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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Breast carcinoma with 21-gene recurrence score lower than 18: rate of locoregional recurrence in a large series with clinical follow-up

Authors: Gulisa Turashvili, Edi Brogi, Monica Morrow, Maura Dickler, Larry Norton, Clifford Hudis, Hannah Y. Wen

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The 21-gene recurrence score (RS) assay determines the benefit of adding chemotherapy to endocrine therapy for patients with early stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. The RS risk groups predict the likelihood of distant recurrence and have recently been associated with an increased risk of locoregional recurrence (LRR). This study analyzed clinicopathologic features of patients with low RS and LRR.

Methods

In our institutional database, we identified 1396 consecutive female patients with lymph node negative, ER+/HER2- invasive breast carcinoma and low RS (<18) results, treated at our center from 2008 to 2013. We collected data on clinicopathologic features, treatment and outcome.

Results

The median patient age was 57 years (range 22–90). The median tumor size was 1.2 cm (range 0.3–5.8). Overall, 66.6% (930/1396) women were treated with breast conserving surgery (BCS) and radiation therapy, 3.4% (48/1396) with BCS alone, 29.7% (414/1396) with total mastectomy, and 0.3% (4/1396) with total mastectomy and radiation therapy. Most patients (84.8%; 1184/1396) received endocrine therapy alone, 12.1% (169/1396) were treated with chemotherapy plus endocrine therapy, and only 3.1% (43/1396) received no systemic therapy. At a median follow-up of 52 months, 0.9% (13/1396) of patients developed LRR. Sites of LRR included the ipsilateral breast (n = 8), chest wall (n = 3), axillary node (n = 1), and internal mammary node (n = 1). All patients with LRR had negative resection margins at the initial surgery. The rate of LRR in patients treated with adjuvant endocrine therapy alone was 0.7% (8/1184). All eight patients received standard local treatment. Three patients had lymphovascular invasion but no other significant risk factors for LRR were identified.

