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Fact Check of Brain Metastasis in Breast Cancer
Joohyuk Sohn, MD
Division of Medical Oncology
Yonsei Cancer Center, Seoul, Korea
Disclaimer
• I have nothing to disclose regarding this talk.
Outlines
• Literature review focusing on epidemiology of BC brain mets
• YCC MBC DB review
• Suggestion for better clinical outcome of BC brain mets
CNS metastasis
• Frequent complication of many solid tumor
• BC is the second most common cause of metastatic brain
disease followed by lung cancer
• CNS metastasis is associated with clinical decline as well as
increased cost of patient care
• Underrepresented due to exclusion from clinical trial and
drug development • Due to poor performance and presumed lack of drug efficacy
because of blood brain barrier
• literature review from 1979-2015
• 106 articles reviewed
• 60,794 breast cancer; 14,599 BC with brain mets (24%)
• Increase in frequency of brain mets from BC over time• 10% --16%--24%
• Due to advances in neuroimaging and longer patient survival
J Neurooncol 2016 Review
BC with brain mets
• 34 months; median interval from BC Dx to brain mets
• 15 months; median interval from BC with brain mets Dx to death
• 54.2%; multiple metastasis
• Cerebellum and frontal lobes; most common sites (33%, 16%)
• 37% ER+ regardless of PR status
• 35% HER2+
• 27% TNBC J Neurooncol 2016 Review
Frequency (%) of common signs and symptoms of brain mets due to BC
J Neurooncol 2016 Review
Factors correlating with short survival in BC with brain mets
J Neurooncol 2016 Review
Factors correlating with short survival in BC with brain mets
J Neurooncol 2016 Review
Late detection matters!
• SEER (Surveillance, Epidemiology and End Results) Data
• 2010-2013, N=238,726
• Breast Cancer c BM at initial diagnosis
• N=968
• 0.41% of the entire cohort; 7.56% of MBC to any site
• HR-HER2+ 1.1%; 11.5% TNBC 0.7%; 11.4%
• Median survival of BC with BM at initial diagnosis; 10 mo.
• ER+HER2+ 21 mo. TNBC 6mo.
JAMA Oncol 2017
BMFS; interval from Dx of MBC until the development of BM; median 19 months BM as first site of MBC was excluded from analysis of BMFS
BJC 2012
Brain metastasis and Trastuzumab
Adjuvant trastuzumab does not increase the risk of CNS relapse in HER2+ EBC
Lancet Oncol 2013
YCC MBC DB (2005~2018)YCC MBC DB
on manuscript preparation
Patients characteristics (N=1252)
sex
male 7 0.60%
female 1245 99.40%
Age at initial diagnosis 48 24-84
Age at stage IV diagnosis 52 25-84
Stage
de novo stage IV 351 28%
relapsed stage IV 901 72%
Breast cancer surgery
No 355 28.40%
Yes 895 71.50%
Unknown 2 0.20%
Neoadjuvant chemotherapy
No 705 56.30%
Yes 196 15.70%
Unknown 351 28%
Patients characteristics (N=1252)
Subtype
ER+HER2- 597 47.70%
ER+HER2+ 184 14.70%
ER-HER2+ 164 13.10%
ER-HER2- 220 17.60%
Unknown 87 6.90%
Brain metastases
No 872 69.60%
Yes 380 30.40%
Brain metastases Treatment
No 49 13.20%
WBRT 182 48.90%
GKS/Surgery 141 37.90%
Number of Brain metastases
Oligometastases 99 31.20%
Multiple metastases 218 68.80%
Incidence of brain mets at initial Dx in MBC DB
YCC MBC DB
HR+/HER2- HR+/HER2+ HR-/HER2+ HR-/HER2- Unknown
P
Initial CNS mets N=597 % N=184 % N=164 % N=220 % N=87 %
Brain 28 4.7 16 8.7 12 7.3 30 13.6 6.0 6.9 0.001
Lepto 6 1.0 0 0.0 1 0.6 7 3.2 2.0 2.3 0.035
CNS 31 5.2 16 8.7 12 7.3 32 14.5 6.0 6.9 <0.001
on manuscript preparation
Cumulative incidence of brain mets in MBC DB
YCC MBC DB
on manuscript preparation
HR+/HER2- HR+/HER2+ HR-/HER2+ HR-/HER2- Unknown
P
Anytime CNS mets N=597 % N=187 % N=164 % N=220 % N=87 %
Brain 111 18.6 76 41.3 63 38.4 83 37.7 22.0 25.3<0.00
1
Lepto 29 4.9 11 6.0 8 4.9 13 5.9 2.0 2.3 0.716
CNS 127 21.3 80 43.5 64 39.0 87 39.5 22.0 25.3<0.00
1
Overall survival of brain mets patients
YCC MBC DB
on manuscript preparation
ER+/HER2-ER+/HER2+ER-/HER2+ER-/HER2-
OS35.9m36.1m28.6m15.3m
ER+/HER2-ER+/HER2+ER-/HER2+ER-/HER2-
OS10.0m16.0m13.0m8.0m
P<0.0001P=0.006
Brain metastases free interval in YCC MBC DB
YCC MBC DB
ER+/HER2-ER+/HER2+ER-/HER2+ER-/HER2-
17.0m15.0m13.0m6.0m
P<0.0001
on manuscript preparation
OS between oligo- and multiple brain metastasis
YCC MBC DB
on manuscript preparation
P<0.0001
Overall survival = 12 mo.(10.2-13.7)-Oligo, 19 mo. (95% CI,14.5-23.3)-Multiple, 9 mo. (95% CI, 6.9-11.0)
OS data (oligo vs multiple) based on subtypes
Oligometastasis(n=99)
multiple metastasis(n=218)
MultipleOligo
MultipleOligo
MultipleOligo
mOS12.0m20.0m
mOS10.0m24.0m
mOS5.0m14.0m
ER+HER2- HER2+ ER-HER2-
on manuscript preparation
P=0.100 P=0.003 P=0.002
N=97 N=129 N=76
YCC MBC DB
Brain metastasis work-up in lung cancer
Can we improve clinical outcome in BC brain mets?
Can we improve clinical outcome in BC brain mets?
1st line chemotherapy
2nd line chemotherapy
3rd line chemotherapy
Brain MRI before 1st line
CTxBrain MRI before 2nd line
CTx
Brain MRI before 3rd line
CTx
Brain metastasis
Brain metastasis
Brain Monitoring for High Risk of Brain Metastases in Metastatic Breast Cancer (NCT03617341)
-TNBC, HER2 positive MBC 200 patients
-Primary endpoint; incidence of brain mets in high risk MBC patients
-Secondary endpoints; incidence of oligomets, intracranial PFS, OS, cognitive impairment assessment
-Study period: 3 year enrollment, 2 year follow up
Prospective cohorts study
Summary
• Increase in frequency of brain mets from BC over time;10-24%
• More brain metastasis in HER2+ and TNBC • (1/3 ER+, 1/3 HER2+, 1/3 TNBC)
• Most common symptoms are nausea and headache
• Adjuvant trastuzumab does not increase the risk of CNS relapse
• Late detection of brain metastasis affects prognosis
• Brain metastasis free survival differs between subtypes
• Unmet need for improved clinical outcome
Acknowledgement
MO Breast Cancer Team Brain mets Collaborators
Kim, Gun Min, MDKim, Jee Hung, MDKim, Min Hwan, MD
YCC BC collaborators
Paik, Soonmyung, MDPark, Byung Woo, MDCho, Youngup, MDKim, Seung Il, MDPark, Hyung Seok, MDKim, Ji Ye, MDKoo, Jaseung, MD
Jang, Jonghee, MD; NeurosurgeryLee, Seunggu, MD; Neuro-imaging
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