GENE EXPRESSION SIGNATURE TO

INFORM ON ADJUVANT TREATMENT

Maria Vittoria Dieci

Department of Surgery, Oncology and Gastroenterology – University of Padova, Italy
Medical Oncology 2 – Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy
OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
TREATMENT INDIVIDUALISATION FOR
EARLY HR+/HER2– BC PATIENTS

100 BC pts 65 HR+/HER2– BC pts candidate to HT 50 HR+/HER2– BC patients

20% HER2+ BC 5% ≥4 node positive potentially candidate CT + HT
15% TN BC 2–3% too frail for CT (5 years or more)
Type of biomarker Clinical question
Prognostic biomarker Who can be spared further treatment (i.e. chemotherapy or extended
endocrine therapy?)

Predictive biomarker Who benefits from a specific treatment (i.e. chemotherapy or extended
endocrine therapy?)
CLINICAL UTILITY OF A BIOMARKER AND LEVEL
OF EVIDENCE 1

Analytical validation Level of evidence Tumour marker study

1A PROSPECTIVE: Prospective clinical trial specifically
designed to test the marker
1B PROSPECTIVE USING ARCHIVED SPECIMENS:
Consistent results from ≥2 prospective clinical trials not
Clinical validation designed to test the marker, but design accommodates
tumour marker utility (preplanned analysis)

Clinical utility

Simon RM, et al. J Natl Cancer Inst 2009;101(21):1446–52

OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
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

CT produces the same proportional risk reduction in all patients (EBCTCG)

This translates into different degrees of absolute benefit, depending on the individual estimate of absolute risk
of recurrence
What is the threshold of absolute risk of recurrence that defines patients that can be safely spared CT?

Absolute distant Relative risk Absolute risk Risk of fatal, life-threatening,

recurrence risk at baseline reduction with CT reduction from CT permanent CT toxicity
50–60% 30% 15–20% 2–3%
10–15% 30% 2–3% 2–3%

Harris LN, et al. J Clin Oncol 2016:34(10):1134–50. ASCO Special Article

 GENOMIC PROFILING AND PROGNOSIS FOR
HR+/HER2- PATIENTS
All tests have at least level 1B evidence for HR+/HER2–, T1–2 and N0–1 early BC

MammaPrint1 OncotypeDX2 PAM50 ROR3 EndoPredict4

Level 1A: data from prospective randomised trials (include tumour size + nodal status)
designed to test the marker
1. From N Engl J Med 2002, van de Vijver M, et al. A Gene-Expression Signature as a Predictor of Survival in Breast Cancer; 347:1999–2009. Copyright © 2002 Massachusetts Medical Society. Reprinted with permission
from Massachusetts Medical Society; 2. From N Engl J Med 2004; Paik S, et al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer; 351:2817–26. Copyright © 2004 Massachusetts
Medical Society. Reprinted with permission from Massachusetts Medical Society; 3. Nanotring Prosgina Package Insert. Prosigna® Breast Cancer Prognostic Gene Signature Assay. Version 10, Sept 2019. ©2012-2019
NanoString Technologies Inc., Seattle, USA. Reproduced with permission from NanoString; 4. Reprinted (or adapted) from Clin Cancer Res, Copyright 2011, 17(18), 6012–20, Filipits M, et al. A New Molecular Predictor of
Distant Recurrence in ER-Positive, HER2-Negative Breast Cancer Adds Independent Information to Conventional Clinical Risk Factors, with permission from AACR.
MINDACT: STUDY DESIGN

Clinical low:
Enrolled N=6,693
◆ T≤1 cm & G3
T 2 cm & G2
Clinical risk (c) Genomic risk (g)
◆

◆ T 3 cm % G1 Adjuvant online 70-gene signature or MammaPrint®

Clinical high: others
32%
N=2745 Discordant N=1806
N=592 N=1550
c-Low/g-Low c-High/g-High
c-Low/g-High c-High/g-Low

R-T

N=644 No chemotherapy Chemotherapy

Primary endpoints: Distant metastasis-free survival (DMFS) at 5 years

Null hypothesis: 5-year DMFS rate in PT population = 92%
Cardoso F, et al. N Engl J Med 2016;375(8):717–29; Piccart M, et al. Presented at AACR 2016.. With permission from Prof M. Piccart.
MINDACT: CHARACTERISTICS OF CLINICAL
HIGH-RISK PATIENTS

cH/gL (n=1550) cH/gH (n=1806) All cH (n=3356)

Age <50y 534 (34.5%) 716 (39.6%) 1250 (37.2%)
Age >50y 1016 (65.5%) 1090 (60.4%) 2106 (62.8%)
T<1 cm 38 (2.5%) 29 (1.6%) 67 (2.0%)
T1-2 cm 610 (39.4%) 914 (50.6%) 1524 (45.4%)
T >2 to 5 cm 843 (54.4%) 843 (46.7%) 1686 (50.3%)
T>5 cm 58 (3.7%) 20 (1.1%) 78 (2.3%)
N0 812 (52.4%) 1329 (73.6%) 2141 (63.8%)
N1 731 (47.2 %) 475 (26.3%) 1206 (35.9%)
>4 N pos 6 (0.4%) 2 (0.1%) 8 (0.2%)
G1 98 (6.3%) 15 (0.6%) 113 (3.4%)
G2 995 (64.2%) 421 (23.3%) 1416 (42.2%)
G3 443 (28.6%) 1365 (75.6%) 1808 (53.9%)
HR+/HER2- 1402 (90.5%) 895 (49.6%) 2297 (68.4%)
HR+/HER2+ 115 (7.4%) 222 (12.3%) 337 (10.0%)
HR-/HER2+ 9 (0.6%) 122 (6.8%) 131 (3.9%)
HR-/HER2– 20 (1.3%) 566 (31.3%) 586 (17.5%)
Cardoso F, et al. N Engl J Med 2016;375(8):717–29.
MINDACT: PRIMARY ENDPOINT
Distant metastasis-free survival in clinical high/genomic low (no CT)

Median FU 5 years Median FU 8.7 years

Patients Events 5-year DMFS (95% CI) Patients Events 5-year DMFS (95% CI)
644 38 94.7 (92.5-96.2) 644 78 95.1 (93.1-96.6)

95% CI excludes 92%: primary endpoint met

Cardoso F, et al. N Engl J Med 2016;375(8):717–29; Piccart M, et al. Presented at AACR 2016; with permission from Prof M Piccart; Cardoso F, et al. J Clin Oncol 38: 2020 (suppl; abstr
506). Presented at ASCO 2020; with permission from Prof F Cardoso.
TAILORx: STUDY DESIGN
HR+/HER2–, N-negative, T1c-2 any grade or T1b and G2/3

Primary analysis: non-inferiority (iDFS) of HT vs. CT+HT in women in the RS 11–25 group

Enrolled 10,071 pts (2006–2010) Oncotype DX® assay 900 sites, 6 countries

Primary study group

RS <11 RS >25
RS 11-25

ARM A: endocrine ARM D: CT plus

Randomise
therapy alone endocrine therapy
N=1626 (15.9%) N=1730 (16.9%)
ARM B: endocrine ARM C: CT plus
therapy alone endocrine therapy
N=6897 (67.3%)

Sparano JA, et al. N Engl J Med 2015;373(21):2005–14.

TAILORx: PATIENTS’ CHARACTERISTICS

All RS 0-10 RS 11-25 RS>26

All 9719 1619 (16.7%) 6711 (69.0%) 1389 (14.2%)
Age <50y 2694 (31.4%) 429 (26%) 2216 (33%) 409 (29%)
Postmenoapausal 6419 (66%) 1141 (70%) 4296 (64%) 982 (71%)
Premenopausal 3300 (34%) 478 (30%) 2415 (36%) 407 (29%)
T, median (range) NA 1.5 (1.2-2.0) 1.5 (1.2-2.0) 1.7 (1.3-2.3)
G1 2512 (27%) 530 (34%) 1893 (29%) 89 (7%)
G2 5242 (55%) 931 (59%) 3721(57%) 590 (43%)
G3 1676 (18%) 111 (7%) 884 (14%) 681 (50%)
PgR neg 951 (10%) 28 (2%) 518 (8%) 405 (30%)
PgR pos 8571 (90%) 1555 (98%) 6061 (92%) 948 (70%)
Clin low risk 6615 (70%) 1227 (78%) 4799 (74%) 589 (43%)
Clin high risk 2812 (30%) 345 (22%) 1697 (26%) 770 (57%)

Sparano JA, et al. N Engl J Med 2015;373(21):2005–14.

 TAILORX: PROGNOSIS OF RS LOW PATIENTS
Invasive disease-free survival Freedom from recurrence of breast cancer at distant site

iDFS event (NEJM 2018) n=185:

Nonbreast primary cancer n=75
5yrs rate 94.0% ±0.6 5yrs rate 99.3% ±0.62
Contralateral invasive BC n=29
9yrs rate 84.0% ±1.3 9yrs rate 96.8% ±0.7
Death without another event n=33
Distant recurrence n=28
Local/regional recurrence n=20 Freedom from recurrence at any site Overall survival

5yrs rate 98.8% ±0.3 5yrs rate 98.0% ±0.4

9yrs rate 95.0% ±0.8 9yrs rate 93.7% ±0.8
From N Engl J Med, Sparano JA, et al. Prospective Validation of a 21-
Gene Expression Assay in Breast Cancer, 373(21), 2005–14. Copyright ©
2015 Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
RECURRENCE SCORE:
PROGNOSTIC ROLE FOR N+ PATIENTS

WSG-PlanB: Trial design

HR–
Pts qualifying for
chemotherapy by DOC75C600 x 6*
◆ HER2– 0-3 LN
and
pN+
RS >11 Randomisation
◆

pN0 high risk E90C600 x 4 →

◆
or DOC100 x 4*
Recurrence ≥4 LN
HR+
score
*pT >2 cm
0-3 LN
G2-3 Endocrine
and
uPA/PAI-1 high therapy*
RS ≤11
HR–
≤35 years

*Endocrine and radiotherapy according to national guidelines

Nitz U, et al. SABCS 2014; Poster P4-11-01; Nitz U, et al. Breast Cancer Res Treat 2017;165(3):573–83
WSG PlanB: 5-YEAR DFS ACCORDING TO RS

pN0 5-yrs DFS rate pN1 5-yrs DFS rate

RS 0-11 94.2% (90.4-98.0) RS 0-11 94.4% (89.5-99.3)

Nitz U, et al. Breast Cancer Res Treat 2017;165(3):573–83; reproduced under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (available at: http://creativecommons.org/licenses/by-
nc/4.0/. Accessed Aug 2020)
BREAST CANCER-SPECIFIC MORTALITY
In patients with node-negative and node-positive breast cancer guided by the
21-gene assay: A SEER-Genomic population-based study
Patients treated with ET alone
N0 N1

Hortobagyi G, et al, Presented at SABCS 2018; poster P3-11-02; with permission from Dr G Hortobagyi.
OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
MINDACT: CT VS. NO CT IN CH/GL
(SECONDARY ENDPOINT)

Distant metastasis free survival (DMFS) Absolute difference in DMFS between CT and no CT
groups:
◆ At 5 years: 0.9 ± 1.1% points
◆ At 8 years: 2.6 ± 1.6% points

Type of first event (n=150)

◆ Distant recurrences: 74.7%
◆ Death of any cause: 25.3%

Cardoso F, et al. J Clin Oncol 38: 2020 (suppl; abstr 506). Presented at ASCO 2020; with permission from Prof F Cardoso.
MINDACT: CT VS. NO CT IN CH/GL, HR+/HER2–
PATIENTS, STRATIFIED BY AGE

Age ≤50 years Age >50 years

5% difference No difference

Cardoso F, et al. J Clin Oncol 38: 2020 (suppl; abstr 506). Presented at ASCO 2020; with permission from Prof F Cardoso.
TAILORx (N0): RS 11–25, PRIMARY ENDPOINT
RS 11–25, randomised to CT+ET or ET alone n=6711

CT+ET iDFS 5 years % 9 years %

ET
ET 92.8 ± 0.5 83.3 ± 0.9
CT+ET 93.1 ± 0.5 84.3 ± 0.8

A 5-year rate of invasive disease–free survival of 90% with chemoendocrine therapy and of 87% or less with endocrine therapy alone, which
corresponds to a 32.2% higher risk of an invasive disease recurrence, second primary cancer, or death as a result of not administering
chemotherapy (hazard ratio, 1.322)

From N Engl J Med; Sparano JA, et al., Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, 379:111–21, Copyright © 2018. Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
TAILORx: FREEDOM FROM RECURRENCE FROM
BREAST CANCER AT A DISTANT SITE, 9-YEAR RATES

All patients
0–11 11–25 ≥26
ET: ET: 94.5% CT + ET:
96.8% CT: 95.0% 86.8%

Young patients (≤50 yrs), n=2216

0–11 11–15 16–20 21–-25 ≥26
ET: ET: 97.2% ET: 93.6% ET: 86.9% CT+ET:
98.5% CT+ET: 98.0% CT+ET: 95.2% CT+ET: 93.4% 88.7%

Sparano JA, et al. N Engl J Med 2018;379(2):111–21.

EFFECT OF AGE AND MENOPAUSAL STATUS
ON CT BENEFIT (RS 16–25)

From N Engl J Med; Sparano JA, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer, 380:2395–405. Copyright © 2019, Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
EARLY BREAST CANCER
ESMO Clinical Practice Guidelines for diagnosis treatment and follow-up

Validated gene expression profiles may be used to gain additional prognostic and/or predictive information to
complement pathology assessment and help in adjuvant ChT decision making [I, A].

In T1/T2, N0 cancers, genomic assays are valuable for determining whether to recommend chemotherapy:
Yes 93.6%, No 4.3%, Abst 2.1%
In T3, N0 cancers, genomic assays are valuable for determining whether to recommend chemotherapy:
Yes 74.5%, No 21.3%, Abst 4.3%
In (T any), N1-3+ cancers, genomic assays are valuable for determining whether to recommend chemotherapy:
Yes 78.7%, No 17.0%, Abst 4.3%
USE OF BIOMARKERS TO GUIDE DECISIONS ON
ADJUVANT SYSTEMIC THERAPY
For women with early-stage invasive breast cancer: ASCO Clinical
Practice Guideline update – Integration of results from TAILORx

Group Recommendation Evidence rating

Clinicians may use the 21-gene RS to guide decision for adj CT Quality: high, Strength: strong

>50 years with RS <26 and ≤50 yrs with RS <16: may offer endocrine therapy Quality: high, Strength: strong
ER+/HER2–
≤50 years with RS 16-25: may offer chemoendocrine therapy Quality: intermediate, Strength: moderate
N0
RS >30: should be considered candidates for chemoendocrine therapy Quality: high, Strength: strong

RS 26-30: may offer chemoendocrine (panel consensus) Quality: insufficient, Strength: moderate

ER+/HER2–
Clinicians should not use the 21-gene RS to guide decision for adj CT Quality: intermediate, Strength: moderate
N+

Andre F, et al. J Clin Oncol 2019;37(22):1956–64. ASCO Special Article.

OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
EXTENDED ADJUVANT THERAPY FOR HR+ BC

After 5 years of adjuvant ET, recurrences continue to occur steadily up to 20 years1

The risk of distant recurrence ranges from 10 to 41%, depending on TN stage and tumour grade1
Impact of extended AI therapy depends on prior endocrine therapy, with larger risk reduction in patients with
prior tamoxifen2
Absolute benefit varies across N categories: Nneg <1-3 pos nodes <4+ pos nodes2
Careful consideration of potential side effects (risk of bone fracture increased by 25%)2
The majority of the trials reported substantial discontinuation rate

1. Pan H, et al. N Engl J Med 2017;377(19):1836–46; 2. Gray R, et al. (EBCTCG), SABCS 2018.
PROGNOSTIC ROLE OF GENE EXPRESSION
SIGNATURES FROM YEAR 5 TO 10

