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Published in: Breast Cancer 5/2015

01-09-2015 | Original Article

Prognostic significance of subtype and pathologic response in operable breast cancer; a pooled analysis of prospective neoadjuvant studies of JBCRG

Authors: Katsumasa Kuroi, Masakazu Toi, Shinji Ohno, Seigo Nakamura, Hiroji Iwata, Norikazu Masuda, Nobuaki Sato, Hitoshi Tsuda, Masafumi Kurosumi, Futoshi Akiyama

Published in: Breast Cancer | Issue 5/2015

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Abstract

Purpose

In the past decade, JBCRG has conducted three studies of neoadjuvant chemotherapy which have examined sequential combination of fluorouracil, epirubicin and cyclophosphamide, and docetaxel. The present study is a pooled analysis of these studies performed to determine the prognostic significance of pathologic complete response (pCR) and predictive variables for pCR.

Methods

A total of 353 patients were included. pCR was defined as the absence of invasive cancer or only a few remaining isolated cancer cells in the breast (quasi-pCR, QpCR).

Results

Disease-free survival (DFS) and overall survival (OS) were not significantly different among studies, and patients who achieved a QpCR had significantly better prognosis (DFS, p < 0.001; OS, p = 0.002). Patients with triple-negative (TN) tumors had worse prognosis than patients with the other subtypes (DFS, p = 0.03; OS, p = 0.10). A Cox proportional hazards model showed node-positive, TN, and QpCR were the significant predictors for DFS and OS among study, age, tumor size, nuclear grade, nodal status, subtype, clinical response, and pathologic response (DFS; node-positive, HR = 2.29, p = 0.001; TN, HR = 3.39, p < 0.001; QpCR, HR = 0.27, p < 0.001: OS; node-positive, HR = 3.05, p = 0.003; TN, HR = 4.92, p < 0.001; QpCR, HR = 0.12, p < 0.001). In a logistic regression analysis, subtype and clinical response before surgery were the significant predictive variables for QpCR (luminal/Her2-positive, odds ratio (OR) = 4.15, p = 0.002; Her2-positive, OR = 6.24, p < 0.001; TN, OR = 4.24, p < 0.001; clinical response before surgery, OR = 2.41, p = 0.019).

Conclusions

This study confirmed the prognostic significance of QpCR and nodal status and the predictive and prognostic significance of subtype in neoadjuvant chemotherapy.
Literature
1.
go back to reference Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24:1940–9.PubMedCrossRef Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24:1940–9.PubMedCrossRef
2.
go back to reference Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.PubMedCrossRef Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.PubMedCrossRef
3.
go back to reference von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef
4.
go back to reference Cortazar P, Zhang L, Untch M, Mehta K, Costantino J, Wolmark N, et al. Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC) S1–11. Cancer Res. 2012;72. Cortazar P, Zhang L, Untch M, Mehta K, Costantino J, Wolmark N, et al. Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC) S1–11. Cancer Res. 2012;72.
5.
go back to reference von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125:145–56.CrossRef von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125:145–56.CrossRef
6.
go back to reference Kuroi K, Toi M, Tsuda H, Kurosumi M, Akiyama F. Issues in the assessment of the pathologic effect of primary systemic therapy for breast cancer. Breast Cancer. 2006;13:38–48.PubMedCrossRef Kuroi K, Toi M, Tsuda H, Kurosumi M, Akiyama F. Issues in the assessment of the pathologic effect of primary systemic therapy for breast cancer. Breast Cancer. 2006;13:38–48.PubMedCrossRef
7.
go back to reference Toi M, Nakamura S, Kuroi K, Iwata H, Ohno S, Masuda N, et al. Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival. Breast Cancer Res Treat. 2008;110:531–9.PubMedCrossRef Toi M, Nakamura S, Kuroi K, Iwata H, Ohno S, Masuda N, et al. Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival. Breast Cancer Res Treat. 2008;110:531–9.PubMedCrossRef
8.
go back to reference Nakamura S, Masuda S, Iwata H, Toi M, Kuroi K, Kurozumi M, et al. Phase II trial of fluorouracil, epirubicin, cyclophosphamide (FEC) followed by docetaxel 100 mg/m2 in primary operable breast cancer-JBCRG02-. Jpn J Breast Cancer. 2008;23:111–7. Nakamura S, Masuda S, Iwata H, Toi M, Kuroi K, Kurozumi M, et al. Phase II trial of fluorouracil, epirubicin, cyclophosphamide (FEC) followed by docetaxel 100 mg/m2 in primary operable breast cancer-JBCRG02-. Jpn J Breast Cancer. 2008;23:111–7.
9.
go back to reference Iwata H, Sato N, Masuda N, Nakamura S, Yamamoto N, Kuroi K, et al. Docetaxel followed by fluorouracil/epirubicin/cyclophosphamide as neoadjuvant chemotherapy for patients with primary breast cancer. Jpn J Clin Oncol. 2011;41:867–75.PubMedCrossRef Iwata H, Sato N, Masuda N, Nakamura S, Yamamoto N, Kuroi K, et al. Docetaxel followed by fluorouracil/epirubicin/cyclophosphamide as neoadjuvant chemotherapy for patients with primary breast cancer. Jpn J Clin Oncol. 2011;41:867–75.PubMedCrossRef
10.
go back to reference Kurosumi M, Akashi-Tanaka S, Akiyama F, Komoike Y, Mukai H, Nakamura S, et al. Histopathological criteria for assessment of therapeutic response in breast cancer (2007 version). Breast Cancer. 2008;15:5–7.PubMedCrossRef Kurosumi M, Akashi-Tanaka S, Akiyama F, Komoike Y, Mukai H, Nakamura S, et al. Histopathological criteria for assessment of therapeutic response in breast cancer (2007 version). Breast Cancer. 2008;15:5–7.PubMedCrossRef
11.
go back to reference Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995;180:297–306.PubMed Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995;180:297–306.PubMed
12.
go back to reference Sinn HP, Schmid H, Junkermann H, Huober J, Leppien G, Kaufmann M, et al. Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy. Geburtshilfe Frauenheilkd. 1994;54:552–8.PubMedCrossRef Sinn HP, Schmid H, Junkermann H, Huober J, Leppien G, Kaufmann M, et al. Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy. Geburtshilfe Frauenheilkd. 1994;54:552–8.PubMedCrossRef
13.
go back to reference Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414–22.PubMedCrossRef Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414–22.PubMedCrossRef
14.
go back to reference Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019–27.PubMedCrossRef Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019–27.PubMedCrossRef
15.
go back to reference Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48:3342–54.PubMedCrossRef Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48:3342–54.PubMedCrossRef
16.
go back to reference Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. 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. 2010;375:377–84.PubMedCrossRef Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. 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. 2010;375:377–84.PubMedCrossRef
17.
go back to reference Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.PubMedCrossRef Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.PubMedCrossRef
18.
go back to reference Ohno S, Kuroi K, Toi M. An overview of the Japan Breast Cancer Research Group (JBCRG) activities. Breast Cancer. 2013 Mar 15. (Epub ahead of print). Ohno S, Kuroi K, Toi M. An overview of the Japan Breast Cancer Research Group (JBCRG) activities. Breast Cancer. 2013 Mar 15. (Epub ahead of print).
19.
go back to reference Kuroi K, Kashiwa K, Toi M, Nakamura S, Iwata H, Ohno S, et al. Japan Breast Cancer Research Group (JBCRG). Clin Oncol. 2010;6:360–8. Kuroi K, Kashiwa K, Toi M, Nakamura S, Iwata H, Ohno S, et al. Japan Breast Cancer Research Group (JBCRG). Clin Oncol. 2010;6:360–8.
20.
go back to reference Manton DJ, Chaturvedi A, Hubbard A, Lind MJ, Lowry M, Maraveyas A, et al. Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy. Br J Cancer. 2006;94:427–35.PubMedCrossRefPubMedCentral Manton DJ, Chaturvedi A, Hubbard A, Lind MJ, Lowry M, Maraveyas A, et al. Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy. Br J Cancer. 2006;94:427–35.PubMedCrossRefPubMedCentral
21.
go back to reference Rousseau C, Devillers A, Sagan C, Ferrer L, Bridji B, Campion L, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2006;24:5366–72.PubMedCrossRef Rousseau C, Devillers A, Sagan C, Ferrer L, Bridji B, Campion L, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2006;24:5366–72.PubMedCrossRef
Metadata
Title
Prognostic significance of subtype and pathologic response in operable breast cancer; a pooled analysis of prospective neoadjuvant studies of JBCRG
Authors
Katsumasa Kuroi
Masakazu Toi
Shinji Ohno
Seigo Nakamura
Hiroji Iwata
Norikazu Masuda
Nobuaki Sato
Hitoshi Tsuda
Masafumi Kurosumi
Futoshi Akiyama
Publication date
01-09-2015
Publisher
Springer Japan
Published in
Breast Cancer / Issue 5/2015
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-013-0511-1

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