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21.11.2019 | Original Article

Expression of ER, PgR, HER-2, and Ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy

verfasst von: Luigi Rossi, Monica Verrico, Silverio Tomao, Fabio Ricci, Antonella Fontana, Gian Paolo Spinelli, Maria Colonna, Patrizia Vici, Federica Tomao

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2020

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Abstract

Purpose

Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among breast cancer subtypes.

Methods

The aim of our study is to evaluate the effect of this treatment on the expression of estrogen and progesterone receptors, human epidermal growth hormone receptor 2 and Ki67 in breast cancer. We identified 125 patients.

Results

The estrogen receptor modified its expression from positive to negative in 8% patients and from negative to positive in 22%; progesterone in 21% and in 37% cases. Median Ki-67 value was 20.9% at biopsy and 18% after, HER-2 status did not show a remarkable change before or after neoadjuvant chemotherapy (NACT). We have identified a significant reduction in Ki-67 expression levels after chemotherapy in patients with a pathologic response. Detection of pretreatment Ki-67 could identify patients most likely to benefit from NACT.

Conclusions

NACT can change the status of ER, PgR, and Ki-67 expression in patients with breast adenocarcinoma, but it did not exert a significant effect on HER-2 status; HER-2 amplification appears to be more stable. We have identified a prognostic role for a decreased expression of PgR and Ki-67 after preoperative chemotherapy in breast cancer patients.

DeSantis C, Ma J, Bryan L, Jemal A (2014) Breast cancer statistics 2013 CA. Cancer J Clin. 64:52–62. https://doi.org/10.3322/caac.21203 CrossRef

American Cancer Society (2009) Breast cancer facts and figures 2007–2008 Atlanta: American Cancer Society. http://www.cancer.org/downloads/stt/bcff-final.pdf

Kaufmann M, von Minckwitz G, Mamounas EP et al (2012) Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 19:1508–1516. https://doi.org/10.1245/s10434-011-2108-2 CrossRefPubMed

Chavez Mac Gregor M, Gonzalez-Angulo AM (2010) Breast cancer, neoadjuvant and residual disease. Clin Trans Oncol 12:461–467. https://doi.org/10.1007/s12094-010-0538-0 CrossRef

Hennessy BT, Hortobagy GN, Rouzier RN et al (2005) Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol 23:9304–9311. https://doi.org/10.1200/JCO.2005.02.5023 CrossRefPubMed

Romero A, Garcia-Saenz JA, Fuentes-Ferrer M et al (2013) Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients. Ann Oncol 24:655–661. https://doi.org/10.1093/annonc/mds493 CrossRefPubMed

Symmans WF, Peintinger F, Hatzis C et al (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 25:4414–4422. https://doi.org/10.1200/JCO.2007.10.6823 CrossRefPubMed

Ge W, Yang B, Zuo W et al (2015) Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki 67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients. Thoracic Cancer. https://doi.org/10.1111/1759-7714.12133 CrossRefPubMedPubMedCentral

Zhou X, Zhang J, Yun H et al. (2015) Alterations of biomarker profiles after neoadjuvant chemotherapy in breast cancer: tumor heterogeneity should be taken into consideration. Oncotarget 6: 36894–36902. 10.18632/oncotarget.5050.

10.

Chen S, Chen CM, Yu KD, Zhou RJ, Shao ZM (2012) Prognostic value of a positive-to-negative change in hormone receptor status after NCT in patients with hormone receptor-positive breast cancer. Ann Surg Oncol 19:3002–3011. https://doi.org/10.1245/s10434-012-2318-2 CrossRefPubMed

11.

Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA (2010) Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 11:174–183. https://doi.org/10.1016/S1470-2045(09)70262-1 CrossRefPubMed

12.

Bottini A, Berruti A, Bersiga A et al (2001) Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer. Br J Cancer 85:1106–1112. https://doi.org/10.1054/bjoc.2001.2048 CrossRefPubMedPubMedCentral

13.

Makris A, Powles TJ, Allred DC et al (1999) Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: a pilot study. Breast Cancer Res Treat 53:51–59CrossRefPubMed

14.

Zhang N, Moran MS, Huo Q, Haffty BG, Yang Q. (2001) The hormonal receptor status in breast cancer can be altered by neoadjuvant chemotherapy: a meta-analysis. Cancer Investig 29: 594–598. https://doi.org/10.3109/07357907.2011.621913.CrossRefPubMed

15.

Tagliabue E, Agresti R, Carcangiu ML et al (2003) Role of HER2 in wound-induced breast carcinoma proliferation. Lancet 362(9383):527–533. https://doi.org/10.1016/S0140-6736(03)14112-8 CrossRefPubMed

16.

Chen X, Zhu S, Fei X et al (2015) Surgery time interval and molecular subtype may influence Ki67 change after core needle biopsy in breast cancer patients. BMC Cancer 15:822. https://doi.org/10.1186/s12885-015-1853-1 CrossRefPubMedPubMedCentral

17.

Kim HS, Park S, Koo JS (2016) Risk factors associated with discordant Ki-67 levels between preoperative biopsy and postoperative surgical specimens in breast cancers. PLoS One 11(3):0151054. https://doi.org/10.1371/journal.pone.0151054.eCollection2016 CrossRef

18.

Criscitiello C, Disalvatore D, De Laurentiis M et al (2014) High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal-B HER2 negative and node-positive breast cancer. Breast 23:69–75. https://doi.org/10.1016/j.breast.2013.11.007 CrossRefPubMed

19.

Andre F, Arnedos M, Goubar A, Ghouadni A, Delaloge S (2015) Ki67—no evidence for its use in node-positive breast cancer. Nat Rev Clin Oncol. 12:296–301. https://doi.org/10.1038/nrclinonc.2015.46 CrossRefPubMed

20.

Jones RL, Salter J, A’Hern R et al (2009) The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 116:53–68. https://doi.org/10.1007/s10549-008-0081-7 CrossRefPubMed

21.

Miglietta L, Morabito F, Provinciali N (2013) A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: extension and analysis of a previously reported cohort of patients. Eur J Surg Oncol 39(10):1046–1052. https://doi.org/10.1016/j.ejso.2013.06.024 CrossRefPubMed

22.

von Minckwiz G, Schmitt WD, Loibl S et al (2013) Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clin Cancer Res 15:4521–4531. https://doi.org/10.1158/1078-0432.CCR-12-3628 CrossRef

23.

Gianni L, Eiermann W, Semiglazov V et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2 negative cohort. Lancet 375:377–384. https://doi.org/10.1016/S0140-6736(09)61964-4 CrossRefPubMed

24.

Untch M, Von MG (2009) Recent advances in systemic therapy: advances in neoadjuvant (primary) systemic therapy with cytotoxic agents. Breast Cancer Res 11:203. https://doi.org/10.1186/bcr2227 CrossRefPubMedPubMedCentral

25.

Untch M, Rezai M, Loibl S et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 28:2024–2031. https://doi.org/10.1200/JCO.2009.23.8451 CrossRefPubMed

26.

Mittendorf EA, Wu Y, Scaltriti M et al (2009) Loss of HER2 amplification following Trastuzumab based neoadjuvant systemic therapy and survival outcomes. Clin Cancer ResClin Cancer Res 15:7381–7388. https://doi.org/10.1158/1078-0432.CCR-09-1735 CrossRef

27.

Goldhirsch A, Winer EP, Coates AS et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223. https://doi.org/10.1093/annonc/mdt303 CrossRefPubMedPubMedCentral

28.

Prat A, Cheang MC, Martin M et al (2013) Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol 31:203–209. https://doi.org/10.1200/JCO.2012.43.4134 CrossRefPubMed

29.

Bossuyt V, Provenzano E, Symmans WF et al (2015) Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol 26:1280–1291. https://doi.org/10.1200/JCO.2012.43.4134 CrossRefPubMedPubMedCentral

30.

