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Erschienen in: Breast Cancer Research and Treatment 2/2017

02.05.2017 | Review

The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy

verfasst von: Jacques Raphael, Sonal Gandhi, Nim Li, Fang-I Lu, Maureen Trudeau

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

Purpose

Estrogen receptor (ER) negative (−) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database “Biomatrix” to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes.

Methods

Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified.

Results

304 patients were included with a median follow-up of 43.3 months (Q1–Q3 28.7–61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99–1.00, p = 0.027 and 0.98 95% CI 0.97–0.99, p < 0.0001, respectively). A cut-off of 60 and 80% predicted best the association with tumor size reduction and pCR, respectively. pCR was shown to be an independent predictor of RFS (HR 0.17, 95% CI 0.07–0.43, p = 0.0002) in all patients. At 5 years, 93% of patients with pCR and 72% of patients with residual tumor were recurrence-free, respectively (p = 0.0012).

Conclusions

Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.
Literatur
1.
Zurück zum Zitat Martei YM, Matro JM (2015) Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes. Breast Cancer 8(7):337–343 (Dove Med Press) Martei YM, Matro JM (2015) Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes. Breast Cancer 8(7):337–343 (Dove Med Press)
2.
Zurück zum Zitat Kaufmann M, von Minckwitz G, Smith R, Valero V, Gianni L, Eiermann W, Howell A, Costa SD, Beuzeboc P, Untch M, Blohmer JU, Sinn HP, Sittek R, Souchon R, Tulusan AH, Volm T, Senn HJ (2003) International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 21(13):2600–2608CrossRefPubMed Kaufmann M, von Minckwitz G, Smith R, Valero V, Gianni L, Eiermann W, Howell A, Costa SD, Beuzeboc P, Untch M, Blohmer JU, Sinn HP, Sittek R, Souchon R, Tulusan AH, Volm T, Senn HJ (2003) International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 21(13):2600–2608CrossRefPubMed
3.
Zurück zum Zitat Osako T, Nishimura R, Okumura Y, Toyozumi Y, Arima N (2012) Predictive significance of the proportion of ER-positive or PgR-positive tumor cells in response to neoadjuvant chemotherapy for operable HER2-negative breast cancer. Exp Ther Med 3(1):66–71 Epub 2011 Oct 3 PubMed Osako T, Nishimura R, Okumura Y, Toyozumi Y, Arima N (2012) Predictive significance of the proportion of ER-positive or PgR-positive tumor cells in response to neoadjuvant chemotherapy for operable HER2-negative breast cancer. Exp Ther Med 3(1):66–71 Epub 2011 Oct 3 PubMed
4.
Zurück zum Zitat Brouckaert O, Paridaens R, Floris G, Rakha E, Osborne K, Neven P (2013) A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative. Ann Oncol 24(1):47–53CrossRefPubMed Brouckaert O, Paridaens R, Floris G, Rakha E, Osborne K, Neven P (2013) A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative. Ann Oncol 24(1):47–53CrossRefPubMed
5.
Zurück zum Zitat 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 88:406–412CrossRefPubMedPubMedCentral 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 88:406–412CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Dowsett M, Dunbier A (2008) Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 14:8019–8026CrossRefPubMed Dowsett M, Dunbier A (2008) Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 14:8019–8026CrossRefPubMed
7.
Zurück zum Zitat Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, Zabaglo L, Mallon E, Green AR, Ellis IO, Howell A, Buzdar AU, Forbes JF (2011) Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol 29:4273–4278CrossRefPubMed Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, Zabaglo L, Mallon E, Green AR, Ellis IO, Howell A, Buzdar AU, Forbes JF (2011) Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol 29:4273–4278CrossRefPubMed
8.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology.; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:e48–e72PubMed Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology.; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:e48–e72PubMed
9.
Zurück zum Zitat Dieci MV, Piacentini F, Dominici M, Omarini C, Goubar A, Ficarra G, Conte P, Guarneri V (2014) Quantitative expression of estrogen receptor on relapse biopsy for ER-positive breast cancer: prognostic impact. Anticancer Res 34(7):3657–3662PubMed Dieci MV, Piacentini F, Dominici M, Omarini C, Goubar A, Ficarra G, Conte P, Guarneri V (2014) Quantitative expression of estrogen receptor on relapse biopsy for ER-positive breast cancer: prognostic impact. Anticancer Res 34(7):3657–3662PubMed
10.
Zurück zum Zitat Edge SB, Byrd DR, Compton CC (2010) AJCC cancer staging manual, 7th edn. Springer, New York Edge SB, Byrd DR, Compton CC (2010) AJCC cancer staging manual, 7th edn. Springer, New York
11.
Zurück zum Zitat Pennisi A, Kieber-Emmons T, Makhoul I, Hutchins L (2016) Relevance of pathological complete response after neoadjuvant therapy for breast cancer. Breast Cancer 25(10):103–106 (Auckl) Pennisi A, Kieber-Emmons T, Makhoul I, Hutchins L (2016) Relevance of pathological complete response after neoadjuvant therapy for breast cancer. Breast Cancer 25(10):103–106 (Auckl)
12.
Zurück zum Zitat McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 93(4):387–391CrossRefPubMedPubMedCentral McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 93(4):387–391CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Hennigs A, Riedel F, Marmé F, Sinn P, Lindel K, Gondos A, Smetanay K, Golatta M, Sohn C, Schuetz F, Heil J, Schneeweiss A (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160(3):491–499CrossRefPubMedPubMedCentral Hennigs A, Riedel F, Marmé F, Sinn P, Lindel K, Gondos A, Smetanay K, Golatta M, Sohn C, Schuetz F, Heil J, Schneeweiss A (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160(3):491–499CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172CrossRefPubMed Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172CrossRefPubMed
15.
Zurück zum Zitat Knight WA, Livingston RB, Gregory EJ, McGuire WL (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37(12):4669–4671PubMed Knight WA, Livingston RB, Gregory EJ, McGuire WL (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37(12):4669–4671PubMed
16.
Zurück zum Zitat Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, Kieback DG, Putter H, Markopoulos C, Kranenbarg EM, Mallon EA, Dirix L, Seynaeve C, Rea D (2011) Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol 29(12):1531–1538CrossRefPubMedPubMedCentral Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, Kieback DG, Putter H, Markopoulos C, Kranenbarg EM, Mallon EA, Dirix L, Seynaeve C, Rea D (2011) Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol 29(12):1531–1538CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hähnel R, Woodings T, Vivian AB (1979) Prognostic value of estrogen receptors in primary breast cancer. Cancer 44(2):671–675CrossRefPubMed Hähnel R, Woodings T, Vivian AB (1979) Prognostic value of estrogen receptors in primary breast cancer. Cancer 44(2):671–675CrossRefPubMed
18.
Zurück zum Zitat Ravdin PM, Green S, Dorr TM, McGuire WL, Fabian C, Pugh RP, Carter RD, Rivkin SE, Borst JR, Belt RJ (1992) Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective southwest oncology group study. J Clin Oncol 10(8):1284CrossRefPubMed Ravdin PM, Green S, Dorr TM, McGuire WL, Fabian C, Pugh RP, Carter RD, Rivkin SE, Borst JR, Belt RJ (1992) Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective southwest oncology group study. J Clin Oncol 10(8):1284CrossRefPubMed
19.
Zurück zum Zitat Ferno M, Andersson C, Fallenius G, Idvall I (1996) Oestrogen receptor analysis of paraffin sections and cytosol samples of primary breast cancer in relation to outcome after adjuvant tamoxifen treatment. The south Sweden breast cancer group. Acta Oncol 35(1):17–22CrossRefPubMed Ferno M, Andersson C, Fallenius G, Idvall I (1996) Oestrogen receptor analysis of paraffin sections and cytosol samples of primary breast cancer in relation to outcome after adjuvant tamoxifen treatment. The south Sweden breast cancer group. Acta Oncol 35(1):17–22CrossRefPubMed
20.
Zurück zum Zitat EBCTCG (2005) EBCTCG Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365(9472):1687–1717CrossRef EBCTCG (2005) EBCTCG Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365(9472):1687–1717CrossRef
