Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy.
OBJECTIVE
Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer.


METHODS
Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy).


RESULTS
Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83).


CONCLUSIONS
Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Houston, TX 77030, USA. tbuchhol@mdanderson.org
Thomas A
TA
Buchholz
Eugene H
EH
Huang
Donald
D
Berry
Lajos
L
Pusztai
Eric A
EA
Strom
Marsha D
MD
McNeese
George H
GH
Perkins
Naomi R
NR
Schechter
Henry M
HM
Kuerer
Aman U
AU
Buzdar
Vicente
V
Valero
Kelly K
KK
Hunt
Gabriel N
GN
Hortobagyi
Aysegul A
AA
Sahin
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D016001:Confidence Intervals; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D015409:Mastectomy, Radical; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011836:Radiation Tolerance; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012044:Regression Analysis; D012189:Retrospective Studies
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen