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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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283 hot topic(s) found with the query "Ovarian cancer"

Lynch Syndrome Ups Risk for Colorectal, Other Cancers
E Herlache, Cancer Care, March 2024 (Posted: Mar 23, 2024 6AM)

From the article: "It’s impossible to change our genes, but with knowledge comes power. In the case of Lynch syndrome, a genetic condition that ups people’s risks for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening as well as genetic testing, when warranted. Lynch syndrome puts a person at a higher risk of developing colorectal, uterine, and ovarian cancer. It’s also associated with other cancers, including kidney, stomach, bladder, brain, prostate, and pancreatic cancer. "

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.
Fangjian Guo et al. JAMA Netw Open 2024 2 (2) e2356078 (Posted: Feb 15, 2024 9AM)

From the abstract: "Is a population-wide genetic testing strategy more cost-effective than the current family history–based testing strategy for breast and ovarian cancer prevention? This economic evaluation found that population-based BRCA1, BRCA2, and PALB2 testing among unselected women was cost-effective for the prevention of breast and ovarian cancer and remained cost-effective in extensive 1-way sensitivity analyses. Population-wide genetic testing was 100% cost-effective for all the simulations in probabilistic sensitivity analyses; it became cost-inefficient only when the cost of the test exceeded a certain threshold ($825). The findings support the need for a shift toward more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management. "

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."

Secondary (additional) findings from the 100,000 Genomes Project: disease manifestation, healthcare outcomes and costs of disclosure
J Nolan et al, Genetics in Medicine, December 19, 2023 (Posted: Dec 20, 2023 9AM)

From the abstract: "The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia, von Hippel-Lindau. Here we report disclosure processes, manifestation of AF-related disease, outcomes and costs. "

Combined population genomic screening for three high-risk conditions in Australia: a modelling study
P Lacaze et al, e Clin Medicine, November 2023 (Posted: Nov 11, 2023 4PM)

From the abstract: "This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. "

Heterogeneity and treatment landscape of ovarian carcinoma.
Ana C Veneziani et al. Nat Rev Clin Oncol 2023 10 (Posted: Oct 06, 2023 7AM)

From the abstract: "Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. "

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. "

Your Family Connects: A Theory-Based Intervention to Encourage Communication About Possible Inherited Cancer Risk among Ovarian Cancer Survivors and Close Relatives
J Zhao et al, Public Health Genomics, July 25, 2023 (Posted: Jul 26, 2023 9AM)

Encouraging family communication about possible genetic risk has become among the most important avenues for achieving the full potential of genomic discovery for primary and secondary prevention. Yet, effective family-wide risk communication (i.e., conveying genetic risk status and its meaning for other family members) remains a critical gap in the field. We aim to describe the iterative process of developing a scalable population-based communication outreach intervention, Your Family Connects.

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.

Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
A Rosen et al, EJHG, July 20, 2023 (Posted: Jul 20, 2023 7AM)

Germline genetic testing often has implications not only for the individual patient but also for their genetic relatives. This is especially true for high-penetrance pathogenic variants associated with conditions such as familial hypercholesterolemia and hereditary cancer risk syndromes like Lynch syndrome and the hereditary breast and ovarian cancer syndrome. For these conditions, targeted prevention programs are available, and cascade screening is cost-effective. It is therefore highly relevant to find effective strategies to disclose information from the genetic investigation to healthy relatives at risk. Informing relatives at risk enables equitable access to pre-test genetic counselling and a possibility for them to make an informed decision about genetic testing as well as prevention.

The Promise of Population-based Genomic Screening for Selected Hereditary Conditions: Contributions of Cost-Effectiveness Analysis
ND Rao et al, CDC Blog Post, July 14, 2023 Brand (Posted: Jul 14, 2023 1PM)

Initial cost-effectiveness research suggests that simultaneous population genomic screening for three CDC Tier 1 genomic applications (hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia) can be cost effective and reduce morbidity and mortality if implemented in adults younger than 40 years old, costs of screening tests are low, and those found carrying a pathogenic variant have access to preventive care.

Germline Genetic Testing After Cancer Diagnosis.
Allison W Kurian et al. JAMA 2023 6 (Posted: Jun 06, 2023 8AM)

Among patients in the Surveillance, Epidemiology, and End Results registries diagnosed with cancer between 2013 and 2019, what was the prevalence of germline genetic testing? In this observational study that included 1?369?602 patients diagnosed with cancer in California and Georgia, germline genetic testing after cancer diagnosis was low (6.8%; n?=?93?052). Testing was highest in males with breast cancer (50%) and in patients with ovarian cancer (38.6%). Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Summary for Patients: Population Genomic Screening for Three Common Hereditary Conditions.
et al. Ann Intern Med 2023 5 (5) I19 (Posted: Jun 02, 2023 9AM)

Patients who have certain genetic test results are at higher risk for diseases that may be preventable. There is ongoing debate about whether physicians should screen for 3 hereditary conditions: Lynch syndrome (at greater risk for colon cancer), hereditary breast and ovarian cancer, and familial hypercholesterolemia (at greater risk for early heart disease and stroke). This modeling study found that screening for these 3 hereditary conditions is likely cost-effective in U.S. adults younger than 40 years if the testing cost is relatively inexpensive and people have access to preventive care.

Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5 (Posted: May 09, 2023 5AM)

The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.

Offering genetic testing at the point of care may increase uptake
Medical Xpress, May 3, 2023 (Posted: May 05, 2023 10AM)

Genetic testing for hereditary cancers, such as breast, colon, pancreatic, and ovarian cancer, helps at-risk individuals understand their familial risk for these diseases and make informed decisions about next steps in care. But fewer than 20 percent of at-risk patients utilize this testing, and even fewer engage in genetic counseling after referral, often due to clinical workflow challenges or barriers to care. A new study researchers haveidentified a streamlined approach in clinical settings that may help advance these efforts by simplifying the process of identifying hereditary cancer risk and determining subsequent care.

Development and Evaluation of a Telephone Communication Protocol for the Delivery of Personalized Melanoma Genomic Risk to the General Population.
Georgina L Fenton et al. J Genet Couns 2017 12 (2) 370-380 (Posted: May 04, 2023 6AM)

This study aimed to develop an online educational program for using PRS for breast and ovarian cancer risk-assessments and evaluate the impact on genetic healthcare providers’ (GHP) attitudes, confidence, knowledge, and preparedness. The educational program comprised of an online module covering theoretical aspects of PRS, and a facilitated virtual workshop with pre-recorded roleplays and case discussions. Data were collected in pre-and post-education surveys.

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)

A medley of resistance in ovarian cancers
B Hernando et al, Nature Genetics, February 27, 2023 (Posted: Feb 28, 2023 7AM)

Multi-omic profiling of lesions at autopsy reveals a plethora of resistance mechanisms present within individual patients with ovarian cancer. This highlights the extreme challenge faced in treating end-stage disease and underscores the need for new methods of early detection and intervention.

Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of four clinical workflows
C Wang et al, Genetics in Medicine, February 10, 2023 (Posted: Feb 11, 2023 0PM)

This study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program, implemented at 27 health care sites in 10 States using one of four clinical workflows: 1) traditional referral, 2) point-of-care scheduling (POC-S), 3) point-of care counseling/telegenetics (POC-C), and 4) point-of-care testing (POC-T). In 2019, 102,542 patients were screened and 33,113 (32%) were identified as high risk and meeting National Comprehensive Cancer Network (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer, Lynch syndrome or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among sites with workflows that included seeing a genetic counselor prior to testing.

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer.
et al. Nature genetics 2022 12 (Posted: Dec 02, 2022 6AM)

A new study indicates that multiple alterations in DNA repair, including evidence of both BRCA1-type and BRCA2-type homologous recombination deficiency5 within a tumor, might result in particularly profound survival outcomes. The long-term survival of patients whose tumors had CCNE1 amplification is intriguing, and suggests that an engaged tumor-immune microenvironment can overcome the poor primary treatment response typically associated with this biomarker.

The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer.
Garsed Dale W et al. Nature genetics 2022 12 (Posted: Dec 02, 2022 6AM)

We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load.

Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort
M Sarki et al, J Per Med, October 19, 2022 (Posted: Oct 20, 2022 8AM)

Among n = 115 relatives who completed the baseline survey, 38% (n = 44) were in the GT (-) group. Being male (OR: 2.79, 95% CI: 1.10–7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03–19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55–0.92). Reasons for forgoing cascade testing were lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs.

Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment
S Enroth et al, Comm Medicine, October 3, 2022 (Posted: Oct 04, 2022 8AM)

Ovarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30–50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass.

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.

ENTPD1/CD39 as a predictive marker of treatment response to gemogenovatucel-T as maintenance therapy in newly diagnosed ovarian cancer
RP Rocconi et al, Comm Medicine, August 29, 2022 (Posted: Aug 29, 2022 9AM)

Using the NanoString Statistical Algorithm (NSA), we identify high expression of ENTPD1/CD39 (which functions as the rate-limiting step in the production of the immune suppressor adenosine from ATP to ADP) as a presumptive predictor of response to Vigil versus placebo regardless of HRP status on the basis of relapse free survival (median not achieved vs 8.1 months, p?=?0.00007) and overall survival.

Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record
G Elhanan et al, Frontiers in Genetics, April 2022 (Posted: May 26, 2022 7AM)

The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans.

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).

Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer
A Vanderstichel et al, NPJ Genomic Medicine, April 28, 2022 (Posted: Apr 29, 2022 0PM)

We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.

Lynch syndrome; towards more personalized management?
J Llach et al, Best Practice & Research Clinical Gastroenterology, March 2022 (Posted: Apr 20, 2022 9AM)

Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes

The promise and pitfalls of gene testing for cancer risk
J Madhusoodanan, Nature, December 2021 (Posted: Feb 10, 2022 11AM)

Knowing you have a genetic mutation that puts you at risk of ovarian cancer can be life-saving. But with complex decisions awaiting anyone who has a disease variant, many people are choosing not to be tested.

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.

Polygenic risk modeling for prediction of epithelial ovarian cancer risk
EO Daring et al, EJHG. January 14, 2022 (Posted: Jan 17, 2022 7AM)

The model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

A Mini-Symposium: Implementing Precision and Equitable Public Health in Cascade Testing for Genetic Disorders
CDC event, Feb 10, 2022 Brand (Posted: Dec 13, 2021 2PM)

While there are Tier 1 evidence-based guidelines supporting cascade testing for hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial hypercholesterolemia, and other genetic disorders, the focus is on whether such testing should be done, rather than how to implement cascade testing in practice, both effectively and equitably. Before the full potential health impact of cascade genetic testing can be reached, we must develop a much stronger understanding of which component procedures and practices work best, and then leverage those good practices toward delivering precision public health. This two-hour virtual mini-symposium will explore several efforts to better understand what works well in programs relevant to cascade testing for genetic disorders.

Studies Focus on Testing Family Members of Cancer Gene Carriers
NCI, November 2021 Brand (Posted: Dec 04, 2021 6AM)

NCI released a funding opportunity to test a “traceback” strategy, where researchers are finding the women who were previously diagnosed with ovarian cancer, communicating with them (or with their family members if they have died), and offering genetic testing. Traceback is a unique approach to genetic testing because the idea is to work backwards and find previously diagnosed cases to test to improve the detection of families at risk. Three grants using different approaches for traceback testing were funded for 4 years; projects are expected to be completed in 2023. The overall goal is to evaluate the best way to communicate sensitive genetic information to ovarian cancer patients and their immediate family members. Challenges associated with privacy laws and ethical concerns, differences in cultural traditions, and medical literacy are taken into account.

Geometric network analysis provides prognostic information in patients with high grade serous carcinoma of the ovary treated with immune checkpoint inhibitors
R Elkin et al, NPJ Genomic Medicine, November 24, 2021 (Posted: Nov 27, 2021 9AM)

Network analysis methods can potentially quantify cancer aberrations in gene networks without introducing fitted parameters or variable selection. A new network curvature-based method is introduced to provide an integrated measure of variability within cancer gene networks. The method is applied to high-grade serous ovarian cancers (HGSOCs) to predict response to immune checkpoint inhibitors (ICIs) and to rank key genes associated with prognosis.

Should women with Lynch syndrome be offered gynaecological cancer surveillance?
NAJ Ryan, BMJ, September 2, 2021 (Posted: Sep 03, 2021 7AM)

Lynch syndrome is an inherited genetic condition associated with an increased risk of endometrial and ovarian cancer in women. Limited low quality evidence from observational studies show that gynaecological surveillance detects cancers in women with Lynch syndrome; but it is uncertain if this improves survival, and the optimal testing strategy is not established. Inform women with Lynch syndrome about their risk of developing cancer and initiate a discussion about their preference for risk reducing surgery which is definitive, or options for annual review and gynaecological surveillance, explaining their risks and benefits.

Health Equity and Genetic Disorders
CDC, August 2021 Brand (Posted: Sep 01, 2021 7AM)

Public health efforts to achieve health equity need to include people with genetic disorders. Thousands of inherited genetic disorders affect millions of people in the United States. Genetic disorders include both single-gene disorders, such as cystic fibrosis and sickle cell disease, and conditions that make people more likely to develop common chronic diseases, such as hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia.

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

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.

Universal Genetic Testing Is Far From a Reality in Patients With Ovarian Cancer
V Forster, Cancer Therapy Advisor, June 2021 (Posted: Jun 14, 2021 8AM)

Rates of genetic testing in ovarian cancer “remain well below the goal of universal testing,” according to authors of a systematic review and meta-analysis. For many years now, the recommendation from multiple organizations, including the Society of Gynecologic Oncology, has been for universal genetic assessment of women with ovarian cancer.

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.

Management of individuals with germline variants in PALB2: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
M Tishkowitz et al, Genetics in Medicine, May 11, 2021 (Posted: May 12, 2021 8AM)

PALB2 heterozygotes should be offered BRCA1/2-equivalent breast surveillance. Risk-reducing mastectomy can be considered guided by personalized risk estimates. Pancreatic cancer surveillance should be considered, but ideally as part of a clinical trial. Typically, ovarian cancer surveillance is not recommended, and risk-reducing salpingo-oophorectomy should only rarely be considered before the age of 50. Given the mechanistic similarities, PALB2 heterozygotes should be considered for therapeutic regimens and trials as those for BRCA1/2.

The ten genes for breast (and ovarian) cancer susceptibility.
Foulkes William D et al. Nature reviews. Clinical oncology 2021 3 (Posted: Mar 15, 2021 4PM)

ATM, BRCA1, BRCA2, CHEK2, PALB2 and TP53 are all established breast cancer susceptibility genes. Over the past 30 years, many other genes have been proposed as candidates. In these two large studies, the candidacy of several questionable genes has been largely resolved, and a final list of ten genes for breast and, importantly, ovarian cancer risk has emerged.

Interventions Facilitating Family Communication of Genetic Testing Results and Cascade Screening in Hereditary Breast/Ovarian Cancer or Lynch Syndrome: A Systematic Review and Meta-Analysis.
Baroutsou Vasiliki et al. Cancers 2021 13(4) (Posted: Mar 09, 2021 9AM)

The study identified interventions designed to facilitate family communication of genetic testing results and/or cancer predisposition cascade genetic testing for HBOC and LS. We conducted a systematic review and meta-analysis of randomized trials that assessed intervention efficacy for these two outcomes. Additional outcomes were also recorded and synthesized when possible. 14 articles met the inclusion criteria and were included in the narrative synthesis.

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean
SHL George et al, JAMA Network Open, March 1, 2021 (Posted: Mar 02, 2021 8AM)

This genetic association study included 1018 adult women and men with breast and ovarian cancer, of which 144 individuals had a pathogenic variant in a moderate- to high-risk gene. This finding was consistent with high rates of premenopausal breast cancer in Black women with Caribbean ancestry.

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)

Preliminary Screening for Hereditary Breast and Ovarian Cancer Using a Chatbot Augmented Intelligence Genetic Counselor: Development and Feasibility Study.
Sato Ann et al. JMIR formative research 2021 Feb 5(2) e25184 (Posted: Feb 09, 2021 10AM)

This study's objective is to develop a chatbot system that uses augmented intelligence for HBOC screening to determine whether patients meet BRCA1/2 testing criteria. The system was evaluated by a doctor specializing in genetic medicine and certified genetic counselors. We prepared 3 scenarios and created a conversation with the chatbot to reflect each one. Then we evaluated chatbot feasibility, the required time, accuracy of conversations and family history, and the final result.

