Identifying Clinicopathological Factors Associated with Oncotype DX® 21-Gene Recurrence Score: A Real-World Retrospective Cohort Study of Breast Cancer Patients in Quebec City, Canada
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Population
2.2. Variables
2.2.1. Oncotype DX Recurrence Score
2.2.2. Clinicopathological and Lifestyle Risk Factors
2.3. Statistical Analyses
2.4. Sensitivity Analyses
3. Results
4. Discussion
5. Conclusions and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Reis-Filho, J.S.; Pusztai, L. Gene expression profiling in breast cancer: Classification, prognostication, and prediction. Lancet 2011, 378, 1812–1823. [Google Scholar] [CrossRef]
- Direction Québécoise de Cancérologie. Utilisation du Test Oncotype DX® pour le Cancer du Sein. Cadre de Référence. Available online: https://publications.msss.gouv.qc.ca/msss/fichiers/2012/12-902-09W.pdf (accessed on 1 July 2021).
- Paik, S.; Shak, S.; Tang, G.; Kim, C.; Baker, J.; Cronin, M.; Baehner, F.L.; Walker, M.G.; 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, 2817–2826. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harris, L.N.; Ismaila, N.; McShane, L.M.; Andre, F.; Collyar, D.E.; Gonzalez-Angulo, A.M.; Hammond, E.H.; Kuderer, N.M.; Liu, M.C.; Mennel, R.G.; et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J. Clin. Oncol. 2016, 34, 1134–1150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gradishar, W.J.; Anderson, B.O.; Balassanian, R.; Blair, S.L.; Burstein, H.J.; Cyr, A.; Elias, A.D.; Farrar, W.B.; Forero, A.; Giordano, S.H.; et al. Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2018, 16, 310–320. [Google Scholar] [CrossRef]
- Senkus, E.; Kyriakides, S.; Ohno, S.; Penault-Llorca, F.; Poortmans, P.; Rutgers, E.; Zackrisson, S.; Cardoso, F. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2015, 26 (Suppl. 5), v8–v30. [Google Scholar] [CrossRef]
- Goldhirsch, A.; Winer, E.P.; Coates, A.S.; Gelber, R.D.; Piccart-Gebhart, M.; Thurlimann, B.; Senn, H.J.; Panel, M. Personalizing the treatment of women with early breast cancer: Highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann. Oncol. 2013, 24, 2206–2223. [Google Scholar] [CrossRef]
- Zhu, X.; Dent, S.; Paquet, L.; Zhang, T.; Tesolin, D.; Graham, N.; Aseyev, O.; Song, X. How Canadian Oncologists Use Oncotype DX for Treatment of Breast Cancer Patients. Curr. Oncol. 2021, 28, 800–812. [Google Scholar] [CrossRef]
- Matikas, A.; Foukakis, T.; Swain, S.; Bergh, J. Avoiding over- and undertreatment in patients with resected node-positive breast cancer with the use of gene expression signatures: Are we there yet? Ann. Oncol. 2019, 30, 1044–1050. [Google Scholar] [CrossRef] [PubMed]
- Eichler, C.; Fromme, J.; Thangarajah, F.; Puppe, J.; Paepke, S.; Warm, M.; Malter, W. Gene-expression Profiling—A Decision Impact Analysis: Decision Dependency on Oncotype DX® as a Function of Oncological Work Experience in 117 Cases. Anticancer Res. 2019, 39, 297–303. [Google Scholar] [CrossRef] [PubMed]
