Clinical and pathological characteristics as well as prognostic analysis of breast cancer patients with brain metastases

doi:10.3969/j.issn.1674-8115.2022.11.007

Abstract

Abstract:

Objective ·To explore clinical and pathological characteristics, prognosis and potential related factors of breast cancer patients with brain metastases. Methods ·Seventy-five female breast cancer patients with brain metastases admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2007 to December 2021 were selected. The clinical and pathological characteristics of the patients were collected through clinical electronic cases, and the overall survival after brain metastases (OSBM) of the patients was collected during the follow-up period. Receiver operating characteristic curve (ROC curve) was used to evaluate the predictive efficiency of different biochemical factors on OSBM. Kaplan-Meier survival curve was used to analyze the correlation between different clinical and pathological characteristics and patients' OSBM. Cox proportional hazards regression analysis was further performed on statistically significant factors to determine independent influencing factors. Results ·The OSBM of 75 patients was 11.0 (5.0, 24.0) months. The results of ROC curve showed that carbohydrate antigen 125 (CA125) had a good prediction effect on OSBM, and its best cut-off value was 22.3 U/mL. The results of Kaplan-Meier survival analysis showed that the patients whose first metastatic site was brain (P=0.046), whose extracranial disease status was progressed (P=0.042), whose brain metastasis involved one side of tentorium (P=0.013), whose CA125 level<22.3 U/mL (P=0.000), whose treatment methods incladed regional therapy (P=0.034) and whose modified Graded Prognostic Assessment (mGPA) score>1 (P=0.001), had longer OSBM. Cox proportional hazards regression analysis showed that brain metastasis involving both sides of tentorium or meningeal (P=0.029), and CA125 level≥22.3 U/mL (P=0.005) were the risk factors for OSBM, and mGPA score>1 (P=0.033) was the protective factor. Conclusion ·The position of brain metastases in breast cancer, the level of CA125 and the mGPA score are important factors affecting the prognosis of patients.

Key words: breast cancer brain metastases (BCBM), pathological features, prognostic score, survival analysis

CLC Number:

R737.9

SU Juncheng, WANG Yuzheng, TANG Lei, XU Yingchun, ZHANG Fengchun. Clinical and pathological characteristics as well as prognostic analysis of breast cancer patients with brain metastases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(11): 1562-1568.

Figures/Tables 5

TrendMD

References 17

1	SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33.
2	国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. 中国晚期乳腺癌规范诊疗指南(2020版)[J]. 中华肿瘤杂志, 2020, 42(10): 781-797.
	Breast Cancer Expert Committee of National Cancer Quality Control Center, Breast Cancer Expert Committee of China Anti-Cancer Association, Cancer Drug Clinical Research Committee of China Anti-Cancer Association. Guidelines for clinical diagnosis and treatment of advanced breast cancer in China (2020 Edition)[J]. Chinese Journal of Oncology, 2020, 42(10): 781-797.
3	MILLS M N, FIGURA N B, ARRINGTON J A, et al. Management of brain metastases in breast cancer: a review of current practices and emerging treatments[J]. Breast Cancer Res Treat, 2020, 180(2): 279-300.
4	GASPAR L, SCOTT C, ROTMAN M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials[J]. Int J Radiat Oncol Biol Phys, 1997, 37(4): 745-751.
5	WELTMAN E, SALVAJOLI J V, BRANDT R A, et al. Radiosurgery for brain metastases: a score index for predicting prognosis[J]. Int J Radiat Oncol Biol Phys, 2000, 46(5): 1155-1161.
6	LORENZONI J, DEVRIENDT D, MASSAGER N, et al. Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems[J]. Int J Radiat Oncol Biol Phys, 2004, 60(1): 218-224.
7	SPERDUTO C M, WATANABE Y, MULLAN J, et al. A validation study of a new prognostic index for patients with brain metastases: the Graded Prognostic Assessment[J]. J Neurosurg, 2008, 109 Suppl: 87-89.
8	SPERDUTO P W, KASED N, ROBERGE D, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases[J]. J Clin Oncol, 2012, 30(4): 419-425.
9	SPERDUTO P W, MESKO S, LI J, et al. Beyond an updated graded prognostic assessment (Breast GPA): a prognostic index and trends in treatment and survival in breast cancer brain metastases from 1985 to today[J]. Int J Radiat Oncol Biol Phys, 2020, 107(2): 334-343.
10	HOSONAGA M, SAYA H, ARIMA Y. Molecular and cellular mechanisms underlying brain metastasis of breast cancer[J]. Cancer Metastasis Rev, 2020, 39(3): 711-720.
11	ZAGAR T M, VAN SWEARINGEN A E, KAIDAR-PERSON O, et al. Multidisciplinary management of breast cancer brain metastases[J]. Oncology (Williston Park), 2016, 30(10): 923-933.
12	ASSI H I, MAHMOUD T, SAADEH F S, et al. Management of leptomeningeal metastasis in breast cancer[J]. Clin Neurol Neurosurg, 2018, 172: 151-159.
13	ETHIER J L, DESAUTELS D, TEMPLETON A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis[J]. Breast Cancer Res, 2017, 19(1): 2.
14	LI J X, LIU L Y, FENG Z W, et al. Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study[J]. Breast Cancer, 2020, 27(4): 621-630.
15	ZENG Y C, WU R, WANG S L, et al. Serum CA125 level predicts prognosis in patients with multiple brain metastases from non-small cell lung cancer before and after treatment of whole-brain radiotherapy[J]. Med Oncol, 2014, 31(7): 48.
16	WANG H, SHEN L H, GENG J H, et al. Prognostic value of cancer antigen-125 for lung adenocarcinoma patients with brain metastasis: a random survival forest prognostic model[J]. Sci Rep, 2018, 8: 5670.
17	张佳玲, 张凤春, 徐迎春. 乳腺癌脑转移系统治疗的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(5): 671-677.
	ZHANG J L, ZHANG F C, XU Y C. Research progress in the systemic treatment for breast cancer with brain metastasis[J]. J Shanghai Jiao Tong Univ (Med Sci), 2021, 41(5): 671-677.

