Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer.
BACKGROUND
Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC.


METHODS
One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6-8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy.


RESULTS
Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR=3.8; 95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity profile was acceptable.


CONCLUSIONS
This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.
Alvarado-Miranda
Alberto
A
Department of Medical Oncology, Instituto Nacional de Cancerologia, Mexico City, Mexico. alberalvarmir@yahoo.com.mx
Arrieta
Oscar
O
Gamboa-Vignolle
Carlos
C
Saavedra-Perez
David
D
Morales-Barrera
Rafael
R
Bargallo-Rocha
Enrique
E
Zinser-Sierra
Juan
J
Perez-Sanchez
Victor
V
Ramirez-Ugalde
Teresa
T
Lara-Medina
Fernando
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D016685:Mitomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine