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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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365 hot topic(s) found with the query "Brca"

Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants
(Posted: Apr 21, 2024 8AM)

From the article: "Is postpartum diagnosis an independent risk factor associated with mortality among patients with young-onset breast cancer with germline BRCA1/2 pathogenic variants (PVs)? Findings: This cohort study including 903 women with BRCA germline PVs found that a breast cancer diagnosis less than 10 years post partum was associated with higher risk of mortality compared with nulliparous women and women diagnosed at least 10 years post partum. Increased risk after childbirth varied, with highest risk at less than 5 years for women with ER-positive breast cancer vs 5 to less than 10 years for women with ER-negative breast cancer, and BRCA1 carriers had peak risk of mortality 5 to less than 10 years post partum, with no associations observed for BRCA2 carriers. Meaning: These findings suggest that a breast cancer diagnosis within 10 years of childbirth was independently associated with increased risk for mortality in patients with germline BRCA1/2 PVs, especially for carriers of BRCA1 PVs."

Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families
WK Ho et al, Lancet Regional Health, February 2024 (Posted: Feb 06, 2024 1PM)

From the abstract: " Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. We found that the absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management."

Pregnancy After Breast Cancer in Young BRCA Carriers An International Hospital-Based Cohort Study
M Lambertini et al, JAMA Network Open, December 7, 2023 (Posted: Dec 08, 2023 2PM)

From the abstract: "Among women carrying germline BRCA pathogenic variants, is pregnancy after breast cancer associated with adverse maternal or fetal outcomes? This international, hospital-based, retrospective cohort study including 4732 BRCA carriers showed that 1 in 5 patients conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with adverse maternal prognosis or fetal outcomes. The cumulative incidence of pregnancy after breast cancer and disease-free survival in this large international cohort of young BRCA carriers may inform care for affected patients. "

Emerging cancer risks in BRCA2 pathogenic germline variant carriers.
Patrick R Benusiglio et al. Eur J Hum Genet 2023 9 (Posted: Sep 28, 2023 11AM)

From the paper: "Carriers of pathogenic germline variants (PGV) in BRCA2 could soon be offered gastric cancer screening using gastroscopy. In the longer term, some might even take part in lung cancer screening programs. Indeed, while the risks of breast, ovarian, pancreatic and prostate cancer have been documented for years, recent data show an increased risk of gastric cancer, and suggest an association with lung cancer. This article focuses specifically on BRCA2, while sidelining its sister gene BRCA1, as evidence for a broad cancer spectrum is much stronger for the former."

Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.
Silvia Actis et al. J Community Genet 2023 9 (Posted: Sep 21, 2023 2PM)

From the abstract: "We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. "

BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype
H Fettle et al, ebiomedicine, August 5, 2023 (Posted: Aug 07, 2023 9AM)

Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. These data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected.

Persistent Underutilization of BRCA Testing for Breast and Ovarian Cancer in the United States: Implications for Health Disparities
L Shi et al, CDC Blog Post, July 25, 2023 Brand (Posted: Jul 25, 2023 11AM)

Two recent studies document ongoing underutilization and disparities in genetic testing for patients with breast and ovarian cancer. The two studies demonstrate the importance of population-level data to track progress in implementation, outcomes, and disparities in genomic medicine. The studies also show how diverse data sources, such as state-based cancer registries, laboratory, EHR, administrative claims, and survey data, each with its own strengths and limitations, can be used to help build the evidence base on genetic testing utilization and disparities.

Germline pathogenic variants in metaplastic breast cancer patients and the emerging role of the BRCA1 gene
G Corso et al, EJHG, July 18, 2023 (Posted: Jul 18, 2023 2PM)

we retrospectively reviewed all BC patients counseled at our Institute for genetic testing of at least BRCA1 or BRCA2 (BRCA) genes and we found that 23 (23/5226?=?0.4%) were affected by MpBC. About 65% (15/23) of MpBC patients harbored a germline pathogenic variant (PV): 13 in BRCA1 (86.7%), including two patients who received genetic testing for known familial PV, one in TP53 (6.7%), and one in MLH1 (6.7%). Our results confirmed that BRCA1 is involved in MpBC predisposition.

Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant.
Mark van Barele et al. J Natl Cancer Inst 2023 6 (Posted: Jul 01, 2023 9AM)

Radiation-induced secondary breast cancer may be a concern after radiotherapy for primary breast cancer (PBC), especially in young germline (g)BRCA-associated breast cancer patients with already high contralateral breast cancer (CBC) risk and potentially increased genetic susceptibility to radiation. The aim of this study is to investigate whether adjuvant radiotherapy for PBC increases the risk of CBC in gBRCA1/2-associated BC patients.

New, fast and cheap prediction tests for BRCA1 gene mutations identification in clinical samples
AJ Walczak et al, Sci Reports, May 5, 2023 (Posted: May 05, 2023 9AM)

Patterns of care and outcomes of risk reducing surgery in women with pathogenic variants in non-BRCA and Lynch syndrome ovarian cancer susceptibility genes.
Zachary P Schwartz et al. Gynecol Oncol 2023 4 1-7 (Posted: Apr 12, 2023 9AM)

Pancreatic Cancer: Beyond Brca Mutations
V Ricci et al, J Per Med, December 16, 2022 (Posted: Dec 17, 2022 9AM)

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide. The outcomes in patients with pancreatic cancer remain unsatisfactory. In the current review, we summarize the genetic and epigenetic architecture of metastatic pancreatic cancer beyond the BRCA mutations, focusing on the genetic alterations and the molecular pathology in pancreatic cancer. This review focuses on the molecular targets for the treatment of pancreatic cancer, with a correlation to future treatments. The potential approach addressed in this review may lead to the identification of a subset of patients with specific biological behaviors and treatment responses.

Combining PARP Inhibitor With Immunotherapy-Does the Promise of Preclinical Data Translate to Clinic?
Thawani Rajat et al. JAMA oncology 2022 11 (Posted: Nov 18, 2022 6AM)

Results from two recent trials warrant further investigation into the underlying biology that resulted in lack of clinical benefit of the study drug combination in the majority of patients with non–BRCA-associated cancers, and apparent lack of improved clinical benefit compared with single agent alone in BRCA-associated cancers.

Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial.
Schram Alison M et al. JAMA oncology 2022 11 (Posted: Nov 18, 2022 6AM)

Is the combination of avelumab and talazoparib effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless of tumor type? In this phase 2b nonrandomized controlled trial with 200 patients, neither the BRCA1/2 nor ATM cohort met the prespecified target of an objective response rate of 40% across cancer types. Durable clinical activity was observed in patients with BRCA1/2-associated tumor types (eg, ovarian, breast, prostate, and pancreatic cancers) vs those with non–BRCA-associated cancer types; a notable exception were patients with BRCA1/2-altered uterine leiomyosarcoma, who had prolonged responses to treatment.

Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review
AL Young et al, EJHG, October 17, 2022 (Posted: Oct 17, 2022 7AM)

Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4–60.0% contacted a genetics clinic and 22.8–76.2% had genetic testing after they were counselled at a genetics clinic.

High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer
N Flaum et al, Genetics in Medicine, September 28, 2022 (Posted: Sep 28, 2022 8AM)

This is the largest report of women with familial EOC undergoing wider testing to date. One-fifth of BRCA-negative women were heterozygous for a pathogenic variant in a potentially actionable gene. Wider genetic testing of women with familial EOC is essential to optimize their treatment and prevention of disease in family members.

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study.
Rose Esther et al. Public health genomics 2022 8 1-14 (Posted: Aug 16, 2022 5PM)

Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.
Torr Bethany et al. Journal of medical genetics 2022 7 (Posted: Jul 24, 2022 11AM)

We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomized comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety.

Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas
F Menghi et al, Sci Trans Med, July 6, 2022 (Posted: Jul 06, 2022 2PM)

The authors examined the differences in response to platinum therapy of patients with TNBC and OvCa who had BRCA loss or genetic alterations as compared to promotor methylation of BRCA. They saw that both patients and mice with promotor methylation were able to adaptively lose methylation, gain BRCA1 expression, and acquire resistance to platinum therapy. These findings have broad implications in using BRCA alteration status to better predict patient.

How does re-classification of variants of unknown significance (VUS) impact the management of patients at risk for hereditary breast cancer?
Kwong Ava et al. BMC medical genomics 2022 6 (1) 122 (Posted: Jun 04, 2022 7AM)

The popularity of multigene testing increases the probability of identifying variants of uncertain significance (VUS). While accurate variant interpretation enables clinicians to be better informed of the genetic risk of their patients, currently, there is a lack of consensus management guidelines for clinicians on VUS. A review of archival variants from BRCA1 and BRCA2 genetic testing changed the management for 31.8% of the families due to increased or reduced risk. We encourage regular updates of variant databases, reference to normal population and collaboration between research laboratories on functional studies to define the clinical significances of VUS better.

An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance
ES Iverson et al, NPJ Genomic Medicine, June 3, 2022 (Posted: Jun 03, 2022 10AM)

We have developed functional assays and a statistical model called VarCall for classifying BRCA1 and BRCA2 VUS. Here we describe a multifactorial extension of VarCall, called VarCall XT, that allows for co–analysis of multiple forms of genetic evidence. We evaluated the accuracy of models defined by the combinations of functional, in silico protein predictors, and family data for VUS classification. VarCall XT classified variants of known pathogenicity status with high sensitivity and specificity, with the functional assays contributing the greatest predictive power

Paired Tumor-Germline Testing as a Driver in Better Cancer Care
JW Henson et al, JAMA Network Open, May 20, 2022 (Posted: May 21, 2022 2PM)

Paired tumor-germline testing can lead to better treatment choices. Hereditary cancer syndromes are caused by inactivated tumor suppressor genes. By comparison, activated oncogenes are poorly tolerated during embryonic development. Variant tumor suppressor genes and their inactive protein products are more challenging to target than are activated oncogenes. Attention thus turns from the gene itself to the aberrant downstream molecular pathway and subsequent effects of the pathway. Two notable examples are the use of checkpoint inhibitors to target high tumor mutation burdens from tumors related to a defective mismatch repair pathway (ie, Lynch syndrome when originating in germline) and poly adenosine diphosphate ribose polymerase inhibitors to exploit single-strand breaks from tumors related to the homologous repair/BRCA pathway (ie, hereditary breast and ovarian cancer syndrome when originating in germline).

Making BRCA1 genetic test reports easier to understand through user-centered design: A randomized trial.
Recchia Gabriel et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 5 (Posted: May 08, 2022 1PM)

Our objective was to apply a user-centered design process to identify phrases, graphics, and ways of communicating numerical risks that could be used to help patients understand their cancer risk and next steps on receiving BRCA1 genetic test results (positive, negative, and variants of uncertain significance). Subjective comprehension, communication efficacy, and actionability were all higher for the user-centered reports, with no difference in perceived risk. Comprehension of participants viewing user-centered reports was significantly better on 2 items, directionally (but not significantly) better on 6 items, and directionally (but not significantly) worse on 2 items.

Prevalent versus incident breast cancers: benefits of clinical and radiological monitoring in women with pathogenic BRCA1/2 variants
C Saule et al, EJHG, February 25, 2022 (Posted: Feb 25, 2022 9AM)

We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N?=?103), whereas the prevalent breast cancer group (PBCG) (N?=?417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p?<?0.00001), and N0 in 90% vs. 75% (p?<?0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p?<?0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p?=?0.004) and more mastectomies (60% vs. 42% p?<?0.0001) in the IBCG vs PBCG groups respectively.

Oral Contraceptive Use in BRCA1 and BRCA2 Mutation Carriers: Absolute Cancer Risks and Benefits.
Schrijver Lieske H et al. Journal of the National Cancer Institute 2022 1 (Posted: Jan 29, 2022 11AM)

To help BRCA1/2 mutation carriers make informed decisions regarding use of combined-type oral contraceptive preparation (COCP), absolute risk-benefit estimates are needed for COCP-associated cancer. For a hypothetical cohort of 10,000 women, we calculated the increased or decreased cumulative incidence of COCP-associated (breast/ovarian/endometrial) cancer, examining 18 scenarios with differences in duration and timing of COCP use, uptake of prophylactic surgeries and menopausal hormone therapy.

Tennis Star Chris Evert Teaches Us That Genetic Testing Is A Lifetime Match
E Matloff, Forbes, January 17, 2022 (Posted: Jan 20, 2022 7AM)

In February 2020, Chris’s younger sister, Jeanne Evert Dubin, died of ovarian cancer at age 62. Before her death, Jeanne had genetic testing, but was not found to have a pathogenic, or disease-causing mutation in the BRCA1 or BRCA2 genes and perhaps the other genes known to be associated with an increased risk of ovarian cancer (there are many such genes – BRCA1 and BRCA2 are only two of them). However, Jeanne was reported to have a “variant of uncertain significance” (VUS) in BRCA1.

Care of men with cancer-predisposing BRCA variants
R Horton et al, BMJ, October 14,2021 (Posted: Oct 15, 2021 6AM)

Men and women are equally likely to inherit or pass on a cancer-predisposing BRCA variant—family history of cancers needs to encompass both sides of the family- Men with cancer-predisposing BRCA variants have an increased risk of developing breast cancer and are advised to be breast aware- Men with cancer-predisposing BRCA2 variants have an increased risk of developing aggressive prostate cancer (men with cancer-predisposing BRCA1 variants may also have an increased risk); it is not yet known whether prostate specific antigen screening reduces mortality in men with cancer-predisposing BRCA variants.

Association of Genetic Testing Results with Mortality Among Women with Breast Cancer or Ovarian Cancer.
Kurian Allison W et al. Journal of the National Cancer Institute 2021 8 (Posted: Aug 23, 2021 7AM)

Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than non-carriers

This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous- PALB2 is not as well known as BRCA, but mutations of the gene can raise a woman’s risk for breast cancer almost as much.
S Berger, NY Times, August 17, 2021 (Posted: Aug 18, 2021 3PM)

For years, women with breast cancer in their families have been getting tested for mutations in two genes, known as BRCA1 and BRCA2, to determine whether they have a sharply elevated risk of the disease. Now, doctors are increasingly recommending that anyone who was tested before 2014 go through genetic testing again — to look for a different mutation, one much less widely known.

Association of Copy Number Variation Signature and Survival in Patients With Serous Ovarian Cancer
P Graf et al, JAMA Network Open, June 28, 2021 (Posted: Jun 30, 2021 7AM)

In this genetic association study of 564 patients with serous ovarian cancer, an internally validated CNV signature from The Cancer Genome Atlas had more discriminatory ability to prognosticate overall survival than age, clinical stage, grade, and race combined, as well as gross CNV burden, total mutational burden, BRCA status, and open-source candidate genome-wide DNA repair deficiency signatures.

Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.
Tutt Andrew N J et al. The New England journal of medicine 2021 6 (25) 2394-2405 (Posted: Jun 24, 2021 6AM)

Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo.

Men With Breast Cancer Need More Treatment Options and Access to Genetic Counseling
FDA, June 2021 (Posted: Jun 17, 2021 9AM)

If a close relative – their mother, father, brother, sister, child – has breast cancer, men are also at slightly higher risk to develop the disease. Men who have a BRCA mutation, a mutation or change in a gene that predisposes them to breast cancer, are at a greater risk. Although their chance of developing breast cancer is still low (only about 5% to 6%), men with a mutation in BRCA2 have a 100 times greater risk of developing breast cancer than men in the general population.

BRCA2: a 25-year journey from gene identification to targeted cancer treatment.
Grinda Thomas et al. The Lancet. Oncology 2021 6 (6) 763-764 (Posted: Jun 06, 2021 7AM)

BRCA2 is the leading susceptibility gene for breast and ovarian cancer, with cumulative risks at age 80 years of up to 69% and 17%, respectively. Germline BRCA2 alterations can be found in around 2·5% of unselected patients with breast cancer and 6% of patients with ovarian cancer. To a lesser extent, deleterious BRCA2 variants also increase the risk of other cancers, including prostate, esophagus, and pancreatic cancer.

Evaluation of BRCA1 and BRCA2 as Indicators of Response to Immune Checkpoint Inhibitors
Z Zhou et al, JAMA Network Open, May 7, 2021 (Posted: May 08, 2021 6AM)

The findings of this cohort study suggest that BRCA2 alteration in combination with TMB was a potential biomarker associated with response to ICIs. BRCA1/2 altered tumors have shown enhanced immunosurveillance in several preclinical studies, but their correlation with ICI treatment outcomes remains uncharacterized

Comparison of Survival After Breast-Conserving Therapy vs Mastectomy Among Patients With or Without the BRCA1/2 Variant in a Large Series of Unselected Chinese Patients With Breast Cancer
Q Wan et al, JAMA Network Open, April 23, 2021 (Posted: Apr 24, 2021 10AM)

n this cohort study, 8396 patients with operable primary breast cancer (187 BRCA1 carriers, 304 BRCA2 carriers, and 7905 noncarriers) underwent BCT, mastectomy with radiotherapy, or mastectomy alone. In multivariable analyses, patients with both the BRCA1 and BRCA2 variants who were treated with BCT had a survival rate at least comparable to those treated with mastectomy with radiotherapy or mastectomy alone.

Impact of national guidelines on use of BRCA1/2 germline testing, risk management advice given to women with pathogenic BRCA1/2 variants and uptake of advice.
Meiser Bettina et al. Hereditary cancer in clinical practice 2021 19(1) 24 (Posted: Apr 13, 2021 9AM)

Racial disparities still persist in genetic testing for BRCA-related breast cancer- West Philly native shares her cancer journey as part of Penn Medicine's effort to boost testing rates among Black patients
T Romero, Philly Voice, April 6, 2021 (Posted: Apr 07, 2021 10AM)

What You Should Know About Your BRCA Status And Ovarian Cancer Risk When it comes to your health, knowledge is power.
K Miller, Good House keeping, February 9, 2021 (Posted: Feb 15, 2021 8AM)

Genetic Testing Challenges in Oncology: Woman Without High Breast Cancer Risk Recommended Surgery
T Ray, Precision Oncology News, December ee, 2020 (Posted: Dec 30, 2020 3PM)

This case is concerning because a breast surgeon recommended unnecessary, invasive surgeries to a patient who is at average population risk for breast cancer, based on a variant of unknown significance result.

Examining the uptake of predictive BRCA testing in the UK; findings and implications
AP Martin et al, EJHG, December 16, 2020 (Posted: Dec 17, 2020 8AM)

Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities.

Mutations in BRCA1 and BRCA2 differentially affect the tumor microenvironment and response to checkpoint blockade immunotherapy
RM Samstein et al, Nature Cancer, November 16, 2020 (Posted: Nov 17, 2020 8AM)

Immune checkpoint blockade (ICB) has improved outcomes for patients with advanced cancer, but the determinants of response remain poorly understood. Here we report differential effects of mutations in the homologous recombination genes BRCA1 and BRCA2 on response to ICB in mouse and human tumors.

How to Live With the Cancer You May Never Get-The waiting game is a different experience for every woman with a BRCA gene mutation
Elemental, November 6, 2020 (Posted: Nov 07, 2020 10AM)

Mutations of the BRCA genes are inherited — parents have a 50% chance to pass it on — and many people discover they have it when a family cancer cluster triggers testing: Margaret and her sister and brother all got tested when their mother was diagnosed with breast cancer. A mutation of the BRCA1 gene gives carriers a 72% chance of developing breast cancer and a 44% chance of ovarian cancer, whereas BRCA2 triggers a 69% chance of breast cancer and a 17% chance of ovarian cancer.

Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance.
Lyra Paulo C M et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Oct (Posted: Oct 23, 2020 7AM)

We have collected, curated, and harmonized functional data for 2701 missense variants representing 24.5% of possible missense variants in BRCA1. Integration of data from validated assays provided ACMG/AMP evidence criteria in favor of pathogenicity for 297 variants or against pathogenicity for 2058 representing 96.2% of current VUS functionally assessed.

Do you dare open Pandora's Box of genetic counseling?
S Yoo, KARE 11, October 8, 2020 (Posted: Oct 09, 2020 7AM)

If you had an opportunity to find out whether you were going to get cancer at an unknown point in your life, would you? Depending on how you see it, it may be a Pandora's Box ... but one that's worth opening. I decided to open my box. The biggest reason? My mom. My rock. My best friend. My mom was diagnosed with breast cancer when she was 39-years-old.

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
DR Barnes et al, Genetics in Medicine, July 15, 2020 (Posted: Jul 17, 2020 11AM)

We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for 18,935 BRCA1 and 12,339 BRCA2 pathogenic variant carriers of European ancestry. PRS are strongly associated with BC and EOC and predict substantial absolute risk differences at PRS distribution extremes.

Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
V Silvestri et al, JAMA Oncology, July 2, 2020 (Posted: Jul 05, 2020 7AM)

In this cohort study of 6902 men with a BRCA1 or BRCA2 pathogenic variant, being affected by cancer, particularly breast, prostate, and pancreatic cancers and developing multiple primary tumors, was associated with a higher probability for a man of being a BRCA2, rather than a BRCA1, pathogenic variant carrier.

Clinical outcomes of a genomic screening program for actionable genetic conditions
AH Buchanan et al, Genetics in Medicine, June 30, 2020 (Posted: Jul 01, 2020 8AM)

A study of electronic health records shows that among individuals with variants in tier1 genes (BRCA, Lynch syndrome, familial hypercholesterolemia, 87% did not have a prior genetic diagnosis. Genomic screening programs can identify individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

Engaging Men With BRCA-Related Cancer Risks: Practical Advice for BRCA Risk Management From Male Stakeholders
M Dean et al, AM J Men's Health, May 25, 2020 (Posted: May 30, 2020 7AM)

Semistructured interviews were conducted with 25 men who either tested positive for a pathogenic variant in BRCA1/2 gene or who had an immediate family member who had tested positive for a pathogenic variant in BRCA. Results showed the need for men to know and understand their cancer risks and communicate that risk information to family members and practitioners

How can Australia integrate routine genetic sequencing in oncology: a qualitative study through an implementation science lens
R O'Shea et al, Genetics in Medicine, May 28, 2020 (Posted: May 28, 2020 7AM)

Qualitative interviews were designed using the Consolidated Framework for Implementation Research. Questions included experiences or views of the BRCA testing processes, implementation needs of oncology health professionals, perceived challenges, and future ideas for interventions to integrate genetic testing into oncology.

Updates in BRCA testing for People of Ashkenazi Jewish Ancestry
L Steinmark, Jackson Labs, May 3, 2020 (Posted: May 07, 2020 8AM)

For the past few decades, genetic providers and researchers have recognized the importance of the three BRCA founder mutations and were able to test specifically for them in individuals at risk, defined as having Ashkenazi ancestry and a personal or family history of breast and/or ovarian cancer.

Association of Rare Pathogenic DNA Variants for Familial Hypercholesterolemia, Hereditary Breast and Ovarian Cancer Syndrome, and Lynch Syndrome With Disease Risk in Adults According to Family History
AP Patel, JAMA Network Open, April 29, 2020 (Posted: Apr 30, 2020 8AM)

In this cohort study of 49?738 participants in the UK Biobank, a pathogenic or likely pathogenic variant associated with the 3 tier 1 genomic conditions (BRCA, Lynch syndrome, FH) was identified in 0.9% of participants. These individuals had an increased risk of disease identified by gene sequencing that was not found through self-reported family history.

Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction.
Stjepanovic Neda et al. European journal of cancer (Oxford, England : 1990) 2020 Apr 13253-60 (Posted: Apr 29, 2020 7AM)

Germline Testing for Patients With BRCA1/2 Mutations on Somatic Tumor Testing.
Vlessis Katherine et al. JNCI cancer spectrum 2020 Feb 4(1) pkz095 (Posted: Apr 15, 2020 10AM)

I Have a BRCA1 Gene Mutation: The Extra Stress of COVID-19 Takes a Toll
N McCoy, blog April 2, 2020 (Posted: Apr 03, 2020 8AM)

For those who already live with uncertainty, these extraordinary times offer new challenges. For those living with hereditary risk for cancer, the increased isolation and increased time to process can also feel overwhelming.

For people with underlying health conditions, the coronavirus presents ‘all the ingredients’ for danger
A Joseph, Stat News, March 23, 2020 (Posted: Mar 23, 2020 8AM)

An infection from the coronavirus can be a formidable threat to anyone. But it is especially pernicious for people whose health is vulnerable, even in the best of conditions. Examples include those with primary immunodeficiency disorders, cystic fibrosis, BRCA mutations, and congenital heart defects.

Genomics took a long time to fulfil its promise
the Economist, March 12, 2020 (Posted: Mar 16, 2020 8AM)

Hype was always going to be hard to live up to, and for a long time the genome project failed comprehensively, prompting a certain Schadenfreude among those who had wanted biology kept small. The role of genetics in the assessment of people’s medical futures continued to be largely limited to testing for specific defects, such as the BRCA mutations.

Disparities in BRCA counseling across providers in a diverse population of young breast cancer survivors.
Reid Sonya et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Feb (Posted: Feb 20, 2020 10AM)

In a diverse population of young breast cancer survivors, only 20% had documented BRCA counseling via a genetics health professional (GHP). GHP involvement was associated with adherence to nationally recommended best practices.

