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Breast Cancer Research and Treatment

, Volume 130, Issue 3, pp 871–877 | Cite as

Invasive lobular carcinoma: response to neoadjuvant letrozole therapy

  • J. Michael DixonEmail author
  • Lorna Renshaw
  • Jonathan Dixon
  • Jeremy Thomas
Clinical Trial

Abstract

Invasive lobular cancer (ILC) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy. We examined the effectiveness of neoadjuvant letrozole in postmenopausal women (PMW) with estrogen receptor (ER)-rich ILC. PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich, large operable, or locally advanced cancers, or were unfit for surgical therapy. Tumor volume was estimated at diagnosis and at 3 months using calipers (clinical), ultrasound, and mammography. At 3 months, if physically fit, women were assessed for surgery. Responsive women with cancers too large for breast-conserving surgery continued with letrozole. Patients had surgery or were switched to alternative therapy if tumor volume was increasing. Sixty-one patients (mean age, 76.2 years) with 63 ILCs were treated with letrozole for ≥3 months. The mean reduction in tumor volume at 3 months was 66% (median, 76%) measured clinically, 61% (median, 73%) measured by ultrasound, and 54% (median, 60%) measured by mammography. Surgery was possible at 3 months in 24 cancers in 24 patients, and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months. At the time of this publication, 40 patients with a total of 41 cancers have undergone surgery. The rate of successful breast conservation was 81% (25/31). Twenty-one patients have continued with letrozole monotherapy, and 19 remain controlled on letrozole at a median of 2.8 years. There is a high rate of response to letrozole in PMW with ER-rich ILC.

Keywords

Carcinoma Endocrine Invasive Lobular Neoadjuvant therapy 

Notes

Acknowledgments

This study was supported by funding from Breakthrough Breast Cancer. Editorial assistance to finalize the article was provided by Novartis Pharmaceuticals. This is an original study and is not under consideration for publication elsewhere. The findings within were previously presented in abstract form at the 2009 San Antonio Breast Cancer Conference in San Antonio, TX.

Conflict of interest

Medical editorial assistance to finalize the manuscript was funded by Novartis Pharmaceuticals; Maria Soushko, PhD, of Phase Five Communications Inc. provided this medical editorial assistance. All authors approved the final draft. The study is solely that of the authors and there has been no input from Novartis Pharmaceuticals in writing this paper. The authors declare no conflict of interest.

