Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

被引：230

作者：

Tolaney, Sara M. ^{[1
]}

Guo, Hao ^{[1
]}

Pernas, Sonia ^{[1
,2
]}

Barry, William T. ^{[1
]}

Dillon, Deborah A. ^{[3
]}

Ritterhouse, Lauren ^{[3
,4
]}

Schneider, Bryan P. ^{[5
]}

Shen, Fei ^{[5
]}

Fuhrman, Kit ^{[6
]}

Baltay, Michele ^{[3
]}

Dang, Chau T. ^{[7
,8
]}

Yardley, Denise A. ^{[9
]}

Moy, Beverly ^{[10
]}

Marcom, P. Kelly ^{[11
]}

Albain, Kathy S. ^{[12
]}

Rugo, Hope S. ^{[13
]}

Ellis, Mathew J. ^{[14
]}

Shapira, Iuliana ^{[15
,16
]}

Wolff, Antonio C. ^{[17
]}

Carey, Lisa A. ^{[18
]}

Overmoyer, Beth ^{[1
]}

Partridge, Ann H. ^{[1
]}

Hudis, Clifford A. ^{[7
,8
,19
]}

Krop, Ian E. ^{[1
]}

Burstein, Harold J. ^{[1
]}

Winer, Eric P. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA

[2] Inst Catala Oncol HU Bellvitge IDIBELL, Barcelona, Spain

[3] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[4] Univ Chicago, Chicago, IL 60637 USA

[5] Indiana Univ Sch Med, Indianapolis, IN 46202 USA

[6] NanoString Technol, Seattle, WA USA

[7] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[8] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[9] Sarah Cannon Canc Ctr, Nashville, TN USA

[10] Massachusetts Gen Hosp, Boston, MA 02114 USA

[11] Duke Canc Inst, Durham, NC USA

[12] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA

[13] Univ Calif San Francisco, San Francisco, CA 94143 USA

[14] Lester & Sue Smith Breast Ctr, Baylor Clin, Houston, TX USA

[15] Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA

[16] SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA

[17] Johns Hopkins Univ, Baltimore, MD USA

[18] Univ N Carolina, Chapel Hill, NC 27515 USA

[19] Amer Soc Clin Oncol, Alexandria, VA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 22期

关键词：

DISTANT RECURRENCE; PAM50; RISK; CHEMOTHERAPY; SURVIVAL; OUTCOMES; SCORE;

D O I：

10.1200/JCO.19.00066

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEThe Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN).PATIENTS AND METHODSIn this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes received paclitaxel (80 mg/m(2)) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer-specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN.RESULTSA total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%).CONCLUSIONWith longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors.

引用

页码：1868 / +

页数：11

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