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Recommendation Statement.
et al. American family physician 2020 Feb 101(4) 233-238 (Posted: Feb 19, 2020 9AM)

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer.
Mills Justin et al. American family physician 2020 Feb 101(4) 239-240 (Posted: Feb 19, 2020 9AM)

Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?
Angeli Davide et al. International journal of molecular sciences 2020 Feb 21(3) (Posted: Feb 19, 2020 9AM)

Testing for Breast Cancer Susceptibility Genes
JAMA Learning Podcast, February 2020 (Posted: Feb 12, 2020 8AM)

Breast cancer is a leading cause of death in women. Some women have a cancer susceptibility gene known as BRCA, and women should be tested for BRCA under some circumstances. This podcast discusses when testing is appropriate and the cost-effectiveness of BRCA screening for women who have had breast cancer.

Association of Germline Genetic Testing Results With Locoregional and Systemic Therapy in Patients With Breast Cancer
AW Kurian et al, JAMA Oncology, February 6, 2020 (Posted: Feb 07, 2020 8AM)

In a population-based study, women with germline pathogenic variants in BRCA and other breast cancer susceptibility genes have been found to have different patterns of breast cancer treatment, which may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
Mavaddat Nasim et al. Breast cancer research : BCR 2020 Jan 22(1) 8 (Posted: Jan 22, 2020 9AM)

We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

BRCA Research Update: Looking Back At 2019 And Plans For The Future
S Domcheck Besser Center webinar, February 20, 2020 (Posted: Jan 16, 2020 8AM)

Susan Domchek, MD, will present a webinar on recent advancements in BRCA-related research. For this annual webinar, she discusses recent clinical trials and scientific advancements, and breakthroughs in cancer treatment such as current FDA approvals.

Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer
HK Kim, J Hum Genetics, January 2020 (Posted: Jan 13, 2020 9AM)

The Reinterpretation of Genetic Tests Is Rare
Wall Street Journal, January 11, 2020 (Posted: Jan 11, 2020 11AM)

Genetics is a field of risks—not absolutes—and specific answers for a specific patient are nuanced and can be difficult. It is extremely rare that genetic testing reports change an interpretation from harmful to less than that. Individuals who have been told that they have a BRCA mutation should know that it is exceedingly unlikely that anything has changed.

New PARP Inhibitor Approval for Pancreatic Cancer
L Schlager, FORCE, January 6, 2020 (Posted: Jan 07, 2020 8AM)

The Food and Drug Administration approved olaparib– a type of targeted therapy known as a PARP inhibitor—for treatment of metastatic pancreatic cancer in people with a BRCA mutation. PARP inhibitors have been approved to treat ovarian cancer since 2014, and to treat metastatic breast cancer patients with a BRCA mutation since 2018.

Changes in Classification of BRCA1/2 Mutations are Extremely Rare
Basser Center, December 2019 (Posted: Dec 27, 2019 5PM)

The most important thing that the Basser Center would like you to know is that it is extremely rare that genetic testing reports change an interpretation from harmful to anything less than that. If you have been told that you have a BRCA1 or BRCA2 mutation, it is exceedingly unlikely that anything has changed.

A Genetic Test Led Seven Women in One Family to Have Major Surgery. Then the Odds Changed.
WSJ, December 20,2019 (Posted: Dec 21, 2019 4PM)

Two sisters, their mother and aunts showed a mutation on a BRCA gene and an elevated risk of breast and ovarian cancer

Is prophylactic mastectomy justified in women without BRCA mutation?
Rutgers Emiel J T et al. Breast (Edinburgh, Scotland) 2019 Nov 48 Suppl 1S62-S64 (Posted: Dec 18, 2019 8AM)

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG).
Pal Tuya et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Dec (Posted: Dec 16, 2019 10AM)

With the advances in sequencing technologies and increasing access to and expanding indications for genetic testing, it remains critical to ensure that implementation of testing is based on evidence. Currently, there is insufficient evidence to recommend genetic testing for BRCA1/2 alone or in combination with multigene panels for all breast cancer patients.

How Genetic Testing Saved One Woman's Life
K Kosko, Cure Magazine, December 6, 2019 (Posted: Dec 07, 2019 7AM)

Two-time cancer survivor Anne Weber feels fortunate to have learned of her BRCA2 gene mutation, as it led to an early diagnosis of aggressive breast cancer.

Retesting of women who are negative for a BRCA1 and BRCA2 mutation using a 20-gene panel.
Lerner-Ellis Jordan et al. Journal of medical genetics 2019 Nov (Posted: Dec 03, 2019 8AM)

Our findings indicate that the retesting of BRCA1/2-negative individuals with an expanded panel of 20 breast and ovarian cancer genes can produce clinically relevant results, with a yield of 5.5% for pathogenic variants in genes other than BRCA1 and BRCA2.

Counseling young women with early breast cancer on fertility preservation.
Ter Welle-Butalid M E Elena et al. Journal of assisted reproduction and genetics 2019 Nov (Posted: Nov 25, 2019 8AM)

Women with early stage of breast cancer and a possible future child wish should be referred to an expertise center in breast cancer, fertility preservation, and genetics. Women who have a genetic predisposition for breast cancer like BRCA mutation should be informed about the possibility of pre-implantation genetic diagnosis.

Knowledge and opinions regarding BRCA1 and BRCA2 genetic testing among primary care physicians.
Dekanek Erin W et al. Journal of genetic counseling 2019 Nov (Posted: Nov 20, 2019 8AM)

The findings from this study suggested that primary care providers were not uniformly ready to provide BRCA1/2 genetic testing. Availability of professional society guidelines and evidence of testing's usefulness might motivate the incorporation of BRCA1/2 genetic testing into primary care practices.

Year in Review: Ovarian Cancer: PARP inhibitors, genetic testing, and novel combinations
I Ingram, Medpage Today, November 1, 2019 (Posted: Nov 03, 2019 7AM)

Two themes dominated the ovarian cancer headlines in 2019 -- moving PARP inhibitors into earlier lines of therapy for advanced-stage disease and genetic testing. Over the summer, the U.S. Preventive Services Task Force (USPSTF) broadened its criteria for BRCA cancer susceptibility gene testing in women.

The BRCA gene is about so much more than breast cancer risk
A Goldman, Well and Good, October 27, 2019 (Posted: Nov 01, 2019 10AM)

BRCA literally stands for “BReast CAncer gene,” so it makes sense that we think of a person’s breast cancer risk when we talk about BRCA gene mutations. The thing is, though, that harmful BRCA mutations can impact a person’s risk of developing several other cancers—including pancreatic cancer and prostate cancer—and they’re just less talked about.

Does preventive oophorectomy increase the risk of depression in BRCA mutation carriers?
Kotsopoulos Joanne et al. Menopause (New York, N.Y.) 2019 Oct (Posted: Oct 30, 2019 8AM)

Calling on Primary Care to Prevent BRCA-Related Cancers.
Armstrong Katrina et al. Journal of general internal medicine 2019 Oct (Posted: Oct 30, 2019 8AM)

As a growing number of companies offer genetic testing directly to consumers and new models of genetic counseling are developed, primary care should capitalize on the opportunity to lead in the prevention of BRCA-related cancers-both to ensure that these services are delivered appropriately and that primary care is not left behind.

25 Years of BRCA: How a Cancer Milestone Has Changed the Field
J Infanti, Penn Medicine Blog, October 2019 (Posted: Oct 29, 2019 9AM)

It’s been 25 years since the BRCA1 gene was first cloned — a discovery that accelerated cancer research and opened a new path for exploration in cancer prevention and treatment. The tremendous amount of research and innovation over the past 25 years has led us to a better understanding of the steps we can take to detect cancers early or prevent them altogether.

Angelina Jolie: Medical Advances in Women's Health Are Important. But They're Only Part of the Picture
A Jolie, Time, October 24, 2019 (Posted: Oct 25, 2019 1PM)

I lost my grandmother and my mother to breast cancer. I remember once holding my mother’s hand, as she was receiving chemotherapy, when she started to turn purple and I had to race to get the nurse. Now there are new ways to identify which chemotherapy medication is best for each patient, resulting in fewer of the horrible side effects

Choosing wisely: Selecting PARP inhibitor combinations to promote anti-tumor immune responses beyond BRCA mutations.
Veneris Jennifer Taylor et al. Gynecologic oncology 2019 Oct (Posted: Oct 23, 2019 8AM)

PARP inhibitors have transformed the management of advanced high-grade serous ovarian cancer. Despite the overwhelming success of PARP inhibition, particularly in BRCA-mutated ovarian cancer, several limitations and unanswered questions remain. The population appropriate to target with PARP inhibitors in patients without BRCA mutations is controversial.

BRCA1/2 Genetic Testing Recommendations Still Leave Issues Unresolved
U Penn Medicine, 2019 (Posted: Oct 20, 2019 11AM)

Leaders in BRCA research say screening recommendations from the US Preventive Services Task Force are a positive step forward, but testing of individuals with the highest risk must improve. “We should think of genetic testing like the internet. It’s a tool, full of information, but there’s nuance in making sense of that information."

What Beyonce’s Dad And Angelina Jolie Have In Common
E Matloff, Forbes, October 18, 2019 (Posted: Oct 19, 2019 7AM)

Beyonce’s father, Matthew Knowles, recently went public with the announcement that he has breast cancer and carries a mutation in a gene called BRCA2. He joins Angelina Jolie as a celebrity who has shared his private medical and genetic history in order to raise awareness and potentially help millions of patients and health care providers.

DNA Tests For Psychiatric Drugs Are Controversial But Some Insurers Are Covering Them
G Dangor, NPR, October 17, 2019 (Posted: Oct 18, 2019 8AM)

Debates over efficacy: As the field of genetic testing to help diagnose and treat disease grows, medicine has embraced certain tests, such as that for the BRCA gene linked to breast cancer. But many researchers say there is not enough evidence tying genetic variants to better outcomes for most psychiatric medications.

