Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944).
OBJECTIVE
To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy.


METHODS
Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy.


RESULTS
Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001).


CONCLUSIONS
After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.
Kimmick
G G
GG
Duke University Medical Center, Duke South, Durham, NC 27710, USA. gretchen.kimmick@duke.edu
Cirrincione
C
C
Duggan
D B
DB
Bhalla
K
K
Robert
N
N
Berry
D
D
Norton
L
L
Lemke
S
S
Henderson
I C
IC
Hudis
C
C
Winer
E
E
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis
D000970:Antineoplastic Agents; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate