Neoadjuvant systemic therapy for breast cancer: Response, subsequent treatment, and prognosis
- William M Sikov, MD, FACP
William M Sikov, MD, FACP
- Associate Professor of Medicine
- Warren Alpert Medical School of Brown University
- Section Editors
- Daniel F Hayes, MD
Daniel F Hayes, MD
- Section Editor — Breast Cancer
- Professor of Medicine
- University of Michigan School of Medicine
- Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
- Section Editor — Breast Surgery
- Associate Professor, Department of Surgery
- Yale University School of Medicine
Neoadjuvant systemic therapy is the accepted approach for women with locally advanced breast cancer for whom immediate surgery is not feasible. It is also an option for women with operable breast cancer who desire an attempt at breast conservation but in whom mastectomy is indicated based on tumor size and location [1-4].
Response assessment during and following neoadjuvant therapy, implications for surgical management of the breast and axillary nodes, pathologic evaluation of the surgical specimen, influence of pathologic findings on prognosis, and options for adjuvant therapy following neoadjuvant treatment will be reviewed here. The rationale for neoadjuvant therapy, patient selection, pre-treatment evaluation, and treatment options are discussed separately. (See "Neoadjuvant therapy for breast cancer: Rationale, pretreatment evaluation, and therapeutic options".)
Clinical response assessment during treatment — Patients undergoing neoadjuvant systemic therapy for breast cancer should undergo periodic clinical evaluations during treatment to assess response and ensure that their tumor is not progressing.
There are no formal guidelines regarding the ideal assessment strategy during neoadjuvant treatment. Our approach is as follows:
●For patients on neoadjuvant chemotherapy (NACT), we perform a clinical examination every two to four weeks (ie, prior to each cycle of treatment). This should include evaluation of the affected breast and ipsilateral axilla.
- Gralow JR, Burstein HJ, Wood W, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol 2008; 26:814.
- 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.
- Schwartz GF, Hortobagyi GN. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania. Cancer 2004; 100:2512.
- Shannon C, Smith I. Is there still a role for neoadjuvant therapy in breast cancer? Crit Rev Oncol Hematol 2003; 45:77.
- 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.
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228.
- Hayward JL, Carbone PP, Heuson JC, et al. Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer 1977; 39:1289.
- Husband JE, Schwartz LH, Spencer J, et al. Evaluation of the response to treatment of solid tumours - a consensus statement of the International Cancer Imaging Society. Br J Cancer 2004; 90:2256.
- Chagpar AB, Middleton LP, Sahin AA, et al. Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg 2006; 243:257.
- Fiorentino C, Berruti A, Bottini A, et al. Accuracy of mammography and echography versus clinical palpation in the assessment of response to primary chemotherapy in breast cancer patients with operable disease. Breast Cancer Res Treat 2001; 69:143.
- Segara D, Krop IE, Garber JE, et al. Does MRI predict pathologic tumor response in women with breast cancer undergoing preoperative chemotherapy? J Surg Oncol 2007; 96:474.
- Peintinger F, Kuerer HM, Anderson K, et al. Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy. Ann Surg Oncol 2006; 13:1443.
- Yuan Y, Chen XS, Liu SY, Shen KW. Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis. AJR Am J Roentgenol 2010; 195:260.
- Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 2013; 14:609.
- Boughey JC, Simon VJ, Mittendorf EA, et al. The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy- results from the ACOSOG Z1071 trial. Cancer Res 2012; 72:94s.
- Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol 2015; 33:258.
- Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17:460.
- 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.
- Kimmick GG, Cirrincione C, Duggan DB, et al. Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944). Breast Cancer Res Treat 2009; 113:479.
- 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.
- van de Ven S, Smit VT, Dekker TJ, et al. Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev 2011; 37:422.
- Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol 2012; 30:3960.
- Thomas E, Holmes FA, Smith TL, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol 2004; 22:2294.
- Alvarez RH, Booser DJ, Cristofanilli M, et al. Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer : long-term results from the University of Texas M. D. Anderson Cancer Center Study ID97-099. Cancer 2010; 116:1210.
- National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines: Breast Cancer (Version 3.2014) http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on November 03, 2014).
- 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.
- Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience. J Clin Oncol 2004; 22:2303.
- Mieog JS, van der Hage JA, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev 2007; :CD005002.
- Kong X, Moran MS, Zhang N, et al. Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer 2011; 47:2084.
- Cortazar P, Zhang L, Untch M, et al. Meta-analysis results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC). Cancer Res 2012; 72:93s.
- 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.
- Mathieu MC, Mazouni C, Kesty NC, et al. Breast Cancer Index predicts pathological complete response and eligibility for breast conserving surgery in breast cancer patients treated with neoadjuvant chemotherapy. Ann Oncol 2012; 23:2046.
- Nahleh Z, Sivasubramaniam D, Dhaliwal S, et al. Residual cancer burden in locally advanced breast cancer: a superior tool. Curr Oncol 2008; 15:271.
- TREATMENT EVALUATION
- Clinical response assessment during treatment
- Clinical response assessment after treatment
- DEFINITIVE SURGICAL TREATMENT
- Breast surgery
- Nodal evaluation
- PATHOLOGIC ASSESSMENT
- Defining efficacy
- - Chemotherapy
- - Endocrine therapy
- Re-testing of pathologic markers
- ADJUVANT THERAPY
- Radiation therapy
- HER2-directed treatment
- Endocrine therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS