Advertisement

Annals of Surgical Oncology

, Volume 22, Issue 5, pp 1408–1415 | Cite as

Landscape of Neoadjuvant Therapy for Breast Cancer

  • Tufia C. Haddad
  • Matthew P. GoetzEmail author
Breast Oncology

Abstract

Neoadjuvant chemotherapy provides clinical outcomes equivalent to those achieved when the same regimen is provided in the adjuvant setting. The therapeutic response to neoadjuvant treatment may include a reduction in tumor burden that alleviates the morbidity associated with locoregional therapy. Important prognostic information can be gained based on the response to treatment and knowing the quantity and biology of the residual disease. The evaluation of investigational agents in the neoadjuvant setting is of particular value for accelerating drug development. This review highlights landmark trials and contemporary perspectives on neoadjuvant chemotherapy and hormonal therapy, treatment response as a prognostic biomarker, use of the neoadjuvant paradigm for new drug development, and clinical advances in neoadjuvant therapy by molecular subtype of breast cancer.

Keywords

Overall Survival Tamoxifen Trastuzumab Lapatinib Letrozole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The authors acknowledge the support provided in part by 1R01CA133049-01 (MPG), the Mayo Comprehensive Cancer Center Grant (CA15083; MPG), the Mayo Clinic Breast Cancer SPORE (CA 116201; MPG), and the Paul Calabresi Program in Clinical-Translational Research at the Mayo Clinic (CA 090628;TCH).

Disclosures

The authors have no relevant financial disclosures.

References

  1. 1.
    Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784–92.CrossRefPubMedGoogle Scholar
  2. 2.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.Google Scholar
  3. 3.
    Peto R, Davies C, Godwin J, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.CrossRefPubMedGoogle Scholar
  4. 4.
    Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360:679–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371:107–18.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010;28:3784–96.CrossRefPubMedGoogle Scholar
  8. 8.
    Dowsett M, Cuzick J, Ingle J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28:509–18.CrossRefPubMedGoogle Scholar
  9. 9.
    Perez EA, Romond EH, Suman VJ, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–73.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Piccart-Gebhart M, Holmes A, Baselga J, et al. First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (TL), or their combination (T + L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). J Clin Oncol. 2014;32:LBA4.CrossRefGoogle Scholar
  11. 11.
    Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMedGoogle Scholar
  13. 13.
    Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008;26:721–28.CrossRefPubMedGoogle Scholar
  14. 14.
    Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483–93.PubMedGoogle Scholar
  15. 15.
    Rastogi P, Anderson SJ, Bear HD, 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.CrossRefPubMedGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94.CrossRefPubMedGoogle Scholar
  18. 18.
    Colleoni M, Bonetti M, Coates AS, et al. Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors: the International Breast Cancer Study Group. J Clin Oncol. 2000;18:584–90.PubMedGoogle Scholar
  19. 19.
    Bear HD, Anderson S, Smith RE, 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Kaufmann M, Hortobagyi GN, Goldhirsch A, 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.CrossRefPubMedGoogle Scholar
  21. 21.
    Von Minckwitz G, Untch M, Blohmer JU, 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.CrossRefGoogle Scholar
  22. 22.
    Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMedGoogle Scholar
  23. 23.
    Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414–22.CrossRefPubMedGoogle Scholar
  24. 24.
    Mittendorf EA, Jeruss JS, Tucker SL, et al. Validation of a novel staging system for disease-specific survival in patients with breast cancer treated with neoadjuvant chemotherapy. J Clin Oncol. 2011;29:1956–62.CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Von Minckwitz G, Schmitt WD, Loibl S, et al. Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clin Cancer Res. 2013;19:4521–31.CrossRefGoogle Scholar
  26. 26.
    Jones RL, Salter J, A’Hern R, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2009;116:53–68.CrossRefPubMedGoogle Scholar
  27. 27.
    Hylton NM, Blume JD, Bernreuter WK, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy: results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663–72.CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    O’Flynn EA, DeSouza NM. Functional magnetic resonance: biomarkers of response in breast cancer. Breast Cancer Res. 2011;13:204.CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Connolly RM, Leal JP, Goetz MP, et al. Early change in 18-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) to predict response to preoperative systemic therapy (PST) in HER2-negative primary operable breast cancer: Translational Breast Cancer Research Consortium (TBCRC008). J Nucl Med. 2015;56(1):31–7.Google Scholar
  30. 30.
    Gebhart G, Gamez C, Holmes E, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO. J Nucl Med. 2013;54:1862–8.CrossRefPubMedGoogle Scholar
  31. 31.
    FDA. Guidance for Industry Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval. Available: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM305501.pdf/.
  32. 32.
    Von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRefGoogle Scholar
  33. 33.
    Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366:310–20.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.CrossRefGoogle Scholar
  35. 35.
    Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13–21.CrossRefPubMedGoogle Scholar
  36. 36.
    Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013;14:933–42.CrossRefPubMedGoogle Scholar
  37. 37.
    Slamon D, Swain S, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. Presented at the San Antonio Breast Cancer Symposium, 2013.Google Scholar
  38. 38.
    Miller K, O’Neill AM, Dang CT, et al. Bevacizumab (BV) in the adjuvant treatment of HER2-negative breast cancer: final results from Eastern Cooperative Oncology Group E5103. J Clin Oncol. 2014;32:(Suppl), abstract 500.Google Scholar
  39. 39.
    Gianni L, Eiermann W, Semiglazov V, 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.CrossRefPubMedGoogle Scholar
  40. 40.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1317–25.CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.CrossRefPubMedGoogle Scholar
  43. 43.
    Guarneri V, Frassoldati A, Bottini A, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30:1989–95.CrossRefPubMedGoogle Scholar
  44. 44.
    Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol .2012;13:25–32.CrossRefPubMedGoogle Scholar
  45. 45.
    Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278–84.CrossRefPubMedGoogle Scholar
  46. 46.
    Swain SM, Kim SB, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–71.CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15:747–56.CrossRefGoogle Scholar
  48. 48.
    Von Minckwitz G, Kummel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008;100:552–62.CrossRefGoogle Scholar
  49. 49.
    Smith IE, Dowsett M, Ebbs SR, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23:5108–16.CrossRefPubMedGoogle Scholar
  50. 50.
    Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol. 2001;12:1527–32.CrossRefPubMedGoogle Scholar
  51. 51.
    Dowsett M, Smith IE, Ebbs SR, et al. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res. 2005;11:951s–8s.PubMedGoogle Scholar
  52. 52.
    Dowsett M, Smith IE, Ebbs SR, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99:167–70.CrossRefPubMedGoogle Scholar
  53. 53.
    Ellis MJ, Tao Y, Luo J, et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008;100:1380–8.CrossRefPubMedCentralPubMedGoogle Scholar
  54. 54.
    Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol. 2011;29:2342–9.CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Dixon JM, Renshaw L, Young O, et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol. 2008;26:1671–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Freedman OC, Amir E, Hanna W, et al. A randomized trial exploring the biomarker effects of neoadjuvant sequential treatment with exemestane and anastrozole in post-menopausal women with hormone receptor-positive breast cancer. Breast Cancer Res Treat. 2010;119:155–61.CrossRefPubMedGoogle Scholar
  57. 57.
    Goss PE, Ingle JN, Pritchard KI, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27—a randomized controlled phase III trial. J Clin Oncol. 2013;31:1398–404.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  1. 1.Department of OncologyMayo ClinicRochesterUSA
  2. 2.Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterUSA

Personalised recommendations