Differences between screen-detected and interval breast cancers among BRCA mutation carriers

  • Melissa PilewskieEmail author
  • Emily C. Zabor
  • Elizabeth Gilbert
  • Michelle Stempel
  • Oriana Petruolo
  • Debra Mangino
  • Mark Robson
  • Maxine S. Jochelson
Clinical Trial



BRCA mutation carriers have an elevated lifetime breast cancer risk and remain at risk for interval cancer development. We sought to compare BRCA mutation carriers with screen-detected versus interval breast cancers.


Women with a known BRCA mutation prior to a breast cancer diagnosis were identified. Clinical and pathologic factors, and imaging within 18 months of diagnosis were compared among screen-detected versus interval cancers. Interval cancers were those detected by physical exam among women undergoing regular screening.


Of 124 breast cancers, 92 were screen and 22 clinically detected, of which 11 were interval cancers among regular screeners, and 10 were incidentally found on prophylactic mastectomy. Women with interval cancers were younger, had lower body mass indexes, and were more likely to be Black than those with screen-detected cancers (p < 0.05). Interval cancers were all invasive, larger, more likely to be node positive, and more likely to require axillary lymph node dissection and chemotherapy (p < 0.05). No significant differences were seen by BRCA mutation, mammographic density, MRI background parenchymal enhancement, tumor grade, or receptor status between cohorts. Women screened with both mammogram and MRI had significantly lower proportions of interval cancers compared to women screened with only mammogram or MRI alone (p < 0.05).


Interval breast cancers among BRCA mutation carriers have worse clinicopathologic features than screen-detected tumors, and require more-aggressive medical and surgical therapy. Imaging with mammogram and MRI is associated with lower interval cancer development and should be utilized among this high-risk population.


BRCA Interval breast cancer Screen-detected breast cancer Mutation carriers 



This study was presented in poster format at the 2018 ASCO Annual Meeting, 1–5 June, Chicago, IL.


This study was funded in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center.

Compliance with ethical standards

Conflict of interest

Dr. Melissa Pilewskie, Emily C. Zabor, Elizabeth Gilbert, Michelle Stempel, Dr. Oriana Petruolo and Dr. Debra Mangino declare that they have no conflict of interest. Dr. Mark Robson discloses Consultant/Advisory roles with AstraZeneca, McKesson, and Pfizer, and research funding to his institution from AstraZeneca, AbbVie, Medication, Myriad, Invitae, Pfizer, and Tesaro. Dr. Maxine Jochelson has received lecture remuneration from General Electric.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.