Treatment of epithelial ovarian cancer
L Kuroki et al, BMJ, November 9, 2020 (Posted: Nov 10, 2020 8AM)

Genetic testing is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the treatment of recurrent ovarian cancer continues to be nuanced and requires extensive review of up to date modalities that balance efficacy with the patient’s quality of life. Maintenance therapy with poly ADP-ribose polymerase inhibitors, bevacizumab, and/or drugs targeting homologous recombination deficiency is widely used.

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.

Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States
GF Gusauskas et al, JAMA Network Open, October 29, 2020 (Posted: Oct 29, 2020 11AM)

his decision analytical model study found that genomic screening for HBOC among unselected women may be cost-effective depending on the age distribution of the women screened. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value.

Implementing Cancer Genomics in State Health Agencies: Mapping Activities to an Implementation Science Outcome Framework.
Green Ridgely Fisk et al. Public health genomics 2020 Sep 1-12 (Posted: Sep 18, 2020 9AM)

We identified state health agency activities addressing hereditary breast and ovarian cancer and Lynch syndrome by reviewing project narratives from Centers for Disease Control and Prevention Cancer Genomics Program funding recipients, leading discussions with state health agencies, and conducting an environmental scan.

Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
AC Fahed et al, Nature Communications, August 20, 2020 (Posted: Aug 21, 2020 9AM)

We study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions — familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background — the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer.

A new test may better predict ovarian cancer survival
L Hopper, USC News, August 17, 2020 (Posted: Aug 20, 2020 7AM)

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.

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 Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer.
Yarmolinsky James et al. JAMA 2020 Feb (7) 646-655 (Posted: Feb 20, 2020 9AM)

Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline.
Konstantinopoulos Panagiotis A et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020 Jan JCO1902960 (Posted: Jan 29, 2020 8AM)

Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer.

Mayo genomic database to use sequencing for 100K participants
G Slabodkin, Health Data Management, January 10, 2020 (Posted: Jan 13, 2020 9AM)

The Mayo Clinic will build a library of genomic sequencing data on 100,000 volunteers, who will be initially screened for three hereditary conditions.Participants in the first part of the study—called Tapestry—will receive screening results for familial hypercholesterolemia, hereditary breast and ovarian cancer (BRCA1 and BRCA2), and Lynch syndrome.

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)

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.

Heartbreaking News, Then Tumor Find Leads to Genetic Testing
V Hackethal, Medscape, December 27, 2019 (Posted: Dec 29, 2019 8AM)

Genetic testing for breast and ovarian cancer has not always been straightforward, and fast-moving research means that genetic testing is becoming more and more complex all the time.

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

Reducing Disparities in Receipt of Genetic Counseling for Underserved Women at Risk of Hereditary Breast and Ovarian Cancer.
Sutton Arnethea L et al. Journal of women's health (2002) 2019 Nov (Posted: Dec 11, 2019 9AM)

Population based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high grade serous ovarian cancer
MedRXIV, December 2019 (Posted: Dec 07, 2019 7AM)

Low rates of cascade genetic testing among families with hereditary gynecologic cancer: An opportunity to improve cancer prevention.
Griffin Natalie E et al. Gynecologic oncology 2019 Nov (Posted: Dec 04, 2019 10AM)

Cascade genetic testing (CGT) of hereditary breast and ovarian cancer (HBOC) or Lynch Syndrome (LS) patients' relatives offers opportunities to prevent cancer, but CGT rates are not well described. We aimed to measure reported disclosure of genetic testing results and CGT rates in these families and evaluate patients' views of educational media.

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.

Diagnostic plasma miRNA-profiles for ovarian cancer in patients with pelvic mass.
Oliveira Douglas Nogueira Perez et al. PloS one 2019 (11) e0225249 (Posted: Nov 21, 2019 7AM)

CMS Aims to Broaden Coverage for NGS Testing in Breast, Ovarian Cancer -Expansion would include patients with risk factors for inherited susceptibility mutations
I Ingram, MedPage Today, October 31, 2019 (Posted: Nov 05, 2019 9AM)

In a proposed decision memo on Tuesday, the agency stated that sufficient evidence exists to support testing when treating physicians determine that patients with breast and ovarian cancer have clinical indications for germline testing, risk factors for an inherited cancer, and have yet to receive such testing.

