Top

Published in:

01-11-2019 | Breast Cancer | Epidemiology

Assessing the effectiveness of the National Comprehensive Cancer Network genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations

Authors: Foluso O. Ademuyiwa, Patricia Salyer, Yinjiao Ma, Sherri Fisher, Graham Colditz, Katherine Weilbaecher, Laura J. Bierut

Published in: Breast Cancer Research and Treatment | Issue 1/2019

Abstract

Purpose

Approximately, 10% of breast cancers are hereditary. Identifying women at high risk for hereditary breast and ovarian cancer allows for early detection, prevention, and individualized disease management for those diagnosed with breast cancer. There is limited data about breast cancer genetic risks among African Americans as the majority of the large studies have been conducted in European Americans. We examined the distribution of deleterious genetic mutations in African American breast cancer patients, and evaluated the effectiveness of the National Comprehensive Cancer Network (NCCN) guidelines for identifying African American women at high risk for deleterious genetic mutations.

Methods

African American participants with breast cancer underwent an interview regarding health and family history, and a 30-gene saliva test. Medical records were accessed to determine whether participants had received prior genetic testing as part of usual care, results of previous testing, and cancer characteristics.

Results

Two hundred and fifty participants were enrolled between February 2016 and May 2018. Twenty (8.0%) had a deleterious mutation in one of the 30 genes; BRCA2 had the highest frequency (40.0%). 187 (74.8%) met eligibility for testing based on NCCN guidelines. Only 110 (58.8%) of participants eligible for genetic testing, according to guidelines, had received prior testing as part of routine care. Using the 30-gene test, we identified deleterious mutations in 17 of 187 (9.1%) of those who met NCCN criteria for testing, and three of 63 (4.8%) of those who did not meet criteria for testing nonetheless had a deleterious mutation associated with breast cancer.

Conclusions

Our results indicate that a large proportion of African American breast cancer patients who meet criteria for genetic testing do not receive it as part of routine care. Even in women who do not meet testing guidelines, nearly 5% have a known deleterious mutation associated with breast cancer.

Available only for authorised users

Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250(4988):1684–1689CrossRef

Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science (New York, NY) 266(5182):66–71CrossRef

King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J, Ford L, Dunn BK, Costantino J, Wickerham L, Wolmark N, Fisher B, National Surgical Adjuvant B, Bowel P (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286(18):2251–2256CrossRef

Duffy SW, Nixon RM (2002) Estimates of the likely prophylactic effect of tamoxifen in women with high risk BRCA1 and BRCA2 mutations. Br J Cancer 86(2):218–221. https://doi.org/10.1038/sj.bjc.6600064 CrossRefPubMedPubMedCentral

Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101(2):80–87. https://doi.org/10.1093/jnci/djn442 CrossRefPubMedPubMedCentral

Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, Weber B, Rebbeck T, Neuhausen SL, Ghadirian P, Foulkes WD, Gershoni-Baruch R, Friedman E, Rennert G, Wagner T, Isaacs C, Kim-Sing C, Ainsworth P, Sun P, Narod SA (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23(30):7491–7496. https://doi.org/10.1200/JCO.2004.00.7138 CrossRefPubMed

Metcalfe K, Gershman S, Lynch HT, Ghadirian P, Tung N, Kim-Sing C, Olopade OI, Domchek S, McLennan J, Eisen A, Foulkes WD, Rosen B, Sun P, Narod SA (2011) Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 104(9):1384–1392. https://doi.org/10.1038/bjc.2011.120 CrossRefPubMedPubMedCentral

Metcalfe K, Lynch HT, Foulkes WD, Tung N, Kim-Sing C, Olopade OI, Eisen A, Rosen B, Snyder C, Gershman S, Sun P, Narod SA (2015) Effect of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers. JAMA Oncol 1(3):306–313. https://doi.org/10.1001/jamaoncol.2015.0658 CrossRefPubMed

Kotsopoulos J, Huzarski T, Gronwald J, Singer CF, Moller P, Lynch HT, Armel S, Karlan B, Foulkes WD, Neuhausen SL, Senter L, Tung N, Weitzel JN, Eisen A, Metcalfe K, Eng C, Pal T, Evans G, Sun P, Lubinski J, Narod SA, Hereditary Breast Cancer Clinical Study G (2017) Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 109(1):89. https://doi.org/10.1093/jnci/djw177 CrossRef

10.

Expert Panel on Breast I, Mainiero MB, Moy L, Baron P, Didwania AD, diFlorio RM, Green ED, Heller SL, Holbrook AI, Lee SJ, Lewin AA, Lourenco AP, Nance KJ, Niell BL, Slanetz PJ, Stuckey AR, Vincoff NS, Weinstein SP, Yepes MM, Newell MS (2017) ACR appropriateness criteria((R)) breast cancer screening. J Am Coll Radiol 14(11S):S383–S390. https://doi.org/10.1016/j.jacr.2017.08.044 CrossRef

11.

Lehman CD, Blume JD, Weatherall P, Thickman D, Hylton N, Warner E, Pisano E, Schnitt SJ, Gatsonis C, Schnall M, DeAngelis GA, Stomper P, Rosen EL, O’Loughlin M, Harms S, Bluemke DA, International Breast MRICWG (2005) Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 103(9):1898–1905. https://doi.org/10.1002/cncr.20971 CrossRefPubMed

12.

Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R, Kuhn W, Schild HH (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23(33):8469–8476. https://doi.org/10.1200/JCO.2004.00.4960 CrossRefPubMed

13.

Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA, Cutrara MR, DeBoer G, Yaffe MJ, Messner SJ, Meschino WS, Piron CA, Narod SA (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292(11):1317–1325. https://doi.org/10.1001/jama.292.11.1317 CrossRefPubMed

14.

Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG, Gilbert FJ, Griebsch I, Hoff RJ, Kessar P, Lakhani SR, Moss SM, Nerurkar A, Padhani AR, Pointon LJ, Thompson D, Warren RM, group Ms (2005) Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 365(9473):1769–1778. https://doi.org/10.1016/S0140-6736(05)66481-1 CrossRefPubMed

15.

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL (2018) Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 379(8):753–763. https://doi.org/10.1056/NEJMoa1802905 CrossRefPubMed

16.

Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533. https://doi.org/10.1056/NEJMoa1706450 CrossRefPubMed

17.

Bustamante CD, Burchard EG, De la Vega FM (2011) Genomics for the world. Nature 475(7355):163–165. https://doi.org/10.1038/475163a CrossRefPubMedPubMedCentral

18.

Collins FS, Manolio TA (2007) Merging and emerging cohorts: necessary but not sufficient. Nature 445(7125):259. https://doi.org/10.1038/445259a CrossRefPubMed

19.

Need AC, Goldstein DB (2009) Next generation disparities in human genomics: concerns and remedies. Trends Genet 25(11):489–494. https://doi.org/10.1016/j.tig.2009.09.012 CrossRefPubMed

20.

James RD, Yu JH, Henrikson NB, Bowen DJ, Fullerton SM, Health Disparities Working G (2008) Strategies and stakeholders: minority recruitment in cancer genetics research. Community Genet 11(4):241–249. https://doi.org/10.1159/000116878 CrossRefPubMed

21.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502. https://doi.org/10.1001/jama.295.21.2492 CrossRefPubMed

22.

Ooi SL, Martinez ME, Li CI (2011) Disparities in breast cancer characteristics and outcomes by race/ethnicity. Breast Cancer Res Treat 127(3):729–738. https://doi.org/10.1007/s10549-010-1191-6 CrossRefPubMed

23.

DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A (2017) Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 67(6):439–448. https://doi.org/10.3322/caac.21412 CrossRefPubMed

24.

Ademuyiwa FO, Gao F, Hao L, Morgensztern D, Aft RL, Ma CX, Ellis MJ (2015) US breast cancer mortality trends in young women according to race. Cancer 121(9):1469–1476. https://doi.org/10.1002/cncr.29178 CrossRefPubMed

25.

Armstrong K, Micco E, Carney A, Stopfer J, Putt M (2005) Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA 293(14):1729–1736. https://doi.org/10.1001/jama.293.14.1729 CrossRefPubMed

26.

Churpek JE, Walsh T, Zheng Y, Moton Z, Thornton AM, Lee MK, Casadei S, Watts A, Neistadt B, Churpek MM, Huo D, Zvosec C, Liu F, Niu Q, Marquez R, Zhang J, Fackenthal J, King MC, Olopade OI (2015) Inherited predisposition to breast cancer among African American women. Breast Cancer Res Treat 149(1):31–39. https://doi.org/10.1007/s10549-014-3195-0 CrossRefPubMed

27.

