Molecular subtype predicts incidence and prognosis of brain metastasis from breast cancer in SEER database

Abstract

Molecular subtype and visceral metastasis should be considered for prediction of prognosis for patients with brain metastasis. The patients with HER2 and TNBC cancer subtypes having visceral metastasis, close surveillance could contribute to early detection of brain metastasis and may putatively lead to improved quality of life and survival.

Upfront brain radiotherapy may improve survival for unfavorable prognostic breast cancer brain metastasis patients with Breast‐GPA 0‐2.0

“…21 Additional to the well-recognized difference in BM risk, the natural history of BM development with regard to different molecular subtypes has been less documented. 14,22 In accord with our previous The Breast-GPA prognostic classification has been accepted to date the strongest prognostic factor associated with survival in BMBC patients. 14 However, there could always be additional information to further improve an established prognostic system.…”

“…Additional to the well‐recognized difference in BM risk, the natural history of BM development with regard to different molecular subtypes has been less documented . In accord with our previous finding, Luminal‐like patients usually present longer latency from initial diagnosis to the development of BM, while triple‐negative and HER2 overexpression patients usually had shorter latency, which may help clinical follow‐up and the awareness of possible early symptoms and signs of BM in different molecular subtypes based on different high‐risk period.…”

Risk factors for breast cancer brain metastases: a systematic review

“…The effect of age on the risk for BCBM progression was examined in 22 studies with unselected BC patient populations; six studies compared the mean/median age of patients with and without BM [10,21,36,52,59,70], ten studies assessed age as a di or trichotomous variable [16,19,24,33,38,50,53,57,75,78], and six assessed age as a continuous variable [29,55,63,71,72,79]. Despite the marked heterogeneity in metrics and cutoff points used, young age at primary or metastatic breast cancer (MBC) diagnosis was constantly associated with BCBM, with fourteen studies reporting a statistically significant univariate association [16,19,21,24,29,33,38,52,53,57,70,75,78,79] and eight studies a statistically significant multivariable association with effect estimates ranging between 0.97 -2.0 [21,24,29,33,38,53,55,57]. Importantly Aversa et al calculated a 6% decrease in the risk for BCBM for e...…”

“…The prognostic value of immunohistochemistry (IHC) defined BC subtypes in predicting BCBM progression was examined in 28 studies [12, 24, 29-31, 33, 36, 38, 41-43, 46, 49-52, 54, 55, 57, 59, 63, 67, 70, 72-74, 78, 79]. Irrespective of the heterogeneity in the definition of BC subtypes and IHC cut-offs used for calling ER/PR positivity across studies (Allred scoring system or >1%, >5% and 10% staining as cut-offs for ER/ PR positivity), the TNBC (effect estimate range: 1.4 -5.5) [24,29,31,36,41,42,46,50,52,54,55,57,59,67,70,72,74,79] and/or HER2-positive subtypes (HR-/HER2+ or HR±/HER2-) were constantly found to associate with a significantly higher cumulative incidence of BM (effect estimate range: 1.916 -6.799) [12, 24, 29, 43, 49, 50, 55, 67, 70, 72-74, 78, 79]. Of note, comparison of the two HR-positive groups revealed HR/HER2 co-positivity to associate with significant higher incidences of BCBM progression over HR+/HER2-tumors [24,43,55,72,74,79] with three studies reporting statistically significant multivariate association (HR: 2.514, p < 0.001; SHR: 1.70, p < 0.037; OR: 1.41, p = 0.001, respectively) [55,72,74].…”

“…Additional primary tumor markers found to associate with BCBM progression by more than one study included Ki67, EGFR, FOXC1 and CK5/6. Although different IHC staining cut-offs were used across studies, Metastatic status 4 [33,38,53,70] 3 [33,38,53] 2 Primary metastatic status M0, SHR:2.64 p = 0.007 [33]; Extracranial distant metastases, AHR=28.46, p < 0.001 [38] Number of nonbrain metastatic sites 6 [29,33,55,70,74,79] 3 [29,33,70] 5 >1 OR: 1.76, p < 0.001 [29]; ≥3, HR = 2.712, p < 0.0001 [55]; <1, sHR: 1.77 p = 0.04 [70] 1 Abnormal serum levels, HR: 3.51 p = 0.005 [64] p16 expression on metastatic lymph nodes 1 [69] 1 [69] 1 High score p = 0.01 [69] CRYAB expression 1 [63] 1 HR:1.2 p = 0.021 [63] 3q gene signature 1 [76] 1 HR: 1.61 p = 0.001 [76] GRP94 Status 2 [35,62] 1 Strong positive vs. negative [35] FN14 Status 2 [35,62] 1 Strong positive vs. negative [35] CTC status 1 [34] 1 Undetectable CTC status OR: 6.17 p = 0.001 [34] SNPs 1 [72] 1 AKT1 -RS3803304, SHR: 2.72 p = 0.008, AKT2 -RS3730050, SHR: 2.06 p = 0.041, PDK1 -RS11686903 SHR: 2.38 p = 0.001, PI3KR1 -RS706716, SHR: 2.42 p = 0.025 [72] HR -Hazard Ratio; OR -Odds Ratio; NS -Non Significant; NR -Not Reported; SHR -Subhazard ratio; IDC -Infiltrating ductal carcinoma; CTC -C...…”