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Current Breast Cancer Reports

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01-06-2020 | Magnetic Resonance Imaging | Breast Cancer Genetics (B Arun, Section Editor)

Risk Management for BRCA1/BRCA2 Mutation Carriers Without and With Breast Cancer

Authors: C. B. Mainor, C. Isaacs

Published in: Current Breast Cancer Reports | Issue 2/2020

Abstract

Purpose of Review

We review the management for unaffected BRCA1/2 mutation carriers and the local management of early-stage breast cancer.

Recent Findings

For unaffected BRCA1/2 mutation carriers, surveillance includes annual magnetic resonance imaging (MRI) and mammogram (MG). Novel imaging modalities, including abbreviated protocol MRI, ultrafast/accelerated MRI, and contrast-enhanced digital mammography are being investigated. Risk-reducing mastectomy (RRM) should be considered, and nipple-areolar sparing mastectomy (NSM) is now an option. Additionally, risk-reducing salpingo-oophorectomy (RRSO) is strongly recommended as it reduces mortality. In BRCA1/2 mutation carriers with breast cancer, BCT is an appropriate treatment option but to reduce risk of second primary, mastectomy and contralateral risk-reducing mastectomy should be considered.

Summary

Breast and ovarian cancer screening and prevention options result in improved outcomes and decreased mortality in BRCA1/2 mutation carriers. In women with BRCA1/2 mutations who have BC, local management of the BC and secondary surgical prevention measures are different than women with sporadic disease.

Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER Cancer Statistics Review, 1975-2016;2019 ASI 4474-35. National Cancer Institute. Bethesda, MD: 2019 April.

Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips K, Mooij TM, Roos-Blom M, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017 Jun 20;317(23):2402–16. https://doi.org/10.1001/jama.2017.7112.CrossRefPubMed

Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. The New England Journal of Medicine. 1997 May 15;336(20):1401–8. https://doi.org/10.1056/NEJM199705153362001.CrossRefPubMed

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 May 1;34(13):1460–8. https://doi.org/10.1200/JCO.2015.65.0747.CrossRef

Markham MJ, Moore K. Management of ovarian cancer associated with BRCA and other genetic mutations [Internet]. [cited 11/21/19]. Available from: https://www.uptodate.com/contents/management-of-ovarian-cancer-associated-with-brca-and-other-genetic-mutations?search=ovarian%20cancer%20BRCA&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.

van der Groep P, van der Wall E, van Diest P. Pathology of hereditary breast cancer. Cell Oncol. 2011 Apr;34(2):71–88. https://doi.org/10.1007/s13402-011-0010-3.CrossRef

Lakhani SR, van de Vijver, Marc J, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, et al. The pathology of familial breast Cancer: predictive value of Immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations inBRCA1andBRCA2. J Clin Oncol 2002 May;20(9):2310–2318. DOI: https://doi.org/10.1200/JCO.2002.09.023.

Casasanta N, Kipnis ST, Linville L, Lipinski S, Knoedler A, Marino A, et al. Relationship between hereditary cancer syndromes and oncotype DX recurrence score. Clinical Breast Cancer. 2019 Aug.. https://doi.org/10.1016/j.clbc.2019.07.004.

Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clinical Cancer Research. 2004 Apr 1;10(7):2473–81. https://doi.org/10.1158/1078-0432.CCR-1029-3.CrossRefPubMed

10.

NCCN practice guidelines BRCA-related breast and/or ovarian cancer syndrome Version 3.2019 [Internet].; 2019 [updated 1/18/; ]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.

11.

Warner E, Hill K, Causer P, Plewes D, Jong R, Yaffe M, et al. Prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging. Journal of Clinical Oncology. 2011 May 1;29(13):1664–9. https://doi.org/10.1200/JCO.2009.27.0835.CrossRefPubMedPubMedCentral

12.

Kriege M, Brekelmans CTM, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. The New England Journal of Medicine. 2004 Jul 29;351(5):427–37. https://doi.org/10.1056/NEJMoa031759.CrossRefPubMed

13.

Warner E. Screening BRCA1 and BRCA2 mutation carriers for breast cancer. Cancers. 2018 Nov 30;10(12):447.CrossRef

14.

Saadatmand S, Obdeijn IM, Rutgers EJ, Oosterwijk JC, Tollenaar RA, Wolingh GH, et al. Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC). Int J Cancer. 2015;137(7):1729–38. https://doi.org/10.1002/ijc.29534.CrossRefPubMed

15.

