J Breast Cancer.  2009 Mar;12(1):41-46. 10.4048/jbc.2009.12.1.41.

The Changes of the Histologic and Biologic Markers Induced by Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

• Choi UJ
• Lee KM

• KMID: 2286578
• DOI: http://doi.org/10.4048/jbc.2009.12.1.41

Abstract

PURPOSE
Neoadjuvant chemotherapy (NAC) has become the standard treatment for locally advanced breast cancer. The postoperatively adjuvant systemic treatment is based on the status of the histological and biological markers of either the pre-NAC or the post-NAC. There have been several reports that have demonstrated the changes of the histological and biological markers after NAC. The aim of this study is to investigate the effects of NAC on the expression of the histological and biological markers of breast cancer.
METHODS
We analyzed the paired pre- and post-NAC tumor specimens from 37 patients with stage IIIA, IIIB or IIIC breast cancer. All the patients received 2 to 6 cycles of anthracycline-containing NAC. Over 6 pieces of pre-NAC tumor specimens were taken by 14 G core needle from multiple sites of a tumor, and the post-NAC specimens were taken at the time of the operation. The histologic grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB2, p53, Ki67, CD31 and p-glycoprotein were analyzed in the paired pre- and post-NAC tumor specimens from 37 patients.
RESULTS
Twenty five patients (67.6%) revealed significant changes of more than one marker. The markers that showed changes of more than two grades were as follows; histologic grade in 1, ER in 4, PR in 9, c-erbB2 in 4, p53 in 1, Ki67 in 4, CD31 in 9 and pglycoprotein in 5 patients. In 12 patients (32.4%), significant changes were found in the markers that can influence the decision-making for adjuvant treatment (i.e. ER, PR and c-erbB2). The ER/PR status changed from positive to negative in 4 patients and c-erbB2 was changed from positive to negative in 3 patients. Among those patients, the strategy of adjuvant treatment was adjusted according to the changes.
CONCLUSION
The specimens for the histologic and biologic markers of a tumor should be taken before NAC because NAC can have an influence on the expression of the prognostic markers of locally advanced breast cancers, and this may subsequently influence predicting the prognosis and making the decision for adjuvant systemic treatment.

Keyword

Breast cancer; Markers; Neoadjuvant chemotherapy

MeSH Terms

Biomarkers
Breast
Breast Neoplasms
Estrogens
Humans
Needles
P-Glycoprotein
Prognosis
Receptors, Progesterone
Estrogens
P-Glycoprotein
Receptors, Progesterone

Figure

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  Figure 1 Pattern of the changes in histologic grade, ER, PR and c-erbB2, p53, Ki67, CD31 and p-glycoprotein more than one grade at least. ER=estrogen receptor; PR=progesterone receptor; Pre=pre-chemotherapy; Post=post-chemotherapy.

Reference

1. Piper GL, Patel NA, Patel JA, Malay MB, Julian TB. Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status. Am Surg. 2004. 70:1103–1106.

2. Taucher S, Rudas M, Gnant M, Thomanek K, Dubsky P, Roka S, et al. Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy. Endocr Relat Cancer. 2003. 10:91–98.

3. Mann GB, Fahey VD, Feleppa F, Buchanan MR. Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer. J Clin Oncol. 2005. 23:5148–5154.

4. Varga Z, Caduff R, Pestalozzi B. Stability of the HER2 gene after primary chemotherapy in advanced breast cancer. Virchows Arch. 2005. 446:136–141.

5. Taucher S, Rudas M, Mader RM, Gnant M, Sporn E, Dubsky P, et al. Influence of neoadjuvant therapy with epirubicin and docetaxel on the expression of HER2/neu in patients with breast cancer. Breast Cancer Res Treat. 2003. 82:207–213.

6. Lee JW, Han WS, Ko EY, Cho JH, Jung SY, Kim EK, et al. Alteration of estrogen receptor, progesterone receptor, and HER-2 expression in breast cancer after neoadjuvant chemotherapy. J Breast Cancer. 2007. 10:206–210.

7. Lee SH, Chung MA, Quddus MR, Steinhoff MM, Cady B. The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer. Am J Surg. 2003. 186:348–350.

8. Arens N, Bleyl U, Hildenbrand R. HER2/neu, p53,Ki67, and hormone receptors do not change during neoadjuvant chemotherapy in breast cancer. Virchows Arch. 2005. 446:489–496.

9. Raemaekers JM, Beex LV, Koenders AJ, Pieters GF, Smals AG, Benraad TJ, et al. Concordance and discordance of estrogen and progesterone receptor content in sequential biopsies of patients with advanced breast cancer: relation to survival. Eur J Clin Oncol. 1984. 20:1011–1018.

10. Mueller-Holzner E, Fink V, Frede T, Marth C. Immunohistochemical determination of HER2 expression in breast cancer from core biopsy specimens: a reliable predictor of HER2 status of the whole tumor. Breast Cancer Res Treat. 2001. 69:13–19.

11. Young SC, Burkett RJ, Stewart C. Discrepancy in ER levels of breast carcinoma in biopsy vs mastectomy specimens. J Surg Oncol. 1985. 29:54–56.

12. Werner M, Chott A, Fabiano A, Battifora H. Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol. 2000. 24:1016–1019.

13. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod pathol. 1998. 11:155–168.

14. Rüdiger T, Höfler H, Kreipe HH, Nizze H, Pfeifer U, Stein H, et al. Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists. Am J Surg Pathol. 2002. 26:873–882.

15. Teicher I, Tinker MA, Auguste LJ, Laufer H, Stein TA, Wise L. Effect of operative devascularization on estrogen and progesterone receptor levels in breast cancer specimens. Surgery. 1985. 98:784–791.

16. MacGrogan G, Mauriac L, Durand M, Bonichon F, Trojani M, de Mascarel I, et al. Primary chemotherapy in breast invasive carcinoma: predictive value of immunohistochemical detection of hormone receptors, p53, c-erbB2, MiB1, pS2 and GSTpi. Br J Cancer. 1996. 74:1458–1465.

17. Dixon JM, Love CD, Bellamy CO, Cameron DA, Leonard RC, Smith H, et al. Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Cancer Res Treat. 2001. 66:191–199.