HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer.
OBJECTIVE
Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2- tumors in terms of relapse-free survival (RFS) and overall survival (OS).


METHODS
Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors.


RESULTS
Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2- tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; CI, 0.32 to 1.16) than in HER2- patients (HR = 1.26).


CONCLUSIONS
Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors.
Moliterni
Angela
A
Medical Oncology Unit, Department of Experimental Oncology, Scientific Direction, Istituto Nazionale Tumori, Italy.
Ménard
Sylvie
S
Valagussa
Pinuccia
P
Biganzoli
Elia
E
Boracchi
Patrizia
P
Balsari
Andrea
A
Casalini
Patrizia
P
Tomasic
Gorana
G
Marubini
Ettore
E
Pilotti
Silvana
S
Bonadonna
Gianni
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D013534:Survival
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases