Figure 1. Flowchart of the Study Population

Supplemental

Table 1. Literature overview concerning outcomes of hepatectomy for breast cancer liver metastases (BCLM).

Long-term outcome
First author / Ref. / Year / Number of / 5-yr OS / Median OS
patients / (%) / (months)
Adam / 8 / 2006 / 85 / 37 / 32
Caralt / 9 / 2008 / 12 / 33 / 35.9
Kollmar / 10 / 2008 / 27 / 50 / -
Lubrano / 11 / 2008 / 16 / 33 / 42
Thelen / 12 / 2008 / 39 / 42 / -
Hoffmann / 13 / 2010 / 41 / 48 / 58
Rubino / 14 / 2010 / 18 / - / 74
Cassera / 15 / 2011 / 2 / - / -
Abbott / 16 / 2012 / 86 / 44 / 57
Duan / 17 / 2012 / 16 / 44 / -
Groeschl* / 18 / 2012 / 115 / 27 / 52
van Walsum / 19 / 2012 / 32 / 37 / 55
Dittmar / 20 / 2013 / 34 / 38 / 48
Kostov / 21 / 2013 / 42 / 39 / 43
Polistina / 22 / 2013 / 12 / 34 / 30
Kim / 23 / 2014 / 13 / 49.2** / -
Weinrich / 24 / 2014 / 29 / 33 / 53
* Multicenter **3 year survival
Abbreviations: OS = overall survival.

Figure 1. Flowchart of the study population.

Table 2. Short outcome (N=139)

N / %
60-day mortality / 3 / 2.2
Morbidity / 38 / 27.3
General complications / 28 / 20.1
Hepatic complications / 19 / 13.7
Biliary leakage / 6 / 4.3
Biliary leakage + infected collection / 2 / 1.4
Biliary leakage + noninfected collection / 1 / 0.7
Infected collection / 4 / 2.9
Noninfected collection / 6 / 4.3
Mean hospital stay, days + SD (M) / 11 + 6 / (10)
(M)=Median

Table 3. Predictive factors of overall survival

Primary Tumor / n / % (N) / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / P §§ / HR / (95% CI)
Surgical treatment
Breast conservation / 67 / 48.2 / 64 / 59 / 62
Mastectomy / 68 / 48.9 / 51 / 38 / 43 / 0.409
Histology subtype
Ductal / 77 / 55.4 / 63 / 53 / 62 / 0.433
Lobular / 10 / 7.2 / 49 / 49 / 25
Differentiation
Well / 4 / 2.9 / 33 / 33 / 19 / 0.280
Moderate / 56 / 40.3 / 72 / 59 / 73
Poor / 26 / 18.7 / 55 / 47 / 49
Hormone receptor status
ER- / 12 / 8.6 / 68 / 68 / 62 / 0.849
ER+ / 55 / 39.6 / 65 / 54 / 73
PR- / 22 / 15.8 / 62 / 44 / 60 / 0.150
PR+ / 41 / 29.5 / 68 / 63 / 75
Double negative (ER&PR) / No / 54 / 38.8 / 65 / 54 / 73 / 0.829
Yes / 9 / 6.5 / 66 / 66 / 62
HER2
Negative / 41 / 29.5 / 64 / 49 / 60 / 0.530
Positive / 11 / 7.9 / 86 / 86 / 73
T Stage
T1-2 / 84 / 60.4 / 62 / 50 / 60 / 0.217
T3-4 / 10 / 7.2 / 76 / 61 / 99
N Stage
N0 / 44 / 31.7 / 57 / 49 / 49 / 0.779
N1-3 / 54 / 38.8 / 66 / 57 / 62
Adjuvant chemo *
No / 134 / 96.4 / 57 / 46 / 54 / 0.401
Yes / 5 / 3.6 / 75 / 75 / 100
Neoadjuvant chemo *
No / 58 / 41.7 / 56 / 44 / 45 / 0.927
Yes / 81 / 58.3 / 60 / 49 / 60
Hormone therapy after resection **
No / 79 / 56.8 / 46 / 36 / 33 / 0.031 / NS
Yes / 60 / 43.2 / 75 / 64 / 75
Targeted therapy after resection ***
No / 101 / 72.7 / 53 / 41 / 45 / 0.074 / NS
Yes / 38 / 27.3 / 80 / 80 / 77
Radiotherapy after resection
No / 45 / 32.4 / 66 / 55 / 62 / 0.161
Yes / 94 / 67.6 / 55 / 44 / 45
Recurrence or new primary breast tumor
No / 107 / 77.0 / 62 / 49 / 60 / 0.560
Yes / 32 / 23.0 / 46 / 42 / 26

HR Hazard Ratio, * Antracyclines, pyrimidine, taxanes, platinum, vinca; single or in combinations, ** Aromatase inhibitor and anti estrogen, *** Monoclonal, § multivariate, §§ (20x imputation of missing values)

Table 3 continued

Liver metastases / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / P §§ / HR / (95% CI)
Time of appearance
Synchronous / 11 / 7.9 / 90 / 90 / - / 0.135
Metachronous / 125 / 89.9 / 55 / 45 / 49
Interval from primary tumor
< 18 months / 27 / 19.4 / 42 / 21 / 27 / 0.009 / NS
≥ 18 months / 104 / 74.8 / 61 / 53 / 62
Tumor number
1 / 56 / 40.3 / 65 / 65 / 82 / 0.010 / 0.003 / 0.000 / 3.389 / 1.853 / 6.199
>1 / 82 / 59.0 / 54 / 36 / 45
Maximal tumor size
< 20 mm / 49 / 35.3 / 75 / 57 / 20 / 0.063 / NS
≥ 20 mm / 76 / 54.7 / 55 / 47 / 49
Distribution
Unilateral / 84 / 60.4 / 56 / 54 / 62 / 0.117
Bilateral / 46 / 33.1 / 58 / 32 / 49
Segments involved
1 / 49 / 35.3 / 67 / 64 / 81 / 0.095 / NS
>1 / 83 / 59.7 / 52 / 39 / 40
Chemotherapy before hepatectomy *
No / 41 / 29.5 / 58 / 54 / 61 / 0.280
Yes / 98 / 70.5 / 58 / 44 / 54
Hormonal therapy before hepatectomy **
No / 120 / 86.3 / 55 / 44 / 45 / 0.048 / NS / NS
Yes / 19 / 13.7 / 84 / 84 / 99
Targeted before hepatectomy ***
No / 106 / 76.3 / 54 / 42 / 45 / 0.083 / NS
Yes / 33 / 23.7 / 80 / 80 / 77
Extra hepatic metastases
No / 98 / 70.5 / 67 / 54 / 73 / 0.022 / NS / 0.036 / 1.736 / 1.036 / 2.910
Yes / 41 / 29.5 / 37 / 29 / 30

Table 3 continued

Hepatectomy / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / P §§ / HR / (95% CI)
Age
<50 yr / 73 / 52.5 / 55 / 46 / 54 / 0.830
≥ 50 yr / 66 / 47.5 / 63 / 48 / 60
Hepatic Resection
Minor (<3) / 57 / 41.0 / 68 / 61 / 77 / 0.079 / NS
Major (≥3) / 82 / 59.0 / 52 / 37 / 40
Type of resection
Anatomical / 49 / 35.3 / 65 / 58 / 62 / 0.268
Both / 42 / 30.2 / 43 / 25 / 32
Not Anatomical / 48 / 34.5 / 65 / 60 / 77
Tumor number
Solitaire / 56 / 40.3 / 74 / 65 / 81 / 0.003 / NS
>1 / 76 / 54.7 / 45 / 34 / 32
Maximal tumor size
<20 mm / 29 / 20.9 / 75 / 57 / 29 / 0.063 / NS
≥ 20 mm / 98 / 70.5 / 55 / 47 / 49
Resection margin
R0 / 77 / 55.4 / 60 / 51 / 61 / 0.007 / NS / NS
R1 / 48 / 34.5 / 56 / 40 / 45
R2 / 3 / 2.2 / 0 / 0 / 18
Negative (R0) / 77 / 55.4 / 60 / 51 / 61 / 0.077 / NS
Positive (R1-2) / 51 / 36.7 / 52 / 37 / 40
Hormone receptor status
ER- / 47 / 33.8 / 34 / 24 / 25 / 0.000 / NS
ER+ / 74 / 53.2 / 72 / 60 / 81
No tumor cells / 7 / 5.0 / 66 / 66 / 62
PR- / 81 / 58.3 / 55 / 42 / 49 / 0.364
PR+ / 40 / 28.8 / 58 / 53 / 77
No tumor cells / 7 / 5.0 / 66 / 66 / 62
HER2- / 83 / 59.7 / 51 / 41 / 40 / 0.579
HER2+ / 35 / 25.2 / 65 / 59 / 75
No tumor cells / 7 / 5.0 / 66 / 66 / 62
Double negative (ER-, PR-)
No / 37 / 26.6 / 61 / 55 / 77 / 0.373
Yes / 84 / 60.4 / 54 / 42 / 45
No tumor cells / 7 / 5.0 / 66 / 66 / 62
Triple negative (ER-, PR-, HER2-)
No / 94 / 67.6 / 68 / 54 / 77 / 0.001 / 0.000 / 0.036 / 1.724 / 1.036 / 2.910
Yes / 27 / 19.4 / 21 / 21 / 25
No tumor cells / 7 / 5.0 / 66 / 66 / 62
Microscopic (Vascular) Invasion
No / 57 / 41.0 / 71 / 60 / 83 / 0.004 / 0.004 / 0.003 / 2.578 / 1.385 / 4.802
Yes / 70 / 50.4 / 46 / 36 / 33
Microscopic (lymphatic) Invasion
No / 49 / 35.3 / 63 / 57 / 81 / 0.204
Yes / 64 / 46.0 / 51 / 38 / 43
Microscopic (Vascular or lymphatic) Invasion
No / 34 / 24.5 / 72 / 64 / 86 / 0.019 / NS
Yes / 94 / 67.6 / 52 / 39 / 40
Lymph Node Invasion
Yes / 18 / 12.9 / 25 / 0 / 32 / 0.288
No / 12 / 8.6 / 57 / 38 / 49
Post hepatectomy Chemo *
No / 44 / 31.7 / 50 / 44 / 32 / 0.781
Yes / 95 / 68.3 / 61 / 48 / 60
Post hepatectomy hormonal therapy **
No / 74 / 53.2 / 36 / 30 / 28 / 0.002 / 0.015 / 0.007 / 0.477 / 0.279 / 0.826
Yes / 65 / 46.8 / 79 / 64 / 81
Post hepatectomy Targeted ***
No / 97 / 69.8 / 47 / 37 / 32 / 0.010 / NS / 0.020 / 0.447 / 0.227 / 0.880
Yes / 42 / 30.2 / 83 / 69 / 77
RFA
No / 129 / 92.8 / 56 / 45 / 49 / 0.597
Yes / 10 / 7.2 / 79 / 63 / 73

