Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study.
Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation.



A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade.



A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors.



Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.
Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France. alexandredenonneville@gmail.com.|Aix-Marseille University, Marseille, France. alexandredenonneville@gmail.com.
Alexandre
0000-0001-6710-8284
A
de Nonneville
Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.|Aix-Marseille University, Marseille, France.
Anthony
A
Gonçalves
Department of Clinical Research and Investigation, Biostatistics and Methodology UnitInstitut Paoli Calmettes, Marseille, France.
Christophe
C
Zemmour
Institut René Gauducheau, St Herblain, France.
Jean M
JM
Classe
Department of Surgical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.
Monique
M
Cohen
Aix-Marseille University, Marseille, France.|Department of Surgical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.
Eric
E
Lambaudie
Institut Curie, Paris, France.
Fabien
F
Reyal
Pôle Santé République, Clermont-Ferrand, France.
Christophe
C
Scherer
Department of Radiotherapy, Hôpital de la Timone, Marseille, France.
Xavier
X
Muracciole
Department of Surgical Oncology, CRLC Val-d'Aurelle, Montpellier, France.
Pierre E
PE
Colombo
Centre Oscar Lambret, Lille, France.
Sylvia
S
Giard
Centre René Huguenin, Saint Cloud, France.
Roman
R
Rouzier
Hôpital des Diaconnesses, Paris, France.
Richard
R
Villet
Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.
Nicolas
N
Chopin
Department of Gynecologic and Breast Cancers, Hôpital Tenon, Paris, France.
Emile
E
Darai
Department of Surgical Oncology, Gustave-Roussy, Villejuif, France.
Jean R
JR
Garbay
Department of Surgical Oncology, Centre Jean-Perrin, Clermont-Ferrand, France.
Pierre
P
Gimbergues
Department of Obstetrics Gynecology, Hôpital de la Conception, Marseille, France.
Laura
L
Sabiani
Department of Surgical Oncology, Centre Georges-François Leclerc, Dijon, France.
Charles
C
Coutant
Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.|Aix-Marseille University, Marseille, France.
Renaud
R
Sabatier
Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.|Aix-Marseille University, Marseille, France.
François
F
Bertucci
Department of Clinical Research and Investigation, Biostatistics and Methodology UnitInstitut Paoli Calmettes, Marseille, France.
Jean M
JM
Boher
Aix-Marseille University, Marseille, France.|Department of Surgical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France.
Gilles
G
Houvenaeghel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Adjuvant chemotherapy; HER2; Subcentimetric breast cancer; Trastuzumab