Supplemental Materials – Breast Cancer Research and Treatment

Predictors associated with MRI surveillance screening in women with a personal history of unilateral breast cancer but without a genetic predisposition for future contralateral breast cancer

John V. Hegde, MD,1 Xiaoyan Wang, PhD,2Deanna J. Attai,3 MD, Maggie L. DiNome, MD,3 Amy Kusske, MD,3Anne Hoyt, MD,4 Sara Hurvitz, MD,5Joanne B. Weidhaas, MD, PhD, MSM1, Michael L. Steinberg, MD1, Susan A. McCloskey, MD, MSHS1

1Department of Radiation Oncology, University of California, Los Angeles (UCLA) Medical Center

2Division of General Internal Medicine and Health Services Research, Department of Medicine, University of California, Los Angeles (UCLA) Medical Center

3Department of Surgery, University of California, Los Angeles (UCLA) Medical Center

4Department of Radiology, University of California, Los Angeles (UCLA) Medical Center

5Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA) Medical Center

Corresponding Author:

Susan McCloskey, MD, MSHS

UCLA Department of Radiation Oncology

1223 16th Street

Suite 1100

Santa Monica, California 90404

Email:

Telephone: 424-259-8777

Fax: 424-259-8796

Table S1. Clinical and Pathologic Characteristics for the Entire Cohort, Stratified by the Use of Breast MRI Surveillance

Entire Cohort
(N=322) / Subset of Women Undergoing MRI Surveillance (N=70) / Subset of Women Not Undergoing MRI Surveillance (N=252) / P-value
Invasive Disease
No
Yes / 71
251 / 15 (21.1%)
55 (21.9%) / 56 (78.9%)
196 (78.1%) / 0.89
Type of Surgery
Lumpectomy
Mastectomy / 251
71 / 44 (17.5%)
26 (36.6%) / 207 (82.5%)
45 (63.4%) / <0.001
Manchester Risk Score / 7.4% (SD 7.2) / 11.5% (SD 8.4) / 6.3% (SD 6.4) / <0.001
Manchester Risk Category
Low
Above Average
Moderate
High / 244
60
14
4 / 40 (16.4%)
23 (38.3%)
5(35.7%)
2 (50.0%) / 204 (83.6%)
37 (61.7%)
9 (64.3%)
2 (50.0%) / <0.001
Age (continuous) / 61.0 (SD 13.4) / 52.3 (SD 11.8) / 63.4 (SD 12.7) / <0.001
Family History
No
Yes / 296
26 / 59 (19.9%)
11 (42.3%) / 237 (80.1%)
15 (57.7%) / 0.01
Use of Pre-Operative MRI
No
Yes / 104
218 / 5 (4.8%)
65 (29.8%) / 99 (95.2%)
153 (70.2%) / <0.001
Dense Breasts
No
Yes / 217
105 / 27 (12.4%)
43 (41.0%) / 190 (87.6%)
62 (59.0%) / <0.001
Previous Imaging-Occult Breast Cancer
No
Yes / 295
27 / 52 (17.6%)
18 (66.7%) / 243 (82.4%)
9 (33.3%) / <0.001
Pathologic Grade
1
2
3 / 93
137
92 / 18 (19.4%)
34 (24.8%)
18 (19.6%) / 75 (80.6%)
103 (75.2%)
74 (80.4%) / 0.97
Pathologic T-Stage
Tis
1
2
3
4 / 71
130
90
25
6 / 15 (21.1%)
22 (16.9%)
24 (26.7%)
7 (28.0%)
2 (33.3%) / 56 (78.9%)
108 (83.1%)
66 (73.3%)
18 (72.0%)
4 (66.7%) / 0.15
Histology
Lobular
Mixed Lobular/Other
Other / 32
19
271 / 12 (37.5%)
2 (10.5%)
56 (20.7%) / 20 (62.5%)
17 (89.5%)
215 (79.3%) / 0.09
Biomarker Status
ER/PR+, Her2-
ER/PR+, Her2+
ER/PR-, Her2-
ER/PR-, Her2+ / 191
27
24
10 / 38 (19.9%)
8 (29.6%)
6 (25.0%)
3(30.0%) / 153 (80.1%)
19 (70.4%)
18 (75.0%)
7 (70.0%) / 0.26
Focality
Unifocal
Multifocal / 263
59 / 47 (17.9%)
23 (39.0%) / 216 (82.1%)
36 (61.0%) / <0.001
Margin Status
Negative
Close
Positive / 274
44
4 / 58 (21.2%)
11 (25.0%)
1 (25.0%) / 216 (78.8%)
33 (75.0%)
3 (75.0%) / 0.71
Pathologic LN Involvement
Negative
Positive / 271
51 / 56 (20.7%)
14 (27.4%) / 215 (79.3%)
37 (72.6%) / 0.28
Chemotherapy
No
Yes / 231
91 / 44 (19.0%)
26 (28.6%) / 187 (81.0%)
65 (71.4%) / 0.06
Timing of Chemotherapy
Neoadjuvant
Adjuvant / 42
49 / 15 (35.7%)
11 (22.4%) / 27 (64.3%)
38 (77.6%) / 0.16
Endocrine Therapy
No
Yes / 121
201 / 25 (20.7%)
45 (22.4%) / 96 (79.3%)
156 (77.6%) / 0.72
Radiation Therapy
No
Yes / 80
242 / 19 (23.8%)
51 (21.1%) / 61 (76.3%)
191 (78.9%) / 0.62

Table S2. Clinical and Pathologic Characteristics for Patients with Invasive Disease and Unilateral Lumpectomy, Stratified by the Use of Breast MRI Surveillance

Entire Cohort
(N=190) / Use of MRI Surveillance
(N=33) / No MRI Surveillance
(N=157) / P-value
Manchester Risk Score, Mean (SD) / 6.3% (6.7%) / 11.7% (8.6%) / 5.1% (5.6%) / <0.001
Manchester Risk Category
Low
Above Average
Moderate
High / 154
27
7
2 / 11.0 % (17/154)
44.4% (12/27)
42.9% (3/7)
50.0% (1/2) / 89.0% (137/154)
55.6% (15/27)
57.1% (4/7)
50.0% (1/2) / <0.001
Age, Mean (SD), years / 62.9 (12.9) / 52.3 (12.7) / 65.1 (11.9) / <0.001
Family History
No
Yes / 172
18 / 14.0% (24/172)
50.0% (9/18) / 86.0% (148/172)
50.0% (9/18) / 0.001
Use of Pre-Operative MRI
No
Yes / 73
117 / 2.7% (2/73)
26.5% (31/117) / 97.3% (71/73)
73.5% (86/117) / <0.001
Dense Breasts
No
Yes / 134
56 / 6.0% (8/134)
44.6% (25/56) / 94.0% (126/134)
55.4% (31/56) / <0.001
Previous Imaging-Occult Breast Cancer
No
Yes / 173
17 / 12.7% (22/173)
64.7% (11/17) / 87.3% (151/173)
35.3% (6/17) / <0.001
Pathologic Grade
1
2
3 / 70
76
44 / 12.9% (9/70)
21.1% (16/76)
18.2% (8/44) / 87.1% (61/70)
78.9% (60/76)
81.8% (36/44) / 0.38
Pathologic T-Stage
1
2
3
4 / 109
69
11
1 / 12.8% (14/109)
24.6% (17/69)
18.2% (2/11)
0 (0/1) / 87.2% (95/109)
75.4% (52/69)
81.8% (9/11)
100% (1/1) / 0.21
Histology
Lobular
Mixed Lobular/Other
Other / 23
13
154 / 26.1% (6/23)
15.4% (2/13)
16.2% (25/154) / 73.9% (17/23)
84.6% (11/13)
83.8% (129/154) / 0.49
Biomarker Status
ER/PR+, Her2-
ER/PR+, Her2+
ER/PR-, Her2-
ER/PR-, Her2+ / 150
19
17
4 / 15.3% (23/150)
26.3% (5/19)
23.5% (4/17)
25.0% (1/4) / 84.7% (127/150)
73.7% (14/19)
76.5% (13/17)
75.0% (3/4) / 0.36
Focality
Unifocal
Multifocal / 163
27 / 14.7% (24/163)
33.3% (9/27) / 85.3% (139/163)
66.7% (18/27) / 0.03
Margin Status
Negative
Close
Positive / 165
24
1 / 17.6% (29/165)
16.7% (4/24)
0 (0/1) / 82.4% (136/165)
83.3% (20/24)
100% (1/1) / 1.00
Pathologic LN Involvement
Negative
Positive / 166
24 / 17.5% (29/166)
16.7% (4/24) / 82.5% (137/166)
83.3% (20/24) / 1.00
Chemotherapy
No
Yes / 126
64 / 11.9% (15/126)
28.1% (18/64) / 88.1% (111/126)
71.9% (46/64) / 0.01
Timing of Chemotherapy
N/A
Neoadjuvant
Adjuvant / 126
24
40 / 11.9% (15/126)
41.7% (10/24)
20.0% (8/40) / 88.1% (111/126)
58.3% (14/24)
80.0% (32/40) / 0.06
Endocrine Therapy
No
Yes / 52
138 / 15.4% (8/52)
18.1% (25/138) / 84.6% (44/52)
81.9% (113/138) / 0.66
Radiation Therapy
No
Yes / 20
170 / 0 (0/20)
19.4% (33/170) / 100% (20/20)
80.6% (137/170) / 0.03

