Cancer Res Treat.  2018 Oct;50(4):1418-1432. 10.4143/crt.2017.552.

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

• Ahn S
• Kim HJ
• Kim M
• Chung YR
• Kang E
• Kim EK
• Kim SH
• Kim YJ
• Kim JH
• Kim IA
• Park SY

• KMID: 2424812
• DOI: http://doi.org/10.4143/crt.2017.552

Abstract

PURPOSE
Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST.
MATERIALS AND METHODS
The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed.
RESULTS
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup.
CONCLUSION
ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

Keyword

Breast neoplasms; Neoadjuvant therapy; Biomarkers; Progesterone receptors; Prognosis

MeSH Terms

Biomarkers
Biopsy
Breast Neoplasms*
Breast*
Disease-Free Survival
Estrogens
Humans
Multivariate Analysis
Neoadjuvant Therapy
Progesterone*
Prognosis
Receptor, Epidermal Growth Factor
Receptors, Progesterone*
Biomarkers
Estrogens
Progesterone
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

• 

  Fig. 1. Representative examples of biomarker alteration after primary systemic therapy. Estrogen receptor (ER) and progesterone receptor (PR) show negative conversion, and the immunohistochemical score for human epidermal growth factor receptor 2 (HER2) is altered from 1+ to 3+ after primary systemic therapy (PST).

• 

  Fig. 2. Survival analyses according to biomarker alteration after primary systemic therapy. Negative conversion of estrogen receptor (ER) (A) and progesterone receptor (PR) (C) status after primary systemic therapy (PST) are associated with decreased disease-free survival. However, positive conversion of ER (B) or PR (D) in receptor-negative cases has no prognostic significance. (E, F) Alteration of human epidermal growth factor receptor 2 (HER2) status after PST is not related to the survival of patients. (G, H) High Ki-67 index in post-PST samples is associated with poor diseasefree survival, irrespective of pre-PST Ki-67 status.

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  Fig. 3. Survival analyses between the tumors showing negative to positive conversion of hormone receptor status and persistent receptor-positive tumors after primary systemic therapy. (A) Negative to positive conversion of estrogen receptor (ER) shows no prognostic significance. (B) However, negative to positive conversion of progesterone receptor (PR) is associated with decreased disease-free survival compared to persistent PR-positive group.

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  Fig. 4. Survival analyses according to changes of Allred score after primary systemic therapy. (A) Change of the Allred score for estrogen receptor (ER) after primary systemic therapy (PST) in the pre-PST ER-positive group has no prognostic significance. (B) Decreased Allred score for progesterone receptor (PR) after PST is associated with poor disease-free survival in the pre-PST PR-positive group.

Reference

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