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Levasseur N.,Ottawa Hospital and Ottawa Hospital Cancer Center | Clemons M.,Ottawa Hospital and Ottawa Hospital Cancer Center | Clemons M.,Ottawa Hospital Research Institute | Hilton J.,Ottawa Hospital Research Institute | And 4 more authors.
Minerva Chirurgica | Year: 2015

Until recently, the use of neoadjuvant endocrine therapy was mainly restricted to those patients whose general frailty or comorbidities were contraindications to surgery. There is now increased evidence that certain patient populations (i.e. older patients with hormonereceptor positive disease) can gain as good a pathologic response, with considerably less toxicity, from neoadjuvant endocrine therapy than from neoadjuvant chemotherapy. Optimization of neoadjuvant endocrine therapy is therefore an important therapeutic goal. However, possibly of greater importance in the overall management of breast cancer, is the increased interest in exploring the effects of brief periods of endocrine therapy on in vivo biomarkers, in so called window of opportunity trials. These trials can not only be used to identify the mechanisms of action of novel agents but also to predict optimal subsequent adjuvant therapy for individual patients. While this paper will briefly review the history of neoadjuvant endocrine therapy, more emphasis will be on the evaluation of pivotal window of opportunity trials that will likely lead to a long awaited paradigm shift in the management of breast cancer.


PubMed | Ottawa Hospital and Ottawa Hospital Cancer Center, Ottawa Hospital Research Institute, Ottawa Hospital and McMaster University
Type: | Journal: International journal of surgical oncology | Year: 2015

The waiting period to surgery represents a valuable window of opportunity to evaluate novel therapeutic strategies. Interventional studies performed during this period require significant multidisciplinary collaboration to overcome logistical hurdles. We undertook a one-year prospective window of opportunity study to assess feasibility.Eligible newly diagnosed postmenopausal, estrogen receptor positive breast cancer patients awaiting primary surgery received anastrozole daily until surgery. Feasibility was assessed by (a) the proportion of patients who consented and (b) completed the study. Comparison of pre- and poststudy Ki67 labelling index and cleaved caspase 3 scores (CC3) was performed.22/131 (16.8%) patients were confirmed eligible and 20/22 (91%) patients completed the study. 19/20 (95%) patients agreed to undergo optional additional tissue biopsies. The mean duration of anastrozole use was 24.7 (15-44) days. There were a statistically significant decline in mean Ki67 indices of 48.8% (p < 0.001) and a trend towards significance in the decline of CC3 (p = 0.17) when comparing pre- with posttreatment values.window of opportunity trials in breast cancer are a feasible way of assessing the biologic efficacy of different therapies in the presurgical setting. The majority of eligible women were willing to participate including undergoing additional tissue biopsies.


PubMed | Ottawa Hospital and Ottawa Hospital Cancer Center
Type: Journal Article | Journal: Minerva chirurgica | Year: 2015

Until recently, the use of neoadjuvant endocrine therapy was mainly restricted to those patients whose general frailty or comorbidities were contraindications to surgery. There is now increased evidence that certain patient populations (i.e. older patients with hormone-receptor positive disease) can gain as good a pathologic response, with considerably less toxicity, from neoadjuvant endocrine therapy than from neoadjuvant chemotherapy. Optimization of neoadjuvant endocrine therapy is therefore an important therapeutic goal. However, possibly of greater importance in the overall management of breast cancer, is the increased interest in exploring the effects of brief periods of endocrine therapy on in vivo biomarkers, in so called window of opportunity trials. These trials can not only be used to identify the mechanisms of action of novel agents but also to predict optimal subsequent adjuvant therapy for individual patients. While this paper will briefly review the history of neoadjuvant endocrine therapy, more emphasis will be on the evaluation of pivotal window of opportunity trials that will likely lead to a long awaited paradigm shift in the management of breast cancer.

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