Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.
OBJECTIVE
The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G(1)-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (e.g., HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study.


METHODS
We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (i.e., performance status, extent of disease, and prior therapy) were also examined.


RESULTS
In univariate analysis, Karnofsky performance status > or = 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P =.075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy.


CONCLUSIONS
The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.
Van Poznak
Catherine
C
Breast Cancer Medicine Service, the Pathology Department, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. vanpoznc@mskcc.org
Tan
Lee
L
Panageas
Katherine S
KS
Arroyo
Crispinita D
CD
Hudis
Clifford
C
Norton
Larry
L
Seidman
Andrew D
AD
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016009:Chi-Square Distribution; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen