J Breast Cancer.  2019 Sep;22(3):439-452. 10.4048/jbc.2019.22.e38.

Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value

• Woo JW
• Chung YR
• Ahn S
• Kang E
• Kim EK
• Kim SH
• Kim JH
• Kim IA
• Park SY

• KMID: 2458864
• DOI: http://doi.org/10.4048/jbc.2019.22.e38

Abstract

PURPOSE
There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis.
METHODS
A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed.
RESULTS
Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer.
CONCLUSION
Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.

Keyword

Biomarkers; Breast neoplasms; Estrogens; Neoplasm metastasis; Survival

MeSH Terms

Biomarkers
Breast Neoplasms*
Breast*
Diagnosis
Estrogens
Follow-Up Studies
Humans
Neoplasm Metastasis
Prognosis
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Biomarkers
Estrogens
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

• 

  Figure 1 A representative image of biomarker conversion. The left column is from the primary tumor, and the right column is from the metastatic tumor. ER (A, B) and PR (C, D) show negative conversion in the metastatic tumor. HER2 (E, F) exhibits positive conversion. Ki-67 index (G, H) reveals alteration from a low to high index. (A-H) Immunohistochemical staining, ×200 magnification. ER = estrogen receptor; PR = progesterone receptor; HER2 = human epidermal growth factor receptor 2.

• 

  Figure 2 Kaplan-Meier survival analysis for OS according to estrogen receptor status change. Patients with persistent ER-negative tumors (blue line) show decreased OS compared to those with persistent ER-positive tumors (green line) (p < 0.001, log-rank test). ER-negative conversion group (yellow line) shows poor OS compared to persistent ER-positive group (green line) (p = 0.001, log-rank test). OS = overall survival; ER = estrogen receptor.

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