J Breast Cancer.  2017 Jun;20(2):170-175. 10.4048/jbc.2017.20.2.170.

High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in Node Metastasis in Primary Breast Cancers

Affiliations
  • 1Department of Oncology, Alexander Fleming Institute, Buenos Aires, Argentina. pablomando@gmail.com
  • 2Department of Breast Surgery, Alexander Fleming Institute, Buenos Aires, Argentina.
  • 3Department of Pathology, Alexander Fleming Institute, Buenos Aires, Argentina.

Abstract

PURPOSE
Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER2) expression may vary during tumoral progression. We aimed to describe and compare ER, PR, and HER2 expressions in primary breast tumors and synchronic axillary nodal metastases, and evaluate phenotypic correlations between them.
METHODS
Patients were identified prospectively through surgical procedures between September 2013 and July 2016. The status of ER, PR, HER2, and Ki-67 were pathologically analyzed in breast cancers and axillary nodal metastases; these patients were classified based on the breast cancer phenotypes into five subgroups.
RESULTS
Synchronic axillary nodal metastases were observed in 127 patients. In breast cancers and nodal metastases, correlation analyses of ER, PR, and Ki-67 expression showed a statistical dependence and concordance between these samples was unambiguously demonstrated through Bland-Altman plots for each determination. Primary breast tumors were classified as follows: luminal A, 41.6%; luminal B, 40.0%; luminal B/HER2, 9.6%; HER2, 2.4%; triple negative, 6.4%. Alterations in phenotype were observed in 28% of patients. The most frequent phenotypic alteration was from luminal B to A (36.4%). Ten cases (30.3%) showed alterations with therapeutic implications; six gained HER2 overexpression, and four, hormonal receptor (HR) expression. A moderate strength of agreement (Cohen's κ coefficient, 0.59; 95% confidence interval, 0.48-0.71) was observed. In multivariate analyses, high histologic grade (odds ratio [OR], 2.79; p<0.047) and high Ki-67 expression (OR, 1.05; p<0.037) were independent factors predictive of phenotypic alterations.
CONCLUSION
Strong correlations were observed in HR and Ki-67 expressions between primary breast tumors and axillary nodal metastases, and a moderate concordance was observed in their phenotypical characteristics. Nevertheless, alterations did exist, and one-third of these changes may have therapeutic implications. The nodal metastases of tumors with high grade and high Ki-67 expression may need to be analyzed, to obtain complete therapeutic information.

Keyword

Breast neoplasms; Ki-67 antigen; Lymphatic metastasis; Phenotype

MeSH Terms

Breast Neoplasms
Breast*
Estrogens
Humans
Ki-67 Antigen
Lymphatic Metastasis
Multivariate Analysis
Neoplasm Metastasis*
Phenobarbital
Phenotype
Prospective Studies
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Estrogens
Ki-67 Antigen
Phenobarbital
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

  • Figure 1 Correlation between estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression in primary breast tumors and synchronous axillary lymph node metastases. Scatter plot shows breast tumor expression (X-axis) and nodal metastases expression (Y-axis) of ER (A), PR (B) and Ki-67 (C). Strong correlation was observed through Spearman correlation in hormonal receptor and Ki-67 between primary breast tumor and axillary nodal metastases (ER Spearman rho 0.77, p<0.001; PR rho 0.81, p<0.001; and Ki-67 rho 0.72, p<0.001). ERBT=ER percentage in breast tumor; ERNM=ER percentage in nodal metastases; PRBT=PR percentage in breast tumor; PRNM=PR percentage in nodal metastases; KiBT=Ki-67 percentage in breast tumor; KiNM=Ki-67 percentage in nodal metastases.

  • Figure 2 Bland-Altman plots for concordance analysis. Agreement in primary breast tumors and synchronous axillary lymph node metastases for (A) estrogen receptor (ER) expression, (B) progesterone receptor (PR) expression and (C) Ki-67 expression. Y-axis shows the difference between the two paired measurements (measurement in primary breast tumors–measurement in nodal metastases) and the X-axis represents the average of these measures ([measurement in primary breast tumors+measurement in nodal metastases]/2). The difference of the two paired measurements is plotted against the mean of the two measurements. Ninety-five percent of the data points lie within±2 SD of the mean difference showing good correlation. ERDIF=ER percentage difference between breast tumor and nodal metastases; ERMEAN=ER percentage mean between breast tumor and nodal metastases; PRDIF=PR percentage difference between breast tumor and nodal metastases; PRMEAN=PR percentage mean between breast tumor and nodal metastases; KIDIF=Ki-67 percentage difference between breast tumor and nodal metastases; KIMEAN=Ki-67 percentage mean between breast tumor and nodal metastases.


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