RESEARCH ARTICLE
Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial
Correction(s) for this article
-
Re: Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial. Journal of Surgical Oncology 2017;115(8):917–923.
- Harry D. Bear MD, PhD,
- Wen Wan PhD,
- André Robidoux MD,
- Peter Rubin MD,
- Steven Limentani MD,
- Richard L. White Jr MD,
- James Granfortuna MD,
- Judith O. Hopkins MD,
- Dwight Oldham MD,
- Angel Rodriguez MD,
- Amy P. Sing MD,
- Volume 118Issue 4Journal of Surgical Oncology
- pages: 722-722
- First Published online: July 28, 2017
-
Erratum
- Volume 124Issue 5Journal of Surgical Oncology
- pages: 914-914
- First Published online: July 27, 2021
Harry D. Bear MD, PhD,
Wen Wan PhD,
André Robidoux MD,
Peter Rubin MD,
Steven Limentani MD,
Richard L. White Jr MD,
James Granfortuna MD,
Judith O. Hopkins MD,
Dwight Oldham MD,
Angel Rodriguez MD, Amy P. Sing MD,
Corresponding Author
Harry D. Bear MD, PhD
Virginia Commonwealth University and Massey Cancer Center, Richmond, Virginia
Correspondence
Harry D. Bear, MD, PhD, Division of Surgical Oncology, VCUHS, Box 980011, Richmond, VA 23298–0011.
Email: [email protected]
Search for more papers by this authorWen Wan PhD
Virginia Commonwealth University and Massey Cancer Center, Richmond, Virginia
Search for more papers by this authorAndré Robidoux MD
Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
Search for more papers by this authorPeter Rubin MD
Cone Health Cancer Center, Greensboro, North Carolina
Search for more papers by this authorSteven Limentani MD
Carolinas Medical Center, Charlotte, North Carolina
Search for more papers by this authorRichard L. White Jr MD
Carolinas Medical Center, Charlotte, North Carolina
Search for more papers by this authorJames Granfortuna MD
Cone Health Cancer Center, Greensboro, North Carolina
Search for more papers by this authorJudith O. Hopkins MD
Forsyth Regional Cancer Center, Winston Salem, North Carolina
Search for more papers by this authorDwight Oldham MD
Lynchburg Hematology Oncology Clinic, Lynchburg, Virginia
Search for more papers by this authorHarry D. Bear MD, PhD,
Wen Wan PhD,
André Robidoux MD,
Peter Rubin MD,
Steven Limentani MD,
Richard L. White Jr MD,
James Granfortuna MD,
Judith O. Hopkins MD,
Dwight Oldham MD,
Angel Rodriguez MD, Amy P. Sing MD,
Corresponding Author
Harry D. Bear MD, PhD
Virginia Commonwealth University and Massey Cancer Center, Richmond, Virginia
Correspondence
Harry D. Bear, MD, PhD, Division of Surgical Oncology, VCUHS, Box 980011, Richmond, VA 23298–0011.
Email: [email protected]
Search for more papers by this authorWen Wan PhD
Virginia Commonwealth University and Massey Cancer Center, Richmond, Virginia
Search for more papers by this authorAndré Robidoux MD
Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
Search for more papers by this authorPeter Rubin MD
Cone Health Cancer Center, Greensboro, North Carolina
Search for more papers by this authorSteven Limentani MD
Carolinas Medical Center, Charlotte, North Carolina
Search for more papers by this authorRichard L. White Jr MD
Carolinas Medical Center, Charlotte, North Carolina
Search for more papers by this authorJames Granfortuna MD
Cone Health Cancer Center, Greensboro, North Carolina
Search for more papers by this authorJudith O. Hopkins MD
Forsyth Regional Cancer Center, Winston Salem, North Carolina
Search for more papers by this authorDwight Oldham MD
Lynchburg Hematology Oncology Clinic, Lynchburg, Virginia
Search for more papers by this authorPresent address of Peter Rubin: Southern Maine Health Care, Biddeford, ME.
