Breast Cancer Research and Treatment

, Volume 105, Issue 2, pp 229–236 | Cite as

Risk for contralateral breast cancers in a population covered by mammography: effects of family history, age at diagnosis and histology

  • Jianguang JiEmail author
  • Kari Hemminki
Original paper



Improved survival for breast cancer is increasing the likelihood of contralateral tumors. Mammographic screening is partially contributing to the survival advantage, while changing many aspects of breast cancer presentation, including age at diagnosis, histology and familial risk. As mammography has become widely used, it is important to quantify the risks for contralateral breast cancer in a population with a national access to mammographic screening service.


The nation-wide Swedish Family-Cancer Database was used to calculate risks for contralateral breast cancer between years 1990 (1993) and 2002. The standardized incidence ratio (SIR) measured the risk for contralateral breast compared to first breast cancer.


The risks for contralateral breast cancer ranged between 1.85 and 3.79, and they tended to be higher when in situ cancer was diagnosed. Family history and early diagnosis of first cancer increased the risks for contralateral breast cancer, approximately equally for invasive and in situ cancers. The risk for contralateral in situ cancer was 9.01 following two independent invasive cancers. The risk for the same, concordant histology between the first and the contralateral cancer was higher than that for discordant histologies. The risks for concordant histologies were particularly high for mucinous (12.16), comedo (11.74) and lobular (5.06) tumors. When the first lobular cancer was diagnosed before age 45 years, the risk for contralateral lobular cancer was 32.20.


In situ breast cancer poses an approximately equally high risk as invasive cancer. Family history and earlier age of onset are associated with high risks needing clinical attention.


Breast cancer Contralateral cancer Multiple breast cancer Family history Onset age 



The Family-Cancer Database was created by linking registries maintained by Statistics Sweden and the Swedish Cancer Register. The study was supported by the Deutsche Krebshilfe, the Swedish Cancer Society, the Swedish Council for Working Life and Social Research and the EU, LSHC-LT-2004-503465.


  1. 1.
    Center for Epidemiology (2002) Cancer Incidence in Sweden 2000. The National Board of Health and Welfware, StockholmGoogle Scholar
  2. 2.
    Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G (2005) Breast cancer. Lancet 365(9472):1727–1741PubMedCrossRefGoogle Scholar
  3. 3.
    Olsson S, Andersson I, Karlberg I, Bjurstam N, Frodis E, Hakansson S (2000) Implementation of service screening with mammography in Sweden: from pilot study to nationwide programme. J Med Screen 7(1):14–18PubMedCrossRefGoogle Scholar
  4. 4.
    Hemminki K, Rawal R, Bermejo JL (2004) Mammographic screening is dramatically changing age-incidence data for breast cancer. J Clin Oncol 22(22):4652–4653PubMedCrossRefGoogle Scholar
  5. 5.
    Pinder SE, Ellis IO (2003) The diagnosis and management of pre-invasive breast disease: ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH)–current definitions and classification. Breast Cancer Res 5(5):254–257PubMedCrossRefGoogle Scholar
  6. 6.
    Rawal R, Lorenzo Bermejo J, Hemminki K (2005) Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening. Br J Cancer 92(1):162–166PubMedCrossRefGoogle Scholar
  7. 7.
    Vainio H, Bianchini F (2002) Breast cancer screening. International Agency for Research on Cancer (IARC) Handbooks of Cancer Prevention., vol 7. IARC Press, LyonGoogle Scholar
  8. 8.
    Moller B, Weedon-Fekjaer H, Hakulinen T, Tryggvadottir L, Storm HH, Talback M, Haldorsen T (2005) The influence of mammographic screening on national trends in breast cancer incidence. Eur J Cancer Prev 14(2):117–128PubMedCrossRefGoogle Scholar
  9. 9.
    Hemminki K, Bermejo JL (2005) Effects of screening for breast cancer on its age-incidence relationships and familial risk. Int J Cancer 117(1):145–149PubMedCrossRefGoogle Scholar
  10. 10.
    Bermejo JL, Hemminki K (2005) Familial risk of cancer shortly after diagnosis of the first familial tumor. J Natl Cancer Inst 97(21):1575–1579PubMedGoogle Scholar
  11. 11.
    Hemminki K, Li X, Plna K, Granstrom C, Vaittinen P (2001) The nation-wide Swedish family-cancer database–updated structure and familial rates. Acta Oncol 40(6):772–777PubMedCrossRefGoogle Scholar
  12. 12.
    Dong C, Hemminki K (2001) Second primary neoplasms in 633,964 cancer patients in Sweden, 1958–1996. Int J Cancer 93(2):155–161PubMedCrossRefGoogle Scholar
  13. 13.
    Harris J, Morrow M, Bonadonna G (1993) Cancer of the breast. In: De Vita VT J, Hellman S, Rosenberg SA (eds) Cancer: principle & practice of oncology, 4th edn. Lippincott, Philadelphia, PaGoogle Scholar
  14. 14.
    Esteve J, Benhamou E, Raymond L (1994) Statistical methods in cancer research. IARC, LyonGoogle Scholar
  15. 15.
    Chen Y, Thompson W, Semenciw R, Mao Y (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 8(10):855–861PubMedGoogle Scholar
  16. 16.
    Dawson LA, Chow E, Goss PE (1998) Evolving perspectives in contralateral breast cancer. Eur J Cancer 34(13):2000–2009PubMedCrossRefGoogle Scholar
  17. 17.
    Frodin JE, Ericsson J, Barlow L (1997) Multiple primary malignant tumors in a national cancer registry–reliability of reporting. Acta Oncol 36(5):465–469PubMedGoogle Scholar
  18. 18.
    Stenmark-Askmalm M, Gentile M, Wingren S, Stahl O (2001) Protein accumulation and gene mutation of p53 in bilateral breast cancer. South-East Sweden Breast Cancer Group. Acta Oncol 40(1):56–62PubMedCrossRefGoogle Scholar
  19. 19.
    Coleman MP, Gatta G, Verdecchia A, Esteve J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M, Berrino F (2003) EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Ann Oncol 14 Suppl 5:v128–149Google Scholar
  20. 20.
    Dunn BK, Wickerham DL, Ford LG (2005) Prevention of hormone-related cancers: breast cancer. J Clin Oncol 23(2):357–367PubMedCrossRefGoogle Scholar
  21. 21.
    Li CI, Anderson BO, Daling JR, Moe RE (2003) Trends in incidence rates of invasive lobular and ductal breast carcinoma. Jama 289(11):1421–1424PubMedCrossRefGoogle Scholar
  22. 22.
    Verkooijen HM, Fioretta G, Vlastos G, Morabia A, Schubert H, Sappino AP, Pelte MF, Schafer P, Kurtz J, Bouchardy C (2003) Important increase of invasive lobular breast cancer incidence in Geneva, Switzerland. Int J Cancer 104(6):778–781PubMedCrossRefGoogle Scholar
  23. 23.
    Tavassoli FA, Peter D (2004) World Health Organization: tumours of the breast and female genital organs (WHO/IARC Classification of Tumours). IARC Press, LyonGoogle Scholar
  24. 24.
    Warnberg F, Yuen J, Holmberg L (2000) Risk of subsequent invasive breast cancer after breast carcinoma in situ. Lancet 355(9205):724–725PubMedCrossRefGoogle Scholar
  25. 25.
    Hartman M, Czene K, Reilly M, Bergh J, Lagiou P, Trichopoulos D, Adami HO, Hall P (2005) Genetic implications of bilateral breast cancer: a population based cohort study. Lancet Oncol 6(6):377–382PubMedCrossRefGoogle Scholar
  26. 26.
    Vaittinen P, Hemminki K (2000) Risk factors and age-incidence relationships for contralateral breast cancer. Int J Cancer 88(6):998–1002PubMedCrossRefGoogle Scholar
  27. 27.
    Bernstein JL, Thompson WD, Risch N, Holford TR (1992) The genetic epidemiology of second primary breast cancer. Am J Epidemiol 136(8):937–948PubMedGoogle Scholar
  28. 28.
    Horn PL, Thompson WD (1988) Risk of contralateral breast cancer: associations with factors related to initial breast cancer. Am J Epidemiol 128(2):309–323PubMedGoogle Scholar
  29. 29.
    Li CI, Daling JR, Malone KE, Bernstein L, Marchbanks PA, Liff JM, Strom BL, Simon MS, Press MF, McDonald JA et al (2006) Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 15(5):946–954PubMedCrossRefGoogle Scholar
  30. 30.
    Couch FJ, Weber BL (1998) Breast cancer. In: Vogelstein B, Kinzler KW (eds) The Genetic Basis of Human Cancer. McGraw-Hill, New York, pp 537–564Google Scholar
  31. 31.
    Lakhani SR, Gusterson BA, Jacquemier J, Sloane JP, Anderson TJ, van de Vijver MJ, Venter D, Freeman A, Antoniou A, McGuffog L et al (2000) The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2. Clin Cancer Res 6(3):782–789PubMedGoogle Scholar
  32. 32.
    Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, Farid LM, Venter D, Antoniou A, Storfer-Isser A et al (1998) Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 90(15):1138–1145PubMedCrossRefGoogle Scholar
  33. 33.
    Hemminki K, Granstrom C (2002) Familial breast carcinoma risks by morphology: a nationwide epidemiologic study from Sweden. Cancer 94(11):3063–3070PubMedCrossRefGoogle Scholar
  34. 34.
    Zahl PH, Strand BH, Maehlen J (2004) Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. Bmj 328(7445):921–924PubMedCrossRefGoogle Scholar
  35. 35.
    Swain SM, Wilson JW, Mamounas EP, Bryant J, Wickerham DL, Fisher B, Paik S, Wolmark N (2004) Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. J Natl Cancer Inst 96(7):516–523PubMedCrossRefGoogle Scholar
  36. 36.
    Weitzel JN, Robson M, Pasini B, Manoukian S, Stoppa-Lyonnet D, Lynch HT, McLennan J, Foulkes WD, Wagner T, Tung N et al (2005) A comparison of bilateral breast cancers in BRCA carriers. Cancer Epidemiol Biomarkers Prev 14(6):1534–1538PubMedCrossRefGoogle Scholar
  37. 37.
    Johnson N, Fletcher O, Naceur-Lombardelli C, dos Santos Silva I, Ashworth A, Peto J (2005) Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study. Lancet 366(9496):1554–1557PubMedCrossRefGoogle Scholar
  38. 38.
    Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst (1999), 91(15):1310–1316Google Scholar
  39. 39.
    Hisada M, Garber JE, Fung CY, Fraumeni JF, Jr., Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90(8):606–611PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Center for Family MedicineKarolinska InstituteHuddingeSweden
  2. 2.Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany

Personalised recommendations