The Role of BRCA Testing in Hereditary Pancreatic and Prostate Cancer Families

2019 ◽  
pp. 79-86 ◽  
Author(s):  
Robert Pilarski
Keyword(s):  
Prostate Cancer ◽  
Parp Inhibitors ◽  
Gleason Grade ◽  
Brca1 And Brca2 ◽  
Direct Evaluation ◽  
Panel Testing ◽  
Post Test ◽  
Uncertain Significance ◽  
Prostate Cancers

Beyond breast and ovarian cancers, mutations in the BRCA1 and BRCA2 genes increase risks for pancreatic and prostate cancers and contribute to the prevalence of these cancers. Mutations in a number of other genes have also been shown to increase the risk for these cancers as well. Genetic testing is playing an increasingly important role in the treatment of patients with pancreatic and prostate cancer and is now recommended for all patients with pancreatic or metastatic prostate cancer, as well as patients with high Gleason grade prostate cancer and a remarkable family history. Identification of an inherited mutation can direct evaluation of the patient for other cancer risks as well as identification and management of disease in at-risk relatives. Growing evidence suggests improved responses to PARP inhibitors and other therapies in patients with mutations in the BRCA and other DNA repair genes. Although more work must be done to clarify the prevalence and penetrance of mutations in genes other than BRCA1 and BRCA2 in patients with pancreatic and prostate cancer, in most cases, testing is now being done with a panel of multiple genes. Because of the complexities in panel testing and the increased likelihood of finding variants of uncertain significance, pre- and post-test genetic counseling are essential.

Limited Sampling of Radical Prostatectomy Specimens With Excellent Preservation of Prognostic Parameters of Prostate Cancer

2009 ◽  
Vol 133 (8) ◽  
pp. 1278-1284
Author(s):  
Kyungeun Kim ◽  
Pil June Pak ◽  
Jae Y. Ro ◽  
Dongik Shin ◽  
Soo-Jin Huh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Sampling Method ◽  
Resection Margin ◽  
Gleason Grade ◽  
Posterior Half ◽  
Margin Involvement ◽  
Partial Sampling ◽  
Prostate Cancers ◽  
Extraprostatic Extension

Abstract Context.—The widespread use of the serum prostate-specific antigen test has increased the early detection of prostate cancer and consequently reduced grossly definable prostate cancers. Objective.—To find the most efficient gross sampling method for radical prostatectomy specimens not only preserving important prognostic factors but also being cost effective. Design.—We initially analyzed clinicopathologic features of the entire prostate sections from 148 radical prostatectomy specimens, which then were used to examine the impact of 5 partial sampling methods on tumor stage, Gleason score, extraprostatic extension, resection margin status, and paraffin block numbers. The methods included submission of (1) alternative slices, (2) alternative slices plus biopsy-positive posterior quarters, (3) every posterior half, (4) every posterior half plus one midanterior half, and (5) alternative slices plus peripheral 3-mm rim of the remaining prostate. Results.—Prostate cancers and their extraprostatic extension and resection margin involvement were commonly located in the right posterior portion of the prostate. Method 5 was most efficient, detecting all cases with extraprostatic extension and resection margin involvement and reducing 25% of paraffin blocks compared with the entire sampling of the prostate. The Gleason scores were retained in most of cases, except reversal of the primary and secondary Gleason grade component in only 2 cases (1%). Only 4 cases (3%) were downstaged within the same T2 stage. Conclusions.—These results demonstrate that sampling of alternative slices plus peripheral rim of the remaining prostate is the most efficient partial sampling method for radical prostatectomy specimens.

scholarly journals Role of Precision Oncology in Type II Endometrial and Prostate Cancers in the African Population: Global Cancer Genomics Disparities

2022 ◽  
Vol 23 (2) ◽  
pp. 628
Author(s):  
Rahaba Marima ◽  
Rodney Hull ◽  
Mandisa Mbeje ◽  
Thulo Molefi ◽  
Kgomotso Mathabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endometrial Cancer ◽  
African Ancestry ◽  
African Population ◽  
Precision Oncology ◽  
Type Ii ◽  
Incidence And Mortality ◽  
Prostate Cancers ◽  
The Relationship

Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.

scholarly journals The role of BRCA1 and BRCA2 in prostate cancer

2012 ◽  
Vol 14 (3) ◽  
pp. 409-414 ◽  
Author(s):  
Elena Castro ◽  
Rosalind Eeles
Keyword(s):  
Prostate Cancer ◽  
Brca1 And Brca2

scholarly journals BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Carlo Messina ◽  
Carlo Cattrini ◽  
Davide Soldato ◽  
Giacomo Vallome ◽  
Orazio Caffo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Brca Mutations ◽  
Primary Tumors ◽  
Receptor Signalling ◽  
Castration Resistant ◽  
Damage Repair ◽  
Poor Outcomes

Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles.

