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A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer.

Robertson JF, Dixon JM, Sibbering DM, Jahan A, Ellis IO, Channon E, Hyman-Taylor P, Nicholson RI, Gee JM - Breast Cancer Res. (2013)

Bottom Line: F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F.In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A.No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer.

Methods: In this double-blind, multicenter trial, 121 patients received fulvestrant 500 mg on Day 1 plus anastrozole 1 mg/day for 14 to 21 days (F + A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2 to 3 weeks before surgery. ER, progesterone-receptor (PgR) and Ki67 expression were determined from tumor biopsies before treatment and at surgery.

Results: A total of 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: -41%, P = 0.0001; F + A: -39%, P = 0.0001; A: -13%, P = 0.0034). F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were -34% to -45%, and -75% to -85%, respectively; all P = 0.0001), with no differences between groups.

Conclusions: In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

Trial registration: Clinicaltrials.gov NCT00259090.

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Study design. ER, estrogen receptor.
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Figure 1: Study design. ER, estrogen receptor.

Mentions: Trial 0057 was a phase II, double-blind, randomized, multicenter trial (9238IL/0057; NCT00259090). Patients were postmenopausal women (>12 months since the last menstrual period and/or castrate levels of follicle-stimulating hormone (>40 IU/liter)) with histologically or cytologically confirmed ER-positive, primary breast cancer (T1, T2 or T3). Patients had to be fit for surgery within one month and have a tumor large enough to provide sufficient biopsy samples. Patients were excluded from the trial if they had evidence of metastatic disease; received prior endocrine treatment for breast cancer, prior neoadjuvant chemotherapy or prior radiotherapy to the primary tumor; abnormal laboratory values; any severe concurrent condition; received hormone replacement therapy within the past four weeks; a history of disease affecting steroid metabolism; a history of bleeding diathesis, thrombocytopenia or a need for long-term anti-coagulant therapy; risk of human immunodeficiency virus, hepatitis B or hepatitis C transmission; evidence of severe systemic disease; baseline hematology or clinical chemistry outside the normal range; or any other reason that could jeopardize the protocol. Prior to surgery of curative intent, patients were randomized 1:1:1 to receive a single administration of fulvestrant 500 mg (2 × 250 mg on Day 1 via intramuscular injection) plus anastrozole (1 mg orally once daily for 14 to 21 days), or fulvestrant 500 mg plus anastrozole placebo or anastrozole plus fulvestrant placebo (Figure 1).


A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer.

Robertson JF, Dixon JM, Sibbering DM, Jahan A, Ellis IO, Channon E, Hyman-Taylor P, Nicholson RI, Gee JM - Breast Cancer Res. (2013)

Study design. ER, estrogen receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672778&req=5

Figure 1: Study design. ER, estrogen receptor.
Mentions: Trial 0057 was a phase II, double-blind, randomized, multicenter trial (9238IL/0057; NCT00259090). Patients were postmenopausal women (>12 months since the last menstrual period and/or castrate levels of follicle-stimulating hormone (>40 IU/liter)) with histologically or cytologically confirmed ER-positive, primary breast cancer (T1, T2 or T3). Patients had to be fit for surgery within one month and have a tumor large enough to provide sufficient biopsy samples. Patients were excluded from the trial if they had evidence of metastatic disease; received prior endocrine treatment for breast cancer, prior neoadjuvant chemotherapy or prior radiotherapy to the primary tumor; abnormal laboratory values; any severe concurrent condition; received hormone replacement therapy within the past four weeks; a history of disease affecting steroid metabolism; a history of bleeding diathesis, thrombocytopenia or a need for long-term anti-coagulant therapy; risk of human immunodeficiency virus, hepatitis B or hepatitis C transmission; evidence of severe systemic disease; baseline hematology or clinical chemistry outside the normal range; or any other reason that could jeopardize the protocol. Prior to surgery of curative intent, patients were randomized 1:1:1 to receive a single administration of fulvestrant 500 mg (2 × 250 mg on Day 1 via intramuscular injection) plus anastrozole (1 mg orally once daily for 14 to 21 days), or fulvestrant 500 mg plus anastrozole placebo or anastrozole plus fulvestrant placebo (Figure 1).

Bottom Line: F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F.In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A.No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer.

Methods: In this double-blind, multicenter trial, 121 patients received fulvestrant 500 mg on Day 1 plus anastrozole 1 mg/day for 14 to 21 days (F + A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2 to 3 weeks before surgery. ER, progesterone-receptor (PgR) and Ki67 expression were determined from tumor biopsies before treatment and at surgery.

Results: A total of 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: -41%, P = 0.0001; F + A: -39%, P = 0.0001; A: -13%, P = 0.0034). F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were -34% to -45%, and -75% to -85%, respectively; all P = 0.0001), with no differences between groups.

Conclusions: In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

Trial registration: Clinicaltrials.gov NCT00259090.

Show MeSH
Related in: MedlinePlus