Re: Germline BRCA Mutations are Associated with Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

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Impact of early versus delayed androgen-deprivation therapy on survival outcomes of patients with localized prostate cancer who underwent radical prostatectomy and later developed metastasis: Can we define a PSA threshold?

10.21203/rs.3.rs-18688/v1 ◽

2020 ◽

Author(s):

Hyun Kyu Ahn ◽

Kwang Suk Lee ◽

Daeho Kim ◽

Koon Ho Rha ◽

Sung Joon Hong ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Radical Prostatectomy ◽

Androgen Deprivation Therapy ◽

Distant Metastasis ◽

Locally Advanced ◽

Androgen Deprivation ◽

Survival Outcomes ◽

Free Survival ◽

The Impact

Abstract Background: The benefits of early administration of androgen-deprivation therapy (ADT) in patients with prostate-specific antigen (PSA)-only recurrent prostate cancer (PCa) following radical prostatectomy (RP) are controversial. We investigated the impact of early versus delayed ADT on survival outcomes in patients with non-metastatic, localized or locally advanced PCa who received radiation therapy following RP and later developed distant metastasis.Methods: A retrospective analysis was performed on 69 patients with non-metastatic, localized or locally advanced PCa who received radiation therapy following RP and later developed distant metastasis between January 2006 and December 2012. Patients were stratified according to the level of PSA at which ADT was administered (<2 ng/mL vs. ≥2 ng/mL). Study endpoints were progression to castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival (CSS) assessed by Kaplan-Meier analysis and Cox-regression models.Results: Patients were stratified according to the level of PSA at which ADT was administered (<2 ng/mL vs. ≥2 ng/mL) based on the Youden sensitivity analysis. Delayed ADT at PSA ≥2 ng/mL was an independent prognosticator of cancer-specific mortality (p=0.047), and a marginally significant prognosticator of progression to CRPC (p=0.051). During the median follow-up of 81.0 (IQR 54.2-115.7) months, patients who received early ADT at PSA <2 ng/mL had significantly higher CSS rates than patients who received delayed ADT at PSA ≥2 ng/mL (p=0.002). Progression to CRPC-free survival was comparable between the two groups (p=0.331).Conclusions: Early ADT at the PSA level of less than 2 ng/mL confers CSS benefits in patients with localized or locally advanced PCa previously treated with RP.

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MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽

10.1038/s41388-021-01654-3 ◽

2021 ◽

Author(s):

Jhih-Kai Pan ◽

Cheng-Han Lin ◽

Yao-Lung Kuo ◽

Luo-Ping Ger ◽

Hui-Chuan Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Survival Outcomes ◽

Poor Survival ◽

Breast Cancer Brain Metastasis ◽

High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Nature Communications ◽

10.1038/s41467-021-21287-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Minh-Phuong Huynh-Le ◽

◽

Chun Chieh Fan ◽

Roshan Karunamuni ◽

Wesley K. Thompson ◽

...

Keyword(s):

Prostate Cancer ◽

Health Disparities ◽

Gleason Score ◽

Cancer Diagnosis ◽

Distant Metastasis ◽

Ethnic Populations ◽

Hazard Ratios ◽

Aggressive Cancer ◽

Screening Accuracy ◽

Fatal Prostate Cancer

AbstractGenetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

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