States SCotU (2013) Association for molecular pathology et al. v. Myriad Genetics, inc., et al.. vol 12-398

28.

Goodman LA (1961) Snowball sampling. Ann Math Stat 32(1):148–170CrossRef

29.

Pal T, Bonner D, Kim J, Monteiro AN, Kessler L, Royer R, Narod SA, Vadaparampil ST (2013) Early onset breast cancer in a registry-based sample of African-american women: BRCA mutation prevalence, and other personal and system-level clinical characteristics. Breast J 19(2):189–192. https://doi.org/10.1111/tbj.12083 CrossRefPubMed

30.

Tung NM, Bobbili PJ, Olufade TO, DerSarkissian M, Bhak R, Reiff J, Briceno JM, Yu H, Shenolikar R, Duh MS (2018) Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among breast cancer patients. J Clin Oncol 36(15_suppl):e13624–e13624. https://doi.org/10.1200/jco.2018.36.15_suppl.e13624 CrossRef

31.

Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130. https://doi.org/10.1086/375033 CrossRefPubMedPubMedCentral

32.

Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31(1):33–36. https://doi.org/10.1038/ng853 CrossRefPubMed

33.

Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62(3):676–689. https://doi.org/10.1086/301749 CrossRefPubMedPubMedCentral

34.

Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, Gumpper KL, Scholl T, Tavtigian SV, Pruss DR, Critchfield GC (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20(6):1480–1490. https://doi.org/10.1200/JCO.2002.20.6.1480 CrossRefPubMed

35.

King MC, Levy-Lahad E, Lahad A (2014) Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA 312(11):1091–1092. https://doi.org/10.1001/jama.2014.12483 CrossRefPubMed

36.

Beitsch PD, Whitworth PW, Hughes K, Patel R, Rosen B, Compagnoni G, Baron P, Simmons R, Smith LA, Grady I, Kinney M, Coomer C, Barbosa K, Holmes DR, Brown E, Gold L, Clark P, Riley L, Lyons S, Ruiz A, Kahn S, MacDonald H, Curcio L, Hardwick MK, Yang S, Esplin ED, Nussbaum RL (2019) Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol 37(6):453–460. https://doi.org/10.1200/JCO.18.01631 CrossRefPubMed

37.

Surgeons ASoB American Society of Breast Surgeons. https://www.breastsurgeons.org/about/statements/PDF_Statements/Hereditary_Genetic_Testing_Patients_With_Without_Breast_Cancer.pdf. Accessed 24 May 2019

38.

Nanda R, Schumm LP, Cummings S, Fackenthal JD, Sveen L, Ademuyiwa F, Cobleigh M, Esserman L, Lindor NM, Neuhausen SL, Olopade OI (2005) Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. JAMA 294(15):1925–1933. https://doi.org/10.1001/jama.294.15.1925 CrossRefPubMed

39.

Fackenthal JD, Olopade OI (2007) Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 7(12):937–948. https://doi.org/10.1038/nrc2054 CrossRefPubMed

40.

Newman B, Mu H, Butler LM, Millikan RC, Moorman PG, King MC (1998) Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 279(12):915–921CrossRef

41.

Haffty BG, Choi DH, Goyal S, Silber A, Ranieri K, Matloff E, Lee MH, Nissenblatt M, Toppmeyer D, Moran MS (2009) Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups. Ann Oncol 20(10):1653–1659. https://doi.org/10.1093/annonc/mdp051 CrossRefPubMed

Title: Assessing the effectiveness of the National Comprehensive Cancer Network genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations
Authors: Foluso O. Ademuyiwa
Patricia Salyer
Yinjiao Ma
Sherri Fisher
Graham Colditz
Katherine Weilbaecher
Laura J. Bierut
Publication date: 01-11-2019
Publisher: Springer US
Keywords: Breast Cancer
Ovarian Cancer
Ovarian Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 1/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05359-w

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge

In BRCA mutation carriers breast conserving surgery may not be the best choice

Improved survival of older patients with advanced breast cancer due to an increase in systemic treatments: a population-based study

Risk of malignancy in papillary neoplasms of the breast

Plasma cell-free DNA chromosomal instability analysis by low-pass whole-genome sequencing to monitor breast cancer relapse

Correction to: Non-contrast MRI for breast screening: preliminary study on detectability of benign and malignant lesions in women with dense breasts

Keynote webinar | Spotlight on antibody–drug conjugates in cancer