Journal Article
. 2017 Nov;12(11).
doi: 10.1371/journal.pone.0187679.

Chemosensitivity to doxorubicin of ER-positive/HER2-negative breast cancers with high 21-gene recurrence score: A study based on in vitro chemoresponse assay

Sung Gwe Ahn 1 Soong June Bae 1 Changik Yoon 1 Yoon Jin Cha 2 Hak Woo Lee 1 Seung Ah Lee 3 Joon Jeong 1 
  • PMID: 29117208
  •     17 References


Aim: The 21-gene recurrence score (RS) predicts a clinical benefit of chemotherapy for individuals with ER-positive/HER2-negative breast cancer. Using in vitro chemoresponse assay, we compared the chemosensitivity according to RS in these patients.

Method: Among the patients with Oncotype Dx assay, we identified 63 patients who had chemotherapy response assays to doxorubicin based on adenosine triphosphate. The degree of chemosensitivity to doxorubicin was translated into the cell death rate (CDR). The RS was also dichotomized with a cutoff of 26.

Results: Of 63 patients, 34 (54%), 17 (27%), and 12 patients (19%) had a low, intermediate, and high RS, respectively. The mean CDR differed significantly according to categorized RS, with 17.3±10.8 in the low RS group vs. 23.6±16.3 in the intermediate RS group vs. 28.8±12.6 in the high RS group (P = 0.024, One-way ANOVA test). The mean CDR was significantly higher in the higher RS (26≥) group compared with the lower RS (<26) group (P = 0.025, the Student's t-test), as well as in the high RS (>30) group compared with the low RS (<18) group (P = 0.012, the Student's t-test). Also, continuous RS and CDR correlated positively (Pearson's R = 0.337; P = 0.007). High RS demonstrated the odds ratio (OR = 26.33; 95% CI = 1.69-410.0) for predicting tumors with chemosensitivity on the multivariate analysis.

Conclusions: The chemosensitivity measured by in vitro chemoresponse assay was different according to the RS. Our findings support that tumors with high RS has the chemosensitivity even though they are luminal/HER2-negative tumors.

Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer.
J M Harvey, G M Clark, C K Osborne, D C Allred.
J Clin Oncol, 1999 May 20; 17(5). PMID: 10334533
Highly Cited.
Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma.
Sanjay Sharma, Michael H Neale, +9 authors, Ian A Cree.
BMC Cancer, 2003 Jul 05; 3. PMID: 12841853    Free PMC article.
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.
Luca Gianni, Milvia Zambetti, +14 authors, Steven Shak.
J Clin Oncol, 2005 Sep 08; 23(29). PMID: 16145055
Highly Cited.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
International Web-based consultation on priorities for translational breast cancer research.
Mitch Dowsett, Aron Goldhirsch, +3 authors, Giuseppe Viale.
Breast Cancer Res, 2007 Nov 24; 9(6). PMID: 18034879    Free PMC article.
Development of the 21-gene assay and its application in clinical practice and clinical trials.
Joseph A Sparano, Soonmyung Paik.
J Clin Oncol, 2008 Feb 09; 26(5). PMID: 18258979
Highly Cited. Review.
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), C Davies, +11 authors, R Peto.
Lancet, 2011 Aug 02; 378(9793). PMID: 21802721    Free PMC article.
Highly Cited.
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.
A Goldhirsch, E P Winer, +5 authors, Panel members.
Ann Oncol, 2013 Aug 07; 24(9). PMID: 23917950    Free PMC article.
Highly Cited.
In vitro chemoresponse assay based on the intrinsic subtypes in breast cancer.
Sung Gwe Ahn, Seung Ah Lee, +2 authors, Joon Jeong.
Jpn J Clin Oncol, 2014 May 08; 44(7). PMID: 24803548
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
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.
Denise A Yardley, Nancy W Peacock, +6 authors, John D Hainsworth.
Breast Cancer Res Treat, 2015 Oct 29; 154(2). PMID: 26507191
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.
Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology.
J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339    Free PMC article.
Highly Cited. Review.
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
Fatima Cardoso, Laura J van't Veer, +32 authors, MINDACT Investigators.
N Engl J Med, 2016 Aug 25; 375(8). PMID: 27557300
Highly Cited.
The impact of Oncotype DX® recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer.
Atilla Soran, Rohit Bhargava, +8 authors, Kandace P McGuire.
Breast Dis, 2016 Sep 24; 36(2-3). PMID: 27662272
Erratum: 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, Wen Wan, +8 authors, Amy P Sing.
J Surg Oncol, 2018 Oct 09; 118(4). PMID: 30295942