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.

PARP Inhibitors Show Promise as Initial Treatment for Ovarian Cancer
NCI, October 29, 2019 Brand (Posted: Oct 31, 2019 0PM)

Drugs known as PARP inhibitors are used to treat some women with advanced ovarian cancer that has returned after earlier treatment. Now, results from three new clinical trials show that the drugs might also benefit women who are newly diagnosed with advanced ovarian cancer.

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.

General “Take Action” Infographic
CDC Cancer, 2019 Brand (Posted: Oct 08, 2019 8AM)

Lower your risk of hereditary breast and ovarian cancer. Asking relatives about their cancer histories can be hard. Follow these tips: Share that you have learned that cancers can run in families. Explain that you are creating a record of your family’s history of cancer. •Encourage family members to respond in a way that is most comfortable to them.

A Patient’s Guide to Endometrial Cancer-This cancer is on the rise. But early detection saves lives.
MO Shroeder, US News, October 4, 2019 (Posted: Oct 05, 2019 9AM)

Risk factors for this cancer include: obesity, diabetes, having close relatives like a parent or sibling who have endometrial cancer or colorectal cancer, and a genetic condition called Lynch syndrome. Having Lynch syndrome greatly increases a woman’s risk of developing endometrial cancer, and other cancers like colon and ovarian cancer

Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing.
Greenberg Samantha et al. Cancer medicine 2019 Sep (Posted: Sep 25, 2019 9AM)

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

Learn Your Family History of Breast and Ovarian Cancer
CDC, 2019 Brand (Posted: Sep 16, 2019 8AM)

Learning your family history of cancer, from both your mother’s and father’s sides, can help you know if you have a higher risk for getting breast or ovarian cancer at a young age.Asking your relatives about their cancer histories can be hard. Here are some tips for talking with your family about this topic.

What you need to know about ovarian cancer
CDC, 2019 Brand (Posted: Sep 05, 2019 8AM)

There is no way to know for sure if you will get ovarian cancer. Most women get it without being at high risk. However, several factors may increase a woman’s risk for ovarian cancer, including if you are middle-aged or older; have close family members who have had ovarian cancer; have a genetic mutation called BRCA1 or BRCA2, or Lynch syndrome.

Diagnostic significance assessment of the circulating cell-free DNA in ovarian cancer: An updated meta-analysis.
Li Boxuan et al. Gene 2019 Sep 714143993 (Posted: Aug 27, 2019 6PM)

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.

Genetic Testing Can Reduce Suffering and Save Lives
L Corduck, AJMC, August 14, 2019 (Posted: Aug 15, 2019 8AM)

I am Oneinforty. In late 2016 at the age of 45, I sought genetic counseling and screening after a friend’s urging. The screening showed I had inherited a BRCA gene mutation, putting my lifetime risk of developing breast cancer between 50% and 80%, and my lifetime risk of developing ovarian cancer (for which there is limited screening) between 40% and 60%.

Appraising the role of previously reported risk factors in epithelial ovarian cancer risk: A Mendelian randomization analysis.
Yarmolinsky James et al. PLoS medicine 2019 Aug (8) e1002893 (Posted: Aug 13, 2019 8AM)

The study employed mendelian randomization to systematically evaluate the association of 12 previously reported risk factors with risk of invasive epithelial ovarian cancer, invasive epithelial ovarian cancer histotypes, and low malignant potential tumours in up to 25,509 cases and 40,941 controls in the Ovarian Cancer Association Consortium. ?

PARP Inhibitors Hit the Pancreatic Cancer Scene
D Ternyila, Oncology Nursing News, August 9, 2019 (Posted: Aug 13, 2019 8AM)

PARP inhibitors, which have approved indications in breast and ovarian cancer, are expanding to additional treatment paradigms, including pancreatic cancer. Data from the phase III POLO trial showed that PARP inhibitor significantly improved progression-free survival among patients with germline BRCA-mutated metastatic pancreatic cancer.

