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Open Access 01-09-2010 | Breast Oncology

The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy

Authors: M. E. Straver, MD, E. J. Th. Rutgers, MD, PhD, S. Rodenhuis, MD, PhD, S. C. Linn, MD, PhD, C. E. Loo, MD, J. Wesseling, MD, PhD, N. S. Russell, MD, PhD, H. S. A. Oldenburg, MD, PhD, N. Antonini, Msc, M. T. F. D. Vrancken Peeters, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2010

Abstract

Background

Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy.

Method

A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed.

Results

The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34–0.49) and 20% (7 of 35, 95% CI 0.10–0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30–0.48), 24% (11 of 45, 95% CI 0.14–0.38), and 45% (20 of 44, 95% CI 0.32–0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004).

Conclusion

In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumors.

Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMed

Mieog JS, van der Hage JA, van de Velde CJ. Neoadjuvant chemotherapy for operable breast cancer. Br J Surg. 2007;94:1189–200.CrossRefPubMed

van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.PubMed

Loo CE, Teertstra HJ, Rodenhuis S, van de Vijver MJ, Hannemann J, Muller SH, et al. Dynamic contrast-enhanced MRI for prediction of breast cancer response to neoadjuvant chemotherapy: initial results. AJR Am J Roentgenol. 2008;191:1331–8.CrossRefPubMed

von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008;100:542–51.CrossRef

Katz A, Saad ED, Porter P, Pusztai L. Primary systemic chemotherapy of invasive lobular carcinoma of the breast. Lancet Oncol. 2007;8:55–62.CrossRefPubMed

Cocquyt VF, Blondeel PN, Depypere HT, Praet MM, Schelfhout VR, Silva OE, et al. Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol. 2003;29:361–7.CrossRefPubMed

Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault RL, et al. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol. 2005;23:41–8.CrossRefPubMed

Tubiana-Hulin M, Stevens D, Lasry S, Guinebretière JM, Bouita L, Cohen-Solal C, et al. Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution. Ann Oncol. 2006;17:1228–33.CrossRefPubMed

10.

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.CrossRefPubMed

11.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMed

12.

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.CrossRefPubMed

13.

Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006;7:96.

14.

Voduc D, Nielsen TO. Basal and triple-negative breast cancers: impact on clinical decision-making and novel therapeutic options. Clin Breast Cancer. 2008;8 Suppl 4:S171–S178.CrossRefPubMed

15.

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.CrossRefPubMed

16.

Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.CrossRefPubMed

17.

Goldstein NS, Decker D, Severson D, Schell S, Vicini F, Margolis J, et al. Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy. Cancer. 2007;110:1687–96.CrossRefPubMed

18.

Straver ME, Glas AM, Hannemann J, Wesseling J, van de Vijver MJ, Rutgers EJ, et al. The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2010;119(3):551–8.CrossRefPubMed

19.

Hannemann J, Oosterkamp HM, Bosch CA, Velds A, Wessels LF, Loo C, et al. Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2005;23:3331–42.CrossRefPubMed

20.

Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:1431–9.CrossRefPubMed

21.

Lebowitz PF, Eng-Wong J, Swain SM, Berman A, Merino MJ, Chow CK, et al. A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer. Clin Cancer Res. 2004;10:6764–9.CrossRefPubMed

22.

O’Shaughnessy JA, Blum JL. Capecitabine/taxane combination therapy: evolving clinical utility in breast cancer. Clin Breast Cancer. 2006;7:42–50.CrossRefPubMed

23.

van Tienhoven G, Borger JH, Passchier DH, Hart AA, Rutgers EJ, van Dongen JA et al. The prognostic significance of the axillary apex biopsy in clinically operable breast cancer. Eur J Cancer. 1995;31A:1965–8.CrossRefPubMed

24.

Mazouni C, Peintinger F, Wan-Kau S, Andre F, Gonzalez-Angulo AM, Symmans WF, et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25:2650–5.CrossRefPubMed

25.

Rieber A, Brambs HJ, Gabelmann A, Heilmann V, Kreienberg R, Kuhn T. Breast MRI for monitoring response of primary breast cancer to neo-adjuvant chemotherapy. Eur Radiol. 2002;12:1711–9.CrossRefPubMed

26.

Rosen EL, Blackwell KL, Baker JA, Soo MS, Bentley RC, Yu D, et al. Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol. 2003;181:1275–82.PubMed

27.

Mathieu MC, Rouzier R, Llombart-Cussac A, Sideris L, Koscielny S, Travagli JP, et al. The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer. 2004;40:342–51.CrossRefPubMed

28.

Bonnefoi H, Potti A, Delorenzi M, Mauriac L, Campone M, Tubiana-Hulin M, et al. Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2007;8:1071–8.CrossRefPubMed

29.

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.CrossRefPubMed

30.

Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.CrossRefPubMed

31.

Bhattacharyya M, Ryan D, Carpenter R, Vinnicombe S, Gallagher CJ. Using MRI to plan breast-conserving surgery following neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2008;98:289–93.CrossRefPubMed

32.

Boetes C, Mus RD, Holland R, Barentsz JO, Strijk SP, Wobbes T, et al. Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent. Radiology. 1995;197:743–7.PubMed

Title: The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy
Authors: M. E. Straver, MD
E. J. Th. Rutgers, MD, PhD
S. Rodenhuis, MD, PhD
S. C. Linn, MD, PhD
C. E. Loo, MD
J. Wesseling, MD, PhD
N. S. Russell, MD, PhD
H. S. A. Oldenburg, MD, PhD
N. Antonini, Msc
M. T. F. D. Vrancken Peeters, MD, PhD
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 9/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-010-1008-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy

Abstract

Background

Method

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Results

Conclusion

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