Skip to main content

Advertisement

SpringerLink
Log in

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P < 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR− or G3, and 17.8 % in ILC/HR−/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P < 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P < 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Li CI, Anderson BO, Daling JR et al (2003) Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 289(11):1421–1424

    Article  PubMed  Google Scholar 

  2. Arpino G, Bardou VJ, Clark GM et al (2004) Infiltrating lobular carcinoma of the breast: tumour characteristics and clinical outcome. Breast Cancer Res 6(3):R149–R156

    Article  PubMed Central  PubMed  Google Scholar 

  3. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410

    Article  CAS  PubMed  Google Scholar 

  4. Li CI, Uribe DJ, Daling JR (2005) Clinical characteristics of different histologic types of breast cancer. Br J Cancer 93(9):1046–1052

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Rakha EA, Ellis IO (2010) Lobular breast carcinoma and its variants. Semin Diagn Pathol 27(1):49–61

    Article  PubMed  Google Scholar 

  6. Orvieto E, Maiorano E, Bottiglieri L et al (2008) Clinicopathologic characteristics of invasive lobular carcinoma of the breast: results of an analysis of 530 cases from a single institution. Cancer 113(7):1511–1520

    Article  PubMed  Google Scholar 

  7. Reis-Filho JS, Simpson PT, Jones C et al (2005) Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity. J Pathol 207(1):1–13

    Article  CAS  PubMed  Google Scholar 

  8. Lips EH, Mulder L, de Ronde JJ et al (2012) Neoadjuvant chemotherapy in ER+ HER2-breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat 131(3):827–836

    Article  CAS  PubMed  Google Scholar 

  9. von Minckwitz G, Untch M, Blohmer J-U et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15):1796–1804

    Article  Google Scholar 

  10. Cristofanilli M, Gonzalez-Angulo A, Sneige N et al (2005) Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol 23(1):41–48

    Article  PubMed  Google Scholar 

  11. von Minckwitz G, Costa SD, Raab G et al (2001) Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol 19(15):3506–3515

    Google Scholar 

  12. Untch M, Loibl S, Bischoff J et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13(2):135–144

    Article  CAS  PubMed  Google Scholar 

  13. Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25(1):118–145

    Article  CAS  PubMed  Google Scholar 

  14. Untch M, Fasching PA, Konecny GE et al (2011) Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 29(25):3351–3357

    Article  CAS  PubMed  Google Scholar 

  15. von Minckwitz G, Rezai M, Loibl S et al (2010) Capecitabine in addition to anthracycline/taxane-based neoadjuvant treatment in patients with primary breast cancer: the phase III GeparQuattro study. J Clin Oncol 28(12):2015–2023

    Article  Google Scholar 

  16. von Minckwitz G, Eidtmann H, Rezai M et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366(4):299–309

    Article  Google Scholar 

  17. von Minckwitz G, Raab G, Caputo A et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23(12):2676–2685

    Article  Google Scholar 

  18. Thomssen C, Scharl A, Harbeck N (2011) AGO recommendations for diagnosis and treatment of patients with primary and metastatic breast cancer. Update 2011. Breast Care (Basel) 6(4):299–313

    Google Scholar 

  19. Purushotham A, Pinder S, Cariati M et al (2010) Neoadjuvant chemotherapy: not the best option in estrogen receptor-positive, HER2-negative, invasive classical lobular carcinoma of the breast? J Clin Oncol 28(22):3552–3554

    Article  PubMed  Google Scholar 

  20. Katz A, Saad ED, Porter P et al (2007) Primary systemic chemotherapy of invasive lobular carcinoma of the breast. Lancet Oncol 8(1):55–62

    Article  CAS  PubMed  Google Scholar 

  21. Goldhirsch A, Winer EP, Coates AS et al (2013) Personalizing the treatment of women with early breast cancer: highlight of the St. Gallen International expert consensus on the primary therapy of early breast cancer. Ann Oncol 24(9):2206–2223

    Article  CAS  PubMed  Google Scholar 

  22. Boughey JC, Wagner J, Garrett BJ et al (2009) Neoadjuvant chemotherapy in invasive lobular carcinoma may not improve rates of breast conservation. Annals Surg Oncol 16(6):1606–1611

    Article  Google Scholar 

  23. Delpech Y, Coutant C, Hsu L et al (2013) Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas. Br J Cancer 108(2):285–291

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Morrow M, Kiney K, Scholtens D et al (2006) Selecting patients for breast conserving surgery – The Importance of Lobular Histology. Cancer 106(12):2563–2568

    Article  PubMed  Google Scholar 

  25. Voogd AC, Nielsen M, Peterse JL et al (2001) Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 19(6):1688–1697

    CAS  PubMed  Google Scholar 

  26. Diepenmaat LA, van der Sangen M, van de Poll-Franse LV et al (2009) The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer. Radiother Oncol 91(1):49–53

    Article  PubMed  Google Scholar 

  27. Biglia N, Maggiorotto F, Liberale V et al (2013) Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Eur J Surg Oncol 39(5):455–460

    Article  CAS  PubMed  Google Scholar 

  28. Vo T, Meric-Bernstam F, Yi Min et al (2006) Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma. Am J Surg 192(4):552–555

    Article  PubMed  Google Scholar 

  29. Colleoni M, Rotmensz N, Maisonneuve P et al (2012) Outcome of special types of luminal breast cancer. Ann Oncol 23(6):1428–1436

    Article  CAS  PubMed  Google Scholar 

  30. Cortazar P, Zhang L, Untch M et al (2012) Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC). Cancer Res 72(24 Suppl.):S1–S11

    Google Scholar 

  31. Noske A, Loibl S, Darb-Esfahani S et al (2011) Comparison of different approaches for assessment of HER2 expression on protein and mRNA level: prediction of chemotherapy response in the neoadjuvant GeparTrio trial (NCT00544765). Breast Cancer Res Treat 126(1):109–117

    Article  CAS  PubMed  Google Scholar 

  32. Denkert C, Huober J, Loibl S et al (2013) HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer. Breast Cancer Res 15:R11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Metzger-Filho O, Procter M, de Azambuja E et al (2013) Magnitude of trastuzumab benefit in patients with HER2-positive, invasive lobular breast carcinoma: results from the HERA trial. J Clin Oncol 31(16):1954–1960

    Article  CAS  PubMed  Google Scholar 

  34. Longacre TA, Ennis M, Quenneville LA et al (2006) Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study. Mod Pathol 19(2):195–207

    Article  PubMed  Google Scholar 

  35. Kiaer H, Andersen JA, Rank F et al (1988) Quality control of patho-anatomical diagnosis of carcinoma of the breast. Acta Oncol 27(6A):745–747

    Article  CAS  PubMed  Google Scholar 

  36. Rakha EA, El-Sayed ME, Menon S et al (2008) Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 111(1):121–127

    Article  PubMed  Google Scholar 

  37. Metzger-Filho O, Michiels S, Bertucci F et al (2013) Genomic grade adds prognostic value in invasive lobular carcinoma. Ann Oncol 24(2):377–384

    Article  CAS  PubMed  Google Scholar 

  38. Rakha EA, El-Sayed ME, Powe DG et al (2008) Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer 44:73–83

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. German Breast Group, GBG Forschungs GmbH, Martin-Behaim-Strasse 12, 63263, Neu-Isenburg, Germany

    Sibylle Loibl, Keyur M. Mehta, Valentina Nekljudova & Gunter von Minckwitz

  2. Department of Gynecology and Obstetrics, Multidisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Duisburg, Germany

    Cristina Volz, Christine Mau & Michael Untch

  3. Department of Gynecology and Obstetrics, St. Gertrauden Krankenhaus, Berlin, Germany

    Jens-Uwe Blohmer

  4. Department of Obstetrics and Gynecology, Otto-von-Guericke-University, Magdeburg, Germany

    Serban D. Costa

  5. Department of Obstetrics and Gynecology, Christian-Albrecht-University, Kiel, Germany

    Holger Eidtmann

  6. Department of Obstetrics and Gynaecology, Friedrich-Alexander University, Erlangen, Germany

    Peter A. Fasching

  7. Department of Obstetrics and Gynecology, Klinikum Süd, Rostock, Germany

    Bernd Gerber

  8. Department of Senology, Rotkreuz-Klinikum, Munich, Germany

    Claus Hanusch

  9. Department of Obstetrics and Gynaecology, Sana Klinikum, Offenbach, Germany

    Sibylle Loibl & Christian Jackisch

  10. Breast Centre, Kliniken-Essen-Mitte, Essen, Germany

    Sherko Kümmel

  11. Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany

    Jens Huober

  12. Department of Pathology, Charité, Berlin, Germany

    Carsten Denkert

  13. Department of Obstetrics and Gynecology, Eilenriedklinik, Hannover, Germany

    Jörn Hilfrich

  14. Division of Hematology-Oncology, University of California, Los Angeles, CA, USA

    Gottfried E. Konecny

  15. Hematological-oncological Practice, Wuppertal, Germany

    Werner Fett

  16. Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany

    Elmar Stickeler

  17. Breast Centre, University of Munich, Munich, Germany

    Nadia Harbeck

  18. Department of Gynaecology and Obstetrics, University Hospital, Frankfurt, Germany

    Gunter von Minckwitz

Authors
  1. Sibylle Loibl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Volz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Mau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jens-Uwe Blohmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serban D. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Holger Eidtmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter A. Fasching
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bernd Gerber
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claus Hanusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christian Jackisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sherko Kümmel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jens Huober
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Carsten Denkert
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jörn Hilfrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Gottfried E. Konecny
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Werner Fett
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Elmar Stickeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Nadia Harbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Keyur M. Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Valentina Nekljudova
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Gunter von Minckwitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Michael Untch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sibylle Loibl.

Additional information

Sibylle Loibl and Cristina Volz, shared first authorship.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 97 kb)

Supplementary material 2 (PDF 82 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loibl, S., Volz, C., Mau, C. et al. Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma. Breast Cancer Res Treat 144, 153–162 (2014). https://doi.org/10.1007/s10549-014-2861-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-2861-6

Keywords

Search

Navigation