Table S3. Clinical and Pathologic Characteristics for Patients with Invasive Disease and Unilateral Mastectomy, Stratified by the Use of Breast MRI Surveillance

Entire Cohort
(N=61) / Use of MRI Surveillance
(N=22) / No MRI Surveillance
(N=39) / P-value
Manchester Risk Score, Mean (SD) / 7.6% (6.7%) / 8.4% (6.4%) / 7.2% (6.9%) / 0.52
Manchester Risk Category
Low
Above Average
Moderate
High / 49
8
4
0 / 38.8% (19/49)
12.5% (1/8)
50.0% (2/4)
0 (0/0) / 61.2% (30/49)
87.5% (7/8)
50.0% (2/4)
0 (0/0) / 0.41
Age, Mean (SD), years / 58.7 (14.4) / 54.7 (11.7) / 60.9 (15.4) / 0.11
Family History
No
Yes / 57
4 / 36.8% (21/57)
25.0% (1/4) / 63.2% (36/57)
75.0% (3/4) / 1.00
Use of Pre-Operative MRI
No
Yes / 9
52 / 22.2% (2/9)
38.5% (20/52) / 77.8% (7/9)
61.5% (32/52) / 0.47
Dense Breasts
No
Yes / 39
22 / 35.9% (14/39)
36.4% (8/22) / 64.1% (25/39)
63.6% (14/22) / 0.97
Previous Imaging-Occult Breast Cancer
No
Yes / 54
7 / 29.6% (16/54)
85.7% (6/7) / 70.4% (38/54)
14.3% (1/7) / 0.01
Pathologic Grade
1
2
3 / 15
29
17 / 46.7% (7/15)
37.9% (11/29)
23.5% (4/17) / 53.3% (8/15)
62.1% (18/29)
76.5% (13/17) / 0.17
Pathologic T-Stage
1
2
3
4 / 21
21
14
5 / 38.1% (8/21)
33.3% (7/21)
35.7% (5/14)
40.0% (2/5) / 61.9% (13/21)
66.7% (14/21)
64.3% (9/14)
60.0% (3/5) / 1.00
Histology
Lobular
Mixed Lobular/Other
Other / 9
6
46 / 66.7% (6/9)
0 (0/6)
34.8% (16/46) / 33.3% (3/9)
100% (6/6)
65.2% (30/46) / 0.03
Biomarker Status
ER/PR+, Her2-
ER/PR+, Her2+
ER/PR-, Her2-
ER/PR-, Her2+ / 40
8
7
6 / 37.5% (15/40)
37.5% (3/8)
28.6% (2/7)
33.3% (2/6) / 62.5% (25/40)
62.5% (5/8)
71.4% (5/7)
66.7% (4/6) / 1.00
Focality
Unifocal
Multifocal / 42
19 / 31.0% (13/42)
47.4% (9/19) / 69.0% (29/42)
52.6% (10/19) / 0.22
Margin Status
Negative
Close
Positive / 53
6
2 / 32.1% (17/53)
66.7% (4/6)
50.0% (1/2) / 67.9% (36/53)
33.3% (2/6)
50.0% (1/2) / 0.28
Pathologic LN Involvement
Negative
Positive / 34
27 / 35.3% (12/34)
37.0% (10/27) / 64.7% (22/34)
63.0% (17/27) / 0.89
Chemotherapy
No
Yes / 34
27 / 41.2% (14/34)
29.6% (8/27) / 58.8% (20/34)
70.4% (19/27) / 0.35
Timing of Chemotherapy
N/A
Neoadjuvant
Adjuvant / 34
18
9 / 41.2% (14/34)
27.8% (5/18)
33.3% (3/9) / 58.8% (20/34)
72.2% (13/18)
66.7% (6/9) / 0.47
Endocrine Therapy
No
Yes / 18
43 / 33.3% (6/18)
37.2% (16/43) / 66.7% (12/18)
62.8% (27/43) / 0.78
Radiation Therapy
No
Yes / 31
30 / 35.5% (11/31)
36.7% (11/30) / 64.5% (20/31)
63.3% (19/30) / 0.92