- Prat, A.; Parker, J.S.; Fan, C.; Cheang, M.C.U.; Miller, L.D.; Bergh, J.; Chia, S.K.L.; Bernard, P.S.; Nielsen, T.O.; Ellis, M.J.; et al. Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen. Ann. Oncol. 2012, 23, 2866–2873. [Google Scholar] [CrossRef]
- Paulden, M.; Franek, J.; Pham, B.; Bedard, P.L.; Trudeau, M.; Krahn, M. Cost-Effectiveness of the 21-Gene Assay for Guiding Adjuvant Chemotherapy Decisions in Early Breast Cancer. Value Health 2013, 16, 729–739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Orucevic, A.; Heidel, R.E.; Bell, J.L. Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: Lessons learned from the 2010 to 2012 National Cancer Data Base analysis. Breast Cancer Res. Treat. 2016, 157, 427–435. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roberts, M.C.; Weinberger, M.; Dusetzina, S.B.; Dinan, M.A.; Reeder-Hayes, K.E.; Carey, L.A.; Troester, M.A.; Wheeler, S.B. Racial Variation in the Uptake of Oncotype DX Testing for Early-Stage Breast Cancer. J. Clin. Oncol. 2016, 34, 130–138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guth, A.A.; Fineberg, S.; Fei, K.; Franco, R.; Bickell, N.A. Utilization of Oncotype DX in an Inner City Population: Race or Place? Int. J. Breast Cancer 2013, 2013, 653805. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le Du, F.; Gonzalez-Angulo, A.M.; Park, M.; Liu, D.D.; Hortobagyi, G.N.; Ueno, N.T. Effect of 21-Gene RT-PCR Assay on Adjuvant Therapy and Outcomes in Patients With Stage I Breast Cancer. Clin. Breast Cancer 2015, 15, 458–466. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, J.; Fang, Y.; Lin, L.; Fei, X.; Gao, W.; Zhu, S.; Zong, Y.; Chen, X.; Huang, O.; He, J.; et al. Distribution patterns of 21-gene recurrence score in 980 Chinese estrogen receptor-positive, HER2-negative early breast cancer patients. Oncotarget 2017, 8, 38706–38716. [Google Scholar] [CrossRef] [Green Version]
- Huang, J.L.; Kizy, S.; Marmor, S.; Altman, A.; Blaes, A.; Beckwith, H.; Tuttle, T.M.; Hui, J.Y.C. Tumor grade and progesterone receptor status predict 21-gene recurrence score in early stage invasive breast carcinoma. Breast Cancer Res. Treat. 2018, 172, 671–677. [Google Scholar] [CrossRef]
- Yu-Qing, Y.; Lei, W.; Mei-Ling, H.; Jing-Jing, X.; Mei-Chen, W.; Jiang, W.; Jun-Sheng, H.; Rui, L.; Nan-Lin, L. Clinical significance of 21-gene recurrence score assay for hormone receptor-positive, lymph node-negative breast cancer in early stage. Exp. Mol. Pathol. 2019, 108, 150–155. [Google Scholar] [CrossRef]
- Kim, H.S.; Christopher, B.U.; Peter, B.I.; Ashley, C.-M.; Soonweng, C.; Nivedita, C.; Maria Cristina, F.-M.; Catherine, P.; Stacie, C.J.; Charles, M.; et al. Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer. J. Clin. Oncol. 2016, 34, 4390–4397. [Google Scholar] [CrossRef]
- Tsai, P.-C.; Glastonbury, C.A.; Eliot, M.N.; Bollepalli, S.; Yet, I.; Castillo-Fernandez, J.E.; Carnero-Montoro, E.; Hardiman, T.; Martin, T.C.; Vickers, A.; et al. Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health. Clin. Epigenetics 2018, 10, 126. [Google Scholar] [CrossRef]
- Reynolds, L.M.; Lohman, K.; Pittman, G.S.; Barr, R.G.; Chi, G.C.; Kaufman, J.; Wan, M.; Bell, D.A.; Blaha, M.J.; Rodriguez, C.J.; et al. Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: The Multi-Ethnic Study of Atherosclerosis (MESA). Epigenetics 2017, 12, 1092–1100. [Google Scholar] [CrossRef]
