A novel germline BRCA2 mutation in a Chinese patient with prostate cancer sensitive to platinum chemotherapy: a case report

Abstract Background Germline BRCA2 mutation is associated with an aggressive prostate cancer phenotype and indicates higher risk for hereditary cancer. Recently, numerous studies have attempted to identify the genomic landscape of prostate cancer to better understand the genomic drivers of this disease and look for the molecular targets to guide treatment selection. Case presentation We report a 67-year-old patient diagnosed with prostate cancer who experienced rapid disease progression after androgen deprivation therapy and subsequent docetaxel treatment. The patient had a strong family history of malignancy as his mother was diagnosed with breast cancer and his father was died of lung cancer. Next generation sequencing demonstrated a novel pathogenic germline BRCA2 mutation (p.Gly2181Glufs*10) in the patient. His mother with breast cancer and his son were found to have the same BRCA2 mutation. The patient experienced impressive and durable responses to carboplatin treatment. Conclusions This case demonstrated that the carboplatin could have a dramatic antitumor effect on patients with prostate cancer with germline BRCA2 mutations and family history will help to ensure that patients and their families can be provided with proper genetic counseling.

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Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

Canadian Urological Association Journal ◽

10.5489/cuaj.1970 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 783 ◽

Cited By ~ 3

Author(s):

Richard Walker ◽

Alyssa Louis ◽

Alejandro Berlin ◽

Sheri Horsburgh ◽

Robert G. Bristow ◽

...

Keyword(s):

Prostate Cancer ◽

Family History ◽

High Risk ◽

Prostate Cancer Screening ◽

Brca2 Mutation ◽

Aggressive Disease ◽

Mutation Carriers ◽

The Family ◽

History Of ◽

Prevention Clinic

Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men.Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012.Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis.Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population.

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Male Breast Cancer: Surgical and Genetic Features and a Multidisciplinary Management Strategy

Breast Care ◽

10.1159/000501711 ◽

2019 ◽

Vol 15 (1) ◽

pp. 14-21 ◽

Cited By ~ 1

Author(s):

Francesca Pellini ◽

Eleonora Granuzzo ◽

Silvia Urbani ◽

Sara Mirandola ◽

Marina Caldana ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Male Breast Cancer ◽

Brca2 Mutation ◽

Positive Family History ◽

Male Breast ◽

Mutation Carriers ◽

History Of ◽

Clinical Records

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role. Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants’ electronic clinical records were reviewed. Patients’ data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives. Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers. Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.

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First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-019-6055-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Zheng-Ju Ren ◽

De-Hong Cao ◽

Qin Zhang ◽

Peng-Wei Ren ◽

Liang-Ren Liu ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Systematic Review ◽

Family History ◽

Cancer Risk ◽

Meta Analysis ◽

Prostate Cancer Risk ◽

History Of

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DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.245 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 245-245

Author(s):

James Vu ◽

Marcus Marie Moses ◽

Lahiru Ranasinghe ◽

Patrick Cotogno ◽

Charlotte Manogue ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Dna Repair ◽

Family History ◽

Treatment Outcomes ◽

Treatment Duration ◽

Pathogenic Mutation ◽

Germline Mutations ◽

Cancer Type ◽

History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

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