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Table 2 Clinical and pathological factors and treatment characteristics after CNS metastasis diagnosis according to BRCA mutation status- carriers (BRCA 1/2 Mt) vs non-carriers (BRCA non-Mt)

From: Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis

Characteristics

BRCA non-Mt (n = 50)

BRCA 1/2 Mt (n = 25)

Total

(n = 75)

P-value

Age at diagnosis of CNS metastasis (yr)

 Median

55.3

44.33

53.05

0.003

 Mean ± SD

55.02 ± 10.37

46.49 ± 13.05

52.17

 Range

26.71–73.93

30.04–78.26

26.7–78.26

ECOG PS at CNS spreada

 ECOS PS 0

1 (2%)

5 (20%)

6 (8%)

0.033

 ECOG PS 1

10 (20%)

2 (8%)

12 (16%)

 ECOG PS 2

21 (42%)

6 (24%)

27 (36%)

 ECOG PS 3

14 (28%)

10 (40%)

24 (32%)

 ECOG PS 4

4 (8%)

2 (8%)

6 (8%)

Resection of brain metastases

 Done

11 (22%)

8 (32%)

19 (25.3%)

0.348

 Not done

39 (78%)

17 (68%)

56 (74.7%)

Brain radiotherapyb

 WBRT

11 (22%)

7 (28%)

18 (24%)

 

 Partial brain

1 (2%)

0

1 (1.3%)

 

 SRS

19 (38%)

12 (48%)

31 (41.3%)

 

 SRS + WBRT

11 (22%)

2 (8%)

13 (17.3%)

 

 None

8 (16%)

4 (16%)

12 (16%)

 

Location of brain metastasesc

 Frontal

33 (66%)

15 (60%)

48 (64%)

0.610

 Temporal

13 (26%)

13 (52%)

26 (34.7%)

0.026

 Parietal

21 (42%)

10 (40%)

31 (41.3%)

0.868

 Occipital

11 (22%)

9 (36%)

20 (26.7%)

0.196

 Cerebellar

32 (64%)

13 (52%)

45 (60%)

0.317

 Midbrain

5 (10%)

5 (20%)

10 (13.3%)

0.230

 Pons

3 (6%)

3 (12%)

6 (8%)

0.367

 Medulla

2 (4%)

1 (4%)

3 (4%)

1

Area of brain metastases

 Supratentorial only

16 (32%)

10 (40%)

26 (34.7%)

0.890

 Infratentorial only

6 (12%)

2 (8%)

8 (10.7%)

 Tumor deposits in both areas

20 (40%)

9 (36%)

29 (38.7%)

 Diffuse spreadd

8 (16%)

4 (16%)

12 (16%)

No. of brain metastases at CNS presentation

 Single deposit

9 (18%)

7 (28%)

16 (21.3%)

0.093

 2–3 deposits

10 (20%)

2 (8%)

12 (16%)

 4–5 deposits

10 (20%)

1 (4%)

11 (14.7%)

 6 or more deposits

4 (8%)

7 (28%)

11 (14.7%)

 Diffuse spreadd

17 (34%)

8 (32%)

25 (33.3%)

Leptomeningeal spread

 Yes

10 (20%)

10 (40%)

20 (26.7%)

0.020

 No

40 (80%)

15 (60%)

55 (73.3%)

Chemotherapy- CNS disease

 Anti-microtubulee

12 (24%)

5 (20%)

17 (22.7%)

0.072

 Platinum based

9 (18%)

6 (24%)

15 (20%)

 Anthracycline based

7 (14%)

4 (16%)

11 (14.7%)

 Capecitabine

11 (22%)

4 (16%)

15 (20%)

None

11 (22%)

6 (24%)

17 (22.7%)

Hormonal therapy- CNS disease

 Tamoxifen

3 (6%)

1 (4%)

4 (5.3%)

0.078

 AIf

5 (10%)

0

5 (6.7%)

 Fulvestrant

4 (8%)

0

4 (5.3%)

 Anti-CDK4/6 g +/−

6 (12%)

0

6 (8%)

 AI/ Fulvestrant

   

 None

32 (64%)

24 (96%)

56 (74.7%)

anti-HER2- CNS disease

 Trastuzumab

1 (2%)

1 (4%)

2 (2.7%)

0.246

 Trastuzumab+Pertuzumab

0

1 (4%)

1 (1.3%)

 TDM1

6 (12%)

3 (12%)

9 (12%)

TKI basedh

8 (16%)

7 (28%)

15 (20%)

 None

35 (70%)

13 (52%)

48 (64%)

Immunotherapy post-CNS metastasis

 Yes

1 (2%)

3 (12%)

4 (5.3%)

0.069

 No

49 (98%)

22 (88%)

71 (94.7%)

No. treatment lines post- CNS metastasis

 No systemic treatment

4 (8%)

3 (12%)

7 (9.3%)

0.543

 1 line

21 (42%)

15 (60%)

36 (48%)

 2 lines

11 (22%)

4 (16%)

15 (20%)

 3 lines

6 (12%)

1 (4%)

7 (9.3%)

 4 lines or more

8 (16%)

2 (8%)

10 (13.3%)

  1. Values are n(%) unless otherwise indicated
  2. ECOG Eastern Cooperative Oncology Group: PS performance status: CNS central nervous system: WBRT whole-brain radiation therapy: SRS stereotactic radiosurgery: AI aromatase inhibitor: CDK cyclin-dependent kinase: HER2 human epidermal growth factor receptor: TDM1 Ado-trastuzumab emtansine: TKI tyrosine-kinase inhibitor
  3. aECOG Performance Status, as published in: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P. Toxicity and response criteria of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655, 1982
  4. bTo test the variable, None/Not done was removed, thus, only the applicable categories were compared
  5. cLocation of brain metastases- according to CT/MRI at diagnosis of CNS spread. A patient can have more than one site of CNS involvement and therefore can be included in more than one category
  6. dDiffuse spread, individual brain deposits cannot be defined
  7. eAnti-microtubule based therapy- including: Taxane (Paclitaxel, Docetaxel), Vinorelbine, Eribulin
  8. fAromatase inhibitor- including: non-steroidal (Letrozole, Anastrozole), steroidal (Exemestane)
  9. gAnti-CDK4/6 based therapy- including: Palbociclib (non-BRCA Mt: n = 4), Ribociclib (n = 0), Abemaciclib (non-BRCA Mt: n = 2)
  10. hTKI based therapy- including: Lapatinib (non-BRCA Mt: n = 6, BRCA Mt: n = 5), Neratinib (non-BRCA Mt: n = 2), Tucatinib (BRCA Mt: n = 2)
  11. iImmunotherapy post-CNS metastasis- including: Pembrolizumab (non-BRCA Mt: n = 1, BRCA Mt: n = 3), Atezolizumab (n = 0)
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