2024 Breast Cancer Congress Friday, February 2, 2024

with Updates from the 2023 SABCS 9:05 AM – 9:30 AM CST

Biomarkers and Gene Panel Testing

in Early-Stage Breast Cancer

Hatem Soliman, MD
Moffitt Cancer Center

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 Goals of molecular testing in early-stage
breast cancer
• Determine prognosis more precisely (natural history of breast cancer)
• Combination of clinical/pathology parameters and molecular performs best
• Predictive biomarkers (how effective a treatment will be)
• Reduce overtreatment with chemotherapy that is not beneficial (de-escalation)
• May help with selecting patients for chemotherapy or other treatments
(intensification)
• Can help personalize therapy discussions but has limitations
• Current genomic tests do not predict an individual’s response or need for
adjuvant therapy based on presence of residual disease

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 2.5cm G2 N0
21-GS=14 in
45 year old

2.5cm G2 N0
21-GS=25 in
45 year old

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
© National Comprehensive Cancer Network, Inc. 2024, All Rights Reserved. No part of this publication may be reproduced or transmitted in any other form or
by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 21 gene recurrence score

Paik S et al. N Engl J Med 2004;351:2817-2826

Paik et al. J Clin Oncol. 2006;24(23)

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 21 GS in node negative stage I-II ER+HER2- BC
TAILORx

>50 years old

≤50 years old

Sparano et al. N Engl J Med. 2018

Sparano et al. JAMA Onc. 2019

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 21 GS in pN1 ER+HER2- BC
RxPONDER S1007

Kalinsky et al. NEJM 2021

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
© National Comprehensive Cancer Network, Inc. 2024, All Rights Reserved. No part of this publication may be reproduced or transmitted in any other form or
by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 70 GS in N0-1 early-stage ER+HER2- BC
• Developed around 2002 using NKI untreated breast cancer cases. FDA cleared in 2004.
• Reported as low or high risk initially, but now includes subsets such as ultra low risk on continuous scale.
• MINDACT prospective trial primary endpoint was lower bound of 95% CI for Clin-High/Genomic low group 5
year DMFS ≥ 92% in no chemotherapy group
• CT 5-year DMFS 95.9% (95% CI, 94.0 to 97.2), No CT 94.4% (95% CI, 92.3 to 95.9) HR=0.78; 95% CI, 0.50
to 1.21; P=0.27)
• Updated 8 year FU showed CT DMFS 92.0% vs. 89.4% HR=.66; 95% CI, .48-.92. Subset analysis in age ≤50
patients showed 5% difference in DMFS 93.6% vs. 88.6%. No significant difference in age >50 subset (90.0
vs. 90.2%).
• For pN1 patients 8 year DMFS 91.2% with CT vs. 89.9%

Cardoso et al. NEJM 2016

Piccart et al. Lancet Onc 2021

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 50-gene assay ROR in N0-1 early-stage ER+HER2- BC
• Developed using RNA quantification device to generate 50 gene subtype signature and risk of recurrence
score (ROR)
• Prognostic across multiple studies (ABCSG 08, DBCG, TransATAC)

Gnant M, et al. Ann Oncol. 2014

Lænkholm AVet al. J Clin Oncol. 2018

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 12 gene assay in N0-1 early-stage ER+HER2- BC

ABCSG 6,8 PTS

Filpits et al. CCR 2011

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
© National Comprehensive Cancer Network, Inc. 2024, All Rights Reserved. No part of this publication may be reproduced or transmitted in any other form or
by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 BCI in N0-1 early-stage
ER+HER2- BC
•Genes: BUB1B, CENPA, NEK2, RACGAP1,
RRM2 (MGI-prognostic) HOXB13/IL17BR
(H/I-predictive)
•For N1 patients: Risk is determined by
incorporating the tumor size and grade with
the BCI gene expression signature

1.Zhang Y,etal.Clin CancerRes.2013;19(15):4196-4205.2.SgroiDC,etal.J N atlCancerInst.2013;105(14):1036-

1042.3.BartlettJM S,etal.Ann Oncol.2019;300(11):1776-1783.4.N oordhoek I,etal.Clin CancerRes.2021;27(1):311-
319.5.M am ounas EP,etal.Abstract501;ASCO June 2021

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
© National Comprehensive Cancer Network, Inc. 2024, All Rights Reserved. No part of this publication may be reproduced or transmitted in any other form or
by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 Future questions to answer
• Role of chemotherapy induced ovarian suppression versus non-chemotherapy ovarian suppression
plus endocrine therapy in node negative/positive premenopausal females
• OFSET trial by NRG may answer

• Can molecular tests enrich for benefit from newer adjuvant therapies besides chemotherapy?
• i.e. NATALEE allowed high risk genomic testing as a criteria for grade 2 node negative stage II

• Can emerging assays better refine individual risk/prognosis?

• As de-escalation of axillary surgery increases, will this affect accuracy of our risk assessments?

• How will newer adjuvant therapies like abemaciclib affect delayed recurrence, particularly in those
that are at higher risk with limited benefit from extended endocrine therapy?

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 Conclusions
• Per NCCN guidelines the 21 gene score test is recommended for both prognosis and prediction of
chemotherapy benefit in:

• Node negative stage I-II ER+HER2- breast cancer in premenopausal and postmenopausal patients

• Node positive (1-3 nodes) ER+HER2- breast cancer in postmenopausal patients. For premenopausal
patients its use may guide discussion of alternatives to chemotherapy (i.e. ovarian suppression) but it
is not known if chemotherapy and OFS are interchangeable in this population.

• Other assays are prognostic with uncertain prediction capability

• 70 GS demonstrating clinical utility in the subset of postmenopausal patients with high clinical risk
(N0 and N1) and low genomic risk to consider omission of chemotherapy

• For extended endocrine therapy after the first 5 years, BCI can provide additional information to aid the
selection of N0 or N1 patients for extended endocrine therapy

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by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.
 NCCN Member Institutions

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devoted to patient care, research,
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Our Mission
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effective, equitable, and accessible
cancer care so all patients can live
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Our Vision
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high-value, patient-centered cancer
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© National Comprehensive Cancer Network, Inc. 2024, All Rights Reserved. No part of this publication may be reproduced or transmitted in any other form or
by any means, electronic or mechanical, without first obtaining express written permission from NCCN®. Contact education@nccn.org with any questions.