scholarly journals Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

2020 ◽  
Vol 21 (8) ◽  
pp. 2991 ◽  
Author(s):  
Phuong Kim To ◽  
Manh Hung Do ◽  
Jin-Hyoung Cho ◽  
Chaeyong Jung
Keyword(s):  
Prostate Cancer ◽  
Mammalian Cells ◽  
Tumor Development ◽  
Cancer Therapeutics ◽  
Underlying Mechanism ◽  
Reproductive Organs ◽  
Zinc Homeostasis ◽  
Prostate Cancer Development ◽  
Prostate Cancers

Zinc is a group IIB heavy metal. It is an important regulator of major cell signaling pathways in most mammalian cells, functions as an antioxidant and plays a role in maintaining genomic stability. Zinc deficiency leads to severe diseases in the brain, pancreas, liver, kidneys and reproductive organs. Zinc loss occurs during tumor development in a variety of cancers. The prostate normally contains abundant intracellular zinc and zinc loss is a hallmark of the development of prostate cancer development. The underlying mechanism of this loss is not clearly understood. The knowledge that excess zinc prevents the growth of prostate cancers suggests that zinc-mediated therapeutics could be an effective approach for cancer prevention and treatment, although challenges remain. This review summarizes the specific roles of zinc in several cancer types focusing on prostate cancer. The relationship between prostate cancer and the dysregulation of zinc homeostasis is examined in detail in an effort to understand the role of zinc in prostate cancer.

scholarly journals Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation

2015 ◽  
Vol 33 (3) ◽  
pp. 244-250 ◽  
Author(s):  
Bella Kaufman ◽  
Ronnie Shapira-Frommer ◽  
Rita K. Schmutzler ◽  
M. William Audeh ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Brca1 And Brca2 ◽  
Recurrent Cancer ◽  
Tumor Response Rate ◽  
Polymerase Inhibitor ◽  
Grade 3 ◽  
Prostate Cancers ◽  
Tumor Types

Purpose Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). Conclusion Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.

The role of BRCA1 and BRCA2 in prostate cancer

10.2741/4191 ◽  
2013 ◽  
Vol 18 (4) ◽  
pp. 1445 ◽  
Author(s):  
Roy Jensen
Keyword(s):  
Prostate Cancer ◽  
Brca1 And Brca2

scholarly journals The role of mpMRI in qualification of patients with ISUP 1 prostate cancer on biopsy to radical prostatectomy

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Łukasz Nyk ◽  
Omar Tayara ◽  
Tomasz Ząbkowski ◽  
Piotr Kryst ◽  
Aneta Andrychowicz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Digital Rectal Examination ◽  
Gleason Grade ◽  
Shared Decision ◽  
Grade Group ◽  
Final Pathology ◽  
Radical Treatment ◽  
Pathological Report

Abstract Background To investigate the role of mpMRI and high PIRADS score as independent triggers in the qualification of patients with ISUP 1 prostate cancer on biopsy to radical prostatectomy. Methods Between January 2017 and June 2019, 494 laparoscopic radical prostatectomies were performed in our institution, including 203 patients (41.1%) with ISUP 1 cT1c-2c PCa on biopsy. Data regarding biopsy results, digital rectal examination, PSA, mpMRI and postoperative pathological report have been retrospectively analysed. Results In 183 cases (90.1%) mpMRI has been performed at least 6 weeks after biopsy. Final pathology revealed ISUP Gleason Grade Group upgrade in 62.6% of cases. PIRADS 5, PIRADS 4 and PIRADS 3 were associated with Gleason Grade Group upgrade in 70.5%, 62.8%, 48.3% of patients on final pathology, respectively. Within PIRADS 5 group, the number of upgraded cases was statistically significant. Conclusions PIRADS score correlates with an upgrade on final pathology and may justify shared decision of radical treatment in patients unwilling to repeated biopsies. However, the use of PIRADS 5 score as a sole indicator for prostatectomy may result in nonnegligible overtreatment rate.

scholarly journals Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 334
Author(s):  
Dhruv Bansal ◽  
Melissa A. Reimers ◽  
Eric M. Knoche ◽  
Russell K. Pachynski
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Immunosuppressive Tumor Microenvironment ◽  
Prostate Cancers ◽  
Past Experiences

Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically “cold” malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents’ combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors. Here, we will review promising immunotherapies in development and ongoing trials for metastatic castration-resistant prostate cancer (mCRPC). These novel trials will build on past experiences and promise to usher a new era to treat patients with mCRPC.

scholarly journals Prostate Cancer Progression: as a Matter of Fats

2021 ◽  
Vol 11 ◽  
Author(s):  
Natalia Scaglia ◽  
Yesica Romina Frontini-López ◽  
Giorgia Zadra
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Synthetic Lethality ◽  
Standard Of Care ◽  
Building Blocks ◽  
Parp Inhibitors ◽  
Tumor Promoter ◽  
New Therapeutic Approaches ◽  
Therapeutic Perspective

Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.

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