Does analysis of biomarkers in tumor cells in lymph node metastases give additional prognostic information in primary breast cancer?
BACKGROUND
Prognostic and treatment-predictive biomarkers in primary breast cancer are routinely analyzed in the primary tumor, whereas metastatic tumor cells in lymph node metastases are not characterized. The present study aimed to define the concordance between biomarkers in matched pairs of breast cancers and lymph node metastases and to relate their expression to clinical outcome.


METHODS
Patients with primary breast cancer treated with adjuvant tamoxifen for 2 years were included. A tissue microarray of primary tumors and lymph node metastases was constructed, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed immunohistochemically in 262, 257, 104, and 101 patients, respectively. Five years' distant disease-free survival (DDFS) was used as the primary end point.


RESULTS
The concordance for biomarker expression in primary tumors and corresponding lymph node metastases was 93% for ER, 84% for PR, 97% for HER2, and 85% for Ki67. The discordant cases for HER2 status were all negative in the tumor but positive in the node. ER positivity was a significant independent predictor of improved 5-year DDFS when analyzed in the primary tumor as well as in the lymph node metastases. Ki67 positivity analyzed in both locations correlated with shortened DDFS. HER2 positivity at both locations was an indicator of early relapse.


CONCLUSIONS
The concordance for the biomarkers analyzed in matched pairs of primary tumors and lymph node metastases was high. Moreover, survival analyses showed that the expression of biomarkers in lymph node metastases can provide prognostic information when no analyses of the primary tumor can be done. Treatment selection based on biomarkers in the lymph node is a topic for further studies.
Falck
Anna-Karin
AK
Department of Surgery, Institution of Clinical Sciences Lund, Lund University Hospital, SE-221 85, Lund, Sweden.
Fernö
Mårten
M
Bendahl
Pär-Ola
PO
Rydén
Lisa
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human