Riedl CC, Luft N, Bernhart C, Weber M, Bernathova M, Tea MM, et al. Triple-modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015 Apr 1;33(10):1128–35. https://doi.org/10.1200/JCO.2014.56.8626.CrossRef

16.

Berg WA, Blume JD, Cormack JB, Mendelson EB, Lehrer D, Böhm-Vélez M, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008 May 14;299(18):2151–63. https://doi.org/10.1001/jama.299.18.2151.CrossRefPubMedPubMedCentral

17.

Berg WA, Zhang Z, Lehrer D, Jong RA, Pisano ED, Barr RG, et al. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA. 2012 Apr 4;307(13):1394–404. https://doi.org/10.1001/jama.2012.388.CrossRefPubMedPubMedCentral

18.

Kuhl CK, Schrading S, Strobel K, Schild HH, Hilgers R, Bieling HB. Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection—a novel approach to breast cancer screening with MRI. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 Aug 1;32(22):2304–10. https://doi.org/10.1200/JCO.2013.52.5386.CrossRef

19.

Greenwood HI. Abbreviated protocol breast MRI: the past, present, and future. Clin Imaging. 2019 Jan;53:169–73. https://doi.org/10.1016/j.clinimag.2018.10.017.CrossRefPubMed

20.

Mann RM, Mus RDM, Zelst Jv, Geppert C, Karssemeijer N, Platel B. A novel approach to contrast-enhanced breast magnetic resonance imaging for screening: high-resolution ultrafast dynamic imaging. Investig Radiol 2014;49(9):579–585. DOI: https://doi.org/10.1097/RLI.0000000000000057.

21.

Sung JS, Lebron L, Keating D, D’Alessio D, Comstock CE, Lee CH, et al. Performance of dual-energy contrast-enhanced digital mammography for screening women at increased risk of breast cancer. Radiology. 2019 Aug 27;293(1):182660–88. https://doi.org/10.1148/radiol.2019182660.CrossRef

22.

Skates SJ, Greene MH, Buys SS, Mai PL, Brown P, Piedmonte M, et al. Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk—combined results from two screening trials. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017 Jul 15;23(14):3628–37. https://doi.org/10.1158/1078-0432.CCR-15-2750.CrossRef

23.

Rebbeck TR, Friebel T, Lynch HT, Neuhausen SL, van’t Veer L, Garber JE, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. Journal of Clinical Oncology. 2004 Mar 15;22(6):1055–62. https://doi.org/10.1200/JCO.2004.04.188.CrossRefPubMed

24.

Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010 Sep 1;304(9):967–75. https://doi.org/10.1001/jama.2010.1237.CrossRefPubMedPubMedCentral

25.

Heemskerk-Gerritsen B, Jager A, Koppert L, Obdeijn A, Collée M, Meijers-Heijboer H, et al. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2019 Oct;177(3):723–33. https://doi.org/10.1007/s10549-019-05345-2.CrossRefPubMedPubMedCentral

26.

Jakub JW, Peled AW, Gray RJ, Greenup RA, Kiluk JV, Sacchini V, et al. Oncologic safety of prophylactic nipple-sparing mastectomy in a population with BRCA mutations: a multi-institutional study. JAMA Surgery. 2018 Feb 1;153(2):123–9. https://doi.org/10.1001/jamasurg.2017.3422.CrossRefPubMed

27.

•• Grobmyer SR, Pederson HJ, Valente SA, Al-Hilli Z, Radford D, Djohan R, et al. Evolving indications and long-term oncological outcomes of risk-reducing bilateral nipple-sparing mastectomy. BJS Open. 2019 Apr;3(2):169–73. https://doi.org/10.1002/bjs5.50117. This study focused on outcomes related to nipple sparing mastectomy in patients without breast cancer at a single institution.

28.

Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Journal of the National Cancer Institute. 2009 Jan 21;101(2):80–7. https://doi.org/10.1093/jnci/djn442.CrossRefPubMedPubMedCentral

29.

Heemskerk-Gerritsen BAM, Seynaeve C, van Asperen CJ, Ausems MGEM, Collée JM, van Doorn HC, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. Journal of the National Cancer Institute. 2015;107(5):1. https://doi.org/10.1093/jnci/djv033.CrossRef

30.

Kotsopoulos J, Huzarski T, Gronwald J, Singer CF, Moller P, Lynch HT, et al. Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute. 2017 Jan;109(1). https://doi.org/10.1093/jnci/djw177.

31.

Terry MB, Daly MB, Phillips KA, Ma X, Zeinomar N, Leoce N, et al. Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk. Journal of the National Cancer Institute. 2018 Nov 28;111(3):331–4. https://doi.org/10.1093/jnci/djy182.CrossRefPubMedCentral

32.

Isaacs C, Peshkin B. Cancer risk management of BRCA carriers without cancer [Internet].; 2019 [updated May; cited Sept 2019]. Available from: https://www.uptodate.com/contents/cancer-risks-and-management-of-brca-carriers-without-cancer#H26548417.

33.

King M, Wieand S, Hale K, Lee M, Walsh T, Owens K, et al. 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. 2001 Nov 14;286(18):2251–6. https://doi.org/10.1001/jama.286.18.2251.CrossRefPubMed

34.

• Finch APM, Lubinski J, Møller P, Singer CF, Karlan B, Senter L, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 May 20;32(15):1547–53. https://doi.org/10.1200/JCO.2013.53.2820. This report focused on the benefit of preventive oophorectomy in women withBRCAmutations.

35.

Shu CA, Pike MC, Jotwani AR, Friebel TM, Soslow RA, Levine DA, et al. Uterine cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations. JAMA Oncology. 2016 Nov 1;2(11):1434–40. https://doi.org/10.1001/jamaoncol.2016.1820.CrossRefPubMedPubMedCentral

36.

Lu KH, Nebgen DR, Norquist B, Bowen DJ, Bakkum-Gamez JN, Romero I, et al. WISP: a prospective, multi-center trial of salpingectomy with delayed oophorectomy versus risk reducing salpingo-oophorectomy in women at increased risk for hereditary ovarian cancer. Gynecol Oncol. 2019 Jun;154:22. https://doi.org/10.1016/j.ygyno.2019.04.055.CrossRefPubMed

37.

Kotsopoulos J, Gronwald J, Karlan BY, Huzarski T, Tung N, Moller P, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncology. 2018 Aug 1;4(8):1059–65. https://doi.org/10.1002/ijc.29386.CrossRefPubMedPubMedCentral

38.

JAMA. Treatment of early-stage breast cancer. Jama. 1991;265(3):391–5.CrossRef

39.

Haffty BG, Harrold E, Khan AJ, Pathare P, Smith TE, Turner BC, et al. Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. The Lancet. 2002 Apr 27;359(9316):1471–7. https://doi.org/10.1016/S0140-6736(02)08434-9.CrossRef

40.

Brekelmans CTM, Tilanus-Linthorst MMA, Seynaeve C, vd Ouweland A, Menke-Pluymers MBE, Bartels CCM, et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 2006;43(5):867–876. DOI: https://doi.org/10.1016/j.ejca.2006.12.009.

41.

Garcia-Etienne C, Barile M, Gentilini O, Botteri E, Rotmensz N, Sagona A, et al. Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer? Ann Surg Oncol. 2009 Dec;16(12):3380–7. https://doi.org/10.1245/s10434-009-0638-7.CrossRefPubMed

42.

Kirova YM, Savignoni A, Sigal-Zafrani B, Rochefordiere A, Salmon RJ, This P, et al. Is the breast-conserving treatment with radiotherapy appropriate in mutation carriers? Long-term results and review of the literature. Breast Cancer Research and Treatment. 2009 Dec 24;120(1):119–26. https://doi.org/10.1007/s10549-009-0685-6.CrossRefPubMed

43.

Pierce LJ, Phillips K, Griffith KA, Buys S, Gaffney DK, Moran MS, et al. Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat. 2010 Jun;121(2):389–98. https://doi.org/10.1007/s10549-010-0894-z.CrossRefPubMedPubMedCentral

44.

Valachis A, Nearchou A, Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144(3):443.CrossRef

45.

van den Broek A, Schmidt M, van’t Veer L, Oldenburg HS, Rutgers E, Russell N, et al. Prognostic impact of breast-conserving therapy versus mastectomy of BRCA1/2 mutation carriers compared with noncarriers in a consecutive series of young breast cancer patients. Ann Surg 2019 Aug;270(2):364–372. DOI: https://doi.org/10.1097/SLA.0000000000002804.

46.

Pierce LJ, Griffith KA, Buys S, Gaffney D, Haffty B, Moran M, et al. Outcomes following breast conservation versus mastectomy in BRCA1/2 carriers with early-stage breast cancer. Journal of Clinical Oncology. 2008 May 20;26(15_suppl):536. https://doi.org/10.1200/jco.2008.26.15_suppl.536.CrossRef

47.

Nilsson M, Hartman L, Kristoffersson U, Johannsson O, Borg Å, Henriksson K, et al. High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer. Breast Cancer Res Treat. 2014 Oct;147(3):571–8. https://doi.org/10.1007/s10549-014-3115-3.CrossRefPubMedPubMedCentral

48.

