Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer : long-term results from the University of Texas M. D. Anderson Cancer Center Study ID97-099.
BACKGROUND
This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross-resistant adjuvant chemotherapy.


METHODS
Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor-positive patients only).


RESULTS
Eighty-eight patients were evaluable. Seventy-four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5-year recurrence-free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5-year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5-year OS rates were 82% for initially operable and 21% for initially inoperable patients (P < or = .001)


CONCLUSIONS
Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long-term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS.
Alvarez
Ricardo H
RH
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Booser
Daniel J
DJ
Cristofanilli
Massimo
M
Sahin
Aysegul A
AA
Strom
Eric A
EA
Guerra
Laura
L
Kau
Shu-Wan
SW
Gonzalez-Angulo
Ana M
AM
Hortobagyi
Gabriel N
GN
Valero
Vicente
V
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008727:Methotrexate; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D043823:Taxoids / Q000008:administration & dosage*
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate