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Division of Hematology-Oncology, Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
Division of Hematology-Oncology, Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDepartment of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
Division of Hematology-Oncology, Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDivision of Hematology-Oncology, Department of Medicine Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
Jung-Il Lee, MD, PhD, Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Addresses for correspondence: Yeon Hee Park, MD, PhD, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Most of the patients with MBC with LM had clinical improvement after VPS.
•
The prognosis of patients with MBC with VPS is worse in the TNBC subtype.
•
Anti-HER2 treatment is necessary in patients with HER2+ BC with CNS metastasis.
Abstract
Background
Leptomeningeal metastasis (LM) is associated with a grave prognosis in breast cancer (BC) and can be controlled with a ventriculoperitoneal shunt (VPS). Information regarding LM and VPS based on intrinsic subtype is limited; thus, we investigated the clinical outcomes of BC treated with VPS.
Patients and Methods
The present retrospective study comprised 70 patients diagnosed with LM who received a VPS. The patients were divided into 4 groups based on BC subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HR+/HER2+, HR−/HER2+, and triple negative BC (TNBC).
Results
The most common indications for VPS were uncontrolled intracranial pressure (57.1%) and uncontrolled headache (55.7%), which improved in 54 (77.1%) of 70 patients after VPS. The median overall survival (OS) after brain or LM and overall survival after VPS were 7.6 and 2.3 months, respectively. Anti-HER2 treatment was a significant prognostic factor for better OS after brain or LM based on multivariate analysis (hazard ratio, 0.15; 95% confidence interval, 0.04-0.57; P = .005), whereas TNBC was correlated with shorter OS after central nervous system metastasis (hazard ratio, 2.82; 95% confidence interval, 1.46-5.48; P = .002).
Conclusions
There were significant differences in clinical outcome based on the intrinsic subtype of patients with BC with LM who received a VPS. Anti-HER2 treatment in patients with HER2+ BC was associated with better survival in patients with metastatic BC with VPS insertion compared with those without. Survival of metastatic BC with VPS remained poor, especially in the TNBC subgroup.
and diagnosis of CNS metastasis has increased owing to advances in neuroimaging. Recent studies have reported a higher incidence of BM ranging from 25% to 46%.
Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.
Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases.
However, more patients are surviving BC owing to improvements in systemic therapy; in fact, a retrospective study of patients with MBC with BM showed a median survival of 14.4 months.
In patients with symptomatic LM, various treatment approaches such as radiotherapy, chemotherapy including intrathecal chemotherapy, and surgery including ventriculoperitoneal shunt (VPS) insertion are used to relieve the symptoms and mitigate increased intracranial pressure (ICP). However, optimal treatment for LM remains to be defined, and there is no United States Food and Drug Association-approved systemic chemotherapy for BC with LM. A number of prospective studies with a combination of chemotherapeutic agents such as temozolomide, capecitabine, cisplatin, sagopilone, and patupilone has been conducted in patients with BC with LM; however, survival after LM usually did not exceed 4 months.
Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study.
Murphy C, Nulsen B, Rump M, et al. Phase II trial of patupilone in patients with breast cancer brain metastases progressing or recurring after whole brain radiotherapy. Presented as an abstract at the 2009 Breast Cancer Symposium: Abstract #234.
Hellenic Cooperative Oncology Group Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) phase II study.
Furthermore, most patients with increased ICP with or without hydrocephalus could not be controlled with medical treatments, and they required implantation of an Ommaya reservoir or a VPS.
Intrathecal chemotherapy can be delivered through an Ommaya reservoir when ICP is controllable. When ICP increases beyond a tolerable range or hydrocephalus develops, VPS becomes an essential palliative treatment, after which intrathecal chemotherapy cannot be continued.
EANO Executive Board and ESMO Guidelines Committee EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours.
Although BC is the malignancy most commonly associated with LM, little information is available regarding patients with BC with LM who received VPS, and the clinical utility and value of VPS need to be defined. In the current study, we investigated the clinical features of patients with VPS based on intrinsic subtype.
Patients and Methods
The aim of the current study was to analyze the treatment outcomes of VPS in patients diagnosed with MBC with LM. We retrospectively analyzed patients who received a VPS owing to BC with LM between October 2001 and December 2017 at Samsung Medical Center. Patients with MBC were treated based on disease course. After diagnosis of CNS metastasis, a VPS and/or Ommaya reservoir were implanted by skilled neurosurgeons. Patients were divided into 4 groups based on BC subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HR+/HER2+, HR−/HER2+, and triple negative BC (TNBC). The subtypes were classified based on immunohistochemical (IHC) staining for estrogen receptor, progesterone receptor, and HER2. Grades 0 and 1 for HER2 based on IHC were defined as negative and grade 3 as positive. In patients who were HER2 2+ based on IHC, fluorescence in situ hybridization was performed to confirm HER2 amplification. TNBC was defined as absence of estrogen receptor, progesterone receptor, and HER2 expression. CNS metastasis was defined as BM, LM, or both. BM was diagnosed using brain magnetic resonance imaging and/or brain computed tomography, and LM was diagnosed using enhanced brain magnetic resonance imaging with T2-weighted and/or fluid-attenuated inversion recovery images
Patient characteristics were compared based on BC subtype. Differences in characteristics were examined using the Pearson χ2 test. OSCNS was defined as the time from CNS metastasis to death or last follow-up, and OSVPS was defined as the time from VPS surgery to death or last follow-up. Patients alive or lost to follow-up were censored. The Kaplan-Meier method was used to evaluate OS. Differences in survival were analyzed using the log-rank test, and a P-value less than .05 was considered statistically significant. A multivariable Cox proportional hazards regression model was used to assess the effect of each prognostic variable on OS. Data were analyzed using the statistical software IBM SPSS 23.0 software (SPSS Inc, Chicago, IL).
This study was approved by the Institutional Review Board of Samsung Medical Center, Seoul, Korea (IRB No.2019-01-121).
Results
Patient Characteristics
After review of the electronic patient database, we identified 70 patients with BC and confirmed LM who received a VPS. Patient characteristics based on subtype are shown in Table 1. The proportions of HR+/HER2−, HR+/HER2+, HR−/HER2+, and TNBC in the study were 30%, 16%, 16%, and 39%, respectively. The median age at diagnosis was 47 years (range, 27-66 years), and the median age at the time of CNS metastasis was 49 years (range, 28-68 years). Approximately two-thirds (44/70; 63%) of patients showed Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. Fifty-one (73%) patients had recurrent disease after treatment with curative aim, and the remaining 19 (27%) patients had stage IV BC at diagnosis. The most common site of metastasis was bone (23/70; 33%), and isolated CNS metastasis was present in 37% (26/70) of patients. More than one-half (41/70; 59%) of the patients underwent Ommaya reservoir insertion before VPS insertion for the purpose of intrathecal chemotherapy. Approximately one-third (22/70; 31%) of patients received more than 3 lines of systemic chemotherapy before diagnosis of CNS metastasis. Whole brain radiotherapy (WBRT) was administered to 67% of patients, and systemic chemotherapy after VPS was administered to 19% of patients.
Table 1Patient Characteristics
Characteristics
No. Patients (%)
All Patients (n = 70)
HR+/HER2− (n = 21)
HR+/HER2+ (n = 11)
HR−/HER2+ (n = 11)
TNBC (n = 27)
Median age, y (range)
At diagnosis, primary BC
47 (27-66)
45 (28-64)
39 (27-47)
53 (29-59)
48 (29-66)
At the time of LM
49 (30-69)
49 (31-66)
41 (31-63)
55 (31-64)
50 (30-69)
ECOG PS
0-1
26 (37)
12 (57)
3 (27)
7 (63)
4 (14)
≥2
44 (63)
9 (43)
8 (73)
4 (36)
23 (85)
Histology
IDC
63 (90)
17 (81)
10 (91)
11 (100)
25 (93)
ILC
4 (5)
3 (14)
1 (9)
0
0
Others
3 (4)
1 (5)
0
0
2 (7)
Initial TNM stage
1
1 (1)
0
0
0
1 (4)
2
19 (27)
3 (14)
1 (9)
5 (46)
10 (37)
3
31 (44)
10 (48)
8 (73)
2 (18)
11 (41)
4
19 (27)
8 (38)
2 (18)
4 (36)
5 (19)
Metastatic sites
Bone
23 (33)
11 (52)
4 (36)
2 (18)
6 (22)
Lung
14 (20)
6 (29)
4 (36)
0
4 (15)
Liver
6 (9)
5 (24)
1 (9)
0
0
Distant lymph node
12 (17)
4 (19)
1 (9)
3 (27)
4 (15)
Isolated CNS metastasis
26 (37)
4 (19)
3 (27)
5 (46)
14 (52)
Ommaya reservoir insertion before VPS
41 (59)
13 (62)
4 (36)
8 (73)
16 (59)
≥3 prior chemotherapy cycles before VPS
22 (31)
12 (55)
4 (18)
1 (5)
5 (23)
Progression of extracranial disease (N = 58)
27 (47)
8/20 (40)
5/8 (63)
3/7 (43)
11/23 (48)
Whole brain RT
Yes, before VPS
34 (49)
7 (33)
6 (55)
10 (91)
11 (41)
Yes, after VPS
13 (19)
6 (29)
3 (27)
0
4 (15)
No
23 (33)
8 (38)
2 (18)
1 (9)
12 (44)
Systemic chemotherapy after VPS
13 (19)
6 (29)
4 (36)
0
3 (11)
Abbreviations: BC = breast cancer; CNS = central nervous system; ECOG PS = Eastern Cooperative Oncology Group performance status; HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; IDC = invasive ductal carcinoma; ILC = invasive lobular carcinoma; LM = leptomeningeal metastasis; RT = radiotherapy; TNBC = triple negative breast cancer; VPS = ventriculoperitoneal shunt.
Indications for VPS and Characteristics of Patients Who Survived More Than 4 Months
Table 2 demonstrates the indications for VPS based on subtype and noted whether patients showed improvement after VPS placement. The most common indications for VPS placement were documented increased ICP (57.1%) and uncontrolled headache (55.7%). Obstructive hydrocephalus, which was a typical indication for VPS, was the fifth most frequent reason for VPS surgery (15.7%). However, 16 (54.5%) patients in the HR+/HER2+ group received VPS owing to obstructive hydrocephalus, and it was the most common cause in that group. In addition, 77.1% of patients who received a VPS experienced clinical improvement in symptoms as well as neurologic signs, in addition to decreased steroid use. VPS ameliorated symptoms related to increased ICP in all patients with HER2+ BC, though lesser improvement was shown in the TNBC group.
Table 3 shows 17 patients who survived more than 4 months after VPS, with a median age of 41 years (range, 31-67 years), of whom patients with HR+ BC accounted for 88% (15/17). Eight (47.0%) of 17 patients received palliative chemotherapy after VPS, and the most common regimen was capecitabine. Seven (41.2%) of 17 patients received WBRT. The median time to death after VPS placement for these 17 patients was 9.6 months (Table 3).
Table 3Summary of 15 Patients Who Survived More Than 4 Months After VPS
Gender/Age
Subtype
Indications for VPS
Chemotherapy After VPS
Radiotherapy After VPS
Time to Death From VPS, mos
Patient 1
F/62
HR+/HER2−
Headache, nausea/vomiting, dizziness
3 cycles of capecitabine
WBRT
9.2
Patient 2
F/49
HR+/HER2−
IICP, headache
11 cycles of capecitabine
WBRT
22.0
Patient 3
F/40
HR+/HER2−
Headache, nausea/vomiting
–
RT to spine
12.5
Patient 4
F/37
HR+/HER2−
IICP, headache
–
WBRT
11.2
Patient 5
F/59
HR+/HER2−
Altered mental status, paraplegia
–
WBRT
21.1
Patient 6
F/35
HR+/HER2−
IICP, headache
8 cycles of docetaxel, 1 cycle of gemcitabine/cisplatin
WBRT
11.4
Patient 7
F/32
HR+/HER2−
Right arm weakness, aphasia, hydrocephalus
–
–
5.3
Patient 8
F/54
HR+/HER2−
IICP, seizure
–
WBRT, RT to breast
5.8
Patient 9
F/36
HR+/HER2−
IICP, headache
–
–
5.8
Patient 10
F/67
HR+/HER2−
IICP, headache
10 cycles of capecitabine, letrozole
RT to bone, WBRT
11.4
Patient 11
F/41
HR+/HER2+
IICP, altered mental status, headache
–
–
13.5
Patient 12
F/40
HR+/HER2+
IICP, headache, dizziness
5 cycles of AC
RT to spinal cord
6.2
Patient 13
F/48
HR+/HER2+
IICP, headache, nausea/vomiting
8 cycles of gemcitabine/cisplatin, 3 cycles of capecitabine
–
16.6
Patient 14
F/40
HR+/HER2+
Hydrocephalus
Letrozole
–
9.6
Patient 15
F/50
HR+/HER2+
Dizziness, hydrocephalus
–
RT to spine & spinal cord
4.2
Patient 16
F/54
TNBC
IICP, paraplegia
–
–
9.0
Patient 17
F/31
TNBC
IICP, headache altered mental status,
3 cycles of paclitaxel/carboplatin
–
6.0
Abbreviations: AC = doxorubicin with cyclophosphamide; F = female; HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; IICP = increased intracranial pressure; RT = radiotherapy; TNBC = triple negative breast cancer; VPS = ventriculoperitoneal shunt; WBRT = whole-brain radiotherapy.
Chemotherapy for Patients With BC With CNS Metastasis
After CNS metastasis, 45 (64%) patients received palliative chemotherapy. Intrathecal chemotherapy via Ommaya reservoir was the most frequently administered treatment before VPS (29/70; 41%) (Table 4). The next most common regimens for BC with CNS metastasis were AC (cyclophosphamide with doxorubicin) and capecitabine monotherapy (see Supplemental Table 1 in the online version). In addition, 7 (32%) of 22 patients with HER2+ BC received anti-HER2 treatment after CNS metastasis, and 41 (59%) patients received VPS insertion without administration of intrathecal therapy, including 15 (15/41; 37%) patients with TNBC (see Supplemental Table 2 in the online version). Patients did not receive intrathecal anti-HER2 treatment because this is not approved in Korea. A summary of 13 patients who received systemic chemotherapy after VPS is shown in Supplementary Table 3 (in the online version). The most common regimen for BC with LM after VPS was capecitabine.
Table 4Frequency of Palliative Chemotherapy After LM or BM
All Patients (n = 70)
HR+/HER2− (n = 21)
HR+/HER2+ (n = 11)
HR−/HER2+ (n = 11)
TNBC (n = 27)
Endocrine therapy only
4
4
0
–
–
Endocrine therapy with targeted therapy
1
1
0
–
–
Cytotoxic chemotherapy only
23
12
2
5
4
HER2-targeted therapy only
1
–
1
0
–
Chemotherapy with HER2-targeted therapy
8
–
4
4
–
Intrathecal chemotherapy
29
9
1
7
12
Abbreviations: HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; TNBC = triple negative breast cancer.
During 36.5 months of median follow-up, the median OSCNS was 7.6 months (95% confidence interval [CI], 5.0-10.2 months) (Figure 1A), and the median OSVPS was 2.3 months (95% CI, 1.8-2.7 months) (Figure 1B) in all patients. The median OSCNS was 14.4 months (95% CI, 7.5-21.2 months) for the non-TNBC group and 5.2 months (95% CI, 3.0-7.4 months) for patients with TNBC (log-rank P < .001) (Figure 1A). The median OSVPS was 2.7 months (95% CI, 1.8-3.6 months) for the non-TNBC group and 2.3 months (95% CI, 1.7-2.9 months) for patients with TNBC (P = .022) (Figure 1B). The median OSCNS was 6.0 months (95% CI, 4.5-7.4 months) for HER2− groups and 15.3 months (95% CI, 12.8-17.8 months) for HER2+ groups (P = .006) (Figure 2A). The median OSVPS was 2.2 months (95% CI, 1.7-2.7 months) for HER2− groups and 2.7 months (95% CI, 1.8-3.6 months) for HER2+ groups (P = .917) (Figure 2B).
Figure 1Kaplan-Meier Curves of Overall Survival after Central Nervous System Metastasis (A) and OS after Ventriculoperitoneal Shunt Insertion (B) in Patients With TNBC and Non-TNBC
Figure 2Kaplan-Meier Curves of Overall Survival after Central Nervous System Metastasis (A) and OS after Ventriculoperitoneal Shunt Insertion (B) in HER2+ and HER2− Patients
The median time to disease progression from primary BC to death based on subtype was investigated in the study cohort (Figure 3). The time from primary BC to LM was significantly longer in patients with HR+ BC. Kaplan-Meier survival curves from primary cancer to death and from metastatic cancer to death based on subtype are shown in Supplemental Figure 1, Supplemental Figure 2, Supplemental Figure 3, Supplemental Figure 4 (in the online version).
Figure 3Median Time to Disease Progression according to Intrinsic Subtype
In univariate analysis using a Cox proportional hazards regression model, patients with TNBC with ECOG PS ≥ 2 had worse OSCNS and OSVPS. In multivariate analysis, progression of extracranial disease, TNBC subtype, isolated CNS metastasis, and anti-HER2 therapy in patients with HER2+ BC were identified as significant prognostic factors for OSCNS (Table 5).
We previously investigated the clinical features of breast cancer with LM based on subtype, and the median survival duration from LM to death was 4.5 months.
In the current study, OSCNS was 7.6 months in patients with MBC with LM who underwent VPS placement. This finding is an encouraging clinical outcome with respect to VPS placement for patients with LM. We show that median OSCNS was 16.2 months in patients with HR−/HER2+ BC and 5.2 months in patients with TNBC. In our previous report regarding patients with HER2+ BC, a median survival of 14.9 months was observed with anti-HER2 treatment
Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.
Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases.
Patients with TNBC have worse outcomes in both OSCNS and OSVPS, even though 44% of patients with TNBC received intrathecal chemotherapy (see Supplemental Table 1 in the online version). In sharp contrast to patients with TNBC, patients with HER2+ BC had significantly longer survival after CNS metastasis (16.2 vs. 5.2 months) (see Supplemental Figure 3 in the online version). Specifically, patients in the HR−/HER2+ group showed early BM and substantial survival from BM to LM. In several studies, improvement of brain metastasis in patients with HER2+ BC treated with trastuzumab was reported, although the drug does not cross the blood-brain barrier.
Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.
In the current study, patients with HER2+ BC were more likely to receive chemotherapy with anti-HER2 therapy than to receive anti-HER2 therapy alone. Active and intensive treatment should be provided to patients with HER2+ BC with CNS metastasis even if the aggressive nature of HER2+ BC results in a higher incidence of CNS metastasis.
Despite advances in survival after brain metastasis, the prognosis is grave for patients with BC with LM, with a median survival of less than 6 months.
In particular, patients in the TNBC group showed early LM, shorter survival, and notable isolated CNS metastasis in the current study. VPS treatment could prolong the survival of patients with BC with CNS metastasis; however, the OSVPS was less than 3 months in the current study. Notably, the 6-month OS rate was 0% and 3.9% in the HR−/HER2+ and TNBC groups, respectively (see Supplemental Figure 4 in the online version). No patients in the HR−/HER2+ group received palliative treatment (chemotherapy or WBRT) after VPS, and less than 15% of patients in the TNBC group were treated with chemotherapy or WBRT after VPS. The worse survival and less treatment after VPS in the HR− groups could have resulted from aggressive tumor behavior, patient selection, and timing of VPS placement, which remain unsolved problems regardless of subtype. Hence, further studies are necessary to determine whether VPS is appropriate only for patients with increased ICP, for patients with LM, or for certain subgroups such as TNBC.
Treatment effects of VPS insertion might be heterogeneous across intrinsic subtypes, because the patients received different palliative therapies before VPS insertion. However, the heterogeneity of treatments before VPS also is owing to the relatively rare presentation of LM. Research on LM with VPS is difficult owing to the limited availability of cases. In addition, selection bias could exist because only patients who could tolerate VPS surgery with general anesthesia were included in the current study. To the best of our knowledge, this is the first study to analyze the clinical outcomes of patients with BC who received a VPS. Our results show the real-world treatment patterns and outcomes of patients with BC who were diagnosed with LM and received a VPS.
Survival of patients with MBC who underwent VPS insertion differed based on intrinsic subtype; anti-HER2 treatment in HER2+ tumors was significantly correlated with better survival, and TNBC had significantly worse outcomes. Based on the study results, the use of VPS in patients with MBC with LM remains debatable; thus, further studies are warranted and should include a case-control study to compare patients with LM with and without VPS in MBC.
Clinical Practice Points
•
Although MBC is commonly associated with LM, little is known about the clinical utility and value of VPS in patients with MBC with LM.
•
Our study aimed to investigate the real-world treatment patterns and outcomes of patients with BC who were diagnosed with LM and received a VPS.
•
We found that most common indications for VPS were uncontrolled ICP (57.1%) and uncontrolled headache (55.7%), which were improved after VPS in 77.1% of the patients.
•
The median OS after BM or LM (OSCNS) was 7.6 months, and the median overall survival after VPS (OSVPS) was 2.3 months.
•
The prognosis of patients with MBC with VPS is worse in the TNBC subtype, and anti-HER2 treatment was identified as a significant prognostic factor for better OS after LM.
•
Our results might support the use of VPS in symptomatic patients with MBC with LM.
Disclosure
The authors have stated that they have no conflicts of interest.
Supplemental Data
Supplemental Figure 1Overall Survival Based on Subtype From Primary Cancer to Death
Supplemental Table 3Summary of 13 Patients Who Received Chemotherapy After VPS Insertion
Gender/Age
Subtype
Chemotherapy After VPS
Time to Death From VPS, mos
Survival Status
Patient 1
F/61
HR+/HER2−
Capecitabine
9.2
Death
Patient 2
F/49
HR+/HER2−
Capecitabine
22.0
Death
Patient 3
F/40
HR+/HER2−
Capecitabine
12.5
Death
Patient 4
F/35
HR+/HER2−
Docetaxel → GP
11.4
Alive
Patient 5
F/54
HR+/HER2−
Letrozole
5.8
Death
Patient 6
F/66
HR+/HER2−
Capecitabine
11.4
Alive
Patient 7
F/41
HR+/HER2+
Docetaxel with herceptin
13.5
Alive
Patient 8
F/41
HR+/HER2+
AC
6.2
Death
Patient 9
F/46
HR+/HER2+
GP → capecitabine
16.6
Death
Patient 10
F/38
HR+/HER2+
Letrozole
9.6
Death
Patient 11
F/35
TNBC
Pactliaxel → GP
3.5
Death
Patient 12
F/47
TNBC
Capecitabine
2.3
Death
Patient 13
F/31
TNBC
AC → paclitaxel/carboplatin
6.0
Death
Abbreviations: AC = doxorubicin with cyclophosphamide; BC = breast cancer; F = female; GP = gemcitabine with cisplatin; HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; TNBC = triple negative breast cancer; VPS = ventriculoperitoneal shunt.
Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.
Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases.
Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study.
Murphy C, Nulsen B, Rump M, et al. Phase II trial of patupilone in patients with breast cancer brain metastases progressing or recurring after whole brain radiotherapy. Presented as an abstract at the 2009 Breast Cancer Symposium: Abstract #234.
Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) phase II study.
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