Relative Contributions of BRCA1 and BRCA2 Mutations to "triple-negative" Breast Cancer in Ashkenazi Women

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2011 Mar 12

PMID 21394499

Citations 41

Authors

E Comen

M Davids

T Kirchhoff

C Hudis

K Offit

M Robson

Affiliations

Soon will be listed here.

Abstract

Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry a founder mutation in BRCA1 or BRCA2. There is an association between BRCA1 mutations and "triple-negative" breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative]. We sought to determine the predictive value of the TNBC phenotype for the presence of a BRCA mutation in AJ women ascertained without respect to family history. DNA samples were collected between 8/2000 and 6/2004 from a prevalent cohort of unselected AJ women with breast cancer (median age at diagnosis 56 years). Samples (n = 451) were genotyped for AJ founder mutations. 352 (78.0%) cancers were ER positive, 254 (56.3%) PR positive, and 91 (20.2%) ER negative/PR negative. 63 (14.0%) cancers were HER2 positive (immunohistochemistry 3+ or FISH >2.2). TNBC was observed in 64 patients (14.2%). Founder mutations were detected in 48 samples (10.6%) including 25/64 TNBC (39.1%; 19 BRCA1, 6 BRCA2). Among TNBC patients with family history (FH) information, 6/15 (40%) mutations were found in women without breast or ovarian cancer in a close relative. The positive predictive value of TNBC for a BRCA1 mutation was 30% overall, 50% in women diagnosed<50 years, and 14% in women diagnosed ≥50. TNBC was significantly associated with detecting a mutation in either BRCA1 or BRCA2, but only 25/52 (48%) mutation-associated cancers were TNBC. The prevalence of BRCA founder mutations exceeds 50% in subsets of AJ women with TNBC. FH is an imperfect predictor of mutation status in this group. A significant number of mutation-associated TNBC are due to BRCA2.

Citing Articles

FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.

Tai Y, Chow A, Han S, Coker C, Ma W, Gu Y EMBO Mol Med. 2024; 16(8):1957-1980.

PMID: 38956205 PMC: 11319505. DOI: 10.1038/s44321-024-00094-2.

Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment.

Adrada B, Moseley T, Kapoor M, Scoggins M, Patel M, Perez F Radiographics. 2023; 43(10):e230034.

PMID: 37792593 PMC: 10560981. DOI: 10.1148/rg.230034.

Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype.

Zang F, Ding X, Chen J, Hu L, Sun J, Zhang J Breast Cancer Res Treat. 2022; 195(3):431-439.

PMID: 35974241 DOI: 10.1007/s10549-022-06702-4.

High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level.

Luo M, Fu A, Wu R, Wei N, Song K, Lim S Int J Biol Sci. 2022; 18(3):1120-1133.

PMID: 35173543 PMC: 8771852. DOI: 10.7150/ijbs.65555.

Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer.

Blum J, Laird A, Litton J, Rugo H, Ettl J, Hurvitz S Clin Cancer Res. 2022; 28(7):1383-1390.

PMID: 35091441 PMC: 9365365. DOI: 10.1158/1078-0432.CCR-21-2080.

References

Chang J, Hilsenbeck S, Sng J, Wong J, Ragu G . Pathological features and BRCA1 mutation screening in premenopausal breast cancer patients. Clin Cancer Res. 2001; 7(6):1739-42. View

Haffty B, Choi D, Goyal S, Silber A, Ranieri K, Matloff E . Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups. Ann Oncol. 2009; 20(10):1653-9. DOI: 10.1093/annonc/mdp051. View

Young S, Pilarski R, Donenberg T, Shapiro C, Hammond L, Miller J . The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009; 9:86. PMC: 2666759. DOI: 10.1186/1471-2407-9-86. View

Lidereau R, Eisinger F, Champeme M, Nogues C, Bieche I, Birnbaum D . Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer. Cancer Res. 2000; 60(5):1206-10. View

Perou C, Jeffrey S, van de Rijn M, Rees C, Eisen M, Ross D . Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96(16):9212-7. PMC: 17759. DOI: 10.1073/pnas.96.16.9212. View

Kauff N, Perez-Segura P, Robson M, Scheuer L, Siegel B, Schluger A . Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. J Med Genet. 2002; 39(8):611-4. PMC: 1735198. DOI: 10.1136/jmg.39.8.611. View

Struewing J, Hartge P, Wacholder S, Baker S, Berlin M, McAdams M . The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997; 336(20):1401-8. DOI: 10.1056/NEJM199705153362001. View

Karp S, Tonin P, Begin L, Martinez J, Zhang J, Pollak M . Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of breast carcinoma in Ashkenazi Jewish women. Cancer. 1997; 80(3):435-41. DOI: 10.1002/(sici)1097-0142(19970801)80:3<435::aid-cncr11>3.0.co;2-y. View

Foulkes W, Stefansson I, Chappuis P, Begin L, Goffin J, Wong N . Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst. 2003; 95(19):1482-5. DOI: 10.1093/jnci/djg050. View

10.

Atchley D, Albarracin C, Lopez A, Valero V, Amos C, Gonzalez-Angulo A . Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol. 2008; 26(26):4282-8. PMC: 6366335. DOI: 10.1200/JCO.2008.16.6231. View

11.

Distelman-Menachem T, Shapira T, Laitman Y, Kaufman B, Barak F, Tavtigian S . Analysis of BRCA1/BRCA2 genes' contribution to breast cancer susceptibility in high risk Jewish Ashkenazi women. Fam Cancer. 2008; 8(2):127-33. DOI: 10.1007/s10689-008-9216-6. View

12.

Kwon J, Gutierrez-Barrera A, Young D, Sun C, Daniels M, Lu K . Expanding the criteria for BRCA mutation testing in breast cancer survivors. J Clin Oncol. 2010; 28(27):4214-20. DOI: 10.1200/JCO.2010.28.0719. View

13.

Turner N, Reis-Filho J . Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006; 25(43):5846-53. DOI: 10.1038/sj.onc.1209876. View

14.

Gonzalez-Angulo A, Timms K, Liu S, Chen H, Litton J, Potter J . Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. 2011; 17(5):1082-9. PMC: 3048924. DOI: 10.1158/1078-0432.CCR-10-2560. View

15.

Newcombe R . Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998; 17(8):857-72. DOI: 10.1002/(sici)1097-0258(19980430)17:8<857::aid-sim777>3.0.co;2-e. View

16.

Zhang L, Kirchhoff T, Yee C, Offit K . A rapid and reliable test for BRCA1 and BRCA2 founder mutation analysis in paraffin tissue using pyrosequencing. J Mol Diagn. 2009; 11(3):176-81. PMC: 2671333. DOI: 10.2353/jmoldx.2009.080137. View

17.

Evans D, Lalloo F, Cramer A, Jones E, Knox F, Amir E . Addition of pathology and biomarker information significantly improves the performance of the Manchester scoring system for BRCA1 and BRCA2 testing. J Med Genet. 2009; 46(12):811-7. DOI: 10.1136/jmg.2009.067850. View

18.

Rakha E, Reis-Filho J, Ellis I . Basal-like breast cancer: a critical review. J Clin Oncol. 2008; 26(15):2568-81. DOI: 10.1200/JCO.2007.13.1748. View

19.

Hammond M, Hayes D, Wolff A, Mangu P, Temin S . American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 2010; 6(4):195-7. PMC: 2900870. DOI: 10.1200/JOP.777003. View

20.

Turner N, Tutt A, Ashworth A . Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004; 4(10):814-9. DOI: 10.1038/nrc1457. View