Provenzano E, Bossuyt V, Viale G et al (2015) Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol 28:1185–1201. https://doi.org/10.1038/modpathol.2015.74 CrossRefPubMed

31.

Guarneri V, Broglio K, Kau SW et al (2006) Prognostic Value of Pathologic Complete Response After Primary Chemotherapy in Relation to Hormone Receptor Status and Other Factors. J Clin Oncol 24:1037–1044. https://doi.org/10.1200/JCO.2005.02.6914 CrossRefPubMed

32.

Balmativola D, Marchio C, Maule M et al (2014) Pathological nonresponse to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study. Breast Cancer Res Treat 148:511–523CrossRefPubMedPubMedCentral

33.

Montagna E, Bagnardi V, Viale G et al (2015) Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy. Ann Oncol 26(2):307–313. https://doi.org/10.1093/annonc/mdu528 CrossRefPubMed

34.

Kurozumi S, Inoue K, Takei H et al (2015) ER, PgR, Ki67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab. BMC Cancer 15:622. https://doi.org/10.1186/s12885-015-1641-y CrossRefPubMedPubMedCentral

35.

Valachis A, Mauri D, Polyzos NP, Chlouverakis G, Mavroudis D, Georgoulias V (2011) Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: a systematic review and meta-analysis. Breast 20(6):485–490. https://doi.org/10.1016/j.breast.2011.06.009 CrossRefPubMed

36.

Nishimura R, Arima N (2008) Is triple negative a prognostic factor in breast cancer? Breast Cancer 15(4):303–308. https://doi.org/10.1007/s12282-008-0042-3 CrossRefPubMed

37.

Cancello G, Maisonneuve P, Rotmensz N et al (2013) Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse. Ann Oncol 24:661–668. https://doi.org/10.1093/annonc/mds430 CrossRefPubMed

38.

Gahlaut R, Bennett A, Fatayer H et al (2016) Effect of neoadjuvant chemotherapy on breast cancer phenotype, ER/PR and HER2 expression – Implications for the practising oncologist. Eur J Cancer 60:40–48. https://doi.org/10.1016/j.ejca.2016.03.006 CrossRefPubMed

39.

van de Ven S, Smit VT, Dekker TJ, Nortier JW, Kroep JR (2011) Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev 37(6):422–430. https://doi.org/10.1016/j.ctrv.2010.11.006 CrossRefPubMed

40.

kai Ge W, Yang B, Zuo W et al (2015) Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki-67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients. Thoracic Cancer 6:64–69. https://doi.org/10.1111/1759-7714.12133 CrossRef

41.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol 2011 22:1736–1747. https://doi.org/10.1093/annonc/mdr304.CrossRefPubMedPubMedCentral

42.

Cserni G, Voros A, Liepniece-Karele I et al (2014) Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values. Breast 23:259–263. https://doi.org/10.1016/j.breast.2014.02.003 CrossRefPubMed

43.

Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ (2003) Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 88:406–412. https://doi.org/10.1038/sj.bjc.6600749 CrossRefPubMedPubMedCentral

44.

Penault-Llorca F, Andre F, Sagan C et al (2009) Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27(17):2809–2815. https://doi.org/10.1200/JCO.2008.18.2808 CrossRefPubMed

45.

Viale G, Giobbie-Hurder A, Regan MM et al (2008) Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 26(34):5569–5575. https://doi.org/10.1200/JCO.2008.17.0829 CrossRefPubMedPubMedCentral

Titel: Expression of ER, PgR, HER-2, and Ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy
verfasst von: Luigi Rossi
Monica Verrico
Silverio Tomao
Fabio Ricci
Antonella Fontana
Gian Paolo Spinelli
Maria Colonna
Patrizia Vici
Federica Tomao
Publikationsdatum: 21.11.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03981-5

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Expression of ER, PgR, HER-2, and Ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy