Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial.
OBJECTIVE
The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) -positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial.


METHODS
Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2)-positive cancers, and tolerability.


RESULTS
There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated.


CONCLUSIONS
Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.
Smith
Ian E
IE
Breast Unit, Royal Marsden Hospital, London SW3 6JJ, UK. ian.smith@rmh.nhs.uk
Dowsett
Mitch
M
Ebbs
Stephen R
SR
Dixon
J Michael
JM
Skene
Anthony
A
Blohmer
J-U
JU
Ashley
Susan E
SE
Francis
Stephen
S
Boeddinghaus
Irene
I
Walsh
Geraldine
G
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D016017:Odds Ratio; D010919:Placebos; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole