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Supplementary Figure 1: Blinded review comparing adjuvant systemic therapy recommendations made by two medical oncologists versus actual systemic therapy given in patients with negative AUS

False Negative AUS Matched True Negative AUS

Actual Reviewer #1 Reviewer #2 Actual Reviewer #1 Reviewer #2

Legend:

Black: Chemotherapy and endocrine therapy Blue: Endocrine therapy

Yellow: Chemotherapy, herceptin and endocrine therapy Green: Chemotherapy

Gray: Observation

Purple: Chemotherapy and herceptin therapy Orange: Herceptin and endocrine therapy Red: Herceptin

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Supplementary Table 1: Univariate analysis comparing negative predictive value of axillary ultrasound by patient and tumor characteristics

N Detection of micrometastatic or

macrometastatic disease Detection of macrometastatic disease only

NPV p-value NPV p-value

Overall 382 84% - 89%

Age

< 50 years 66 77% 0.15 85% 0.19

> 50 years 316 85% 90%

Histology

Ductal 310 83% 0.06 89% 0.17

Lobular 33 76% 85%

Other 39 95% 97%

Tumor size

T1 264 86% 0.04 90% 0.47

T2 118 77% 87%

Grade

I/II 265 83% 0.77 89% >0.99

III 116 85% 89%

ER

Positive 309 82% 0.22 89% 0.53

Negative 73 89% 92%

HER2

Positive 49 76% 0.15 84% 0.22

Negative 330 85% 90%

TNBC

Yes 56 89% 0.25 91% 0.82

No 323 82% 89%

NPV, negative predictive value; ER, estrogen receptor; TNBC, triple negative breast cancer

(estrogen receptor negative, progesterone receptor negative, and HER-2 negative)

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Supplementary Table 2: Demographic and clinicopathologic characteristics of blinded review patients in Group 1 (False Negative AUS) and Group 2 (True Negative AUS)

Characteristics Group 1 Group 2 p-value

Age (years) 0.31

Median (range) 61 (33-88) 62 (35-83)

Tumor Histology 0.013

Invasive ductal 52(84) 59 (98)

Invasive lobular 8 (13) 0 (0)

Other 2 (3) 1 (2)

Tumor Size < 0.001

T1 34 (55) 59 (98)

T2 28 (45) 1 (2)

Tumor Grade 0.387

I 15(24) 21 (36)

II 29(47) 24 (41)

III 18(29) 14 (23)

ER status 0.200

Positive 54 (87) 47 (78)

Negative 8 (13) 13 (22)

Unknown 0 (0) 0 (0)

PR status 0.096

Positive 53 (86) 44 (73)

Negative 9 (15) 16 (27)

Unknown 0 (0) 0 (0)

HER2 status 0.290

Positive 11 (18) 6 (10)

Negative 51 (82) 53 (88)

Unknown 0 (0) 1 (2)

TNBC 0.168

No 56 (90) 49 (82)

Yes 6 (10) 11 (18)

Neoadjuvant therapy 0.384

Chemotherapy 6 (10) 2 (3)

Endocrine 1 (2) 1 (2)

None 54 (87) 57 (95)

Median F/U, months (range) 36 (1-61) 36 (2-60) 0.805

Recurrence

Breast 1 (2) 1 (2) 0.981

Axilla 0 (0) 1(2) 0.307

Distant 3 (5) 3(5) 0.967

ER, estrogen receptor; PR, progesterone receptor; TNBC, triple negative breast cancer; F/U,

followup

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