Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.
OBJECTIVE
We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy.


METHODS
Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses.


RESULTS
The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci (</= 2 v > 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases (</= 2 v > 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143).


CONCLUSIONS
The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.
Rizzieri
D A
DA
Duke University Medical Center Marrow and Stem Cell Transplantation Program, Durham, NC 27710, USA. rizzi003@mc.duke.edu
Vredenburgh
J J
JJ
Jones
R
R
Ross
M
M
Shpall
E J
EJ
Hussein
A
A
Broadwater
G
G
Berry
D
D
Petros
W P
WP
Gilbert
C
C
Affronti
M L
ML
Coniglio
D
D
Rubin
P
P
Elkordy
M
M
Long
G D
GD
Chao
N J
NJ
Peters
W P
WP
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D004965:Estrogen Antagonists; D013629:Tamoxifen; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate