole or tamoxifen 18 . The study permitted concurrent chemotherapy at the investigator's discretion, with such treatment being given to 29% of the patients treated with anastrozole and 32% of those treated with tamoxifen.…”

“…Neoadjuvant endocrine therapy trials such as P024 (4 months) 16 , impact (3 months) 17 , and proact (3 months) 18 generally-and relatively arbitrarily-set the duration of neoadjuvant endocrine therapy to 3-4 months, although some trials occasionally used long durations, such as the 4-8 months in the German Neoadjuvant Letrozole trial 20 and the 6 months in the stage trial 19 , thus leaving open the question of the optimal duration of such therapy.…”

Neoadjuvant endocrine therapy: for whom, for how long?

“…Previous studies have evaluated the role of neoadjuvant or preoperative endocrine therapy (PET) in operable hormone receptor (HR)-positive early breast cancer, some comparing the effi cacy of tamoxifen and aromatase inhibitors (e.g., the P024 letrozole trial [2], the IMPACT [3] and PROACT [4] trials). In most of these studies the duration of neoadjuvant therapy was 3-4 months, decided arbitrarily in part due to the fear of progressive disease and loss of operability.…”

Neoadjuvant Systemic Therapy in Breast Cancer

“…Although there remained no difference in this group in ORR, a significantly higher number of women were deemed suitable for breast-conserving surgery following treatment with anastrozole, compared with tamoxifen (46% vs. 22%; p = 0.03). In the Preoperative Arimidex Compared with Tamoxifen trial, the entry criteria was similar to the IMPACT trial, although this study also included patients who were inoperable (Cataliotti et al, 2006). This study also differed in that it included a group of patients who were given concurrent neoadjuvant chemotherapy.…”