Beyoncé’s Dad Has a Mutation More African-Americans Should Be Tested For An inherited gene that can be discovered early caused Matthew Knowles’s breast cancer.
E Stallings, NY Times, October 16, 2019 (Posted: Oct 17, 2019 8AM)

Researchers at the Moffitt Cancer Center in Florida found that among young breast cancer patients who met the national guidelines for receiving genetic counseling, only 37 percent of black women had discussed it with a provider compared to 86 percent of white women. Just 36 percent of black women received testing for BRCA compared to 65 percent of white women.

Population BRCA sequencing; time to move to the next phase?
Gourley Charlie et al. BJOG : an international journal of obstetrics and gynaecology 2019 Oct (Posted: Oct 16, 2019 9AM)

Exome Sequencing Reveals a High Prevalence of BRCA1 and BRCA2 Founder Variants in a Diverse Population-Based Biobank
NS Abul-Husn et al, BioRXIV, October 13, 2019 (Posted: Oct 15, 2019 8AM)

The study investigated BRCA1/2 prevalence and impact using exome sequencing and electronic health record (EHR) data from 30,223 adult participants of the BioMe Biobank in New York City. There were 218 (0.7%) individuals harboring expected pathogenic variants, resulting in an overall prevalence of 1 in 139.

BRCA testing in unaffected young women in the United States, 2006-2017.
Guo Fangjian et al. Cancer 2019 Sep (Posted: Oct 09, 2019 8AM)

Over the past decade, there was increased use of BRCA testing for cancer prevention. Additional efforts are needed to maximize the early detection of women with BRCA pathogenic variants so that these cancers may be prevented.

After a Breast Cancer Diagnosis, Men May Be More Likely to Die than Women
NCI, October 2, 2019 Brand (Posted: Oct 04, 2019 9AM)

Men may be more likely than women to die after being diagnosed with breast cancer, particularly during the first 5 years after diagnosis. Fewer than 1% of breast cancers diagnosed each year occur in men and many of them aree associated with BRCA mutations.

Why BRCA mutations are not tumour-agnostic biomarkers for PARP inhibitor therapy
NJ Curtin et al, Nature Rev Clin Oncology, October 3, 2019 (Posted: Oct 04, 2019 9AM)

The activity of PARP inhibitors seems to vary considerably across BRCA1/2-mutant cancers and new insights into the tumour-lineage dependency of this synthetic lethal relationship might explain why BRCA1/2 mutations are not tumour-agnostic biomarkers of a response to PARP inhibitors.

Mathew Knowles reveals he is battling breast cancer: 'We need men to speak out'
H FitzPatrick et al, ABC Good Morning America, October 2, 2019 (Posted: Oct 02, 2019 9AM)

"My mother’s sister died of breast cancer, my mother’s sister’s two and only daughters died of breast cancer and my sister-in-law died in March of breast cancer with three kids – a 9-, 11- and a 15-year-old -- and my mother-in-law had breast cancer...The results from my BRCA test were that I had a mutation on my BRCA2."

Health professional and at-risk BRCA young adult perspectives about information needs: What does Gen Y need to know?
Young Alison Luk et al. Journal of genetic counseling 2019 Sep (Posted: Sep 25, 2019 9AM)

Cancer: more genetic BRCA testing for men
M Marabelli et al, Nature, September 17, 2019 (Posted: Sep 20, 2019 8AM)

The most recent guidelines from the US National Comprehensive Cancer Network recommend BRCA testing for men with metastatic or advanced prostate cancer and a family history of the disease. Broader genetic data on males will improve patient diagnosis and management, and increase treatment and clinical-trial options.

Parental disclosure of positive BRCA1/2 mutation status to children 10 years after genetic testing.
Troïan Jaïs et al. Psychology, health & medicine 2019 Sep 1-11 (Posted: Sep 18, 2019 10AM)

Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes.
Manchanda R et al. BJOG : an international journal of obstetrics and gynaecology 2019 Sep (Posted: Sep 18, 2019 9AM)

Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximize primary prevention for breast-and-ovarian cancer. The study compared long-term outcomes of Ashkenazi jewish population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life

Scientists call for population-wide BRCA testing for higher risk group
B Warman, Cancer Research UK, September 13, 2019 (Posted: Sep 18, 2019 9AM)

Genetic testing for BRCA: Which NCCN criteria tell the tale?
B Kronemyer, Contemporary Ob/Gyn, September 9, 2019 (Posted: Sep 10, 2019 9AM)

USPSTF Recommendation Expands Cancer Screening Pool, Concerns Still Remain
KL Kahl, Cure, August 26, 2019 (Posted: Aug 27, 2019 7AM)

Many see the new USPSTF guidelines as a major step forward in genetics. However, the updated recommendation still comes with concerns: It failed to include newly diagnosed patients with breast or ovarian cancer as well as patients with advanced cancers. In addition, it did not include men. Fifty percent of people with a BRCA mutation are men.

Cancer Patient Says Question Could Save Lives: 'Do You Have Eastern European Jewish Ancestry?'
C Goldberg, WBUR, August 21, 2019 (Posted: Aug 23, 2019 9AM)

"It's really primary care physicians and gynecologists that need to be educated on this matter so that they start identifying their patients who are at this heightened risk. Asking the simple question: 'Do you have Eastern European Jewish ancestry?' will save so many lives."

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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