Table 3 continued

Post hepatectomy course / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / P §§ / HR / (95% CI)
Chemotherapy* around hepatectomy
No / 15 / 10.8 / 49 / 36 / 30 / 0.285
Yes / 124 / 89.2 / 59 / 48 / 57
Hormonal therapy around hepatectomy **
No / 65 / 46.8 / 35 / 28 / 27 / 0.002 / NS
Yes / 74 / 53.2 / 77 / 63 / 77
Targeted around hepatectomy ***
No / 84 / 60.4 / 45 / 35 / 32 / 0.006 / NS
Yes / 55 / 39.6 / 83 / 70 / 77
Hepatic Recurrence
No / 73 / 52.5 / 56 / 46 / 45 / 0.820
Yes / 66 / 47.5 / 60 / 49 / 57
Interval from first hepatectomy to recurrence****
< 1 year / 32 / 23.0 / 30 / 25 / 25 / 0.006 / 0.006 / 0.006 / 0.383 / 0.194 / 0.757
≥ 1 year / 33 / 23.7 / 81 / 65 / 81
Tumor number****
Solitaire / 22 / 15.8 / 63 / 56 / 61 / 0.483
>1 / 40 / 28.8 / 62 / 50 / 73
Repeat hepatectomy (two or more)****
No / 47 / 33.8 / 40 / 27 / 32 / 0.000 / 0.000 / 0.000 / 0.137 / 0.053 / 0.351
Yes / 19 / 13.7 / 95 / 84 / 100

Table 4. Predictive factors of survival for hepatectomies after the year 2000

Liver metastases / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / Hazard Ratio / (95% CI)
Maximal tumor size
< 20 mm / 24 / 30.0 / 94 / 71 / - / 0.074
≥ 20 mm / 56 / 70.0 / 68 / 59 / 77
Hormonal therapy before hepatectomy *
No / 68 / 79.1 / 70 / 55 / 73 / 0.068
Yes / 18 / 20.9 / 92 / 92 / 99
Hepatectomy / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / Hazard Ratio / (95% CI)
Resection margin
R0 / 46 / 57.5 / 69 / 69 / - / 0.000 / 0.001 / 3.340 / 1.627 / 7.087
R1 / 31 / 38.8 / 88 / 59 / 77
R2 / 3 / 3.8 / 0 / 0 / 18
Hormone receptor status
ER- / 21 / 26.3 / 48 / 48 / 30 / 0.050
ER+ / 54 / 67.5 / 83 / 72 / 83
Triple negative (ER-, PR-, HER2-)
No / 62 / 77.5 / 82 / 72 / 83 / 0.005
Yes / 13 / 16.3 / 32 / 32 / 21
Microscopic (Vascular) Invasion
No / 38 / 54.3 / 81 / 74 / 99 / 0.016
Yes / 40 / 57.1 / 67 / 50 / 77
Microscopic (Vascular or lymphatic) Invasion
No / 22 / 27.8 / 76 / 76 / - / 0.067
Yes / 57 / 72.2 / 73 / 49 / 60
Post hepatectomy hormonal therapy *
No / 43 / 50.0 / 49 / 49 / 35 / 0.017 / 0.001 / 0.189 / 0.073 / 0.493
Yes / 43 / 50.0 / 90 / 71 / 83
Post hepatectomy course / Patients with recurrence / N / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / Hazard Ratio / (95% CI)
Interval from first hepatectomy to recurrence**
< 12 months / 18 / 51.4 / 53 / 39 / 40 / 0.049 / 0.012 / 0.169 / 0.042 / 0.681
≥ 12 months / 17 / 48.6 / 87 / 66 / 83
Repeat hepatectomy (two or more)**
No / 26 / 72.2 / 51 / 17 / 40 / 0.002 / 0.002 / 0.066 / 0.012 / 0.358
Yes / 10 / 27.8 / 100 / 89 / -

Aromatase inhibitor and anti estrogen, ** Patient with recurrence, § multivariate

Table 5. Predictive factors of disease-free survival

Hepatectomy / n / % / 3 yr % / 5 yr % / Median (Mo) / Log rank / P § / Hazard Ratio / (95% CI)
Microscopic vascular invasion
No / 55 / 39.6 / 67 / 56 / 63 / 0.000 / 0.000 / 2.953 / 1.665 / 5.235
Yes / 70 / 50.4 / 28 / 19 / 19
Post-hepatectomy chemotherapy
No / 43 / 30.9 / 72 / 54 / - / 0.045 / NS
Yes / 94 / 67.6 / 40 / 33 / 25
§ Multivariate