Characteristic	Patient （n=75） /n（%）	Characteristic	Patient （n=75） /n（%）	Characteristic	Patient （n=75） /n（%）
TNM stage		Infratentorial	6 （8.0）	Stable	30 （40.0）
Ⅰ	9 （12.0）	Both	20 （26.7）	Progressed	18 （24.0）
Ⅱ	16 （21.3）	Unspecified	19 （25.3）	Unknown	27 （36.0）
Ⅲ	23 （30.7）	First metastatic site		Treatment for BM
Ⅳ	10 （13.3）	Extracranial	52 （69.3）	Regional therapy
Unspecified	17 （22.7）	Intracranial	23 （30.7）	Surgery	13 （17.3）
Molecular subtype		KPS at BM/score		Whole-brain radiotherapy	52 （69.3）
Luminal A	16 （21.3）	≤70	30 （40.0）	SBRT	35 （46.7）
Luminal B	6 （8.0）	>70	45 （60.0）	Chemotherapy
HER2 hyperexpression		RPA/score		Before BM/line
HR positive	13 （17.3）	1	49 （65.3）	0	6 （8.0）
HR negative	17 （22.7）	2	6 （8.0）	1	30 （40.0）
TNBC	12 （16.0）	3	20 （26.7）	2	22 （29.3）
Unspecified	11 （14.7）	GPA/score		≥3	17 （22.7）
Pathologic type		［0，1］	35 （46.7）	After BM/line
Ductal carcinoma	48 （64.0）	（1，2］	25 （33.3）	0 or unknown	30 （40.0）
Lobular carcinoma	1 （1.3）	（2，3］	15 （20.0）	1	29 （38.7）
Others	13 （17.3）	mGPA/score		2	7 （9.3）
Unknown	13 （17.3）	［0，1］	6 （8.0）	≥3	9 （12.0）
Histological grade		（1，2］	26 （34.7）	Target therapy
Ⅱ	22 （29.3）	（2，3］	28 （37.3）	Before BM	27 （36.0）
Ⅲ	15 （20.0）	（3，4］	5 （6.7）	After BM	24 （32.0）
Unspecified	38 （50.7）	Unknown	10 （13.3）	Endocrine therapy
Number of BM/n		Extracranial metastases		Before BM	37 （49.3）
1	27 （36.0）	Lung	45 （60.0）	After BM	11 （14.7）
2	4 （5.3）	Liver	21 （28.0）	Immune checkpoint therapy
≥3	44 （58.7）	Bone	35 （46.7）	Before BM	2 （2.7）
Position of BM		Other sites	20 （26.7）	After BM	1 （1.3）
Supratentorial	30 （40.0）	Extracranial disease status

Characteristic	Patient （n=75） /n（%）	Characteristic	Patient （n=75） /n（%）	Characteristic	Patient （n=75） /n（%）
TNM stage		Infratentorial	6 （8.0）	Stable	30 （40.0）
Ⅰ	9 （12.0）	Both	20 （26.7）	Progressed	18 （24.0）
Ⅱ	16 （21.3）	Unspecified	19 （25.3）	Unknown	27 （36.0）
Ⅲ	23 （30.7）	First metastatic site		Treatment for BM
Ⅳ	10 （13.3）	Extracranial	52 （69.3）	Regional therapy
Unspecified	17 （22.7）	Intracranial	23 （30.7）	Surgery	13 （17.3）
Molecular subtype		KPS at BM/score		Whole-brain radiotherapy	52 （69.3）
Luminal A	16 （21.3）	≤70	30 （40.0）	SBRT	35 （46.7）
Luminal B	6 （8.0）	>70	45 （60.0）	Chemotherapy
HER2 hyperexpression		RPA/score		Before BM/line
HR positive	13 （17.3）	1	49 （65.3）	0	6 （8.0）
HR negative	17 （22.7）	2	6 （8.0）	1	30 （40.0）
TNBC	12 （16.0）	3	20 （26.7）	2	22 （29.3）
Unspecified	11 （14.7）	GPA/score		≥3	17 （22.7）
Pathologic type		［0，1］	35 （46.7）	After BM/line
Ductal carcinoma	48 （64.0）	（1，2］	25 （33.3）	0 or unknown	30 （40.0）
Lobular carcinoma	1 （1.3）	（2，3］	15 （20.0）	1	29 （38.7）
Others	13 （17.3）	mGPA/score		2	7 （9.3）
Unknown	13 （17.3）	［0，1］	6 （8.0）	≥3	9 （12.0）
Histological grade		（1，2］	26 （34.7）	Target therapy
Ⅱ	22 （29.3）	（2，3］	28 （37.3）	Before BM	27 （36.0）
Ⅲ	15 （20.0）	（3，4］	5 （6.7）	After BM	24 （32.0）
Unspecified	38 （50.7）	Unknown	10 （13.3）	Endocrine therapy
Number of BM/n		Extracranial metastases		Before BM	37 （49.3）
1	27 （36.0）	Lung	45 （60.0）	After BM	11 （14.7）
2	4 （5.3）	Liver	21 （28.0）	Immune checkpoint therapy
≥3	44 （58.7）	Bone	35 （46.7）	Before BM	2 （2.7）
Position of BM		Other sites	20 （26.7）	After BM	1 （1.3）
Supratentorial	30 （40.0）	Extracranial disease status

Variable	P value	HR	95% CI
First metastatic site
Intracranial	‒	1	‒
Extracranial	0.498	1.562	0.430‒5.672
Extracranial disease status
Stable	‒	1	‒
Progress	0.799	0.839	0.216‒3.261
Position of BM
One side of tentorium	‒	1	‒
Both sides of tentorium or meningeal	0.029	4.692	1.172‒18.787
CA125 level
<22.3 U·mL^-1	‒	1	‒
≥22.3 U·mL^-1	0.005	6.841	1.814‒25.803
Regional therapy
No	‒	1	‒
Yes	0.075	0.271	0.065‒1.139
mGPA score
≤1	‒	1	‒
>1	0.033	0.100	0.012‒0.834

Variable	P value	HR	95% CI
First metastatic site
Intracranial	‒	1	‒
Extracranial	0.498	1.562	0.430‒5.672
Extracranial disease status
Stable	‒	1	‒
Progress	0.799	0.839	0.216‒3.261
Position of BM
One side of tentorium	‒	1	‒
Both sides of tentorium or meningeal	0.029	4.692	1.172‒18.787
CA125 level
<22.3 U·mL^-1	‒	1	‒
≥22.3 U·mL^-1	0.005	6.841	1.814‒25.803
Regional therapy
No	‒	1	‒
Yes	0.075	0.271	0.065‒1.139
mGPA score
≤1	‒	1	‒
>1	0.033	0.100	0.012‒0.834

[1]	CHU Yunkai, LIAO Chunhua, DENG Huayun, HUANG Lei. Study of the regulatory network of MUC1 and tumor-associated proteins [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1024-1033.
[2]	Yan-li XU, Wen-bin GUAN, Wei-wei MAO, Chuan-ying ZHU, Qin ZHANG, Xiao-jun YUAN, Zhen TAN. Clinical characteristics and survival analysis of 52 cases with intracranial atypical teratoid/rhabdoid tumor [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(9): 1222-1227.
[3]	Lei XIONG, Qian YI, Ming-fang XU, Jian CHEN. Expression and prognosis analysis of MRPL12 in lung adenocarcinoma [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(8): 1033-1040.
[4]	Ren-yan WU, Xiao-lin GUO, Deng-li HONG, Lei CHEN. Identification of potential therapeutic target genes in pediatric acute leukemia of ambiguous lineage based on bioinformatics analysis [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(3): 320-327.
[5]	CHEN Si, LIU Chun-liang, ZHAO Qian, SUN Hai-peng, LIU Yun-xia. Identification of hub genes and key pathways in breast cancersurvival-based bioinformatics analysis [J]. , 2020, 40(3): 294-.
[6]	CHEN Si-lu, JI Wei-dong, FANG Yi-ru, et al. Survival analysis of patients with first diagnosed bipolar disorder [J]. , 2014, 34(4): 446-.
[7]	HE Chao, SHEN Yan-ying, NI Xing-zhi, et al. Clinicopathological features and prognosis of 12 cases of gastric Schwannomas [J]. , 2012, 32(10): 1343-.