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Clinical Trial
. 2023 Apr;30(4):2111-2118.
doi: 10.1245/s10434-022-12972-5. Epub 2023 Jan 18.

Local-Regional Recurrence After Neoadjuvant Endocrine Therapy: Data from ACOSOG Z1031 (Alliance), a Randomized Phase 2 Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women with Estrogen Receptor-Positive Clinical Stage 2 or 3 Breast Cancer

Kelly K Hunt  1 , Vera J Suman  2 , Hannah F Wingate  3 , A Marilyn Leitch  4 , Gary Unzeitig  5 , Judy C Boughey  6 , Funda Meric-Bernstam  3 , Matthew J Ellis  7 , John Olson  8
Affiliations
Clinical Trial

Local-Regional Recurrence After Neoadjuvant Endocrine Therapy: Data from ACOSOG Z1031 (Alliance), a Randomized Phase 2 Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women with Estrogen Receptor-Positive Clinical Stage 2 or 3 Breast Cancer

Kelly K Hunt et al. Ann Surg Oncol. 2023 Apr.

Abstract

Background: The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to neoadjuvant chemotherapy (NCT) after 4 weeks of receiving NAI with Ki67 greater than 10% increases pathologic complete response (pCR) in postmenopausal women with estrogen receptor-enriched (Allred score 6-8) breast cancer (BC).

Methods: The study enrolled 622 women with clinical stage 2 or 3 estrogen receptor-positive (ER+) BC. Cohort A comprised 377 patients, and cohort B had 245 patients. The analysis cohort consisted of 509 patients after exclusion of patients who did not meet the trial eligibility criteria, switched to NCT or surgery due to 4-week Ki67 greater than 10%, or withdrew before surgery. Distribution of time to local-regional recurrence (LRR) was estimated using the competing-risk approach, in which distant recurrence and second primaries were considered to be competing-risk events. Patients who died without LRR, distant recurrence, or a second primary were censored at the last evaluation.

Results: Of the 509 patients, 342 (67.2%) had breast-conserving surgery (BCS). Of 221 patients thought to require mastectomy at presentation, 50% were able to have BCS. Five (1%) patients had no residual disease in the breast or nodes at surgery. Among 382 women alive at this writing, 90% have been followed longer than 5 years. The 5-year cumulative incidence rate for LRR is estimated to be 1.53% (95% confidence interval 0.7-3.0%).

Conclusions: Rarely does NAI result in pCR for patients with stage 2 or 3 ER+ BC. However, a significant proportion will have downstaged to allow for BCS. Local-regional recurrence after surgery is uncommon (1.5% at 5 years), supporting the use of BCS after NAI.

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Conflict of interest statement

Disclosure of commercial interest:

Kelly K. Hunt: Consulting or Advisory Role: Armada Health, AstraZeneca, Merck & Co.; Research funding to MD Anderson Cancer Center: Cairn Surgical, Eli Lilly & Co, Lumicell

Vera J. Suman: No relationship to disclose

Hannah F. Wingate: No relationship to disclose

A. Marilyn Leitch: Consulting or Advisory Role: Celgene, Genomic Health, Castle Biosciences

Gary Unzeitig: No relationships to disclose

Funda Meric-Bernstam: Membership on Board of Directors or Advisory Committees (includes consulting)

Protai Bio Ltd; Astra Zeneca; Seagen (formerly Seattle Genetics); Zymeworks; OnCusp Therapeutics; Harbinger Health; Tallac Therapeutics; Daiichi Sankyo; Lengo Therapeutics; Sanofi Pharmaceuticals; FogPharma; Karyopharm; LOXO Oncology; Biovica; F. Hoffmann La-Roche

Judy C. Boughey: Consulting or Advisory Role: Cairn Surgical, SymBioSis; Research funding to Mayo Clinic: Eli Lilly & Co.

John Olson: Stock or Other Ownership: Core Prognostex

Matthew J. Ellis: Employment: AstraZeneca; Patents, Royalties, Other Intellectual Property: PAM50-based diagnostics, including Prosigna (Veracyte)

Figures

FIGURE 1:
FIGURE 1:
CONSORT Diagram
See this image and copyright information in PMC

References

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