Supplementary Appendix E: Summary of Case Reports (71)

Study and Year of Publication

Breast Cancer Subtype (HR+/ HER2+/TNBC)

Age at diagnosis of LC-BC

Concomitant systemic disease? (Y/N)

Concomitant parenchymal brain metastases? (Y/N)

Time between initial BC diagnosis and LC-BC diagnosis

Pre-diagnosis treatments received for metastatic disease (not including adjuvant/neoadjuvant therapy)

Reported treatment of LC-BC

Overall Survival following LC-BC diagnosis

Toxicity of LC-BC treatments

IT Therapy

Systemic Therapy

RT

Chen 20151

TNBC

36

Y

Y

1 year

Docetaxel / Epirubicin / Cyclophosphamide, Capecitabine, Vinorelbine / Cisplatin, Uracil-tegafur, WBRT

Methotrexate

Bevacizumab / Cisplatin / Etoposide (BEEP)

Nil

8 months

NR

TNBC

54

N

Y

< 1 year

WBRT, SRS

Methotrexate

Bevacizumab / Cisplatin / Etoposide (BEEP)

Nil

7.5 months

NR

Kakani 20152

HR+

64

N

N

42 months

Nil

Methotrexate

Anastrozole, Systemic high dose methotrexate, Capecitabine

WBRT, lumbar spinal RT

12+ months

Myelosuppression

Le Rhun 20153

HER2+

34

Y

N

5 years

Docetaxel / Trastuzumab

Trastuzumab, Liposomal cytarabine

Trastuzumab / Capecitabine, Lapatinib, Bevacizumab / Vinorelbine

Lumbosacral and cerebellar RT

NR

NR

Park 20154

TNBC

42

N

Y

< 1 year

SRS

Methotrexate, Etoposide, Cytarabine

Nil

WBRT

NR

NR

Park 20155

HR+/HER2+

55

Y

Y

8 years

WBRT, Goserelin / Anastrozole, Tamoxifen, Surgical resection of brain metastases, Docetaxel / Doxorubicin, Trastuzumab, Capecitabine / Lapatinib, Gemcitabine / Cisplatin, Cyclophosphamide / Methotrexate / 5-fluorouracil, SRS

Methotrexate / Trastuzumab

Nil

Nil

20+ months

NR

HER2+

45

N

Y

42 months

Surgical resection of brain metastases, Capecitabine

Trastuzumab

Trastuzumab / Paclitaxel

WBRT

29+ months

NR

Karakolevska-Ilova 20146

HR+

35

N

Y

3 years

Nil

Nil

Nil

Nil

NR

NR

Salgia 20147

HR+

56

Y

N

5 years

NR

Liposomal cytarabine, Topotecan

Eribulin

WBRT

32+ weeks

NR

Torres 20148

HER2+

55

Y

Y

7 years

Nab-paclitaxel / trastuzumab

Nil

Capecitabine / lapatinib, trastuzumab / lapatinib, T-DM1

WBRT

32+ months

NR

Dumitrescu 20139

HER2+

65

Y

Y

8 years

Systemic chemotherapy (unspecified), Focal and whole brain RT, Trastuzumab / vinorelbine

Trastuzumab

Trastuzumab / Lapatinib,

Nil

8 weeks

GI toxicity – unspecified (Lapatinib)

Loghin 2013*10

HER2+

52

N

Y

6 years

Lapitinib

Trastuzumab, Topotecan

Trastuzumab

Nil.

18+ months

NR

Martens 201311

HER2+

36

Y

Y

4.5 years

Systemic chemotherapy (unspecified) / trastuzumab, brain tumour resection, SRS, WBRT

Trastuzumab / Methotrexate

Nil

Nil

6 months

NR

Singh 201312

HR+

57

Y

N

0 months

Nil

Nil

Nil

Nil

30+ months

NR

Tanaka 201313

HR+

63

Y

N

2 years

Tamoxifen / Zoledronic acid,

Nil

Capecitabine

Nil

Not stated.

Grade 1 hand-foot syndrome. (Capecitabine)

Vincent 201314

HER2+

49

Y

Y

4 years

Paclitaxel / Carboplatin / Trastuzumab, SRS, Surgical resection of brain metastases, Intensity modulated radiation therapy, Lapatinib

Nil

Capecitabine / Bevacizumab

Nil

29 months

Anemia

Brandt 201215

HER2+

48

N

Y

5 years

WBRT / Temozolomide / Trastuzumab, Lapatinib

Methotrexate, Thiotepa, Trastuzumab

Capecitabine / Lapatinib, Trastuzumab

SRS

44+ months

NR

Hofer 201216

HER2+

75

Y

Y

NR

SRS, Capecitabine / Lapatinib

Trastuzumab

Trastuzumab

WBRT

9+ months

NR

Machado 2012*17

HER2+

41

NR

NR

NR

NR

Trastuzumab

NR

NR

1.6 months

NR

HR+/HER2+

44

NR

NR

NR

NR

Trastuzumab

NR

NR

23.7 months

NR

HR+/HER2+

31

NR

NR

NR

NR

Trastuzumab

NR

NR

2.4 months

NR

Orgel 2012*18

HR+

55

Y

N

0 months

Nil

Liposomal cytarabine

Capecitabine, Letrozole

Nil

15+ months

NR

Santa-Maria 201219

HER2+

56

Y

Y

16 months

Surgical resection, SRS, Paclitaxel / Lapatinib

Nil

High dose systemic methotrexate, Trastuzumab

Nil

18+ months

Paclitaxel toxicity (unspecified)

Stebel 201220

TNBC

56

Y

N

7 months

Nil

Nil

Nab-paclitaxel / carboplatin

WBRT

4 months

Neutropenia, anemia

Wilson 201221

HR+

55

Y

N

3 years

Exemestane / Zoledronate, Spinal RT

Methotrexate

Docetaxel

Nil

9 months

NR

Yaghmour 2012*22

HR+/HER2+

43

Y

N

NR

Systemic chemotherapy (unspecified)

Trastuzumab

Nil

Nil

NR

Nausea / vomiting, Obtundation, Urinary incontinence, Dizziness

Butto 201123

HR+

56

NR

NR

NR

NR

Liposomal Cytarabine

Nil

Nil

NR

Fulminant chemical ventriculomeningitis, death

Mego 201124

HER2+

43

Y

Y

52 months

WBRT, Trastuzumab, systemic chemotherapy (unspecified)

Cytarabine, Methotrexate, Trastuzumab

Trastuzumab

WBRT

13.5 months

NR

HER2+

39

Y

Y

Not stated

Lapatinib / Capecitabine

Cytarabine, Methotrexate, Trastuzumab

Unspecified

WBRT

7.5 months

NR

Oliveira 201125

HER2+

44

Y

Y

58 months

Docetaxel, Trastuzumab, Letrozole, WBRT

Methotrexate, Cytarabine, Trastuzumab

Exemestane / Trastuzumab, Capecitabine, Cisplatin / Etoposide

WBRT

27 months

NR

Onishi 201126

TNBC

45

Y

Y

50 months

Cyclophosphamide, Epirubicin, Paclitaxel, Capecitabine, Vinorelbine

Nil

Lapatinib

Nil

12+ months

NR

Peroukides 201127

HR+

60

N

N

5 years

Tamoxifen

Methotrexate

Letrozole

Nil

36+ months

NR

Taylor 2011*28

HR+

59

N

N

12 years

Tamoxifen

Cytarabine

Nil

Nil

NR

NR

Ackermann 201029

NR

54

NR

NR

NR

NR

Methotrexate

NR

WBRT

NR

Neutropenia, Myelopathy (Methotrexate)

Hrabalek 201030

HR+

41

N

N

7.5 years

Nil

Nil

Nil

RT

4 months

NR

Walker 2010*31

NR

NR

NR

NR

NR

NR

Topotecan

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

Topotecan

NR

NR

NR

NR

Bidard 200932

HER2+

68

NR

NR

NR

NR

Methotrexate

Trastuzumab, Docetaxel

NR

2+ months

NR

HER2+

43

NR

NR

NR

NR

Methotrexate

Fucontin

NR

5 months

NR

HR+/HER2+

37

NR

NR

NR

NR

Methotrexate

Capecitabine, Lapatinib

NR

8+ months

NR

HR+/HER2+

38

NR

NR

NR

NR

Methotrexate

Paclitaxel, Trastuzumab

NR

17 months

NR

HER2+

57

NR

NR

NR

NR

Methotrexate

Vinorelbine, Trastuzumab

NR

17 months

NR

HR+/HER2+

44

NR

NR

NR

NR

Methotrexate

Capecitabine, Lapatinib

NR

18+ months

NR

Ferrario 200933

HER2+

31

Y

Y

72 months

Carboplatin, Paclitaxel, Trastuzumab

Capecitabine, Surgical resection, WBRT

Trastuzumab, Methotrexate, Thiotepa

Pegylated liposomal doxorubicin, Vinorelbine, Paclitaxel

RT lumbar, spine

24+ months

Cough, fatigue, stomatitis, thrombocytopenia, neutropenia, anemia, lethargy, skin rash, herpes zoster

Gaviani 200934

HR+

51

Y

N

15 years

Tamoxifen

Methotrexate, Liposomal cytarabine

Nil

Nil

43+ months

NR

Hoffman 200935

HER2+

43

Y

N

70 months

Tamoxifen, Goserelin, Paclitaxel / Trastuzumab, RT

Liposomal cytarabine

Temozolomide

WBRT

10 months

NR

HER2+

42

Y

N

12 years

Paclitaxel / Trastuzumab, Goserelin, RT, Vinorelbine

Liposomal cytarabine

Temozolomide, Capecitabine, lapatanib

Nil

16.8 months

Severe diarrhea

Shigekawa 200936

HER2+

52

Y

N

8 years

Trastuzumab

Nil

Trastuzumab/vinorelbine/capcetiabine

WBRT

10+ months

NR

Glas 200837

TNBC

55

N

Y

NR

Nil

Liposomal cytarabine

Nil

WBRT

12+ months

NR

Mir 200838

HR+/HER2+

56

Y

Y

1 year

Docetaxel / Epirubicin, Paclitaxel / Trastuzumab, WBRT

Tratuzumab

Nil

Nil

7 months

NR

Stemmler 200839

HER2+

52

Y

Y

4 years

Trastuzumab / Capecitabine, WBRT, Vinorelbine, Paclitaxel, Lapatinib / Capecitabine

Trastuzumab, Methotrexate

Lapatinib / Capecitabine, Gemcitabine / Cisplatin Trastuzumab

Nil

24 months

NR

Carmona-Bayonas 200740

TNBC

38

N

N

NR

Nil

Methotrexate, Cytarabine

Capecitabine, High dose systemic methotrexate, Weekly paclitaxel

WBRT

12 months

NR

Hikino 200641

HER2+

55

N

Y

17 months

Nil

Nil

Capecitabine

WBRT

12+ months

Grade 2 neutropenia

Platini 200642

HR+

41

Y

N

5 years

Paclitaxel / Trastuzumab

Trastuzumab, Thiotepa

Systemic high dose methotrexate, Paclitaxel / trastuzumab, Liposomal doxorubicin, Letrozole

Nil

17+ months

Grade 4 mucositis and myelosuppression, Leucoencephalopathy

Stemmler 200643

HER2+

39

N

Y

8 months

Surgical resection of brain metastasis, WBRT

Methotrexate, Trastuzumab

Trastuzumab, Capecitabine, Temozolomide

Nil

NR

NR

Tham 200644

TNBC

53

N

Y

2 years

Nil

Nil

Capecitabine

WBRT

44+ months

NR

Navarro Martin 200545

HER2+

46

Y

N

13 years

Paclitaxel / Trastuzumab, Anastrozole, Docetaxel / Epirubicin

Methotrexate

Etoposide, Exemestane

Nil

12 months

Etoposide toxicity (unspecified)

Rogers 200446

HR+

42

Y

N

11 years

Doxorubicin, Paclitaxel, Autologous bone marrow transplant, Vinorelbine, Gemcitabine, Capecitabine

Nil

Capecitabine

Nil

12+ months

NR

Ozdogan 200347

HR+

44

Y

N

3 years

Tamoxifen

Methotrexate, Cytarabine

Cisplatin and etoposide, Letrozole

WBRT

23 months

Grade 4 neutropenia

Robins 200248

NR

51

NR

Y

NR

NR

Nil

Docetaxel / trastuzumab

WBRT

NR

NR

NR

50

NR

Y

NR

NR

None

Trastuzumab / paclitaxel

WBRT

8+ months

NR

Baculi 200149

HER2+

38

N

Y

2 years

Surgical resection of brain metastasis

Cytarabine, experimental agent (unspecified)

Trastuzumab, high dose systemic chemotherapy (unspecified)

WBRT, Lumbosacral RT

NR

NR

Lauby 200150

TNBC

40

N

N

1 year

Nil

Methotrexate

Nil

Nil

NR

NR

Laufman 200151

HER2+

48

Y

Y

9 months

WBRT, Trastuzumab / Paclitaxel

Methotrexate, Trastuzumab, Thiotepa

Trastuzumab / Vinorelbine, Paclitaxel

Thoracic spine RT

NR

NR

Boogerd 200052

HR+

33

N

Y

12 months

Tamoxifen / Goserelin

Nil

Goserelin / Tamoxifen, Megestrol, Epirubicin / Cyclophosphamide

Cervical / thoracic spine RT

19 months

NR

HR+

52

N

N

9 years

No treatment

N

Tamoxifen, Anastrozole, Megestrol

Spinal RT

14+ months

NR

Del Colle 200053

NR

59

Y

N

7 years

Lumbar spine RT

Methotrexate

Nil

Nil

12+ months

NR

Hara 200054

NR

48

Y

N

9 years

Cyclophosphamide / Methotrexate / 5-fluorouracil

Methotrexate

Nil

Nil

9 months

NR

Kastenbauer 200055

NR

33

N

Y

2 years

WBRT

Methotrexate

Nil

Nil

NR

Cerebral vasculopathy (IT Methotrexate)

Kosmas 200056

NR

46

Y

N

6 years

Docetaxel, Mitoxantrone, Megestrol

Methotrexate

Nil

WBRT

11+ months

NR

Allanore 199957

NR

74

Y

N

13 years

Lung radiation, systemic chemotherapy (unspecified), Tamoxifen

Methotrexate

Nil

Nil

9 months

NR

Herrington 199858

NR

41

N

N

3 years

Nil

Methotrexate, Thiotepa

Docetaxel

Cervical and thoracic spine RT

33 months

NR

Lokich 199859

NR

82

Y

N

6 years

NR

Nil

Nil

Nil

NR

NR

Petit 199760

NR

42

N

Y

7 months

WBRT

Methotrexate / Calcium folinate

Nil

Nil

6 weeks

NR

NR

45

Y

N

5 years

Mitoxantrone / Navelbine / Medroxyprogesterone, Cisplatin / 5-fluorouracil

Methotrexate

Nil

Nil

3 months

NR

Moots 199561

NR

53

Y

N

7 years

Bilateral oopherectomy

Methotrexate

Tamoxifen, Megestrol, Aminoglutethimide

WBRT

8 years

Leukoencephalopathy

Gasecki 199262

NR

62

N

Y

NR

Nil

Methotrexate, Cytarabine

Nil

CSI

6 weeks

Obtundation, chemical meningitis

NR

44

N

N

3 years

Bilateral oopherectomy

Nil

Vincristine

Nil

6 months

NR

Boogerd 199063

NR

35

N

N

< 1 year

Nil

Methotrexate, cytarabine

Nil

Nil

6 weeks

NR

Shibutani 198964

NR

33

NR

NR

NR

Nil

Methotrexate

Nil

WBRT

NR

NR

Harrison 198865

HR-

51

N

N

8 years

Nil

Methotrexate

Nil

WBRT

6 months

NR

HR+

69

N

N

2 years

Nil

Methotrexate

Nil

Nil

2 months

NR

HR-

36

N

N

2 years

Nil

Methotrexate / Thiotepa, Cytarabine

Nil

CSI

10 months

NR

HR-

54

N

N

NR

Nil

Methotrexate

Nil

WBRT

7 months

NR

HR-

28

Y

N

NR

Cyclophosphamide / Methotrexate / 5-fluorouracil, Doxorubicin / Mitomycin-C / Vincristine

Methotrexate

Nil

WBRT

1 year

NR

Heimann 198666

NR

70

Y

N

0 months

Nil

Methotrexate

Tamoxifen

RT (unspecified)

9 months

NR

Marcus 198167

ER+

71

Y

N

8 years

Diethylstilbestrol, Fluoxymesterone, Tamoxifen, Left pelvic RT, 5-fluorouracil / Vincristine / Doxorubicin / Mitomycin-C, Lumbar spine RT

Methotrexate

Tamoxifen

WBRT

12 months

NR

Sondak 198168

ER+

56

Y

Y

7 months

Diethylstilbestrol, WBRT, Cyclophosphamide / Methotrexate / 5-fluorouracil

Methotrexate

NR

CSI

5 months

Myelosuppression

Cantillo 197969

NR

63

Y

N

4 years

Doxorubicin / 5-fluorouracil

Cytarabine

5-fluorouracil / Vincristine / Methotrexate / Cyclophosphamide

WBRT

10 months

NR

HR+

49

Y

N

5 years

Bilateral oophorectomy, Doxorubicin, Vincristine / 5-fluorouracil, Methotrexate, Cyclophosphamide

Cytarabine

Nil

WBRT

3 months

NR

Bramlet 197670

NR

37

N

N

5 years

Oopherectomy

Methotrexate

Cyclophosphamide, 1-(2-chlorethyl-)-3-cyclohexyl-1-nistrosurea (CCNU)

Total head cobalt therapy

29 months

Severe nausea and vomiting (cyclophosphamide), Myelosuppresion / emesis / stomatitis (CCNU)

Dommasch 197671

NR

51

N

N

3 months

Nil

Methotrexate

Drostanolonum, Methotrexate / Cyclophosphamide

Nil

19+ months

Myelosuppression

* = Denotes study published in abstract form only.CSI = Craniospinal irradiationGI = GastrointestinalHR = Hormone receptorN/A = Not applicableNR = Not reportedRT = RadiotherapySRS = Stereotactic radiosurgeryTNBC = Triple negative breast cancerWBRT = Whole brain radiotherapy

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