Patient group
Node-negative disease (n=535) Node-positive disease (n=154)
Gene signature HR (95% CI)a C Index (95% CI) HR (95% CI)a C Index (95% CI)
CTS 1.95 (1.43-2.65) 0.721 (0.654-0.788) 1.61 (1.05-2.47) 0.644 (0.534-0.753)
IHC4 1.59 (1.16-2.16) 0.660 (0.576-0.745) 1.20 (0.79-1.81) 0.579 (0.460-0.697)
RS 1.46 (1.09-1.96) 0.585 (0.467-0.702) 1.24 (0.81-1.90) 0.555 (0.418-0.693)
BCI 2.30 (1.61-3.30) 0.749 (0.668-0.830) 1.60 (1.04-2.47) 0.633 (0.514-0.751)
ROR 2.77 (1.93-3.96) 0.789 (0.724-0.854) 1.65 (1.08-2.51) 0.643 (0.528-0.758)
EPclin 2.19 (1.62-2.97) 0.768 (0.701-0.835) 1.87 (1.27-2.76) 0.697 (0.594-0.799)

Sestak I, et al. JAMA Oncol 2018;4(4):545–53.

PREDICTIVE ROLE OF BCI IN THE
TRANS-ATTOM STUDY

Relative benefit Absolute benefit

Bartlett JMS, et al. Ann Oncol 2019;30(11):1776–83. Reproduced under the terms of the Creative Commons Attribution Non-Commercial License (available at: http://creativecommons.org/licenses/by-nc/4.0/; accessed
August 2020).
OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
AGREEMENT AMONG TESTS
Summary of head to head comparisons of risk classifications by 6 prognostic signatures

100
11.5 16.2
30.7
80
45.8
Patients per risk group (%)

48.4
35.9 27.3 63.0
60
30.3 High risk
Intermediate risk
40
Low risk
52.6 56.6 51.6 54.2
20 39.0 37.0

0
RS BCI ROR EP Epclin MMP

Varga Z, et al. Int J Cancer 2019;145(4):882–93. © 2019 UICC. Reproduced with permission from John Wiley and Sons.
PERFORMANCE OF 6 PROGNOSTIC SIGNATURES
IN TRANSATAC

◆ Differences may be related, at least in part, to: clinicopathological features in EpClin, differing ability to predict late recurrences
◆ Potential selection bias can not be excluded (n=928 out of the n=9366 enrolled in ATAC)
◆ Comparison studies on different clinical platforms may be useful

Sestak I, et al. JAMA Oncol 2018;4(4):545–53. Reproduced under the terms of the CC-BY License (available at: https://creativecommons.org/licenses/. Accessed August 2020). © 2018.
OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
MINDACT: EFFECT OF CLINICAL RISK ON PROGNOSIS

Distant metastasis free survival

Within the same clinical risk category, genomic risk
discriminates groups at different prognosis

Within the same genomic risk category, clinical risk

discriminates groups at different prognosis

Cardoso F, et al. J Clin Oncol 38: 2020 (suppl; abstr 506). Presented at ASCO 2020; with permission from Prof F Cardoso.
TAILORx: EFFECT OF CLINICAL RISK ON PROGNOSIS

From N Engl J Med; Sparano JA, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer, 380:2395–405. Copyright © 2019, Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
TAILORx: EFFECT OF CLINICAL RISK ON PREDICTION
OF CT BENEFIT (RS 11-25)

From N Engl J Med; Sparano JA, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer, 380:2395–405. Copyright © 2019, Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
TAILORx: EFFECT OF CLINICAL RISK ON PREDICTION
OF CT BENEFIT (DISTANT RECURRENCE RATES)
<50 years, RS 16-25

Estimated absolute chemo benefit Estimated absolute chemo

Clinical risk No.
not stratified by clinical risk benefit stratified by clinical risk
Δ -0.2%
Low 671 (76%)
Δ +1.6% (±SE 2.1%)
RS 16-20 (N=886)
(±SE 1.9%) Δ +6.5%
High 215 (24%)
(±SE 4.9%)
Δ +6.4%
Low 319 (67%)
Δ +6.5% (±SE 4.9%)
RS 21-25 (N=476)
(±SE 3.7%) Δ +8.7%
High 157 (33%)
(±SE 6.2%)

Sparano JA, ASCO 2019; Sparano JA, et al. N Engl J Med;2019;380:2395–405.

