ORLANDO – Anastrozole led the pack in a new analysis of a clinical trial that found neoadjuvant aromatase inhibitor therapies can shrink large, endocrine-rich tumors in postmenopausal women scheduled for mastectomy.
Half of these women were able to have successful breast-conserving surgery instead, lead author Dr. John A. Olson Jr. reported at a symposium sponsored by the Society of Surgical Oncology. Conversion rates ranged from 25% to 70.4%, based on tumor stage and the aromatase inhibitor (AI) that was used.
Dr. John A. Olson Jr.
"Even in the absence of a randomized clinical trial, we feel it’s reasonable to consider neoadjuvant endocrine therapy for selected women who desire breast-conserving surgery," said Dr. Olson, who recently joined the University of Maryland, Baltimore, as chief of its division of general and oncologic surgery. He had been at Duke University in Durham, N.C.
Among all patients initially considered inoperable or mastectomy candidates, breast-conserving surgery was made possible in 48.2% of those on exemestane (Aromasin), 43.1% of those on letrozole (Femara), and 64.7% of those on anastrozole (Arimidex), reported Dr. Olson. The differences between these AIs were not statistically significant, however, and he noted that the study was not powered to detect differences among the individual drugs by surgical assignment.
The phase III American College of Surgeons Oncology Group (ACOSOG) Z1031 trial randomized 377 women with stage II or III estrogen-receptor (ER)-positive breast cancer. This analysis addressed 163 women who were considered to have inoperable disease or were scheduled for mastectomy. Treatment-naïve women with stage T2 through T4c with any nodal involvement but not metastases and palpable tumors greater than 2 cm were enrolled.
Women in the trial received 16-18 weeks of neoadjuvant exemestane 25 mg daily, letrozole 2.5 mg, or anastrozole 1 mg. Following surgery, they continued on AI therapy where possible, and received adjuvant radiotherapy and chemotherapy at the treating physician’s discretion. The overall clinical tumor response rate to neoadjuvant AI therapy was 69% (258 of 374 patients).
At the end of AI therapy, 91 (56%) of the 163 women classified as having inoperable disease or requiring a mastectomy at baseline were considered to be suitable candidates for a breast-conserving procedure. The remaining 72 were assigned to mastectomy. One-third of women who underwent breast-conserving surgery after AI therapy required additional surgery to ensure adequate resection margins, Dr. Olson noted.
Eleven of the women assigned to breast conservation eventually had a mastectomy, for a total mastectomy-to-breast-conserving surgery conversion rate of 51%. Conversely, 4 (5%) of the women scheduled for mastectomy at the end of neoadjuvant therapy went on to a breast-conserving procedure.
Among 189 considered eligible for breast-conserving surgery before treatment, 17 were recommended for mastectomy following AI therapy, and 16 went on to undergo it, while 1 had a breast-conserving procedure instead.
Of the 172 recommended for conservation surgery after neoadjuvant treatment, 16 went on to mastectomy, and 156 had the recommended conservation surgery. In all, 64 of the 172 patients (37%) required re-excision for inadequate margins on the first go-round.
In a breakdown by drug and tumor type, 70.4% of women with T2 tumors on either exemestane or anastrozole had successful conversion to breast conservation, compared with 55.2% of patients on letrozole. Among patients with T3 tumors, 25% of those on exemestane went on to breast-conserving surgery, compared with 28.6% of those on letrozole and 60% of those on anastrozole. Of those with higher tumor stages (T4a-c), exemestane accounted for 28.6% of conversions, compared with 37.5% for letrozole and 50% for anastrozole.
The investigators performed a multivariate analysis controlling for clinical T and N stage, surgical impression, assigned treatment arm, tumor size, and tumor response to therapy. This analysis revealed that the factors significantly predicting conversion to breast-conserving operations were clinical stage T2 (odds ratio, 2.11; P = .0364) and smaller vs. larger tumors (OR, 4.03; P = .006) for those not larger than 2.0 cm in their largest dimension prior to surgery compared with tumors 5.1 cm or greater. Intermediate-size tumors (2.1-5.0 cm) trended toward but did not reach significance.
"Importantly, there was no tumor feature or clinical factor that predicted the change in surgical plan. This shows that biological response to the aromatase inhibitor was the driver of the final surgical procedure chosen," Dr. Olson said.
The overall incidence of pathologic stage 1 disease following surgery was 24.3% among mastectomy patients and 44.8% in conservation surgery patients; this difference was not significant.
"The relatively high incidence of stage I disease following AI therapy suggests significant downstaging of this group of patients who presented with clinical stage II or III disease," Dr. Olson said.