1
Title page
Is there a place for repeat hepatectomy combined with systemic treatment for recurrent
breast cancer liver metastases after first hepatectomy?
Description
Retrospective single institution treatments comparison study.
Author
Aldrick Ruiz M.D.1, 2, Carlos Castro-Benitez M.D.2, 4, Mylene Sebahg M.D.2, Edward Castro-Santa
M.D.2, 3,Richard van Hillegersberg M.D. PhD1, Bernard Paule M.D.2, Denis Castaing M.D.2, René
Adam M.D. PhD.2
Department and institution
1. University Medical Center Utrecht
2. Centre Hepatobiliar Paul Brousse
3. Hospital Nacional de Niños
4. Hospital Mexico Costa Rica
Correspondence concerning the manuscript
Pr René Adam
Centre Hépato-Biliaire
9 avenue Paul Vaillant Couturier
94804 Villejuif
rene.adam@pbr.aphp.fr
Tel: 00 33 1 45 59 30 49
Fax: 00 33 1 45 59 38 57
Requests for reprints
2
Sources of support
The Netherlands Organization for Scientific Research (NWO) provided funding for a
research fellow.
Mini Abstract (45)
Patients with hepatic recurrence after initial hepatectomy for breast cancer liver metastasis
carry a poor prognosis. This retrospective study shows that repeat hepatectomy should be
considered in selected patients leading to 3-year and 5-year survivals of 61% and 49 %
respectively.
Abstract (268)
Objective
To analyze the possible benefit of repeat hepatectomy (RH) in the treatment of recurrent
breast cancer liver metastases after initial hepatectomy compared to only systemic treatment
after recurrence.
Summary background data
Breast cancer liver metastasis (BCLM) is accompanied by poor prognosis. Resection of liver
metastasis is still a controversial approach.
Methods
Between 1985 and 2012, 139 consecutive patients underwent liver resection for BCLM at
our institution. Patients with recurrent breast cancer liver metastases after first hepatectomy
were divided into a single hepatectomy (SH) or RH group. Clinicopathological data were
prospectively collected and analyzed for survival and prognostic factors.
Results
3
Recurrent hepatic disease occurred in 66 patients (48%) of which 19 (29%) had RH. The
overall median survival (n=66) was 57 months from the first hepatectomy. The 3-year and 5year survivals were 61% and 49 % respectively. In 27 (41%) patients, extra hepatic disease at
the time of hepatic recurrence was present. SH group had more major than limited resections
(68% vs. 32%) and more recurrences within one year than after one-year (61% vs. 39%). RH
group had fewer major than limited resections (42 vs. 58%) and fewer recurrences within one
year then after one year (26% vs. 74%). Patients without and with vascular invasion had 5 year
OS of 69% and 39% respectively P=0.005. Patients who had recurrence within one year had a
worse prognosis compared to beyond one year after first hepatectomy (5-year OS of 12% vs
70% P= 0.002). Patients who underwent a SH and RH, both combined with systemic treatment,
had a 5 year OS of 30% vs. 95% P<0.001 respectively. The only significant factor for survival in
the RH group was having the combination of vascular invasion at first hepatectomy and
recurrence within one year after first hepatectomy (5 year OS of 50% vs. 92% p=0.026).
Conclusions
In patients with breast cancer liver metastases, RH is a valid option in case of liver
recurrence leading to an overall survival comparable to the first hepatectomy.
Text of paper
Introduction
After years of treatment development, breast cancer is still the number one killer of women
around the world 1, 2. Even though there has been a lot of progress in the systemic treatment of
metastatic breast cancer, dissemination is still accompanied by bad prognosis 3. Liver metastasis
compared to other sites (such as the lung, bone or brain) of metastases is the most lethal in
breast cancer patients4. Resection of liver metastasis is an established option in colorectal
metastases but in breast cancer still very controversial 5. Most of what we know regarding the
resection of breast metastases comes from small series experiences 6, 7. At our institution,
4
selected patients with breast cancer liver metastasis underwent resection since 1985 (n=85)
with previously reported promising results8. Similar to colorectal liver metastases, recurrent
liver metastases have been re-resected in a selected group of patients. The purpose of this study
is to answer the question whether there is a place for re-hepatectomy in the treatment of
recurrent breast cancer liver metastases. To date there is no study available addressing this
question.
Methods
Population & Data
Between1985-2012, all patients who underwent liver resections for breast cancer
metastases were screened for inclusion. Patients who had recurrent breast cancer liver metastases
after a first hepatectomy were selected. Clinical and pathological information was
retrospectively updated in our database using Openclinica v3.0 clinical data management
system. After each hepatectomy, patients were followed at one-month post hepatectomy, then
every 3 month for the first year and every 6 months after one year. Abdominal ultrasound and
computer tomography were performed alternating before each visit. Several medical doctors
reviewed all dossiers for medical accuracy and as a referral center, we conducted a written and
digital survey to all physicians who had contact with the patients for follow up status. Additional
immunohistochemistry analysis was conducted in those re-hepatectomy patients with missing
information.
Statistical consideration
The chi-square test was used to compare characteristic of the two groups. Survival was
analyzed using the Kaplan Meyer method together with log rank test for significance. Univariate
and multivariate analysis was conducted to determine possible prognostic factors according to
Cox proportional hazards regression methodology. Variables with a P-value of less than 0.10 in
univariate analysis were included in multivariate analysis. Statistical significance with a P-value
5
of less than 0.05 was considered significant. For statistical analysis, multiple clinical, operative,
postoperative, and pathologic factors were recorded and to facilitate comparisons, several
variables were dichotomized. The extend of hepatic resection was classified as major (> 3
hepatic segments) or limited (≤ 3 hepatic segments), according to Couinaud’s classification.
Postoperative complications were classified as local when occurring near the field of liver
surgery (eg, biliary fistula) and general when occurring distant from the field of liver surgery
(eg, pneumonia). Overall survivals (OS) were calculated using the Kaplan and Meier. Univariate
associations between study factors and outcomes were determined using the log-rank test with
a P-value <0.05. All study variables with a significance level of P ≤0.1 in univariate analysis were
then entered into a Cox proportional hazard model. In multivariate analysis, independent
statistical significance was determined by a P value < 0.05. All statistical analyses were
performed using SPSS software, version 21.0 (SPSS, Inc., Chicago, IL).
Results
Clinical Characteristics
Between 1985-2012, 139 consecutive female patients underwent liver resection for breast
cancer liver metastases at our institution. In 66 patients (48%) recurrent hepatic disease
occurred of which 19 had re-hepatectomies (Figure 1). When referred to our center all patients
were discussed in a multi disciplinary team including oncologists, radiologists, hepatologists
and surgeons to come up with the best treatment. The policy was to consider repeat
hepatectomy in those patients with technically resectable liver recurrence when controlled by
preoperative chemotherapy and in the absence of extra hepatic disease.
First hepatectomy
In the patient with recurrent hepatic disease (n=66) the median age at first hepatectomy
was 47 years (30-70 years.) At the first hepatectomy, in 26 (39%) a limited resection and in 40
(61%)patients a major resection was performed. Resection margin status of the first
6
hepatectomy was positive (R1) in 19 patients (35 %). The median maximum size and number of
resected tumors was 25 mm (range 5-170mm) and 2 tumors (1-13) respectively. Hepatic
complication was encountered in 11 patients (18%) mainly caused by biliary fistula in 6
patients. Immunohistochemistry data (estrogen [ER], progesterone [PR]) of initial resected liver
tumors were available in 40 (61%) of the patients, including 18 (45%) ER+ PR- tumors 14
(35%) ER- PR- tumors and 8 (20 %) ER+ PR+ tumors. In 50 patients (75%) a second line
chemotherapy or hormonal therapy was initiated post first hepatectomy.
Hepatic recurrence
The median age at the time of recurrence was 49 years (range 30-71 years). Hepatic
recurrence occurred at a median interval of 12 months (range, 0 to 103 months) after the first
hepatectomy. In 20 (33%) patients a solitary recurrence was found. The median maximal tumor
size was 1.6 cm (0,5 cm – 14.1 cm). The median number of tumor diagnosed before surgery was
2 (1-8 tumors). Recurrence distribution was unilateral in two thirds and bilateral in one third of
the patients. In 27 (41%) patients, extra hepatic disease at the time of hepatic recurrence was
present. Forty-seven patients (63%) received a new (line switch) chemotherapy or hormonal
therapy after discovery of the recurrence.
Comparison of clinical characteristic for single vs. repeat hepatectomy
A wide variety of clinical variables were compared and are illustrated in table 1. A significant
difference was seen in extension of resection. Patients who underwent a single hepatectomy
had more major than limited resections (68% vs. 32%) while patients in the repeat
hepatectomy had fewer major then limited resections (42% vs. 58%). In the single hepatectomy
group more patients had a hepatic recurrence within one year than after one year (61% vs.
39%) and in the repeat hepatectomy group fewer patients had a recurrence before one year
then after one year (26% vs. 74%).
Clinical feature and short-term outcome of 2nd hepatectomy
7
Nineteen patients underwent a second hepatectomy and 4 had a third hepatectomy. The
median interval to recurrence in these patients was 20 months (range 2-103 months). As
median, 2 tumors were diagnosed before surgery varying between 1 and 6 tumors. The median
max size of tumors was 17 mm (range 5-141mm). The tumor(s) were located unilateral in 14
patients (74%) and bilateral in 5 patients (26%). Six patients had extra hepatic metastasis at the
time of hepatic recurrence. Seven patients (39%) underwent major resection while twelve
patients (63%) had limited resections. No patients died within 90 day after surgery. Perioperative comorbidity was low; 1 patient (5.3) had a complication. According to Clavien Dindo
classification, one patient had grade I (6%) and two patient grade II (12%). Median hospital stay
post hepatectomy was nine days ranging from 6 to 13 days. In 14 patients the surgical margin
was microscopically free (R0) of tumor cells. Four patients had a positive surgical margin (R1).
Number of tumors found histologically was the same as at the time of diagnoses; 2 (range 1-8
tumors). Resected tumors had a median max size of 15 mmm (range 8-60 mm). Estrogen
hormone receptor status was positive in 13 patients (68%) and progesterone hormone receptor
was positive in 10 patients (52%). Cerb2 was positive in 7 patients (39%). Five patients (31%)
had vascular invasion and 11 (68%)did not. Table 2 summarizes the cases.
Overall Survival
The overall median survival in the study population (n=66) was 57 months from the first
hepatectomy. The 3-year and 5-year survivals were 61% and 49 % respectively. The median
follow-up interval was 76 months after the first hepatectomy (Figure 1).
When comparing the group of patients who received re-hepatectomy to those who did not, a
significant difference in survival can be seen. Patients who in total underwent a single
hepatectomy (n=47) had a median survival of 32 months compared to 100 months for those
who had more then one hepatectomy (n=19)(figure 2).
Prognostic Factors of Overall Survival
8
All recorded study variables were analyzed to determine association with survival (table 3).
In univariate analysis, study variables that were associated with poor overall survival (P≤ 0.1)
were whether there was vascular invasion in the first liver resection (P=0.085), whether there
was one or more tumors (P = 0.005), whether there was history of extra hepatic metastases at
the time of first hepatectomy (P=0.005), one year disease free interval between hepatectomy
and hepatic recurrence, whether a new systemic treatment has been started after diagnoses of
hepatic recurrence (P= 0.020), whether patients had extra hepatic disease at the time of hepatic
recurrence
(P=0.100)
and
whether
patients
under
went
a
single
or
repeat
hepatectomy(P<0.001). Subsequent multivariate regression determined that 3 out the 7
variables were independently associated with poor outcome. Patients with no vascular invasion
at first hepatectomy (5 yr OS 69%) were 3.3 times less likely to die compared to patients with
vascular invasion at the time of first hepatectomy (5-year OS, 39% P=0.005) figure 3. Patients
who had recurrence within one year after first hepatectomy (5-year OS, 12%) were 4.0 times
more likely to die compared to patient the had a recurrence after one year (5 year OS, 70% P=
0.002) figure 4. Lastly, patients who underwent a single hepatectomy (5 year OS, 30%) were
11.4 times more likely to die compared to patients who had repeat hepatectomy(5 year OS, 95%
P<0.001) over the course of their disease figure 5. Patients who had repeat hepatectomy with
vascular invasion noted in the first hepatectomy and a recurrence within 1 year (5 year OS,
95%) were 10 times more likely to die compared to patients who did not have this combination
5 year OS, 0% p=0.026.
Discussion
Conclusion
Surgery for breast cancer liver metastases is still controversial and this study attempted to
take it a step further. All patients who had liver resection with recurrence were analyzed to see
if there was any benefit of multiple surgeries together with systemic treatment. To our
9
knowledge this is the only study that focuses on this population as a way to add evidence to the
idea of hepatic resection for breast cancer liver metastases.
Our analysis shows that performing more hepatectomies, was the only significant action for
better survival in our study population. Disease characteristic such as vascular invasion and
time period to recurrence were also significant for overall survival in this group. For the repeat
hepatectomy group, the combination of vascular invasion in the first hepatectomy and a
recurrence within one year was associated with a significant worst survival. These latter
variables may also have a role in selecting the patients in the future.
Limitations
Selection of patients for resection has developed together with that of colorectal liver
metastases. At our institution only patients, on whom R0 resection was possible for hepatic and
extra hepatic disease, were operated. Remnant liver after resection must have been at least 30%
and the response to chemotherapy should have been stable or in regression. Some publication
has shown that the fact of having a biopsy is significant for overall survival; we did not analysis
this variable. Biopsies at our institution are performed to confirm presence of tumor cells and
not to adjust chemotherapy as describe in these publication. For the decision to resect this was
irrelevant9.
As with all retrospective study, missing information is a real downfall. During our data
gathered period we reviewed the entire dossiers, which are kept indefinitely at our institution.
One
experienced
pathologist
reviewed
histopathology
tissue
slides
again
and
immunohistochemistry was conducted when missing and possible.
In this study, no attempts were made to match the 2 groups because of the small number
patient and the rarity of the stated procedure. Instead; a group-comparison was conducted to
present any significant differences and univariate and multivariate analysis was conducted on
the whole population.
10
During the years there has been many improvements in systemic treatment that need to be
consider. Hepatic resection technique has evolved to be widely implemented and safe. The
study period was over a wide interval 1985-2012 and in order to weight time period and
possible innovations, the study period was divided in surgeries before and after the year 2000.
This date was chosen arbitrarily and it is close to half the study period. Univariate and
multivariate analysis on this population did not show significance in overall survival.
Similarities and originality
An interesting observation was the similarity of overall survival of recurrent patients with
no recurrence after surgery in previously published articles while you would expect a worst
outcome after recurrence. The benefit of multiple hepatectomy is so big that it distorts this
population as a whole. When grouped and the multiple hepatectomy patients is disregarded,
one can observe the expected worst outcome in those patients who did not receive a rehepatectomy. In the past 5 years there has been articles describing the possible benefit of
surgery in mostly small study population varying from 2-115 patients with a 5-year survival
rate ranging from 27%-50% (Table 4)10-23. A 5-year survival rate of 30% for the patients who
underwent one hepatectomy that we report is similar to these previous publications. Our shortterm outcome of 2nd hepatectomy was also similar to other publications on hepatectomies
regardless of indication6.
Conclusion statement
Repeat hepatectomy when possible should be considered and integrated in the
multidisciplinary approach in the aggressive treatment of breast cancer liver metastases.
Further investigation needs to be conducted to add to the new evidence we supplied with this
study.
Acknowledgments
11
The Netherlands Organization for Scientific Research (NWO) provided funding for a
research fellow. Figures and tables
139 hepatectomies
1985-2012
66 (48%) Hepatic
recurrence
47 (71%)
Systemic treatments
Figure 1: Population
19 (29%)
Rehepatectomy plus
systemic treatment
72 (52%) No hepatic
recurrence
12
Table 1: Clinical characteristic comparison
Variable
Single or multiple hepatectomies
Single N=46
Multiple N=19
P
Count
N%
Count
N%
Year < 2000
21
45%
9
47%
Year ≥ 2000
26
55%
10
53%
# Segments resected ± SD (M)
3 ± 1 (4)
First hepatectomy
Before and after
3 ± 1 (2)
0.843
0.222
Extend of resection
Limited
15
32%
11
58%
Major
32
68%
8
42%
Anatomical
15
32%
9
47%
Non anatomical
15
32%
6
32%
Both
17
36%
4
21%
0.050
Type of resection
0.394
Histological surgical margin hepatic metastases
R0
22
56%
12
80%
R1
16
41%
3
20%
R2
1
3%
0
0%
Mean Hospital stay + SD (M)
11 ± 4 (10)
11 ± 4 (10)
0.259
0.860
Differentiation of resected tumor(s)
Well differentiated
4
13%
1
8%
Moderately differentiated
14
44%
10
77%
Poorly differentiated
14
44%
2
15%
Anaplastic
0
0%
0
0%
ER -
13
46%
1
13%
ER +
15
54%
7
87%
PR -
22
85%
6
75%
PR +
4
15%
2
25%
Cerb2 -
16
64%
3
50%
Cerb2 +
9
36%
3
50%
No
4
31%
1
50%
Yes
9
69%
1
50%
No
4
67%
0
0%
Yes
2
33%
0
0%
0.123
Receptor Status
0.115
0.609
0.653
Regional lymph nodes invasion
1.000
Distant lymph nodes invasion
-
13
Extra hepatic disease
No History
31
66%
17
90%
History
16
34%
2
10%
Yes
32
68%
17
90%
No
15
32%
2
10%
0.069
Adjuvant Chemotherapy
0.119
Recurrence
Age at hepatic recurrence Mead (M)
51+9 (50)
Interval hepatectomy recurrence 14 ± 15 (8)
Mean ± SD (M)
Interval first hepatectomy and recurrence
48+11 (44)
0.276
26 ± 23 (20)
0.083
≤ 12 months
28
61%
5
26%
> 12 months
18
39%
14
74%
Number of tumors + SD (M)
3 ± 2 (2)
2 ± 1 (2)
0.015
0.068
Tumor number solitaire recurrence
Solitary
11
26%
9
47%
>1
31
74%
10
53%
Mean Max Size, mm + SD
20 ± 12 (15)
27 ± 31 (17)
0.103
0.100
Maximum size of hepatic metastases (3cm)
< 30 mm
24
100%
17
94%
≥ 30 mm
0
0%
1
6%
Unilateral right
12
28%
6
32%
Unilateral left
16
37%
8
42%
Bilateral
15
35%
5
26%
0.429
Location of hepatic metastases
0.801
Concomitant extra hepatic disease
Lung
6
Lung and Bone
2
Bone
5
Brain
3
Lymph Node
5
None
26
13%
4%
11%
6%
11%
55%
1
0
4
1
0
13
5%
0%
21%
5%
0%
68%
0.410
14
30
+/+
-
R0
6
19
Alive
9
Right lobe
2
Non-anatomical
9
No
Well
2
8
+/+
-
R0
No
24
Dead
3
40
Bilateral
2
Both
N/A
No
Poor
2
15
+/+
-
N/A
20
41
Dead
32
2
11
Bone
Bilateral
1
Non-anatomical
6
No
Moderate
1
9
+/-
+
R0
No
25
Alive
5
33
1
9
Bone
Right lobe
2
Non-anatomical
9
Grade II
Poor
+
2
10
+/-
+
R0
No
24
Alive
6
15
1
10
Left lobe
1
Non-anatomical
11
No
Poor
+
1
24
+/-
-
R1
8
35
Alive
7
8
1
35
Left lobe
3
Non-anatomical
10
N/A
Moderate
3
50
+/+
N/A
R0
26
122
Alive
8
20
2
22
Left lobe
2
Non-anatomical
10
N/A
N/A
3
15
+/+
-
R1
11
73
Dead
9
41
2
15
Left lobe
3
Both
13
No
Moderate
1
10
+/+
-
R0
13
43
Alive
10
11
1
5
Left lobe
6
Non-anatomical
11
No
N/A
4
8
+/+
+
R0
No
1
Alive
11
16
1
10
Right lobe
3
Non-anatomical
9
No
Poor
3
30
+/+
-
R0
2
25
Dead
12
43
2
50
Bilateral
4
Anatomical
12
No
Well
1
45
+/+
+
R0
No
83
Dead
13
5
3
-
Right lobe
1
Anatomical
N/A
Grade I
Moderate
1
37
+/-
-
R0
No
15
Dead
14
3
6
32
Right lobe
5
Both
6
No
N/A
6
60
-/-
+
R0
20
37
Dead
15
28
1
25
Left lobe
2
Anatomical
11
No
Well
1
25
-/-
+
R0
No
33
Dead
16
103
1
141
Bone
Left lobe
1
Non-anatomical
8
No
Moderate
1
12
-/-
-
R1
No
12
Dead
17
16
4
17
Brain
Bilateral
1
Anatomical
8
No
Moderate
1
30
-/-
+
R0
23
24
Dead
18
25
4
16
Left lobe
3
Non-anatomical
11
No
N/A
3
15
-/+
-
R1
23
139
Alive
19
33
1
17
Right lobe
3
Non-anatomical
9
Grade II
N/A
2
9
-/-
N/A
R0
11
40
Alive
8
1
3
48
4
Cerb2:
Bone
0,1
=
Negative
(-),
2=
doubtful
+
+
(±),
3
Cerb2
ER/PR
Max Size of tumor
Histological number
Differentiation
Clavein
classification
Hospital stay
Type of resection
#
of
resected
Location of hepatic
metastases
# Diagnosed
Case
2
=
Yes
Yes
Yes
Yes
Positive
Follow-up
2
Lung
Third hepatectomy
Interval
2nd
hepatectomy to 3rd
recurrence
Moderate
30
Lymph node invasion
No
2
Dindo
8
14
segments
Anatomical
1
Liver metastases plus
2
Max size of hepatic
metastases (mm)
Bilateral
Interval 1st resection
to recurrence Months
Surgical margin
Follow-up since 2nd
resection (months
Table 2: Case summaries of patients who underwent a second hepatectomy
(+)
15
Figure 2: Overall survival since 1st hepatectomy
Patients
Total
66
3 years
29
5 years
19
10 years
4
Median (months)
57
Figure 3: Overall survival since 1st hepatectomy according to vascular invasion during first
hepatectomy
Vascular embolus 1st hepatectomy
Yes
No
Total
47
19
3 years
11
11
5 years
4
10
10 years
2
3
Median (months)
49
83
16
Figure 4:Overall survival since 1st hepatectomy according to interval recurrence and 1st
hepatectomy.
Interval first hepatectomy and recurrence
≤ 12 months
> 12 months
Total
33
32
3 years
6
23
5 years
5
14
10 years
1
3
Median (months)
25
83
Figure 5: Overall survival since 1st hepatectomy according to number of hepatectomies
Patient group
Single hepatectomy
Multiple hepatectomies
Total
47
19
3 years
11
18
5 years
5
14
10 years
1
4
Median (months)
32
100
17
Figure 6: Overall survival since first hepatectomy according to whether patients in repeat
hepatectomy group had vascular invasion at first hepatectomy and recurrence within one year.
Vascular invasion at first hepatectomy plus
recurrence within one year in repeat hepatectomy
group
No
Yes
Total
3
years
5
years
10
years
Median
(months)
14
2
14
1
11
0
4
0
126
33
18
Table 3: Prognostic factor after recurrence
N
%
3 yr
%
5 yr
%
Median
(Mo)
Log
rank
Cox
Limited (< 3)
26
39
70
70
81
0.029
NS
Major (≥ 3)
40
61
56
36
49
R0
34
63
64
56
75
0.291
-
R1
19
35
54
52
45
R2
1
2
0
0
32
ER +
27
66
75
58
75
0.110
-
ER -
14
34
51
51
61
PR +
8
20
69
69
94
0.744
-
PR -
32
80
70
52
61
Cerb2 +
11
30
83
83
75
0.778
-
Cerb2 -
27
70
67
49
57
No
18
38
76
69
83
0.085
0.005
Yes
29
62
51
39
49
No
16
53
63
56
75
0.812
-
Yes
14
47
64
51
77
Yes
10
100
30
15
32
-
-
No
0
0
-
-
0.695
-
0.672
-
0.005
NS
0.418
-
0.005
NS
Variable
Odds
Ratio
(95% CI)
First hepatectomy
Extend of resection
Resection margin
Receptor status
Vascular invasion
Lymphatic invasion
Lymph node invasion
Post hepatectomy complication
No
45
69
61
51
61
Yes
20
31
57
43
49
Post hepatectomy systemic treatment
Yes
50
75
62
52
61
No
17
25
45
45
30
Solitaire
25
42
75
69
81
>1
35
58
46
33
33
> 50 mm
8
14
43
43
33
≤ 50 mm
51
86
64
52
61
40
24
30
Tumor number
Max tumor size
History of EHM prior to hepatectomy
Yes
18
27
0.3 (0.0 – 0.7)
19
No
48
73
68
58
75
Post hepatectomy Systemic treatment
Yes
50
78
63
49
57
No
14
22
35
35
30
≤ 50 years
36
54
64
48
57
> 50 years
30
46
57
51
61
0.903
-
0.677
-
0.002
0.002
0.509
-
0.371
-
0.164
-
0.020
NS
0.100
-
0.000
0.000
Liver metastases recurrence
Age
Interval from first hepatectomy
≤ 12 months
33
51
29
24
25
> 12 months
32
49
83
70
83
Solitaire
20
33
63
56
61
>1
41
67
63
51
73
< 50 mm
33
78
65
55
61
≥ 50 mm
9
22
89
89
94
Unilateral
42
68
65
62
75
Bilateral
20
32
56
33
49
Yes
41
71
67
53
61
No
17
29
23
23
25
Yes
31
47
53
35
40
No
35
53
68
63
75
Single
47
70
39
30
30
Repeat
19
30
95
84
100
4.0 (1.7-9.7)
Tumor number
Maximal tumor size
Distribution
New systemic treatment
Extra hepatic metastases
Hepatectomy
11.4 (3.2-40.6)
Vascular invasion plus recurrence within a year after hepatectomy in repeat hepatectomy patients
No
14
88
100
92
126
0.007
0.026
0.1 (0.0-0.8)
Yes
2
12
50
50
33
CI indicates confidence interval; ER, estrogen receptor; PR, progesterone receptor; EHM, extra hepatic
metastases; R0, margin-negative; R1, margin microscopically positive; R2, gross residual intrahepatic
disease; NS, not significant.
20
Table 4: Publication of the past 5 years describing resection for breast cancer liver metastases.
Author
Year
of
publication
Study
population
5-yr (%)
Median
survival
(months)
Caralt
2008
12
33
35.9
Kollmar
2008
27
50
-
Lubrano
2008
16
33
42
Thelen
2008
39
42
-
Hoffmann
2010
41
48
58
Rubino
2010
18
-
74
Cassera
2011
2
-
-
Abbott
2012
86
44
57
Duan
2012
16
44
-
Groeschl*
2012
115
27
52
van Walsum
2012
32
37
55
Dittmar
2013
34
38
48
Kostov
2013
42
39
43
Polistina
2013
12
*Multi center population
34
30
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