Genetic testing in women with early-onset breast cancer: a Traceback pilot study

Abstract Purpose In Sweden, a Traceback approach, i.e., a retrospective genetic outreach activity, among cancer patients is not normally used in clinical practice. In this pilot study, we wanted to evaluate a Traceback strategy for possible future clinical implementation and investigate why not all women with early-onset breast cancer underwent genetic testing when they were first diagnosed. Methods Out of all women (n = 409) diagnosed with breast cancer at ≤ 35 years in Southern Sweden between 2000 and 2017, 63 had not previously been tested. These women were offered an analysis of the genes BRCA1, BRCA2, PALB2, CHEK2, and ATM through a standardized letter. Subsequently, women with normal test results were informed through a letter and carriers of pathogenic variants were contacted through a telephone call and offered in-person genetic counseling. All tested women were asked to complete a follow-up questionnaire regarding previously not having attended genetic counseling and testing and their experiences of the current retrospective approach. Results Out of the invited women, 29 (46%) underwent genetic testing and 27 (43%) answered the questionnaire. Pathogenic variants were identified in BRCA1 (n = 2), CHEK2 (n = 1), and ATM (n = 1). The main reason for previously not having undergone genetic testing was not having received any information from their physicians. Most study participants were satisfied with both written pre- and post-test information. Conclusion The process with retrospective identification, written pre-test information, and genetic testing, followed by in-person counseling for carriers of pathogenic variants only, was well accepted. This has implications for future Traceback implementation programs.

Download Full-text

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-107347 ◽

2021 ◽

pp. jmedgenet-2020-107347

Author(s):

D Gareth Evans ◽

Elke Maria van Veen ◽

Helen J Byers ◽

Sarah J Evans ◽

George J Burghel ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Ductal Carcinoma ◽

Cancer Genes ◽

Early Onset Breast Cancer ◽

Younger Women ◽

Pathogenic Variants ◽

Younger Age ◽

Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Download Full-text

Referral and Experience with Genetic Testing Among Women with Early Onset Breast Cancer

Genetic Testing ◽

10.1089/gte.2005.9.301 ◽

2005 ◽

Vol 9 (4) ◽

pp. 301-305 ◽

Cited By ~ 26

Author(s):

Karen L. Brown ◽

Robin Hutchison ◽

Randi E. Zinberg ◽

Margaret M. McGovern

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Early Onset ◽

Early Onset Breast Cancer

Download Full-text

Variations in the Referral Pattern for Genetic Counseling of Patients with Early-Onset Breast Cancer: A Population-Based Study in Southern Sweden

Public Health Genomics ◽

10.1159/000508684 ◽

2020 ◽

Vol 23 (3-4) ◽

pp. 100-109

Author(s):

Annelie Augustinsson ◽

Carolina Ellberg ◽

Ulf Kristoffersson ◽

Håkan Olsson ◽

Hans Ehrencrona

Keyword(s):

Breast Cancer ◽

Genetic Counseling ◽

Early Onset ◽

Population Based ◽

Referral Pattern ◽

Early Onset Breast Cancer ◽

Southern Sweden ◽

Population Based Study

Download Full-text

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study)

The Journal of Pathology Clinical Research ◽

10.1002/cjp2.133 ◽

2019 ◽

Vol 5 (3) ◽

pp. 189-198 ◽

Cited By ~ 6

Author(s):

Kate Packwood ◽

Guy Martland ◽

Matthew Sommerlad ◽

Emily Shaw ◽

Karwan Moutasim ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Early Onset ◽

Early Onset Breast Cancer ◽

Pathogenic Variants ◽

Tumour Characteristics

Download Full-text

Prevalence of BRCA1 and BRCA 2 and other mutations in Chilean population.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13553 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13553-e13553

Author(s):