- McVeigh, T.P.; Kerin, M.J. Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer. Breast Cancer 2017, 9, 393–400. [Google Scholar] [CrossRef] [Green Version]
- Berube, S.; Provencher, L.; Robert, J.; Jacob, S.; Hebert-Croteau, N.; Lemieux, J.; Duchesne, T.; Brisson, J. Quantitative exploration of possible reasons for the recent improvement in breast cancer survival. Breast Cancer Res. Treat. 2007, 106, 419–431. [Google Scholar] [CrossRef]
- Sparano, J.A.; Gray, R.J.; Makower, D.F.; Pritchard, K.I.; Albain, K.S.; Hayes, D.F.; Geyer, C.E., Jr.; Dees, E.C.; Perez, E.A.; Olson, J.A., Jr.; et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N. Engl. J. Med. 2015, 373, 2005–2014. [Google Scholar] [CrossRef] [PubMed]
- Sparano, J.A.; Gray, R.J.; Makower, D.F.; Pritchard, K.I.; Albain, K.S.; Hayes, D.F.; Geyer, C.E., Jr.; Dees, E.C.; Goetz, M.P.; Olson, J.A., Jr.; et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N. Engl. J. Med. 2018, 379, 111–121. [Google Scholar] [CrossRef] [Green Version]
- Paik, S.; Tang, G.; Shak, S.; Kim, C.; Baker, J.; Kim, W.; Cronin, M.; Baehner, F.L.; 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, 3726–3734. [Google Scholar] [CrossRef]
- Wolf, I.; Ben-Baruch, N.; Shapira-Frommer, R.; Rizel, S.; Goldberg, H.; Yaal-Hahoshen, N.; Klein, B.; Geffen, D.B.; Kaufman, B. Association between standard clinical and pathologic characteristics and the 21-gene recurrence score in breast cancer patients: A population-based study. Cancer 2008, 112, 731–736. [Google Scholar] [CrossRef]
- Partin, J.F.; Mamounas, E.P. 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. [Google Scholar] [CrossRef] [PubMed]
- Orucevic, A.; Bell, J.L.; McNabb, A.P.; Heidel, R.E. Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data. Breast Cancer Res. Treat. 2017, 163, 51–61. [Google Scholar] [CrossRef] [PubMed]
- Ministère de la Santé et des Services Sociaux. Statistiques et Données sur la Santé et le Bien-Être. Available online: https://www.msss.gouv.qc.ca/professionnels/statistiques-donnees-sante-bien-etre/ (accessed on 1 July 2021).
- Lohrisch, C.A.; Davidson, A.; Chia, S.K.L.; Gelmon, K.A.; Shenkier, T.N.; Ellard, S.; Woods, R.; Wong, L.; Pope, J. Relationship between body mass index (BMI) at diagnosis of ER+ node negative breast cancer (BC) and Oncotype DX recurrence score. J. Clin. Oncol. 2012, 30, 582. [Google Scholar] [CrossRef]
- Benefield, H.; Reeder-Hayes, K.E.; Wheeler, S.B.; Carey, L.A.; Olshan, A.F.; Troester, M. Association of race, reproductive factors, and lifestyle factors with tumor subtype defined by Oncotype DX recurrence score. J. Clin. Oncol. 2018, 36, e13581. [Google Scholar] [CrossRef]
- Picardo, S.; Sui, J.; Greally, M.; Woulfe, B.; Prior, L.; Corrigan, L.; O’Leary, C.; Mullally, W.; Walshe, J.; McCaffrey, J.; et al. 193POncotype DX score, menopausal status and body mass index. Ann. Oncol. 2017, 28 (Suppl. 5). [Google Scholar] [CrossRef]
