Clinicopathologic significance of excision repair cross-complementation 1 expression in patients treated with breast-conserving surgery and radiation therapy.
OBJECTIVE
The excision repair cross-complementation 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in cancers of the head and neck and the lung. The purpose of this study was to evaluate the clinicopathologic and prognostic significance of ERCC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy.


METHODS
Paraffin specimens from 504 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The array was stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and ERCC1. This was then correlated with clinicopathologic factors and outcomes data.


RESULTS
ERCC-1 expression was evaluable in 366 cases (72%). In this group, 32% and 38% of patients received adjuvant chemotherapy and hormonal therapy, respectively. Increased ERCC-1 expression was found to be correlated with ER positivity (p < 0.005), lower T stage (p < 0.017), nodal negativity (p < 0.013), age >50 (p < 0.006), reduced use of adjuvant chemotherapy (p < 0.02), and increased use of adjuvant hormonal therapy (p < 0.004). ERCC1 expression did not correlate with locoregional recurrence-free survival, distant metastasis-free survival, cause-specific survival, or overall survival. In patients who were both ERCC1-negative and -positive, the use of chemotherapy predicted for worse distant metastasis-free survival (p = 0.05 and p = 0.07, respectively) but not cause-specific survival or overall survival.


CONCLUSIONS
Although ERCC1 expression did not predict for outcome measures in this dataset, overexpression correlated with favorable prognostic factors such as ER positivity, lower T stage, nodal negativity, and age >50. To our knowledge, this is the first study investigating ERCC1 expression in patients receiving adjuvant radiation therapy for breast cancer.
Goyal
Sharad
S
Department of Radiation Oncology, The Cancer Institute of New Jersey, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. goyalsh@umdnj.edu
Parikh
Rahul R
RR
Green
Camille
C
Schiff
Devora
D
Moran
Meena S
MS
Yang
Qifeng
Q
Haffty
Bruce G
BG
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases