Can patients' likelihood of benefiting from primary chemotherapy for breast cancer be predicted before commencement of treatment?
OBJECTIVE
Primary chemotherapy is commonly used in patients with breast cancer to downstage the primary tumour prior to surgery. There is a need to establish, prior to commencement of chemotherapy, predictors of clinical and pathological response, which may then be surrogate markers for patient survival and thus allow identification of patients who are most likely to benefit from such treatment.


METHODS
A total of 104 patients with large and locally advanced breast cancers received an anthracycline/docetaxel-based regimen prior to surgery. Immunohistochemistry was carried out on pre-treatment core biopsies of the tumour to detect hormone receptors (oestrogen-ER; progesterone-PR), a proliferation marker (MIB-1), the oncoprotein Bcl-2, an extracellular matrix degradation enzyme (cathepsin D), p53, and an oestrogen associated protein (pS2). Both clinical and pathological response were assessed following completion of chemotherapy.


RESULTS
Patients whose tumours did not express oestrogen receptor (p = 0.02) or did not express Bcl-2 (p < 0.01) had a better pathological response in a univariate analysis. However, in a multivariate model, it was only the absence of detectable Bcl-2 protein that predicted a better pathological response (p = 0.001).


CONCLUSIONS
This study has identified that patients whose breast cancers are most likely to experience the greatest degree of tumour destruction by primary chemotherapy do not express either oestrogen receptors or Bcl-2. This may have important implications in the selection of patients with breast cancer for primary chemotherapy who are most likely to gain a survival benefit.
Department of Surgery, University of Aberdeen, UK.
Keith N
KN
Ogston
Iain D
ID
Miller
Andrew C
AC
Schofield
Andreas
A
Spyrantis
Eleni
E
Pavlidou
Tarun K
TK
Sarkar
Andrew W
AW
Hutcheon
Simon
S
Payne
Steven D
SD
Heys
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D014750:Vincristine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone