Prognostic implication of 21-gene expression assay in

luminal B type hormone receptor-positive breast cancer

patients younger than 40 years

Jaewon Hyung, M.D.

Department of Oncology
Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Korea

Singapore, December 3rd, 2022

DECLARATION OF INTERESTS

Jaewon Hyung, M.D.

No conflict of interest to declare.

Jaewon Hyung, M.D. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Background & Methods

Background

• Recurrence score (RS) based on 21-gene expression assay (Oncotype Dx, ODx) is widely used to evaluate prognosis and
guide decision for adjuvant chemotherapy in HR (+) breast cancer patients.

• In this study, we investigated the prognostic significance of RS in premenopausal HR (+) breast cancer patients.

Methods
•Patients : Premenopausal HR (+) HER2 (-) breast cancer patients with age < 50 years at Asan Medical Center, Seoul, Korea
who had ODx testing after surgery with least 3 years of follow-up from surgery (June 2005 to July 2018)
•Outcomes : Invasive breast cancer-free survival (iBCFS) by STEEP version 2.01
•Analysis : Outcomes according to RS along with other variables

1Tolaney et al. J Clin Oncol, 2021

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Results – Study population
<Baseline characteristics>
• Total 554 patients included in the study
(N=554)

Age (years) median 44 (range, 22-49) • All patients received tamoxifen after surgery as adjuvant endocrine therapy
≥ 40 years 318 (71.9%) • Median follow-up duration of 5.9 years (IQR, 4.8-8.0 years)
< 40 years 116 (20.9%)

Luminal subtype1

Luminal A 316 (57.0%)

• Overall, 42 patients (7.6%) with iBCFS event, including 16 patients (2.9%) with
Luminal B 118 (43.0%) ipsilateral breast or loco-regional recurrence, 6 patients (1.1%) with contralateral
Histologic grade (n=547) invasive breast cancer, and 20 patients (3.6%) with distant metastasis
Grade 1-2 487 (89.0%)
<Risk groups> <Adjuvant chemotherapy>
Grade 3 60 (11.0%)
(N=554) RS 0-25 RS > 25
Pathologic T stage
Recurrence score median 16 (range, 0-72) pN0
T1 349 (63.0%)
RS 0-25 471 (85.0%)
T2-3 205 (37.0%) Adjuvant chemotherapy 22 (6.2%) 49 (79.0%)
RS >25 83 (15.0%)
Pathologic N stage No adjuvant chemotherapy 330 (93.8%) 13 (21.0%)
Clinical risk group2
N0 414 (85.0%)
pN1
High 295 (51.9%)
N1 140 (25.3%)
Low 252 (46.1%) Adjuvant chemotherapy 12 (10.1%) 16 (76.2%)
Surgery
1Luminal B subtype defined as high Ki67 (≥ 20%) and HER2 (+) patients were not included No adjuvant chemotherapy 107 (89.9%) 5 (23.8%)
Breast conserving surgery 412 (74.4%) 2Clinical high-risk defined as below. Otherwise, low risk. (Cardoso et al. N Engl J Med 2016)
i) Regional LN involvement with HG 2-3 or HG 1 & tumor size > 2 cm
Mastectomy 142 (25.6%) ii) Regional LN (-) with HG 3 & tumor size > 1 cm
iii) Regional LN (-) with HG 2 & tumor size > 2 cm
iv) Regional LN (-) with HG 1 & tumor size > 3 cm

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Results – iBCFS according to RS and other factors

iBCFS according to RS

Cox proportional hazards regression according to RS and other

5-year iBCFS rate 8-year iBCFS rate
potential prognostic variables
95.8% (95% CI 93.9-97.7) Univariable Multivariable
100% ||||||||||||||||||||||||||||||||| 91.6% (95% CI 88.3-95.1)
|||||||||||||||||||||||||| |||||||||
||| |||||||| ||||||||| |||||||||||||| |||||||
Invasive breast cancer−free survival (%)

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|| ||||||||| |||||| ||||| | ||| ||||||||| ||| ||||| || | || | |
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HR (95% CI) P HR (95% CI) P
75% 85.4% (95% CI 78.1-93.4) 83.6% (95% CI 75.8-92.3) Age 0.029 0.054

