Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer.
OBJECTIVE
To determine whether pretreatment clinical features and molecular markers, together with changes in these factors, can predict treatment response and survival in patients with primary operable breast cancer who receive neoadjuvant therapy.


METHODS
Mitoxantrone, methotrexate (with or without mitomycin), and tamoxifen chemoendocrine therapy was administered to 158 patients before surgery. Clinical response was assessed after four cycles of treatment. Fine-needle aspiration cytology for estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53, bcl-2, Ki67, S-phase fraction (SPF), and ploidy were performed pretreatment and repeated on day 10 or day 21 after the first cycle of treatment.


RESULTS
Good clinical response (GCR, defined as complete response or minimal residual disease) was achieved in 31% of patients (49 of 158). Tumor size, nodal disease, response, ER, PgR, c-erbB-2, p53, bcl-2, Ki67, SPF, and ploidy were analyzed as predictors of survival. By univariate analysis, node-positive disease (P =.05), lack of ER (P <.05) and PgR (P <.05), and failure to attain GCR (P =.008) were associated with a significantly increased risk of relapse. A significantly increased risk of death was associated with node-positive disease (P =.02), lack of ER expression (P =.04), and failure to attain GCR. By multivariate analysis, GCR was an independent predictor for survival (P =.05). ER expression (P =.03), absence of c-erbB-2 (P =.03), and a decrease in Ki67 on day 10 or day 21 of the first cycle (P <.05) significantly predicted for subsequent GCR.


CONCLUSIONS
Molecular markers may be used to predict the likelihood of achieving GCR, which seems to be a valid surrogate marker for survival.
Chang
J
J
Departments of Medicine and Computing, The Royal Marsden Hospital, Sutton, Surrey, United Kingdom. mdcccn@nus.edu.sg
Powles
T J
TJ
Allred
D C
DC
Ashley
S E
SE
Clark
G M
GM
Makris
A
A
Assersohn
L
L
Gregory
R K
RK
Osborne
C K
CK
Dowsett
M
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000601:surgery*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D008942:Mitoxantrone; D008727:Methotrexate