Conclusions

Our study of node negative, ER+/HER2- breast cancer patients with low RS observed extremely low rates of LRR: 0.9% (13/1396) in the whole cohort and 0.7% (8/1184) in patients treated with endocrine therapy alone. As the largest series to date, we report detailed clinicopathologic data and clinical outcomes of this cohort and provide a comprehensive characterization of patients who developed LRR.
Literature
1.
van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.CrossRefPubMed
2.
van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRefPubMed
3.
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.CrossRefPubMed
4.
Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.CrossRefPubMed
5.
Gyorffy B, Hatzis C, Sanft T, Hofstatter E, Aktas B, Pusztai L. Multigene prognostic tests in breast cancer: past, present, future. Breast Cancer Res. 2015;17:11.CrossRefPubMedPubMedCentral
6.
Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr, American Society of Clinical O. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287–312.CrossRefPubMed
7.
Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, 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(1):55–65.CrossRefPubMed
8.
Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol. 2010;28(10):1671–6.CrossRefPubMed
9.
Ademuyiwa FO, Miller A, O'Connor T, Edge SB, Thorat MA, Sledge GW, Levine E, Badve S. The effects of oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort. Breast Cancer Res Treat. 2011;126(3):797–802.CrossRefPubMed
10.
Geffen DB, Abu-Ghanem S, Sion-Vardy N, Braunstein R, Tokar M, Ariad S, Delgado B, Bayme M, Koretz M. The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy. Ann Oncol. 2011;22(11):2381–6.CrossRefPubMed
11.
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(12):3399–406.CrossRefPubMed
12.
Albanell J, Gonzalez A, Ruiz-Borrego M, Alba E, Garcia-Saenz JA, Corominas JM, Burgues O, Furio V, Rojo A, Palacios J, et al. Prospective transGEICAM study of the impact of the 21-gene recurrence score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer. Ann Oncol. 2012;23(3):625–31.CrossRefPubMed
13.
Joh JE, Esposito NN, Kiluk JV, Laronga C, Lee MC, Loftus L, Soliman H, Boughey JC, Reynolds C, Lawton TJ, 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(11):1520–6.CrossRefPubMedPubMedCentral
14.
Eiermann W, Rezai M, Kummel S, Kuhn T, Warm M, Friedrichs K, Schneeweiss A, Markmann S, Eggemann H, Hilfrich J, et al. The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use. Ann oncol. 2013;24(3):618–24.CrossRefPubMed
15.
Carlson JJ, Roth JA. The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;141(1):13–22.CrossRefPubMedPubMedCentral
16.
Dinan MA, Mi X, Reed SD, Lyman GH, Curtis LH. Association between use of the 21-gene recurrence score assay and receipt of chemotherapy among Medicare beneficiaries with early-stage breast cancer, 2005-2009. JAMA oncology. 2015;1(8):1098–109.CrossRefPubMed
17.
Levine MN, Julian JA, Bedard PL, Eisen A, Trudeau ME, Higgins B, Bordeleau L, Pritchard KI. Prospective evaluation of the 21-gene recurrence score assay for breast cancer decision-making in Ontario. J Clin Oncol. J Clin Oncol. 2016;34:1065–71.
18.
Mamounas EP, Tang G, Fisher B, Paik S, Shak S, Costantino JP, Watson D, Geyer CE Jr, Wickerham DL, Wolmark N. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28(10):1677–83.CrossRefPubMedPubMedCentral
19.
Jegadeesh NK, Kim S, Prabhu RS, Oprea GM, Yu DS, Godette KG, Zelnak AB, Mister D, Switchenko JM, Torres MA. The 21-gene recurrence score and locoregional recurrence in breast cancer patients. Ann Surg Oncol. 2015;22(4):1088–94.CrossRefPubMed
20.
Solin LJ, Gray R, Goldstein LJ, Recht A, Baehner FL, Shak S, Badve S, Perez EA, Shulman LN, Martino S, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the eastern cooperative oncology group E2197 study. Breast Cancer Res Treat. 2012;134(2):683–92.CrossRefPubMedPubMedCentral
21.
Turashvili G, Chou JF, Brogi E, Morrow M, Dickler M, Norton L, Hudis C, Wen HY. 21-gene recurrence score and locoregional recurrence in lymph node-negative, estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2017;166(1):69–76.
22.
Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual, 7th edn. New York, NY: Springer; 2010.
23.
Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127–32.CrossRefPubMed
24.
Hassett MJ, Silver SM, Hughes ME, Blayney DW, Edge SB, Herman JG, Hudis CA, Marcom PK, Pettinga JE, Share D, et al. Adoption of gene expression profile testing and association with use of chemotherapy among women with breast cancer. J Clin Oncol. 2012;30(18):2218–26.CrossRefPubMedPubMedCentral
25.
Wen HY, Krystel-Whittemore M, Patil S, Pareja F, Bowser ZL, Dickler MN, Norton L, Morrow M, Hudis CA, Brogi E. Breast carcinoma with an Oncotype Dx recurrence score <18: rate of distant metastases in a large series with clinical follow-up. Cancer. 2017;123(1):131–7.
26.
Yamashita H, Ogiya A, Shien T, Horimoto Y, Masuda N, Inao T, Osako T, Takahashi M, Endo Y, Hosoda M, et al. Clinicopathological factors predicting early and late distant recurrence in estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer. 2016;23(6):830–43.CrossRefPubMed
27.
28.
Wapnir IL, Anderson SJ, Mamounas EP, Geyer CE Jr, Jeong JH, Tan-Chiu E, Fisher B, Wolmark N. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and bowel project node-positive adjuvant breast cancer trials. J Clin Oncol. 2006;24(13):2028–37.CrossRefPubMed
29.
Fredholm H, Magnusson K, Lindstrom LS, Garmo H, Falt SE, Lindman H, Bergh J, Holmberg L, Ponten F, Frisell J, et al. Long-term outcome in young women with breast cancer: a population-based study. Breast Cancer Res Treat. 2016;160(1):131–43.CrossRefPubMedPubMedCentral
30.
Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, Theriault RL, Blayney DW, Niland JC, Winer EP, et al. Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34(27):3308–14.CrossRefPubMed
31.
Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006;7(4):347–50.CrossRefPubMed
32.
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.
33.
Ramsey SD, Barlow WE, Gonzalez-Angulo AM, Tunis S, Baker L, Crowley J, Deverka P, Veenstra D, Hortobagyi GN. Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes. Contemp Clin Trials. 2013;34(1):1–9.CrossRefPubMed
Metadata
Title
Breast carcinoma with 21-gene recurrence score lower than 18: rate of locoregional recurrence in a large series with clinical follow-up
Authors
Gulisa Turashvili
Edi Brogi
Monica Morrow
Maura Dickler
Larry Norton
Clifford Hudis
Hannah Y. Wen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3985-y

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