≥ 40 years 1 (Ref) 1 (Ref)

50% Recurrence score
< 40 years 2.02 (1.07-3.80) 1.87 (0.98-3.53)
| RS 0−25
| RS >25 Recurrence score 0.003 0.069
25%
p = 0.002 RS 0-25 1 (Ref) 1 (Ref)
HR 2.70 (95% CI 1.40-5.19),
log-rank P = 0.002
RS > 25 2.70 (1.40-5.19) 1.89 (0.95-3.73)
0%
0 2 4 6 8 10 12 14 16 Clinical risk 0.104 0.248
Years
High 1 (Ref) 1 (Ref)

Low 0.59 (0.31-1.12) 0.68 (0.35-1.31)

RS 0−25 471 466 458 220 119 16 2 1 1
Luminal subtypes 0.001 0.011

RS >25 83 78 72 44 19 3 0 0 0 Luminal A 1 (Ref) 1 (Ref)

0 2 4 6 8 10 12 14 16 Luminal B 3.08 (1.60-5.93) 2.42 (1.22-4.79)

Years

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Results – iBCFS according to age and luminal subtypes

iBCFS according to age and luminal subtype iBCFS according to Age-Luminal prognostic group
5-year iBCFS rate
8-year iBCFS rate
95.2% (95% CI 93.2-97.1)
100% ||||||||||||||||||||||||||||||||||||||||
|||||||||||||||||||||||| |||| ||| ||||||| ||||||||||| ||||||| 100% 100% 92.7% (95% CI 90.0-95.6)
||||||||||||||||||||||||||||||||||||||
100% |||| |||||||||| ||| | ||||| || | ||| | ||| | | || ||| |||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||| |||||||||||| ||||||||||||||| |||||
Invasive breast cancer−free survival (%)

||||||||||| |||| | | | | | | || | | | | || | ||||| ||||||||| || | |||| || || ||||| | ||||| | | | |

Invasive breast cancer−free survival (%)

|||||||||||||||||||||| |||||||||||| ||||||||||||||| ||||| |||||||||||||||| |||| |||||||||||| |||||||||| |||||| |||| ||| ||||| | ||||| | |

Invasive breast cancer−free survival (%)

|| ||||| ||||| | |||| ||||||| ||||||| |||| ||| |||| ||| | || ||||||||||||||||||||
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| | |
|
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Invasive breast cancer−free survival (%)

| |||||||||||||||| |||| |||||||||||| |||||||||| |||||| |||| ||| ||||| | ||||| | | |

| | | | ||| | | | | | | | | | | ||||
| | | || | | | | |||| | | | ||
| | | | | ||
| | | | |||| |
| | |||||| | | | | | | | | | || |
| 86.6% (95% CI 78.4-95.7) | | |||||| | | | | | | | | |||||
| | | | | | |
75% || | | | | ||| ||| || |||||| | | | ||
| | |
75% 75% || | | | | ||| || | || || | | | | ||| || | ||
75% || || | | ||| || | ||

79.4% (95% CI 69.0-89.9)

Age and luminal subtypes
50% | Age
Age>=
≥ 40 & Luminal
years A
+ Luminal A 50%
50% Age-Luminal Prognostic group
50% | Age ≥ 40 &
Age>= years + Luminal
Luminal B B | Age >= A
40 OR Luminal A
| Age >= 40 OR
Good Luminal
+Age
A >= 40A OR Luminal A
|
| Age<<40
Age 40&years
LuminalLuminal
25% | Age |
Poor< 40 AND Age < 40
Luminal B AND Luminal B
Age<<40
Age
|
40&years +Age
Luminal B < 40 BAND Luminal B
Luminal 25% 25%
25% Log-rank, pP=<0.00031
0.001 |
p = 0.00022
p = 0.00022 p = 0.00022
HR 3.29 (95% CI 1.69-6.44),
log-rank P < 0.001
0%
0% 0%
0 20% 4 6 8 10 12 14 16
Years 0 2 0 4 2 6 4 8 6 10 8 12 10 14 12 16 14 16
0 2 4 6 8 10 12 14 16 Years
Years
Years