Present address of Wen Wan: University of Chicago. Chicago, IL.
Present address of Steven Limentani: Novant Health, Charlotte, NC.
Preliminary results of this study were presented, in part, at the 39th Annual San Antonio Breast Cancer Symposium, December 8, 2016. The work described in this manuscript is original research.
Trial Registration: ClinicalTrials.gov: NCT01293032; CTRP ID: NCI-2010-02342.
Abstract
Objective
We hypothesized that the Oncotype Dx® 21-gene Recurrence Score (RS) could guide neoadjuvant systemic therapy (NST) to facilitate breast conserving surgery (BCS) for hormone receptor positive (HR+) breast cancers.
Methods
This study enrolled patients with HR+, HER2-negative, invasive breast cancers not suitable for BCS (size ≥ 2 cm). Core needle biopsy blocks were tested. For tumors with RS < 11, patients received hormonal therapy (NHT); patients with RS > 25 tumors received chemotherapy (NCT); patients with RS 11-25 were randomized to NHT or NCT. Primary endpoint was whether 1/3 or more of randomized patients refused assigned treatment.
Results
Sixty-four patients were enrolled. Of 33 patients with RS 11-25, 5 (15%) refused assignment to NCT. This was significantly lower than the 33% target (binomial test, P = 0.0292). Results for clinical outcomes (according to treatment received for 55 subjects) included successful BCS for 75% of tumors with RS < 11 receiving NHT, 72% for RS 11-25 receiving NHT, 64% for RS 11-25 receiving NCT, and 57% for RS > 25 receiving NCT.
Conclusions
Using the RS to guide NST is feasible. These results suggest that for patients with RS < 25 NHT is a potentially effective strategy.
REFERENCES
- 1 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: 2483–2493.
- 2 Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998; 16: 2672–2685.
- 3 Gianni L, Baselga J, Eiermann W, et al. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European cooperative trial in operable breast cancer. J Clin Oncol. 2009; 27: 2474–2481.
- 4 Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-27. J Clin Oncol. 2003; 21: 4165–4174.
- 5 Bonadonna G, Valagussa P, Brambilla C, et al. Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol. 1998; 16: 93–100.
- 6 Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012; 366: 310–320.
- 7 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: 164–172.
- 8 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: 2342–2349.
- 9 Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016; 2: 1477–1486.
- 10 Leal F, Liutti VT, Antunes dos Santos VC, et al. Neoadjuvant endocrine therapy for resectable breast cancer: a systematic review and meta-analysis. Breast. 2015; 24: 406–412.
- 11 Van Dam PA, van DV, Altintas S, Papadimitriou K, Rolfo C, Trinh XB. Neoadjuvant endocrine treatment in early breast cancer: an overlooked alternative? Eur J Surg Oncol. 2016; 42: 333–342.
- 12 Chiba A, Hoskin TL, Heins CN, Hunt KK, Habermann EB, Boughey JC. Trends in neoadjuvant endocrine therapy use and impact on rates of breast conservation in hormone receptor-positive breast cancer: a national cancer data base study. Ann Surg Oncol. 2017; 24: 418–424.
- 13 Gianni L, Baselga J, Eiermann W, et al. Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy. Clin Cancer Res. 2005; 11: 8715–8721.
- 14 Chang JC, Makris A, Gutierrez MC, et al. Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat. 2008; 108: 233–240.
- 15 Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351: 2817–2826.
- 16 Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006; 24: 3726–3734.
- 17National Comprehensive Cancer Network. Clinical practice guidelines in oncology—version 2. 2006.
- 18Early Breast Cancer Trialists Collaborative Group 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: 1687–1717.
- 19 Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003; 21: 3357–3365.
- 20 Eifel P, Axelson JA, Costa J, et al. National institutes of health consensus development conference statement: adjuvant therapy for breast cancer, november 1–3, 2000. J Natl Cancer Inst. 2001; 93: 979–989.
- 21 Carlson RW, Brown E, Burstein HJ, et al. NCCN task force report: adjuvant therapy for breast cancer. J Natl Compr Canc Netw. 2006; 4: S1–26.
- 22 Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014; 106: dju055.
- 23 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017; 67: 7–30.
- 24 Swain SM, Nunes R, Yoshizawa C, Rothney M, Sing AP. Quantitative gene expression by recurrence score in ER-positive breast cancer, by age. Adv Ther. 2015; 32: 1222–1236.
- 25 Joh JE, Esposito NN, Kiluk JV, et al. The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist. 2011; 16: 1520–1526.
- 26 Partin JF, Mamounas EP. Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer. Ann Surg Oncol. 2011; 18: 3399–3406.
- 27 Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008; 26: 721–728.
- 28 Oratz R, Paul D, Cohn AL, Sedlacek SM. Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer. J Oncol Pract. 2007; 3: 182–186.
- 29 Williams C, Brunskill S, Altman D, et al. Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy. Health Technol Assess. 2006; 10:iii-xi, 1–210.
- 30 Issa AM, Chaudhari VS, Marchant GE. The value of multigene predictors of clinical outcome in breast cancer: an analysis of the evidence. Expert Rev Mol Diagn. 2015; 15: 277–286.
- 31 Lynch JA, Berse B, Petkov V, et al. Implementation of the 21-gene recurrence score test in the United States in 2011. Genet Med. 2016; 18: 982–990.
- 32 Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010; 11: 55–65.
- 33 Yardley DA, Peacock NW, Shastry M, et al. A phase II trial of ixabepilone and cyclophosphamide as neoadjuvant therapy for patients with HER2-negative breast cancer: correlation of pathologic complete response with the 21-gene recurrence score. Breast Cancer Res Treat. 2015; 154: 299–308.
- 34 Soran A, Bhargava R, Johnson R, et al. The impact of Oncotype DX(R) recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer. Breast Dis. 2016; 36: 65–71.
- 35 Akashi-Tanaka S, Shimizu C, Ando M, et al. 21-Gene expression profile assay on core needle biopsies predicts responses to neoadjuvant endocrine therapy in breast cancer patients. Breast. 2009; 18: 171–174.
- 36 Ueno T, Masuda N, Yamanaka T, et al. Evaluating the 21-gene assay Recurrence Score(R) as a predictor of clinical response to 24 weeks of neoadjuvant exemestane in estrogen receptor-positive breast cancer. Int J Clin Oncol. 2014; 19: 607–613.
- 37 Straver ME, Glas AM, Hannemann J, et al. The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2010; 119: 551–558.
- 38 Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009; 27: 1160–1167.
- 39 Iwao-Koizumi K, Matoba R, Ueno N, et al. Prediction of docetaxel response in human breast cancer by gene expression profiling. J Clin Oncol. 2005; 20: 422–431.
- 40 Parker JS, Prat A, Cheang MCU, Lenburg ME, Paik S, Perou CM. Breast cancer molecular subtypes predict response to anthracycline/taxane-based chemotherapy. Cancer Res. 2009; 69: 598s–598s.
- 41 Wolff AC, Hammond ME, Schwartz JN, et al. 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. 2007; 25: 118–145.
- 42 Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013; 31: 3997–4013.
- 43 Kutner MH, Nachtsheim CJ, Neter J, Li W. Applied Linear Statistical Models. New York: McGraw-Hill; 2005.
- 44 Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015; 373: 2005–2014.
- 45 Gluz O, Nitz UA, Christgen M, et al. West German Study Group phase III plan B trial: first prospective outcome data for the 21-gene recurrence score assay and concordance of prognostic markers by central and local pathology assessment. J Clin Oncol. 2016; 34: 2341–2349.
- 46 Petkov VI, MIller DP, Howlader N, et al. Breast-cancer-specific mortality in patients treated based on the 21-gene assy: a SEER population-based study. Breast Cancer. 2016; 2: 1–9.
