HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade

被引：113

作者：

Prat, Aleix ^{[1
,2
,3
]}

Pascual, Tomas ^{[1
,2
,3
]}

De Angelis, Carmine ^{[4
,5
]}

Gutierrez, Carolina ^{[4
,5
]}

Llombart-Cussac, Antonio ^{[6
]}

Wang, Tao ^{[4
]}

Cortes, Javier ^{[7
,8
,9
]}

Rexer, Brent ^{[10
]}

Pare, Laia ^{[1
,2
,3
]}

Forero, Andres ^{[11
]}

Wolff, Antonio C. ^{[12
]}

Morales, Serafin ^{[13
]}

Adamo, Barbara ^{[1
,2
]}

Braso-Maristany, Fara ^{[1
,2
]}

Vidal, Maria ^{[1
,2
]}

Veeraraghavan, Jamunarani ^{[4
,5
]}

Krop, Ian ^{[14
]}

Galvan, Patricia ^{[1
,2
]}

Pavlick, Anne C. ^{[4
]}

Bermejo, Begona ^{[15
]}

Izquierdo, Miguel ^{[16
]}

Rodrik-Outmezguine, Vanessa ^{[16
]}

Reis-Filho, Jorge S. ^{[17
]}

Hilsenbeck, Susan G. ^{[4
,5
]}

Oliveira, Mafalda ^{[9
,18
]}

Vittoria Dieci, Maria ^{[20
,21
]}

Griguolo, Gaia ^{[20
,21
]}

Fasani, Roberta ^{[9
]}

Nuciforo, Paolo ^{[9
]}

Parker, Joel S. ^{[19
]}

Conte, PierFranco ^{[20
,21
]}

Schiff, Rachel ^{[4
,22
,23
]}

Guarneri, Valentina ^{[20
,21
]}

Osborne, C. Kent ^{[4
,5
,22
,23
]}

Rimawi, Mothaffar F. ^{[4
,5
,22
]}

机构：

[1] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain

[2] August Pi & Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain

[3] SOLTI Breast Canc Cooperat Grp, Dept Sci, Barcelona, Spain

[4] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA

[5] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA

[6] Hosp Arnau Vilanova, Dept Med Oncol, Valencia, Spain

[7] IOB Inst Oncol, Quironsalud Grp, Madrid, Spain

[8] IOB Inst Oncol, Quironsalud Grp, Barcelona, Spain

[9] Vall dHebron Inst Oncol VHIO, Breast Canc Grp, Barcelona, Spain

[10] Vanderbilt Univ, Dept Med, Nashville, TN USA

[11] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[12] Johns Hopkins Univ, Baltimore, MD USA

[13] Hosp Arnau Vilanova, Dept Med Oncol, Lleida, Spain

[14] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[15] Hosp Clin Valencia, Dept Med Oncol, Valencia, Spain

[16] Novartis Oncol, Basel, Switzerland

[17] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[18] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain

[19] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[20] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy

[21] IRCCS, Med Oncol 2, Ist Oncol Veneto, Padua, Italy

[22] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[23] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2020年 / 112卷 / 01期

关键词：

PERTUZUMAB PLUS TRASTUZUMAB; OPEN-LABEL; INTRINSIC SUBTYPES; PHASE-II; CLINICAL-IMPLICATIONS; SURVIVAL OUTCOMES; LAPATINIB; CHEMOTHERAPY; MULTICENTER; COMBINATION;

D O I：

10.1093/jnci/djz042

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI]=35.4% to 53.9% vs 11.6%, 95% CI=6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI=3.10 to 11.80, P<.001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI=22.3% to 95.7% vs 14.7% in others, 95% CI=4.9% to 31.1%; adjusted OR=11.60, 95% CI = 1.66 to 81.10, P=.01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR]=0.52, 95% CI = 0.35 to 0.79, P<.001); higher ORR (16.3%, 95% CI=8.9% to 26.2% vs 3.7%, 95% CI=0.8% to 10.3%, P=.02); and longer OS (HR=0.66, 95% CI=0.44 to 0.97, P=.01). Conclusions Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer.

引用

页码：46 / 54

页数：9

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