Ovarian Cancer Risk Influenced by Vaginal Microbiome?
P Harrison, eMdscape, July 2019 (Posted: Jul 28, 2019 4PM)

Infographic: “What Every Young Woman Needs to Know About Hereditary Breast and Ovarian Cancer”
CDC, 2019 Brand (Posted: Jul 17, 2019 9AM)

The 2019 HBOC and Lynch Syndrome Family Day
Michigan Public Health Institute, Register for event, September 21, 2019 (Posted: Jul 12, 2019 8AM)

The 2019 HBOC and Lynch Syndrome Family Day is a patient-focused educational event designed to bring together people and families who have been impacted by hereditary breast and ovarian cancer (HBOC) or Lynch syndrome. Attendees at this free event will learn about hereditary cancer risks and ways to manage risk.

Fifteen-year survival of invasive epithelial ovarian cancer in women with BRCA1/2 mutations - the National Israeli Study of Ovarian Cancer.
Lavie Ofer et al. Gynecologic oncology 2019 153(2) 320-325 (Posted: Jul 10, 2019 8AM)

Identifying disparities in germline and somatic testing for ovarian cancer.
Huang Marilyn et al. Gynecologic oncology 2019 153(2) 297-303 (Posted: Jul 10, 2019 8AM)

The objectives of this study were to determine the rate of germline and somatic testing in women with ovarian cancer and to identify disparities in testing at a comprehensive cancer center (CCC) and a safety net hospital (SNH).Patients treated for ovarian cancer from 2011 to 2016 were included. There was no difference in germline or somatic testing by race/ethnicity. Disparities in both germline and somatic testing exist

BRCA germline mutation test for all woman with ovarian cancer?
Paradiso A V et al. BMC cancer 2019 Jun 19(1) 641 (Posted: Jul 02, 2019 9AM)

Nevada Health Study Using Genetics To Fight Disease Statewide
N Glick, KUNR, June 28, 2019 (Posted: Jul 01, 2019 1PM)

The Healthy Nevada Project kicked off in 2016, and so far, has around 50,000 participants. Its aim is to eventually reach 1 million people across Nevada. Anyone can sign up, which is what makes it the largest community-based population health study of its kind in the world. For now, the study is looking for three gene variants that are linked to colon cancer, high cholesterol and breast and ovarian cancer.

Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.
Harris Holly R et al. International journal of epidemiology 2019 Jun (Posted: Jun 21, 2019 1PM)

Genetic counseling of patients with ovarian carcinoma: acceptance, timing, and psychological wellbeing.
Van de Beek I et al. Journal of community genetics 2019 Jun (Posted: Jun 12, 2019 7AM)

Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives.
Gori Stefania et al. Critical reviews in oncology/hematology 2019 May 14067-72 (Posted: Jun 12, 2019 7AM)

Tumor-Stroma Proportion as a Predictive Biomarker of Resistance to Platinum-Based Chemotherapy in Patients With Ovarian Cancer
E Lou et al, JAMA Oncology, June 1, 2019 (Posted: Jun 03, 2019 10AM)

Developing a culturally targeted video to enhance the use of genetic counseling in Latina women at increased risk for hereditary breast and ovarian cancer.
Hurtado-de-Mendoza Alejandra et al. Journal of community genetics 2019 May (Posted: May 22, 2019 8AM)

Epithelial ovarian cancer risk: a review of the current genetic landscape.
Flaum Nicola et al. Clinical genetics 2019 May (Posted: May 20, 2019 8AM)

Novel Nanochip Paves Way for Early Ovarian Cancer Detection.
Abbasi Jennifer et al. JAMA 2019 May (18) 1759 (Posted: May 16, 2019 7AM)

Genetic counseling referral for ovarian cancer patients: a call to action.
Garcia Christine et al. Familial cancer 2019 Apr (Posted: Apr 24, 2019 7AM)

Evaluation of telephone genetic counselling to facilitate germline BRCA1/2 testing in women with high-grade serous ovarian cancer.
Tutty Erin et al. European journal of human genetics : EJHG 2019 Apr (Posted: Apr 10, 2019 0PM)

Association between family history, mutation locations, and prevalence of BRCA1 or 2 mutations in ovarian cancer patients.
Singer Christian F et al. Cancer medicine 2019 Mar (Posted: Mar 03, 2019 10AM)

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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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