REFINING THE RISK ASSESSMENT:
THE TEXT-SOFT ADJUVANT TRIAL ANALYSIS

ER expression
100

80
More than 10% difference in the 5-year BCFI
60 according to the level of ER expression
BCFI (%)

40
No. of 5-year BCFI
patients Events (% ± SE)
20 ≥50% 3,892 293 92.6 ± 0.5
20% to 49% 400 66 85.9 ± 1.8
<20% 509 103 81.4 ± 1.8
0
0 1 2 3 4 5 6
Time since random assignment (years)

Regan MM, et al. J Clin Oncol 34(19), 2016: 2221–3. Reprinted with permission. © (2016) American Society of Clinical Oncology. All rights reserved.
 PERFORMANCE OF CLINICAL SELECTION

From N Engl J Med; Francis PA, et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer, 379:122–37. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts
Medical Society
OUTLINE

Introduction

Clinical utility of gene expression signatures

◆ Prognostic role: who can be spared CT?
◆ Predictive role: CT benefit
◆ Extended adjuvant

Optimising the use of gene expression signatures

◆ Are all tests the same?
◆ Classic prognostic features
◆ Impact on clinical practice
GENE EXPRESSION SIGNATURES IN CLINICAL PRACTICE

PONDx1 Pooled European2 ROXANE3 Clin Low: 73 (29.1%)

Characteristics
(N=866), n (%) (n=565), n (%) (n=251), n (%) Clin High: 178 (70.9%)
Age >50 yrs 633 (73) >55: 394 (70) 159 (63)
Age ≤50 yrs 233 (27) <55: 171 (30) 92 (37)
Pre/peri-menopausal 283 (32) 105 (43)
NA
Postmenopausal 579 (67) 142 (57)
T ≤2cm 570 (66) 397 (70) 171 (69)
T >2cm 296 (34) 167 (30) 77 (31)
N0 613 (71) 565 (100) 152 (61)
N1 253 (29) 0 99 (39)
Grade 1 120 (14) 99 (18) 17 (7)
Grade 2 589 (68) 387 (69) 142 (57)
Grade 3 157 (18) 75 (13) 92 (37)
PgR pos 744 (86) 489 (87) 211 (84)
PgR neg 122 (14) 71 (13) 40 (16)
CT indication 66% 45% 52%
Treatment change 44% 32% 30%
CT net reduction 37% 30% 16%

1. Curtit E, et al. Breast 2019;44:39–45; 2. Albanell J, et al. Eur J Cancer 2016;66:104–13; 3. Dieci MV, et al. Oncologist 2019;24(11):1424–31.
OPTIMISING THE USE OF GENOMIC
PROGNOSTIC TESTS
Decision on adjuvant CT for HR+/HER2- BC: clinical utility demonstrated
Decision on extended adjuvant endocrine tx: clinical validity demonstrated (Endopredict, prosigna, BCI), clinical utility to be proved
Regulatory restrictions still limit the use outside clinical studies in many countries.
Classic clinicopathological features still matter!
It is challenging to provide a universally accepted definition of the patients for whom the test would be most useful:
◆ Avoid offering the test to patients not suitable for chemotherapy
◆ Avoid offering the test to patients for whom the decision is highly unlikely to change (clinical judgement)
Avoid multiple testing for the same patient
Once you have the results (i.e. RS for N0):
◆ RS<16: avoid CT
◆ RS 16-25: decision based on age and clinical risk
◆ RS>26: consider CT
◆ Word of caution on substituting CT with OFS in young patients: compliance, OFS was beneficial in SOFT patients who
remained premenopausal after CT
THANK YOU!