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