Manning A, Wood C, Eaton A, Stempel M, Capko D, Pusic A, et al. Nipple-sparing mastectomy in patients with BRCA 1/2 mutations and variants of uncertain significance. The British journal of surgery. 2015 Aug 27;102(11):1354–9. https://doi.org/10.1002/bjs.9884.CrossRefPubMedPubMedCentral

49.

Drooger J, Akdeniz D, Pignol J, Koppert L, McCool D, Seynaeve C, et al. Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age. Breast Cancer Res Treat. 2015 Nov 1;154(1):171–80. https://doi.org/10.1007/s10549-015-3597-7.CrossRefPubMedPubMedCentral

50.

Bernstein JL, Thomas DC, Shore RE, Robson M, Boice JD, Stovall M, et al. Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: a WECARE study report. Eur J Cancer. 2013;49(14):2979–85. https://doi.org/10.1016/j.ejca.2013.04.028.CrossRefPubMedPubMedCentral

51.

Pierce LJ, Strawderman M, Narod SA, Oliviotto I, Eisen A, Dawson L, et al. Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. Journal of Clinical Oncology. 2000 Oct 19;18(19):3360–9. https://doi.org/10.1200/JCO.2000.18.19.3360.CrossRefPubMed

52.

Shanley S, McReynolds K, Arden-Jones A, Ahern R, Fernando I, Yarnold J, et al. Late toxicity is not increased in BRCA1/BRCA2 mutation carriers undergoing breast radiotherapy in the United Kingdom. Clinical Cancer Research. 2006 Dec 1;12(23):7025–32. https://doi.org/10.1158/1078-0432.CCR-06-1244.CrossRefPubMed

53.

Ahmed F, Christos PJ, Singh P, Parashar B, Wernicke AG. Analysis of outcomes in patients with BRCA1/2 breast cancer mutations treated with accelerated partial breast irradiation (APBI). American journal of clinical oncology. 2019 Apr 9;42(5):446–53. https://doi.org/10.1097/COC.0000000000000542.CrossRefPubMed

54.

Graeser MK, Engel C, Rhiem K, Gadzicki D, Bick U, Kast K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. Journal of Clinical Oncology. 2009 Dec 10;27(35):5887–92. https://doi.org/10.1200/JCO.2008.19.9430.CrossRefPubMed

55.

Malone KE, Begg C, Rhiem K, Gadzicki D, Bick U, Kast K, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. Journal of Clinical Oncology. 2010 May 10;28(14):2404–10. https://doi.org/10.1200/JCO.2009.24.2495.CrossRefPubMedPubMedCentral

56.

van den Broek AJ, van’t Veer Laura J, Hooning MJ, Cornelissen S, Broeks A, Rutgers EJ, et al. Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Feb 10;34(5):409–18. https://doi.org/10.1200/JCO.2015.62.3942.CrossRef

57.

Evans D, Ingham S, Baildam A, Ross G, Lalloo F, Buchan I, et al. Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer. Breast Cancer Res Treat. 2013 Jul;140(1):135–42. https://doi.org/10.1007/s10549-013-2583-1.CrossRefPubMed

58.

van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJT, et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. British journal of cancer. 2005 Aug 8;93(3):287–92. https://doi.org/10.1038/sj.bjc.6602703.CrossRefPubMedPubMedCentral

59.

Metcalfe K, Gershman S, Ghadirian P, Lynch HT, Snyder C, Tung N, et al. Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ : British Medical Journal. 2014 Feb 11;348(feb11 9):g226. https://doi.org/10.1136/bmj.g226.CrossRefPubMed

60.

Metcalfe K, Lynch HT, Foulkes WD, Tung N, Kim-Sing C, Olopade OI, et al. Effect of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers. JAMA Oncology. 2015 Jun;1(3):306–13. https://doi.org/10.1001/jamaoncol.2015.0658.CrossRefPubMed

Title: Risk Management for BRCA1/BRCA2 Mutation Carriers Without and With Breast Cancer
Authors: C. B. Mainor
C. Isaacs
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Magnetic Resonance Imaging
Mastectomy
Magnetic Resonance Imaging
Breast Cancer
Ovarian Cancer
Ovarian Cancer
Breast Cancer
Breast MRI
Published in: Current Breast Cancer Reports / Issue 2/2020
Print ISSN: 1943-4588
Electronic ISSN: 1943-4596
DOI: https://doi.org/10.1007/s12609-019-00350-2

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