Table S4. Clinical and Pathologic Characteristics for Patients with DCIS and Unilateral Lumpectomy, Stratified by the Use of Breast MRI Surveillance

Entire Cohort
(N=61) / Use of MRI Surveillance
(N=11) / No MRI Surveillance
(N=50) / P-value
Manchester Risk Score, Mean (SD) / 9.9% (8.2%) / 14.4% (10.8%) / 8.9% (7.2%) / 0.08
Manchester Risk Category
Low
Above Average
Moderate
High / 37
20
2
2 / 10.8% (4/37)
30.0% (6/20)
0 (0/2)
50.0% (1/2) / 89.2% (33/37)
70.0% (14/20)
100% (2/2)
50.0% (1/2) / 0.16
Age, Mean (SD), years / 58.9 (12.6) / 50.6 (10.7) / 60.7 (12.4) / 0.02
Family History
No
Yes / 57
4 / 17.5% (10/57)
25.0% (1/4) / 82.5% (47/57)
75.0% (3/4) / 0.56
Use of Pre-Operative MRI
No
Yes / 19
42 / 5.3% (1/19)
23.8% (10/42) / 94.7% (18/19)
76.2% (32/42) / 0.15
Dense Breasts
No
Yes / 41
20 / 9.8% (4/41)
35.0% (7/20) / 90.2% (37/41)
65.0% (13/20) / 0.03
Previous Imaging-Occult Breast Cancer
No
Yes / 59
2 / 16.9% (10/59)
50.0% (1/2) / 83.1% (49/59)
50.0% (1/2) / 0.33
Pathologic Grade
1
2
3 / 8
32
21 / 25.0% (2/8)
21.9% (7/32)
9.5% (2/21) / 75.0% (6/8)
78.1% (25/32)
90.5% (19/21) / 0.47
Margin Status
Negative
Close
Positive / 51
9
1 / 21.6% (11/51)
0 (0/9)
0 (0/1) / 78.4% (40/51)
100% (9/9)
100% (1/1) / 0.34
Endocrine Therapy
No
Yes / 43
18 / 16.3% (7/43)
22.2% (4/18) / 83.7% (36/43)
77.8% (14/18) / 0.72
Radiation Therapy
No
Yes / 19
42 / 21.1% (4/19)
16.7% (7/42) / 78.9% (15/19)
83.3% (35/42) / 0.73