Carolina Selman ◽

Mabel Hurtado ◽

Badir Chahuan ◽

Fabiola Mella ◽

Hugo Marsiglia

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Triple Negative ◽

Genetic Test ◽

Pathogenic Variants ◽

Brca 2 ◽

Post Test ◽

History Of ◽

Chilean Population

e13553 Background: Arturo López Pérez Foundation (FALP) is a Chilean Institution aimed to treatment of cancer patients. Since 2016 it has an Unit for Oncological Genetic Counseling (AGO) for patients with warning flags of potential cases of cancer of genetic origin AGO Unit is aimed to capture patients with warning flags and deliver information through pre-test counseling, offer possibility of a genetic test and post-test counseling. The purpose of this review is to provide relevant results of four years of this Unit. Methods: A descriptive study was carried out from patient care in the Oncological Genetic Counseling Unit of FALP between 2016 and 2019. It was considered those cases in which the process of pretest/post-test counseling was performed. Six "warningflags" were established: cancer in patients under 50 years of age, triple negative breast cancer, breast cancer in men, ovarian cancer, history of 2 or more primary cancers and a family history of cancer The number of test performed was analyzed. The results were expressed in positive pathogenic variants, uncertain variants and negative results. Results: 365 genetic counseling processes were carried out during the period. The average consultation age was 43.2 years (20.8 and 75.5) and 90.1% (329 attentions ) were female. Of the patients, 79.7% (294) perform the genetic test. 18.5% tested positive for a pathogenic variant, 6.5% for a pathogenic variant plus an uncertain variable, and 2.8% for two pathogenic variants. The mutations found were BRCA2 32.6% BRCA1 29.1%, ATM 10.1% RAD51C 6.7% CDKN2 A 5.6%, MUTYH 3.4% TP53 3.4%, MSH2 3.4% RAD51D 2.4%), NF1 1.1%, NTHL1 1.1%, RET 1.1% A 64.9% (237 patients) had cancer diagnosed at the time of the consultation, versus 33.1% of healthy care. 2% had no information. The type of cancer present was 79.7% breast cancer (189), 8.0% ovarian cancer, 2.1% thyroid cancer, 1.7% breast and ovarian cancer, 0.9% colon and/or endometrial cancer and 7.6% other cancers. The warning flags present were 41.2% age below 50 years, 26.2% family history, 15.4% relatives of people with positive results, 8.5% patients with triple-negative breast cancer, 5.3% patients with ovarian cancer, 2.8% patients with 2 or more primary cancers, and 0.6% male breast cancer patients. Conclusions: The highest percentage of patient care was for women with breast cancer, under 50 years of age. The overall test positivity rate is a cumulative 29%. Mutations in BRCA 1 and BRCA 2 were the most detected mutations, as reported in the literature. The slight predominance of BRCA 2 may be due to a familiar component. This is the largest report made in the Chilean population.

Download Full-text

Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70471-5 ◽

2006 ◽

Vol 2006 ◽

pp. 269-270

Author(s):

L.P. Shulman

Keyword(s):

Breast Cancer ◽

Oral Contraceptive ◽

Early Onset ◽

Contraceptive Use ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Oral Contraceptive Use ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

Download Full-text

Extended gene panel testing in lobular breast cancer

Familial Cancer ◽

10.1007/s10689-021-00241-5 ◽

2021 ◽

Author(s):

Elke M. van Veen ◽

D. Gareth Evans ◽

Elaine F. Harkness ◽

Helen J. Byers ◽

Jamie M. Ellingford ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Detection Rate ◽

Gene Panel ◽

Lobular Breast Cancer ◽

Germline Variants ◽

Panel Testing ◽

Pathogenic Variants ◽

Gene Panel Testing ◽

Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

Download Full-text

Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-021-00176-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lucie G. Hallenstein ◽

Carol Sorensen ◽

Lorraine Hodgson ◽

Shelly Wen ◽

Justin Westhuyzen ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cancer Genetics ◽

Eligibility Criteria ◽

Pathogenic Variants ◽

Genetics Services ◽

Age Of Diagnosis ◽

Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

Download Full-text

Identification and management of familial breast cancer in Austria

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2017-0025 ◽

2017 ◽

Vol 32 (2) ◽

Cited By ~ 1

Author(s):

Christian F. Singer ◽

Yen Y. Tan ◽

Christine Rappaport

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Familial Breast Cancer ◽

Prophylactic Surgery ◽

Management Options ◽

Counseling And Testing ◽

Legal Implications

AbstractAimThe aim of this study is to review the legal implications, the technology, the indications and the management of women with a familial background of breast and/or ovarian cancer.MethodsWe have reviewed the literature and national Austrian guidelines to describe the uptake of genetic counseling and the management options offered in Austria.ResultsGenetic testing for theConclusionWhile readily available country-wide counseling has led to an increase in counseling and testing, Austrian legislation mandates “non-directional counseling” resulting in a comparatively low uptake of prophylactic surgery.

Download Full-text