  1. 1.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol Off J Am Soc Clin Oncol 25(11):1329–1333. CrossRefGoogle Scholar
  2. 2.
    King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646. CrossRefGoogle Scholar
  3. 3.
    Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416. CrossRefGoogle Scholar
  4. 4.
    National Comprehensive Cancer Network (NCCN) NCCN clinical practice guidelines in oncology. BRCA-related breast and/or ovarian cancer syndrome. Accessed 30 Aug 2018
  5. 5.
    American Cancer Society (2015) American Cancer Society recommendations for the early detection of breast cancer. Accessed 3 July 2018
  6. 6.
    Evans DG, Graham J, O’Connell S, Arnold S, Fitzsimmons D (2013) Familial breast cancer: summary of updated NICE guidance. BMJ 346:f3829. CrossRefGoogle Scholar
  7. 7.
    Monticciolo DL, Newell MS, Moy L, Niell B, Monsees B, Sickles EA (2018) Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. J Am Coll Radiol 15(3 Pt A):408–414. CrossRefGoogle Scholar
  8. 8.
    National Comprehensive Cancer Network (NCCN) NCCN clinical practice guidelines in oncology. Accessed 3 July 2018
  9. 9.
    Bare M, Tora N, Salas D, Sentis M, Ferrer J, Ibanez J et al (2015) Mammographic and clinical characteristics of different phenotypes of screen-detected and interval breast cancers in a nationwide screening program. Breast Cancer Res Treat 154(2):403–415. CrossRefGoogle Scholar
  10. 10.
    Blanch J, Sala M, Ibanez J, Domingo L, Fernandez B, Otegi A et al (2014) Impact of risk factors on different interval cancer subtypes in a population-based breast cancer screening programme. PLoS ONE 9(10):e110207. CrossRefGoogle Scholar
  11. 11.
    Collett K, Stefansson IM, Eide J, Braaten A, Wang H, Eide GE, Thoresen SO, Foulkes WD, Akslen LA (2005) A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cospons Am Soc Prev Oncol 14(5):1108–1112. CrossRefGoogle Scholar
  12. 12.
    Domingo L, Sala M, Servitja S, Corominas JM, Ferrer F, Martinez J et al (2010) Phenotypic characterization and risk factors for interval breast cancers in a population-based breast cancer screening program in Barcelona, Spain. Cancer Causes Control 21(8):1155–1164. CrossRefGoogle Scholar
  13. 13.
    Eriksson L, Czene K, Rosenberg LU, Tornberg S, Humphreys K, Hall P (2013) Mammographic density and survival in interval breast cancers. Breast Cancer Res 15(3):R48. CrossRefGoogle Scholar
  14. 14.
    Gilliland FD, Joste N, Stauber PM, Hunt WC, Rosenberg R, Redlich G, Key CR (2000) Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 92(9):743–749CrossRefGoogle Scholar
  15. 15.
    Holm J, Humphreys K, Li J, Ploner A, Cheddad A, Eriksson M, Tornberg S, Hall P, Czene K (2015) Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol 33(9):1030–1037. CrossRefGoogle Scholar
  16. 16.
    Jose Bento M, Goncalves G, Aguiar A, Antunes L, Veloso V, Rodrigues V (2014) Clinicopathological differences between interval and screen-detected breast cancers diagnosed within a screening programme in northern Portugal. J Med Screen 21(2):104–109. CrossRefGoogle Scholar
  17. 17.
    Kerlikowske K, Zhu W, Tosteson AN, Sprague BL, Tice JA, Lehman CD, Miglioretti DL (2015) Identifying women with dense breasts at high risk for interval cancer: a cohort study. Ann Intern Med 162(10):673–681. CrossRefGoogle Scholar
  18. 18.
    Porter GJ, Evans AJ, Burrell HC, Lee AH, Ellis IO, Chakrabarti J (2006) Interval breast cancers: prognostic features and survival by subtype and time since screening. J Med Screen 13(3):115–122. CrossRefGoogle Scholar
  19. 19.
    Porter GJ, Evans AJ, Cornford EJ, Burrell HC, James JJ, Lee AH, Chakrabarti J (2007) Influence of mammographic parenchymal pattern in screening-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival. Am J Roentgenol 188(3):676–683. CrossRefGoogle Scholar
  20. 20.
    Vitak B, Stal O, Mannson JC, Thomas BA, Arnesson LG, Ekelund L et al (1997) Interval cancers and cancers in non-attenders in the Ostergotland mammographic screening programme. Duration between screening and diagnosis, S-phase fraction and distant recurrence. Eur J Cancer 33(9):1453–1460. CrossRefGoogle Scholar
  21. 21.
    Wang H, Bjurstam N, Bjorndal H, Braaten A, Eriksen L, Skaane P, Vitak B, Hofvind S, Thoresen SO (2001) Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT. Int J Cancer 94(4):594–598CrossRefGoogle Scholar
  22. 22.
