Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.
OBJECTIVE
To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.


METHODS
Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.


RESULTS
RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.


CONCLUSIONS
RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.
Symmans
W Fraser
WF
Department of Pathology, Unit 85, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. fsymmans@mdanderson.org
Peintinger
Florentia
F
Hatzis
Christos
C
Rajan
Radhika
R
Kuerer
Henry
H
Valero
Vicente
V
Assad
Lina
L
Poniecka
Anna
A
Hennessy
Bryan
B
Green
Marjorie
M
Buzdar
Aman U
AU
Singletary
S Eva
SE
Hortobagyi
Gabriel N
GN
Pusztai
Lajos
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models