Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes.
OBJECTIVE
To evaluate HER2 status in residual tumor identified at the time of surgery in patients not achieving a pathologic complete response (pCR) and to determine the effect of alterations in HER2 status on recurrence-free survival (RFS).


METHODS
Clinicopathologic data for patients with HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. Surgical specimens for patients achieving less than a pCR were assessed to determine if there was enough residual tissue to evaluate posttreatment HER2 status. RFS was determined using the Kaplan-Meier method and compared by the log-rank statistic.


RESULTS
A pCR was achieved in 72 of the 142 (50.7%) patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 patients. Fluorescence in situ hybridization done on pretreatment specimens confirmed HER2 amplification before beginning therapy. Eight (32.0%) posttreatment tumors were found to be HER2-negative by fluorescence in situ hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS was significantly better for patients with tumors that retained HER2 amplification (87.5% versus 50%, P = 0.04).


CONCLUSIONS
High pCR rates are achieved in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab in combination with anthracyclines and taxanes. One third of patients with significant residual disease loses HER2 amplification, and this change is associated with poor RFS. Residual tumor identified at the time of surgery should be reassessed for HER2 status, and novel adjuvant therapy strategies need to be studied in this population.
Mittendorf
Elizabeth A
EA
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Wu
Yun
Y
Scaltriti
Maurizio
M
Meric-Bernstam
Funda
F
Hunt
Kelly K
KK
Dawood
Shaheenah
S
Esteva
Francisco J
FJ
Buzdar
Aman U
AU
Chen
Huiqin
H
Eksambi
Sameena
S
Hortobagyi
Gabriel N
GN
Baselga
Jose
J
Gonzalez-Angulo
Ana M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D043823:Taxoids / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human