Real-World data (RWD) of physician’s advice on BRCA genetic testing for ovary (OC) and breast cancer (BC) patients (pts).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19357-e19357
Author(s):  
Daniel A. Vorobiof
Keyword(s):  
Genetic Testing ◽  
Mobile Application ◽  
Triple Negative ◽  
Task Force ◽  
Brca Testing ◽  
Real World Data ◽  
History Of ◽  
Treatment Changes ◽  
Stage 1 ◽  
Brca Genetic Testing

e19357 Background: The 2019 US Preventive Services Task Force (USPSTF) recommends that women with a personal and familiar history of BC and OC undergo a BRCA genetic testing so that risk assessment, prevention options and treatment changes are considered. Methods: BC and OC members of Belong.life global mobile application for cancer pts and caregivers, replied to a 9 question's survey regarding the incidence of BRCA testing. The survey included questions on demographics, BRCA testing performed, who advised it, and on treatment changes. This RWD was analyzed by data scientists using AI and machine learning engines. Results: 377 pts with BC (302/80%) and OC (75/20%) replied to the survey. BC pts ages were < 50 yrs in 32%, 36% were 51-60 yrs and 32% > 61 yrs. 24% of OC pts were < 50 yrs, 35% were 51-60 yrs and 41% > 61 yrs. 73% of BC pts were USA based and 27% from rest of the world (RoW). OC pts were 62% from USA and 38% from RoW. Most of BC pts were stage 1-2 (58%) and 35% stages 3-4. OC pts stages were 3-4 (73%) and 15% stage 1-2. BRCA testing was performed in 192/302 BC pts (64%). In the OC group 60/75 pts (80%) had BRCA testing. Physicians advised to have BRCA testing to 57% of BC pts and 76% of OC, while families/friends suggested it to 4% of BC and OC pts. BRCA test was positive in 19% of BC and 48% of OC pts. 110 BC pts(36%) didn’t undergo the test of whom 74 pts (67%) didn’t receive physician’s advice to have it . Of those pts, 24 (32%) fell under the USPSTF recommendation criteria for testing. Conclusions: BRCA testing should be recommended for all pts with recently diagnosed BC and OC and in those with a higher chance of having a mutation, as defined by the USPSTF guidelines. In this RWD evaluation of Belong.life BC and OC pts, BRCA testing in BC was done in 192/302 pts (64%) while in OC pts it was done in 60/75 pts (80%). Overall, physicians requested the BRCA test in only 57% of BC pts and 76% of the OC pts. In spite of the current USPSTF guidelines, a number of BC pts who didn’t receive advise from their physician (32%) fell under those recommendations, most having their disease diagnosed at < 50 yrs and triple negative disease < 60 yrs. Physicians should be encouraged to follow published guidelines recommendations for BRCA testing for all newly diagnosed BC and OC pts.

scholarly journals BRCA Detection Rate in an Italian Cohort of Luminal Early-Onset and Triple-Negative Breast Cancer Patients without Family History: When Biology Overcomes Genealogy

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1252 ◽  
Author(s):  
Angela Toss ◽  
Eleonora Molinaro ◽  
Marta Venturelli ◽  
Federica Domati ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Detection Rate ◽  
Triple Negative ◽  
Brca2 Mutation ◽  
Brca Testing ◽  
Brca Genetic Testing

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31–40, 16.1% for those aged 41–50 and 7.9% in 51–60 s. A total of 40% of patients with estrogen receptors (ER) 1–9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0–25 years, 9% between 26–30 years and 6% between 31–35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

Prevalence of BRCA2 mutations and other clinical characteristics in women with triple-negative breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 160-160
Author(s):  
Jennifer Chun ◽  
Freya Ruth Schnabel ◽  
Shira Schwartz ◽  
Jessica Billig ◽  
Karen Hiotis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Personal History ◽  
Breast Cancers ◽  
History Of ◽  
Brca2 Mutations

160 Background: Triple-negative breast cancers (TNBC) represent 10%–20% of invasive breast cancers. Current guidelines recommend genetic testing for women who are diagnosed with TNBC. Studies have shown that BRCA1 mutations are associated with TNBC, but there is little information on the relationship of BRCA2 mutations and TNBC. The purpose of this study was to look at the clinical characteristics of TNBC compared to non-TNBC in a cohort of women with newly diagnosed breast cancer. Methods: The Breast Cancer Database at our institution was queried for patients with invasive breast cancer. We included the following variables: age, race, BRCA1,2, tumor characteristics, and personal history of breast cancer (PHBC). Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: Out of a total of 1,332 women, 125 (9%) had TNBC. The median age for both TNBC and non-TNBC was 59 years. Majority of women had early stage breast cancer (92%) with ductal carcinoma (80%). There was a significantly higher proportion of Blacks and Asians with TNBC (p < 0.0001). Women with TNBC had higher Ki-67 (p < 0.0001). Within the TNBC group, there were 12 (29%) patients who tested positive for BRCA1,2 mutation and 23 (8%) who tested positive for BRCA 1,2 mutations in the non-TNBC group. Interestingly, BRCA1 was not associated with TNBC (p = 0.40) and BRCA2 was significantly associated with TNBC (p < 0.0001). We also found a higher proportion of TNBC in women who had a PHBC (p = 0.01). Conclusions: In our study, women with TNBC were similar in age to women who did not have TNBC. We found that the women with TNBC in our cohort had elevated rates of BRCA2 mutations. We also found that women with a personal history of breast cancer were at risk for developing TNBC. This may be related to the use of hormonal therapy that reduces the risk of ER/PR-positive tumors. Women of all ages are at risk for developing TNBC and older age at TNBC should not deter from genetic testing.

Decision support for family history intake to determine eligibility for BRCA testing among multiethnic women.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1586-1586 ◽  
Author(s):  
Julia E. McGuinness ◽  
Meghna S. Trivedi ◽  
Alejandro Vanegas ◽  
Hilary Colbeth ◽  
Rossy Sandoval ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Counseling ◽  
Decision Support ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Self Report ◽  
Brca Testing ◽  
The Family ◽  
Brca Genetic Testing

1586 Background: The U.S. Preventive Services Task Force (USPSTF) recommends that women who meet family history criteria for hereditary breast and ovarian cancer (HBOC) be referred for genetic counseling. However, HBOC genetic testing is under-utilized, particularly among racial/ethnic minorities. We evaluated different methods of family history intake, including a validated family history screener, documentation in the electronic health record (EHR), and a web-based decision aid (DA). Methods: Among women undergoing screening mammography, we administered a validated family history screener to determine eligibility for BRCA genetic testing based upon USPSTF guidelines. We developed a patient-centered DA ( RealRisks) which includes modules on breast cancer risk, collection of detailed family history, and information on HBOC genetic testing. Women who met high-risk criteria for breast cancer were enrolled in an intervention trial to determine whether exposure to RealRisks increases referrals for high-risk consultations. BRCA genetic counseling/testing uptake was assessed by self-report and EHR review. Results: From November 2014 to June 2016, 3077 women completed the family history screener. Median age was 59 years (range, 29-99), including 76% Hispanic, 4% Ashkenazi Jewish, and 60% with a high school education or less. 12% met family history criteria for BRCA genetic testing based upon the family history screener, of which only 5.9% had previously undergone genetic counseling or testing. Sixty high-risk women were enrolled to access RealRisks. When family histories based upon the screener, DA, and EHR were compared, 12 (20%) had discrepancies in number of affected relatives, type of cancer, and age at diagnosis which changed eligibility for BRCA testing. Follow-up is ongoing to determine whether the DA facilitates appropriate referrals for genetic counseling. Conclusions: In a population of predominantly Hispanic and less educated women, a large proportion met USPSTF family history criteria for BRCA testing, but uptake of genetic counseling was low. Developing decision support for accurate family history intake is critical to identifying appropriate candidates for genetic referrals.

scholarly journals Barriers and Opportunities in Genetic Testing for BRCA Gene Mutations in Europe: A Strategic Policy Response to Support Women and Families At Risk for Breast Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 141s-141s
Author(s):  
S. Ahmed ◽  
J. Tate ◽  
M. Thrift-Perry ◽  
S. Wait
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Triple Negative ◽  
Unmet Needs ◽  
Gene Mutations ◽  
Cancer Control ◽  
Brca Mutations ◽  
Brca Gene ◽  
Brca Genetic Testing

Background and context: An estimated 12.5% of women are at risk for breast cancer. 5%-10% of these cases are hereditary, and of these, 20%-25% are due to BRCA gene mutations. Women with BRCA mutations are at higher risk of early onset, recurrence and of triple-negative breast cancer, with fewer treatment options. These women need to be supported to seek genetic testing as early as possible. They also need support and guidance to inform family members, consider preventive interventions and obtain appropriate care and counseling. Aim: To provide an overview of the BRCA genetic testing policy landscape in Europe and highlight barriers to women and their families to access testing, information and support. Strategy: A pragmatic review of international published and gray literature. With a focus on Europe and Israel, we looked for epidemiologic data in six countries and assessed the systems, policies and services in place for genetic testing, counseling and care. This was complemented by semistructured telephone interviews with healthcare professionals, researchers and patient representatives. Policy process: We must develop comprehensive cancer control plans that provide for high-quality prevention, treatment and care for all women with BRCA mutations, whether they develop breast cancer. The unmet needs of later-stage and more difficult-to-treat breast cancers, such as BRCA-mutated or triple-negative must not be neglected. Outcomes: Current BRCA genetic testing guidelines are insufficient. Testing eligibility is restricted to high-risk patients, despite evidence that over half of women diagnosed with BRCA-related breast cancer could be missed with this approach. Access barriers to information and services include: too few genetic counselors to provide information and support to women and their families; limited primary care genetics knowledge which may lead to low referral rates and unequal testing access based on region, age and race. Individuals may also forego testing for fear of discrimination by employers or insurance companies or the effect a positive test might have on families and relationships. What was learned: Opportunities to address the unmet needs of women considering BRCA genetic testing include: greater public awareness and understanding of testing; building professional capacity to better support those getting tested and policies to protect women against discrimination from employers or insurers. The emotional impact on women who undergo testing must also be considered, as well as the provision of appropriate information, support and care through every stage of a woman's experience. This research offers a starting point for discussion with policymakers and patient organizations to ensure pathways and policies are place which integrate the patient experience into comprehensive care pathways and national cancer control plans.

scholarly journals BRCA detection rate in an Italian cohort of luminal early-onset and triple-negative breast cancer patients without family history: when biology overcomes genealogy.

2020 ◽  
Author(s):  
Angela Toss ◽  
Eleonora Molinaro ◽  
Marta Venturelli ◽  
Federica Domati ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Detection Rate ◽  
Triple Negative ◽  
Brca2 Mutation ◽  
Mutational Status ◽  
Brca Genetic Testing

Abstract BACKGROUND: NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. This analysis aimed to evaluate the rate of BRCA mutations in triple-negative breast cancer (TNBC) patients diagnosed ≤60 years and luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family history. METHODS: 159 TNBC patients diagnosed ≤60 years and 109 luminal-like BC patients diagnosed ≤35 years without family history were retrospectively identified. Mutation prevalence and clinical-pathological characteristics associated with mutational status were evaluated. RESULTS: In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1 and 1.2% BRCA2). BRCA1-related TNBC patients were younger (p <0.001). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31-40, 16.1% for those aged 41-50 and 7.9% for those between 51 and 60 years of age. A total of 40% of patients with estrogen receptor (ER) 1-9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (1.8% BRCA1 and 4.6% BRCA2). Mutation prevalence was 0% 0-25 years, 9% 26-30 years and 6% 31-35 years. BRCA2-positive luminal-like early-onset BCs were more likely associated with low progesterone receptor (PR) expression (p = 0.049). CONCLUSIONS: BRCA genetic testing is recommended in TNBC diagnosed ≤ 60 years, regardless of cancer family history, histotype and by using immunohistochemical staining <10% of nuclei for both ER and/PR as a cut-off. In luminal-like early-onset BC patients, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes.

scholarly journals Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

2015 ◽  
Vol 33 (4) ◽  
pp. 304-311 ◽  
Author(s):  
Fergus J. Couch ◽  
Steven N. Hart ◽  
Priyanka Sharma ◽  
Amanda Ewart Toland ◽  
Xianshu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Deleterious Mutations ◽  
Brca1 And Brca2 ◽  
Predisposition Genes ◽  
History Of

Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives.

scholarly journals National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer

2017 ◽  
Vol 35 (34) ◽  
pp. 3800-3806 ◽  
Author(s):  
Christopher P. Childers ◽  
Kimberly K. Childers ◽  
Melinda Maggard-Gibbons ◽  
James Macinko
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Unmet Need ◽  
Cancer Control ◽  
The United States ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Age Of Diagnosis ◽  
History Of ◽  
Interview Survey

Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.

scholarly journals R1352Q CACNA1A Variant in a Patient with Sporadic Hemiplegic Migraine, Ataxia, Seizures and Cerebral Oedema: A Case Report

2021 ◽  
pp. 123-130
Author(s):  
Anker Stubberud ◽  
Emer O’Connor ◽  
Erling Tronvik ◽  
Henry Houlden ◽  
Manjit Matharu
Keyword(s):  
Mental Retardation ◽  
Case Report ◽  
Genetic Testing ◽  
Head Trauma ◽  
Cerebral Oedema ◽  
De Novo ◽  
Minor Head Trauma ◽  
Hemiplegic Migraine ◽  
Wide Range ◽  
History Of

Mutations in the <i>CACNA1A</i> gene show a wide range of neurological phenotypes including hemiplegic migraine, ataxia, mental retardation and epilepsy. In some cases, hemiplegic migraine attacks can be triggered by minor head trauma and culminate in encephalopathy and cerebral oedema. A 37-year-old male without a family history of complex migraine experienced hemiplegic migraine attacks from childhood. The attacks were usually triggered by minor head trauma, and on several occasions complicated with encephalopathy and cerebral oedema. Genetic testing of the proband and unaffected parents revealed a de novo heterozygous nucleotide missense mutation in exon 25 of the <i>CACNA1A</i> gene (c.4055G&#x3e;A, p.R1352Q). The R1352Q <i>CACNA1A</i> variant shares the phenotype with other described <i>CACNA1A</i> mutations and highlights the interesting association of trauma as a precipitant for hemiplegic migraine. Subjects with early-onset sporadic hemiplegic migraine triggered by minor head injury or associated with seizures, ataxia or episodes of encephalopathy should be screened for mutations. These patients should also be advised to avoid activities that may result in head trauma, and anticonvulsants should be considered as prophylactic migraine therapy.

scholarly journals Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hormone Replacement ◽  
Breast Cancers ◽  
Younger Women ◽  
Alternative Pathways ◽  
Increased Risk ◽  
History Of ◽  
Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

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