21.
Zurück zum Zitat Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level metaanalysis of randomised trials. Lancet 378(9793):771–784CrossRefPubMed Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level metaanalysis of randomised trials. Lancet 378(9793):771–784CrossRefPubMed
22.
Zurück zum Zitat Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17(5):1474–1481CrossRefPubMed Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17(5):1474–1481CrossRefPubMed
23.
Zurück zum Zitat Brouckaert O, Paridaens R, Floris G, Rakha E, Osborne K, Neven P (2013) A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative. Ann Oncol 24(1):47–53CrossRefPubMed Brouckaert O, Paridaens R, Floris G, Rakha E, Osborne K, Neven P (2013) A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative. Ann Oncol 24(1):47–53CrossRefPubMed
24.
Zurück zum Zitat Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A (2016) Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol 2(11):1477–1486CrossRefPubMed Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A (2016) Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol 2(11):1477–1486CrossRefPubMed
25.
Zurück zum Zitat Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107(3):309–330CrossRefPubMed Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107(3):309–330CrossRefPubMed
26.
Zurück zum Zitat Colleoni M, Montagna E (2012) Neoadjuvant therapy for ER-positive breast cancers. Ann Oncol 23(Suppl 10):x243–x248CrossRefPubMed Colleoni M, Montagna E (2012) Neoadjuvant therapy for ER-positive breast cancers. Ann Oncol 23(Suppl 10):x243–x248CrossRefPubMed
27.
Zurück zum Zitat Spring L, Greenup R, Reynolds K et al (2016) Pathological complete response after neoadjuvant chemotherapy predicts improved survival in all major subtypes of breast cancer: systematic review and meta-analyses of over 18,000 patients. AACR Annual Meeting. Abstract 1439. Presented 18 April 2016 Spring L, Greenup R, Reynolds K et al (2016) Pathological complete response after neoadjuvant chemotherapy predicts improved survival in all major subtypes of breast cancer: systematic review and meta-analyses of over 18,000 patients. AACR Annual Meeting. Abstract 1439. Presented 18 April 2016
28.
Zurück zum Zitat Rose BS, Winer EP, Mamon HJ (2016) Perils of the Pathologic Complete Response. Clin Oncol pii: JCO681718 Rose BS, Winer EP, Mamon HJ (2016) Perils of the Pathologic Complete Response. Clin Oncol pii: JCO681718
29.
Zurück zum Zitat Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, van’t Veer L, Hylton N (2012) Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol 30(26):3242–3249CrossRefPubMedPubMedCentral Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, van’t Veer L, Hylton N (2012) Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol 30(26):3242–3249CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat De Mattos-Arruda L, Shen R, Reis-Filho JS, Cortés J (2016) Translating neoadjuvant therapy into survival benefits: one size does not fit all. Nat Rev Clin Oncol 13(9):566–579CrossRefPubMed De Mattos-Arruda L, Shen R, Reis-Filho JS, Cortés J (2016) Translating neoadjuvant therapy into survival benefits: one size does not fit all. Nat Rev Clin Oncol 13(9):566–579CrossRefPubMed
31.
Zurück zum Zitat Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN (2017) Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol JCO2015631010 Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN (2017) Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol JCO2015631010
32.
Zurück zum Zitat Allred DC, Mohsin SK (2005) ER expression is not bimodal in breast cancer. Am J Clin Pathol 124(3):474–475. author reply 475–486PubMed Allred DC, Mohsin SK (2005) ER expression is not bimodal in breast cancer. Am J Clin Pathol 124(3):474–475. author reply 475–486PubMed
Metadaten
Titel
The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy
verfasst von
Jacques Raphael
Sonal Gandhi
Nim Li
Fang-I Lu
Maureen Trudeau
Publikationsdatum
02.05.2017
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4269-6

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