Predicting early failure after adjuvant chemotherapy in high-risk breast cancer patients with extensive lymph node involvement.
OBJECTIVE
There is limited knowledge of risk factors for breast cancer recurrence within 2 years. This study aimed to predict early failure and identify high-risk patients for prognostic and therapeutic purposes.


METHODS
We studied 739 patients from a randomized trial who were <56 years of age and had >/=4 or more positive lymph nodes, no distant metastases, and no previous other malignancies. After complete surgical treatment, patients received conventional-dose anthracycline-based chemotherapy or a high-dose scheme of anthracycline-based plus alkylating chemotherapy. We assessed clinical and (immuno)histological parameters to predict recurrence within 2 years.


RESULTS
Early failure occurred in 19% (n = 137). Median survival after early failure was limited to 0.7 year. Estrogen and progesterone receptor negativity and visceral relapse predicted poor prognosis. Early failure was associated with young age, large tumors, high histological grade, angio-invasion, apical node metastasis, and >/=10 involved nodes. Estrogen receptor, progesterone receptor, and p27 negativity; HER2 overexpression; and p53 positivity also predicted early failure. The surgical or chemotherapy regimen and histological type did not. The same parameters except tumor size were associated with early death. Grade III, >/=10 involved nodes, and estrogen receptor negativity were independently associated with early failure and together identified a subset of patients (7%) with 3-fold increased early failure and 5-fold increased early death.


CONCLUSIONS
Early failure is associated with poor survival. The combination of three commonly determined parameters constitutes a strong predictive model for early failure and death.
Faneyte
Ian F
IF
Department of Pathology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Peterse
Johannes L
JL
Van Tinteren
Harm
H
Pronk
Corina
C
Bontenbal
Marijike
M
Beex
Louk V A M
LV
van der Wall
Elsken
E
Richel
Dick J
DJ
Nooij
Marianne A
MA
Voest
Emile E
EE
Hupperets
Pierre
P
Ten Vergert
Elisabeth M
EM
de Vries
Elisabeth G E
EG
Rodenhuis
Sjoerd
S
van de Vijver
Marc J
MJ
D000328:Adult; D018943:Anthracyclines / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018943:Anthracyclines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53