Table S5. Clinical and Pathologic Characteristics for Patients with DCIS and Unilateral Mastectomy, Stratified by the Use of Breast MRI Surveillance

Entire Cohort
(N=10) / Use of MRI Surveillance
(N=4) / No MRI Surveillance
(N=6) / P-value
Manchester Risk Score, Mean (SD) / 13.0% (7.4%) / 18.4% (2.0%) / 9.5% (7.7%) / 0.14
Manchester Risk Category
Low
Above Average
Moderate
High / 4
5
1
0 / 0 (0/4)
80.8% (4/5)
0 (0/1)
0 (0) / 100% (4/4)
20.0% (1/5)
100% (1/1)
0 (0) / 0.05
Age, Mean (SD), years / 52.0 (13.9) / 43.3 (4.0) / 57.8 (15.4) / 0.20
Family History
No
Yes / 10
0 / 40.0% (4/0)
0 (0/0) / 60.0% (6/10)
0 (0/0) / N/A
Use of Pre-Operative MRI
No
Yes / 3
7 / 0 (0/3)
57.1% (4/7) / 100% (3/3)
42.9% (3/7) / 0.20
Dense Breasts
No
Yes / 3
7 / 33.3% (1/3)
42.9% (3/7) / 66.7% (2/3)
57.1% (4/7) / 1.00
Previous Imaging-Occult Breast Cancer
No
Yes / 9
1 / 44.4% (4/9)
0 (0/1) / 55.6% (5/9)
100% (1/1) / 1.00
Pathologic Grade
1
2
3 / 0
0
10 / 0 (0)
0 (0)
40.0% (4/10) / 0 (0)
0 (0)
60.0% (6/10) / N/A
Margin Status
Negative
Close
Positive / 5
5
0 / 20.0% (1/5)
60.0% (3/5)
0 (0) / 80.0% (4/5)
40.0% (2/5)
0 (0) / 0.52
Endocrine Therapy
No
Yes / 8
2 / 50.0% (4/8)
0 (0/2) / 50.0% (4/8)
100% (2/2) / 0.47
Radiation Therapy
No
Yes / 10
0 / 40.0% (4/10)
0 (0) / 60.0% (6/10)
0 (0) / N/A

Table S6. Significant Variables for Multivariate Logistic Regression Analysis without Manchester Model for Patients with Invasive Breast Cancer

Multivariate Analysis
Odds Ratio / 95% Confidence Interval / p-value
Type of Surgery / 2.50 / 1.16-5.38 / 0.019
Age at Diagnosis
Every 1 year decrease in age
Every 5 year decrease in age
Every 10 year decrease in age / 1.06
1.33
1.77 / 1.03-1.09
1.13-1.56
1.28-2.45 / 0.0006
Breast Density / 3.19 / 1.48-6.87 / 0.0031
Previous Imaging-Occult Breast Cancer / 15.90 / 5.25-48.2 / <0.0001

Table S7. Significant Variables for Multivariate Logistic Regression Analysis without Manchester Model for Patients with DCIS

Multivariate Analysis
Odds Ratio / 95% Confidence Interval / p-value
Age at Diagnosis
Every 1 year decrease in age
Every 5 year decrease in age
Every 10 year decrease in age / 1.10
1.58
2.48 / 1.03-1.17
1.16-2.15
1.34-4.60 / 0.0038

aAUC under ROC curve= 0.7786 (95% CI 0.6455, 0.9116)

bHosmer and Lemeshow Goodness-of-Fit Test p=0.3989