    Burrell HC, Sibbering DM, Wilson AR, Pinder SE, Evans AJ, Yeoman LJ et al (1996) Screening interval breast cancers: mammographic features and prognosis factors. Radiology 199(3):811–817. CrossRefGoogle Scholar
  23. 23.
    Porter PL, El-Bastawissi AY, Mandelson MT, Lin MG, Khalid N, Watney EA et al (1999) Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 91(23):2020–2028CrossRefGoogle Scholar
  24. 24.
    Raja MA, Hubbard A, Salman AR (2001) Interval breast cancer: is it a different type of breast cancer? Breast (Edinb Scotl) 10(2):100–108. CrossRefGoogle Scholar
  25. 25.
    Rayson D, Payne JI, Abdolell M, Barnes PJ, MacIntosh RF, Foley T, Younis T, Burns A, Caines J (2011) Comparison of clinical-pathologic characteristics and outcomes of true interval and screen-detected invasive breast cancer among participants of a Canadian breast screening program: a nested case–control study. Clin Breast Cancer 11(1):27–32. CrossRefGoogle Scholar
  26. 26.
    Brekelmans CT, Peeters PH, Deurenberg JJ, Collette HJ (1995) Survival in interval breast cancer in the DOM screening programme. Eur J Cancer (Oxf Engl 1990) 31a(11):1830–1835CrossRefGoogle Scholar
  27. 27.
    Domingo L, Blanch J, Servitja S, Corominas JM, Murta-Nascimento C, Rueda A, Redondo M, Castells X, Sala M (2013) Aggressiveness features and outcomes of true interval cancers: comparison between screen-detected and symptom-detected cancers. Eur J Cancer Prev Off J Eur Cancer Prev Organ 22(1):21–28. CrossRefGoogle Scholar
  28. 28.
    Lawrence G, Wallis M, Allgood P, Nagtegaal ID, Warwick J, Cafferty FH et al (2009) Population estimates of survival in women with screen-detected and symptomatic breast cancer taking account of lead time and length bias. Breast Cancer Res Treat 116(1):179–185. CrossRefGoogle Scholar
  29. 29.
    Zackrisson S, Janzon L, Manjer J, Andersson I (2007) Improved survival rate for women with interval breast cancer—results from the breast cancer screening programme in Malmo, Sweden 1976–1999. J Med Screen 14(3):138–143. CrossRefGoogle Scholar
  30. 30.
    Friedenreich CM (2001) Review of anthropometric factors and breast cancer risk. Eur J Cancer Prev Off J Eur Cancer Prev Organ 10(1):15–32CrossRefGoogle Scholar
  31. 31.
    van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527CrossRefGoogle Scholar
  32. 32.
    Komenaka IK, Ditkoff BA, Joseph KA, Russo D, Gorroochurn P, Ward M, Horowitz E, El-Tamer MB, Schnabel FR (2004) The development of interval breast malignancies in patients with BRCA mutations. Cancer 100(10):2079–2083. CrossRefGoogle Scholar
  33. 33.
    Sung JS, Stamler S, Brooks J, Kaplan J, Huang T, Dershaw DD, Lee CH, Morris EA, Comstock CE (2016) Breast cancers detected at screening MR imaging and mammography in patients at high risk: method of detection reflects tumor histopathologic results. Radiology 280(3):716–722. CrossRefGoogle Scholar
  34. 34.
    Passaperuma K, Warner E, Causer PA, Hill KA, Messner S, Wong JW et al (2012) Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer 107(1):24–30. CrossRefGoogle Scholar
  35. 35.
    Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292(11):1317–1325. CrossRefGoogle Scholar
  36. 36.
    Brinton JT, Barke LD, Freivogel ME, Jackson S, O’Donnell CI, Glueck DH (2012) Breast cancer risk assessment in 64,659 women at a single high-volume mammography clinic. Acad Radiol 19(1):95–99. CrossRefGoogle Scholar
  37. 37.
    Hill DA, Haas JS, Wellman R, Hubbard RA, Lee CI, Alford-Teaster J et al (2018) Utilization of breast cancer screening with magnetic resonance imaging in community practice. J Gen Intern Med 33(3):275–283. CrossRefGoogle Scholar
  38. 38.
    Miles R, Wan F, Onega TL, Lenderink-Carpenter A, O’Meara ES, Zhu W et al (2018) Underutilization of supplemental magnetic resonance imaging screening among patients at high breast cancer risk. J Women’s Health (2002) 27(6):748–754. CrossRefGoogle Scholar
  39. 39.
    Lowry KP, Lee JM, Kong CY, McMahon PM, Gilmore ME, Cott Chubiz JE et al (2012) Annual screening strategies in BRCA1 and BRCA2 gene mutation carriers: a comparative effectiveness analysis. Cancer 118(8):2021–2030. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Breast Service, Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Biostatistics Service, Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Breast Medicine Service, Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations