Use of multi gene-panel testing to detect hereditary breast cancer gene variants in patients attending to a breast cancer clinic, Peradeniya, Sri Lanka

Breast cancer is one of the most common malignancies and the leading cause of death among women worldwide. About 20% of breast cancers are hereditary. Approximately 30% of the mutations have remained negative after testing BRCA1/2 even in families with a Mendelian inheritance pattern for breast cancer. Additional non-BRCA genes have been identified as predisposing for breast cancer. Multi gene panel testing tries to cover and explain the BRCA negative inherited breast cancer, improving efficiency, speed and costs of the breast cancer screening. We identified 23 studies reporting results from individuals who have undergone multi gene panel testing for hereditary breast cancer and noticed a prevalence of 1-12% of non-BRCA genes, but also a high level of variants of uncertain significance. A result with a high level of variants of uncertain significance is likely to be more costly than bring benefits, as well as increase the anxiety for patients. Regarding further development of multi gene panel testing, more research is required to establish both the optimal care of patients with cancer (specific treatments like PARP inhibitors) and the management of unaffected individuals (chemoprevention and/or prophylactic surgeries). Early detection in these patients as well as prophylactic measures will significantly increase the chance of survival. Therefore, multi gene panel testing is not yet ready to be used outside clear guidelines. In conclusion, studies on additional cohorts will be needed to better define the real prevalence, penetrance and the variants of these genes, as well as to describe clear evidence-based guidelines for these patients.

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Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.16 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 16-16

Author(s):

Nimmi S. Kapoor ◽

Lisa D. Curcio ◽

Carlee A. Blakemore ◽

Amy K. Bremner ◽

Rachel E. McFarland ◽

...

Keyword(s):

Breast Cancer ◽

At Risk ◽

Genetic Testing ◽

Hereditary Breast Cancer ◽

Diagnostic Yield ◽

Gene Panel ◽

Panel Testing ◽

Gene Testing ◽

Gene Panel Testing ◽

Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

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Abstract PD7-05: Multi-gene panel testing and the cancers identified in patients at risk for hereditary breast cancer

10.1158/1538-7445.sabcs15-pd7-05 ◽

2016 ◽

Author(s):

NS Kapoor ◽

LD Curcio ◽

M Patrick ◽

J Swisher ◽

JD West ◽

...

Keyword(s):

Breast Cancer ◽

At Risk ◽

Hereditary Breast Cancer ◽

Gene Panel ◽

Panel Testing ◽

Gene Panel Testing ◽

Patients At Risk

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Routine use of gene panel testing in hereditary breast cancer should be performed with caution

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2016.10.008 ◽

2016 ◽

Vol 108 ◽

pp. 33-39 ◽

Cited By ~ 13

Author(s):

Cedric van Marcke ◽

Anne De Leener ◽

Martine Berlière ◽

Miikka Vikkula ◽

Francois P. Duhoux

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Gene Panel ◽

Panel Testing ◽

Gene Panel Testing

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Gene panel testing for hereditary breast cancer

The Medical Journal of Australia ◽

10.5694/mja15.01335 ◽

2016 ◽

Vol 204 (5) ◽

pp. 188-190 ◽

Cited By ~ 6

Author(s):

Ingrid Winship ◽

Melissa C Southey

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Gene Panel ◽

Panel Testing ◽

Gene Panel Testing

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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.

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