Low HER2/neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer.
OBJECTIVE
The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response.


METHODS
Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m(2) twice a week for a total of 8 weeks, and radiation delivered Weeks 2--6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of < or = 10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, beta-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR).


RESULTS
A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p = 0.009 and p = 0.006, respectively). Conversely, p53 protein expression measured by IHC did not appear to be associated with pathological response (p = 0.67).


CONCLUSIONS
Further studies in LABC should assess whether patient selection for treatment based on the original tumor molecular characteristics could affect their chance to achieve a pathological response.
Formenti
Silvia C
SC
Radiation Oncology and Medicine, New York University School of Medicine, New York, NY 10016, USA. silvia.formenti@med.nyu.edu
Spicer
Darcy
D
Skinner
Kristin
K
Cohen
Deidre
D
Groshen
Susan
S
Bettini
Anna
A
Naritoku
Wesley
W
Press
Michael
M
Salonga
Dennis
D
Tsao-Wei
Denice
D
Danenberg
Kathy
K
Danenberg
Peter
P
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D011838:Radiation-Sensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53