Age ≥ 40Age
years
>= +40Luminal A A
& Luminal 260 258 254 116 63 10 0 0 0
Age ≥ 40Age
years
>= +40Luminal B B 178
& Luminal 174 168 89 37 3 1 0 0 Age >=A40 OR
Age >= 40 OR Luminal 494Luminal
487A 494
476 487
235 476
120 23516 120 2 16 1 2 1 1 1
Age < 40 years
Age <+40 Age
Luminal A >=
& Luminal A 40 OR
56 Luminal
55 A 494
54 487
30 476
20 235
3 120
1 16
1 12 1 1Good
Age < 40 years
Age <+40
Luminal B B
& Luminal 60 57 54 29 18 3 0 0 0 Poor
Age < 40
Age < 40 AND Luminal B AND
60Luminal57B 6054 5729 5418 29 3 18 0 3 0 0 0 0 0
Age < 40 AND Luminal B 60 57 54 29 18 3 0 0 0
0 2 4 6 8 10 12 14 16
Years 0 2 0 4 2 6 4 8 6 10 8 12 10 14 12 16 14 16
0 2 4 6 8 10 12 14 16 Years
Years
Years

Good Poor
Age-Luminal prognostic group (n=494) (n=60)
-Good : 1) Age ≥ 40 years + Any Luminal, 2) Age < 40 years + Luminal A Event (iBCFS) 30 (6.1%) 12 (20.0%)
-Poor : Age < 40 years + Luminal B Distant metastasis 13 (2.6%) 7 (11.7%)

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Results – Age-Luminal prognostic group

<Clinical characteristics according to Age-Luminal prognostic group>

Age-Luminal prognostic group
Good Poor P
(n=494) (n=60) -Good : 1) Age ≥ 40 years + Any Luminal, 2) Age < 40 years + Luminal A
Adjuvant chemotherapy < 0.001 -Poor : Age < 40 years + Luminal B
Yes 78 (15.8%) 21 (35.0%)

No 416 (84.2%) 39 (59.0%) Prognostic association of RS according to Age-Luminal prognostic group

Recurrence score 0.013
<Good, (n=494)>
RS 0-25 427 (86.4%) 44 (73.3%)
HR (95% CI) P 8-year survival rate
RS > 25 67 (13.6%) 16 (26.7%) (95% CI)

Histologic grade (n=488) (n=59) < 0.001 Recurrence score 0.005

Grade 1-2 444 (91.0%) 43 (72.9%) RS 0-25 1 (Ref) 93.9% (91.0-96.8)

Grade 3 44 (9.0%) 16 (27.1%) RS > 25 2.88 (1.32-6.30) 85.7% (77.4-94.9)

Pathologic T stage 1.000

<Poor, (n=60)>
T1 311 (63.0%) 38 (63.3%)
HR (95% CI) P 8-year survival rate
T2-3 183 (37.0%) 22 (36.7%) (95% CI)

Pathologic N stage 1.000 Recurrence score 0.51

N0 369 (74.7%) 45 (75.0%) RS 0-25 1 (Ref) 73.6% (57.5-94.3)

N1 125 (25.3%) 15 (25.0%) RS > 25 1.49 (0.45-4.95) 75.0% (56.5-99.5)

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Conclusion
Among premenopausal HR (+) HER2 (-) breast cancer patients who had 21-gene expression assay,

1) Overall, patients with RS > 25 showed tendency with inferior outcomes in terms of iBCFS.

2) Patients with age < 40 years and luminal B subtype showed significantly worse outcomes in terms of iBCFS

compared to patients with age < 40 years and luminal A subtype or those with age ≥ 40 years regardless of luminal

subtypes even with higher proportion of patients receiving adjuvant chemotherapy.

3) While RS > 25 was associated with inferior iBCFS outcomes among patients with age ≥ 40 years or

age < 40 years & luminal A subtypes, significant association in iBCFS according to RS was not observed

among patients with age < 40 years and luminal B subtypes.

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