- Namuche, F.; Ruiz, R.E.; Morante Cruz, Z.D.; Urrunaga, D.; Ziegler, G.; Mantilla, R.; Leon Rivera, M.; Chavez Mac Gregor, M.; Gomez Moreno, H.L. 211POncotype Dx results in patients ≤40 years: Does age matter? New insights. Ann. Oncol. 2018, 29 (Suppl. 8), viii67–viii68. [Google Scholar] [CrossRef]
- Carr, D.N.; Vera, N.; Sun, W.; Lee, M.C.; Hoover, S.; Fulp, W.; Acs, G.; Laronga, C. Menopausal status does not predict Oncotype DX recurrence score. J. Surg. Res. 2015, 198, 27–33. [Google Scholar] [CrossRef]
- Lee, M.H.; Han, W.; Lee, J.E.; Kim, K.S.; Park, H.; Kim, J.; Bae, S.Y.; Shin, H.J.; Lee, J.W.; Lee, E.S. The clinical impact of 21-gene recurrence score on treatment decisions for patients with hormone receptor-positive early breast cancer in Korea. Cancer Res. Treat. Off. J. Korean Cancer Assoc. 2015, 47, 208–214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Characteristics | Total (N = 425) | % |
---|---|---|
Mean Recurrence Score (RS) [SD] | 17.8 [9.2] | |
Recurrence score | ||
Low risk (0 to 17) | 237 | 55.8 |
Intermediate risk (18 to 30) | 148 | 34.8 |
High risk (more than 30) | 40 | 9.4 |
Age | ||
≤50 | 105 | 24.7 |
>50 | 320 | 75.3 |
Estrogen receptor (% cells staining positive) | ||
1–90 | 50 | 11.7 |
90–100 | 375 | 88.2 |
Progesterone receptor (% cells staining positive) | ||
<1 | 31 | 7.3 |
1–90 | 228 | 53.6 |
90–100 | 166 | 39.1 |
Human Epidermal Growth Factor Receptor-2 | ||
Negative | 417 | 98.1 |
Positive | 2 | 0.5 |
Equivocal result | 5 | 1.2 |
Missing values | 1 | 0.2 |
Histological type | ||
Invasive ductal carcinoma | 317 | 74.6 |
Others | 108 | 25.4 |
Tumor stage | ||
I | 234 | 55.1 |
II | 191 | 44.9 |
Histological grade | ||
I | 347 | 81.7 |
II | 78 | 18.3 |
Tumor size | ||
≤20 mm | 256 | 60.2 |
>20 mm | 169 | 39.8 |
Ganglion node | ||
No | 379 | 89.2 |
Yes | 36 | 8.4 |
Missing values | 10 | 2.4 |
Smoking status | ||
Non-smoker | 200 | 47.0 |
Smoker | 220 | 51.8 |
Missing values | 5 | 1.2 |
Alcohol consumption | ||
No | 104 | 24.5 |
0.1–9.9 | 250 | 58.8 |
≥10 | 34 | 8.0 |
Missing values | 37 | 8.7 |
Menopause | ||
No | 122 | 28.7 |
Yes | 291 | 68.5 |
Missing values | 12 | 2.8 |
Body mass index | ||
<25 | 205 | 48.2 |
25–29.9 | 144 | 33.9 |
≥30 | 76 | 17.9 |
Age at first menstruation | ||
<12 | 87 | 20.5 |
12–14 | 274 | 64.5 |
≥15 | 52 | 12.2 |
Missing values | 12 | 2.8 |
Recurrence Score (RS) | ||||
---|---|---|---|---|
Clinicopathological Factors | Low | Intermediate | High | p-Value |
(N = 237) | (N = 148) | (N = 40) | ||
Age | 0.1537 | |||
≤50 | 66 (15.5) | 33 (7.8) | 6 (1.4) | |
>50 | 171 (40.2) | 115 (27.1) | 34 (8.0) | |
Estrogen receptor | 0.0661 | |||
1–90 | 23 (5.4) | 18 (4.2) | 9 (2.1) | |
90–100 | 214 (50.4) | 130 (30.6) | 31 (7.3) | |
Progesterone receptor | <0.0001 | |||
<1 | 6 (1.4) | 15 (3.5) | 10 (2.4) | |
1–90 | 102 (24.0) | 98 (23.1) | 28 (6.6) | |
90–100 | 129 (30.4) | 35 (8.2) | 2 (0.5) | |
Histological type | 0.0307 | |||
Invasive ductal carcinoma | 168 (39.5) | 113 (26.6) | 36 (8.5) | |
Other | 69 (16.2) | 35 (8.2) | 4 (0.9) | |
Tumor stade | 0.7528 | |||
I | 131 (30.8) | 79 (18.6) | 24 (5.6) | |
II | 106 (24.9) | 69 (16.2) | 16 (3.8) | |
Histological grade | <0.0001 | |||
I | 217 (51.1) | 116 (27.3) | 14 (3.3) | |
II | 20 (4.7) | 32 (7.5) | 26 (6.1) | |
Tumor size | 0.6692 | |||
≤20 mm | 147 (34.6) | 85 (20.0) | 24 (5.6) | |
>20 mm | 90 (21.2) | 63 (14.8) | 16 (3.8) | |
Smoker status | 0.3096 | |||
Non-smoker | 105 (25.0) | 73 (17.4) | 22 (5.2) | |
Smoker | 131 (31.2) | 71 (16.9) | 18 (4.3) | |
Alcohol consumption | 0.3768 | |||
No | 60 (14.1) | 35 (8.2) | 9 (2.1) | |
0.1–9.9 | 141 (33.2) | 88 (20.7) | 21 (4.9) | |
≥10 | 21 (4.9) | 10 (2.4) | 3 (0.7) | |
Missing values | 15 (3.5) | 15 (3.5) | 7 (1.6) | |
Menopause | 0.1148 | |||
No | 78 (18.9) | 34 (8.2) | 10 (2.4) | |
Yes | 154 (37.3) | 109 (26.4) | 28 (6.8) | |
Body mass index | 0.5218 | |||
<25 | 114 (26.8) | 75 (17.6) | 16 (3.8) | |
25–29.9 | 76 (17.9) | 52 (12.2) | 16 (3.8) | |
≥30 | 47 (11.1) | 21 (4.9) | 8 (1.9) | |
Age at first menstruation | 0.2344 | |||
<12 | 50 (12.1) | 29 (7.0) | 8 (1.9) | |
12–14 | 158 (38.3) | 91 (22.0) | 25 (6.1) | |
≥15 | 21 (5.1) | 25 (6.1) | 6 (1.5) |
Recurrence Score (RS) | ||
---|---|---|
Clinicopathological Factors | Intermediate vs. Low RS | High vs. Low RS |
Adjusted OR (95% CI) | Adjusted OR (95% CI) | |
Age | ||
≤50 | 1 | 1 |
> 50 | 0.77 (0.33–1.82) | 3.31 (0.72–15.34) |
Estrogen receptor | ||
1–90 | 1 | 1 |
90–100 | 0.83 (0.41–1.71) | 0.31 (0.10–0.96) |
Progesterone receptor | ||
<1 | 3.51 (1.21–10.21) | 10.34 (2.60–41.15) |
1–90 | 1 | 1 |
90–100 | 0.29 (0.17–0.47) | 0.05 (0.01–0.23) |
Histological type | ||
Invasive ductal carcinoma | 1 | 1 |
Other | 0.73 (0.43–1.24) | 0.36 (0.11–1.19) |
Tumor grade | ||
I | 1 | 1 |
II | 3.16 (1.65–6.05) | 23.04 (8.91–59.55) |
Menopausal | ||
No | 1 | 1 |
Yes | 1.35 (0.59–3.13) | 0.28 (0.07–1.13) |
Recurrence Score (RS) | p-Value | |||
---|---|---|---|---|
Adjuvant Chemotherapy | Low Risk | Intermediate Risk | High Risk | <0.0001 |
No | 234 (98.7) | 85 (57.4) | 3 (7.5) | |
Yes | 3 (1.3) | 63 (42.6) | 37 (92.5) |
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Gagnet, S.; Diorio, C.; Provencher, L.; Mbuya-Bienge, C.; Lapointe, J.; Morin, C.; Lemieux, J.; Nabi, H. Identifying Clinicopathological Factors Associated with Oncotype DX® 21-Gene Recurrence Score: A Real-World Retrospective Cohort Study of Breast Cancer Patients in Quebec City, Canada. J. Pers. Med. 2021, 11, 858. https://doi.org/10.3390/jpm11090858
Gagnet S, Diorio C, Provencher L, Mbuya-Bienge C, Lapointe J, Morin C, Lemieux J, Nabi H. Identifying Clinicopathological Factors Associated with Oncotype DX® 21-Gene Recurrence Score: A Real-World Retrospective Cohort Study of Breast Cancer Patients in Quebec City, Canada. Journal of Personalized Medicine. 2021; 11(9):858. https://doi.org/10.3390/jpm11090858
Chicago/Turabian StyleGagnet, Simon, Caroline Diorio, Louise Provencher, Cynthia Mbuya-Bienge, Julie Lapointe, Claudya Morin, Julie Lemieux, and Hermann Nabi. 2021. "Identifying Clinicopathological Factors Associated with Oncotype DX® 21-Gene Recurrence Score: A Real-World Retrospective Cohort Study of Breast Cancer Patients in Quebec City, Canada" Journal of Personalized Medicine 11, no. 9: 858. https://doi.org/10.3390/jpm11090858