World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 6, December 2025, pages 555-564

A Simplified Novel Algorithm to Predict the 21-Gene Recurrence Score

Figure 1. Proposed PR% and grade in relation to RS. PR: progesterone receptor; RS: recurrence score.

Figure 2. Proposed algorithm to predict Oncotype DX risk category using histologic grade and PR percentage. PR: progesterone receptor.

**Table 1.** Pathological Features for All Patients
Feature	N (%)
ER: estrogen receptor; FISH: fluorescence in situ hybridization; HER2: human epidermal growth factor receptor-2; ODx: Oncotype DX; PR: progesterone receptor; RS: recurrence score.
ER (%)
Positive	528 (100%)
PR (%)
Negative	30 (5.7%)
Positive	498 (94.3%)
HER2
Equivocal (FISH-negative)	59 (11.2%)
Negative	469 (88.8%)
HER2 score
0	263 (49.8%)
1+	206 (39.0%)
2+ (FISH negative)	59 (11.2%)
ER (ODx value)
Negative	11 (2.1%)
Positive	517 (97.9%)
PR (ODx value)
Negative	72 (13.6%)
Positive	456 (86.4%)
HER2 (ODx value)
Equivocal	3 (0.6%)
Negative	523 (99.0%)
Positive	2 (0.4%)
Histological type
Invasive ductal carcinoma	438 (82.9%)
Invasive lobular carcinoma	68 (12.9%)
Invasive mucinous carcinoma	10 (1.9%)
Invasive tubular carcinoma	7 (1.3%)
Invasive cribriform carcinoma	1 (0.2%)
Invasive solid papillary carcinoma	3 (0.6%)
Invasive breast carcinoma with apocrine features	1 (0.2%)
Group
Learning set	377 (71.3%)
Validation set	151 (28.7%)
Grade
1	99 (18.8%)
2	323 (61.2%)
3	106 (20.1%)
RS
High	96 (18.2%)
Low	432 (81.8%)

Table 1. Pathological Features for All Patients

Feature

N (%)

ER: estrogen receptor; FISH: fluorescence in situ hybridization; HER2: human epidermal growth factor receptor-2; ODx: Oncotype DX; PR: progesterone receptor; RS: recurrence score.

ER (%)

Positive

528 (100%)

PR (%)

Negative

30 (5.7%)

Positive

498 (94.3%)

HER2

Equivocal (FISH-negative)

59 (11.2%)

Negative

469 (88.8%)

HER2 score

263 (49.8%)

206 (39.0%)

2+ (FISH negative)

59 (11.2%)

ER (ODx value)

Negative

11 (2.1%)

Positive

517 (97.9%)

PR (ODx value)

Negative

72 (13.6%)

Positive

456 (86.4%)

HER2 (ODx value)

Equivocal

3 (0.6%)

Negative

523 (99.0%)

Positive

2 (0.4%)

Histological type

Invasive ductal carcinoma

438 (82.9%)

Invasive lobular carcinoma

68 (12.9%)

Invasive mucinous carcinoma

10 (1.9%)

Invasive tubular carcinoma

7 (1.3%)

Invasive cribriform carcinoma

1 (0.2%)

Invasive solid papillary carcinoma

3 (0.6%)

Invasive breast carcinoma with apocrine features

1 (0.2%)

Group

Learning set

377 (71.3%)

Validation set

151 (28.7%)

Grade

99 (18.8%)

323 (61.2%)

106 (20.1%)

High

96 (18.2%)

Low

432 (81.8%)

**Table 2.** Comparison of Various Variables Between the Learning Set and the Validation Set Showing No Significant Differences
Feature	Total, N (%)	Groups	P-value
CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor; RS: recurrence score; SD: standard deviation.
Grade				0.88
1	99 (19.2%)	68 (18.0%)	31 (20.5%)
2	323 (61.7%)	231 (61.2%)	92 (60.9%)
3	106 (19.0%)	78 (20.7%)	28 (18.5%)
Actual RS				0.54
High	96 (18.2%)	72 (19.1%)	24 (15.9%)
Low	432 (82.5%)	305 (81.9%)	127 (84.1%)
Age (years)				0.46
Mean (95% CI)		52.8 (51.9, 53.7)	53.6 (52.1, 55.2)
Median (Min, Max)		52.0 (21.0, 76.0)	53.0 (24.0, 79.0)
SD		10.3	11.4
ER (%)				0.34
Mean (95% CI)		89.8 (88.7 ,91.0)	88.5 (86.5, 90.5)
Median (Min, Max)		95.0 (1.0, 100)	90.0 (5.0, 100)
SD		13.7	15.0
PR (%)				0.87
Mean (95% CI)		66.4 (63.5, 69.3)	67.6 (63.0, 72.2)
Median (Min, Max)		85.0 (0.0, 100)	90.0 (0.0, 100)
SD		34.2	34.1

Table 2. Comparison of Various Variables Between the Learning Set and the Validation Set Showing No Significant Differences

Feature

Total, N (%)

Groups

P-value

Learning set

Validation set

CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor; RS: recurrence score; SD: standard deviation.

Grade

0.88

99 (19.2%)

68 (18.0%)

31 (20.5%)

323 (61.7%)

231 (61.2%)

92 (60.9%)

106 (19.0%)

78 (20.7%)

28 (18.5%)

Actual RS

0.54

High

96 (18.2%)

72 (19.1%)

24 (15.9%)

Low

432 (82.5%)

305 (81.9%)

127 (84.1%)

Age (years)

0.46

Mean (95% CI)

52.8 (51.9, 53.7)

53.6 (52.1, 55.2)

Median (Min, Max)

52.0 (21.0, 76.0)

53.0 (24.0, 79.0)

10.3

11.4

ER (%)

0.34

Mean (95% CI)

89.8 (88.7 ,91.0)

88.5 (86.5, 90.5)

Median (Min, Max)

95.0 (1.0, 100)

90.0 (5.0, 100)

13.7

15.0

PR (%)

0.87

Mean (95% CI)

66.4 (63.5, 69.3)

67.6 (63.0, 72.2)

Median (Min, Max)

85.0 (0.0, 100)

90.0 (0.0, 100)

34.2

34.1

**Table 3.** Relationship Between RS and Grade and RS and PR% in the Learning Set
Variable	Total	Actual RS	P-value
PR: progesterone receptor; RS: recurrence score; SD: standard deviation.
Grade
Grade 1	68 (18.7%)	0	68 (22.9%)	0.00
Grade 2	231 (62.3%)	25 (10.8%)	206 (89.2%)
Grade 3	78 (19.0%)	47 (61.8%)	31 (9.5%)
PR%, mean (SD)		33.7 (35.2)	73.7 (29.5)	< 0.0001

Table 3. Relationship Between RS and Grade and RS and PR% in the Learning Set

Variable

Total

Actual RS

P-value

High, N (%)

Low, N (%)

PR: progesterone receptor; RS: recurrence score; SD: standard deviation.

Grade

Grade 1

68 (18.7%)

68 (22.9%)

0.00

Grade 2

231 (62.3%)

25 (10.8%)

206 (89.2%)

Grade 3

78 (19.0%)

47 (61.8%)

31 (9.5%)

PR%, mean (SD)

33.7 (35.2)

73.7 (29.5)

< 0.0001

**Table 4.** PR% Cut-Offs Combined With Grade as Determined by ROC Curves and Those Yielding a 100% Sensitivity
Variable	PR cut-off (%)	Total	RS	P-value
PR: progesterone receptor; ROC: receiver operating characteristics; RS: recurrence score.
Learning set - all grade (PR cut-off ROC 50)	< 50	99 (26.4%)	43 (63.2%)	56 (18.2%)	0.000
	≥ 50	276 (73.6%)	25 (36.8%)	251 (81.8%)
Learning set - grade 2 (PR cut-off ROC 30)	< 30	58 (24.9%)	22 (84.6%)	36 (17.4%)	0.000
	≥ 30	175 (75.1%)	4 (15.4%)	171 (82.6%)
Learning set - grade 3 (PR cut-off ROC 70)	< 70	28 (39.4%)	24 (57.1%)	4 (13.8%)	0.000
	≥ 70	43 (60.6%)	18 (42.9%)	25 (86.2%)
Learning set - grade 2 (PR at 60) The sensitivity for this cut-off 60 = 100% The specificity for this cut-off 60 = 69.1%	< 60	76 (35.6%)	25 (100%)	51 (27.5%)	0.000
	≥ 60	155 (64.4%)	0	155 (72.5%)
Learning set - grade 3 (PR at 40) The sensitivity for this cut-off 40 = 100% The specificity for this cut-off 40 = 65%	< 40	22 (23.9%)	22 (40.5%)	0	0.000
	≥ 40	56 (76.1%)	25 (59.5%)	31 (100%)

Table 4. PR% Cut-Offs Combined With Grade as Determined by ROC Curves and Those Yielding a 100% Sensitivity

Variable

PR cut-off (%)

Total

P-value

High

Low

PR: progesterone receptor; ROC: receiver operating characteristics; RS: recurrence score.

Learning set - all grade (PR cut-off ROC 50)

< 50

99 (26.4%)

43 (63.2%)

56 (18.2%)

0.000

≥ 50

276 (73.6%)

25 (36.8%)

251 (81.8%)

Learning set - grade 2 (PR cut-off ROC 30)

< 30

58 (24.9%)

22 (84.6%)

36 (17.4%)

0.000

≥ 30

175 (75.1%)

4 (15.4%)

171 (82.6%)

Learning set - grade 3 (PR cut-off ROC 70)

< 70

28 (39.4%)

24 (57.1%)

4 (13.8%)

0.000

≥ 70

43 (60.6%)

18 (42.9%)

25 (86.2%)

Learning set - grade 2 (PR at 60)
The sensitivity for this cut-off 60 = 100%
The specificity for this cut-off 60 = 69.1%

< 60

76 (35.6%)

25 (100%)

51 (27.5%)

0.000

≥ 60

155 (64.4%)

155 (72.5%)

Learning set - grade 3 (PR at 40)
The sensitivity for this cut-off 40 = 100%
The specificity for this cut-off 40 = 65%

< 40

22 (23.9%)

22 (40.5%)

0.000

≥ 40

56 (76.1%)

25 (59.5%)

31 (100%)