References

  1. 1.
    Fisher ER, Gregorio RM, Fisher B et al (1975) The pathology of invasive breast cancer: a syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no 4). Cancer 36:1–85PubMedCrossRefGoogle Scholar
  2. 2.
    Martinez V, Azzopardi JG (1979) Invasive lobular carcinoma of the breast: incidence and variants. Histopathology 3:467–488PubMedCrossRefGoogle Scholar
  3. 3.
    Dixon JM, Anderson TJ, Page DL et al (1982) Infiltrating lobular carcinoma of the breast. Histopathology 6:149–161PubMedCrossRefGoogle Scholar
  4. 4.
    du Toit RS, Locker AP, Ellis IO et al (1989) Invasive lobular carcinoma of the breast: the prognosis of histopathological subtypes. Br J Cancer 60:605–609PubMedCrossRefGoogle Scholar
  5. 5.
    Sastre-Garau X, Jouve M, Asselain B et al (1996) Infiltrating lobular carcinoma of the breast: clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer 77:113–120PubMedCrossRefGoogle Scholar
  6. 6.
    Cleton-Jansen AM (2002) E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer? Breast Cancer Res 4:5–8PubMedCrossRefGoogle Scholar
  7. 7.
    de Leeuw WJ, Berx G, Vos CB et al (1997) Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol 183:404–411PubMedCrossRefGoogle Scholar
  8. 8.
    Dillon DA, Guidi AJ, Schnitt SJ (2010) Pathology of invasive cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK (eds) Diseases of the Breast. Lippincott Williams & Wilkins, Philadelphia, pp 374–407Google Scholar
  9. 9.
    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 23:41–48PubMedCrossRefGoogle Scholar
  10. 10.
    Mathieu MC, Rouzier R, Llombart-Cussac A et al (2004) The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer 40:342–351PubMedCrossRefGoogle Scholar
  11. 11.
    Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer: I. The value of histological grade in breast cancer: experience from a large study with long term follow up. Histopathology 19:403–410PubMedCrossRefGoogle Scholar
  12. 12.
    Geisler J, King N, Anker G et al (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4:2089–2093PubMedGoogle Scholar
  13. 13.
    Geisler J, Haynes B, Anker G et al (2002) Influence of letrozole (Femara) and anastrozole (Arimidex) on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over-designed study. J Clin Oncol 20:751–757PubMedCrossRefGoogle Scholar
  14. 14.
    Geisler J, Helle H, Ekse D et al (2008) Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels. Clin Cancer Res 14:6330–6335PubMedCrossRefGoogle Scholar
  15. 15.
    Dixon JM, Renshaw L, Young O et al (2008) Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol 26:1671–1676PubMedCrossRefGoogle Scholar
  16. 16.
    Eiermann W, Paepke S, Appfelstaedt J et al (2001) Letrozole Neo-Adjuvant Breast Cancer Study Group: preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12:1527–1532PubMedCrossRefGoogle Scholar
  17. 17.
    Ellis MJ, Coop A, Singh B et al (2001) Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 19:3808–3816PubMedGoogle Scholar
  18. 18.
    Dixon JM, Renshaw L, Macaskill EJ et al (2009) Increase in response rate by prolonged treatment with neoadjuvant letrozole. Breast Cancer Res Treat 113:145–151PubMedCrossRefGoogle Scholar
  19. 19.
    The World Health Organization (2003) The World Health Organization classification of tumours—pathology and genetics of tumours of the breast and female genital organs. IARC Press, Lyon, pp 23–26Google Scholar
  20. 20.
    Harvey JM, Clark GM, Osborne CK et al (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 17:1474–1481PubMedGoogle Scholar
  21. 21.
    Moore MM, Borossa G, Imbrie JZ et al (2000) Association of infiltrating lobular carcinoma with positive surgical margins after breast-conservation therapy. Ann Surg 231:877–882PubMedCrossRefGoogle Scholar
  22. 22.
    Boughey JC, Wagner J, Garrett BJ et al (2009) Neoadjuvant chemotherapy in invasive lobular carcinoma may not improve rates of breast conservation. Ann Surg Oncol 16:1606–1611PubMedCrossRefGoogle Scholar
  23. 23.
    Cocquyt VF, Blondeel PN, Depypere HT et al (2003) Different responses to preopreative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol 29:361–367PubMedCrossRefGoogle Scholar
  24. 24.
    Newman LA, Buzdar AU, Singletary SE et al (2002) A prospective trial of preoperative chemotherapy in respectable breast cancer: predictors of breast conservation therapy feasibility. Ann Surg Oncol 9:228–234PubMedCrossRefGoogle Scholar
  25. 25.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumours. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  26. 26.
    Moran MS, Yang Q, Haffty BG (2009) The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive-ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes and molecular expression of COX-2, Bcl-2 and p53 as a function of histology. Breast J 15:571–578PubMedCrossRefGoogle Scholar
  27. 27.
    Domagala W, Markiewski M, Kubiak et al (1993) Immunohistochemical profile of invasive lobular carcinoma of the breast: predominantly vimentin and p53 protein negative cathepsin D and oestrogen receptor positive. Virchows Arch A 423:497–502CrossRefGoogle Scholar
  28. 28.
    Kneeshaw PJ, Turnbull LW, Smith A et al (2003) Dynamic contrast enhanced magnetic resonance imaging aids the surgical management of invasive lobular breast cancer. Eur J Surg Oncol 29:32–37PubMedCrossRefGoogle Scholar
  29. 29.
    Mann RM, Hoogeveen YL, Blickman JG et al (2008) MRI compared to conventional diagnostic work-up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature. Breast Cancer Res Treat 107:1–14PubMedCrossRefGoogle Scholar
  30. 30.
    Molland J, Donnellan M, Janu N et al (2004) Infiltrating lobular carcinoma—a comparison of diagnosis, management and outcomes with infiltrating duct carcinoma. Breast 13:389–396PubMedCrossRefGoogle Scholar
  31. 31.
    Carpenter R, Doughty JC, Wilson CR et al (2010) A multicentre study to determine the optimum duration of neoadjuvant letrozole on tumour regression to permit breast conserving surgery: updated analyses. J Clin Oncol 28:670 (suppl; abstr 6700)CrossRefGoogle Scholar
  32. 32.
    Dixon JMJ, Renshaw L, Keys J et al (2010) Factors affecting local recurrence after breast conserving surgery following neoadjuvant endocrine therapy with letrozole. Cancer Res 70:175a (suppl; abstr P1-12-05)CrossRefGoogle Scholar
  33. 33.
    Dixon JMJ, Renshaw L, Keys J et al (2010) Outcome of frail, elderly patients treated with letrozole alone. Cancer Res 70:175s–176s (suppl; abstr P1-12-06)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • J. Michael Dixon
    • 1
    Email author
  • Lorna Renshaw
    • 1
  • Jonathan Dixon
    • 1
  • Jeremy Thomas
    • 2
  1. 1.Breakthrough Research Unit, Edinburgh Breast UnitWestern General HospitalEdinburghScotland, UK
  2. 2.Department of PathologyWestern General HospitalEdinburghScotland, UK

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