Skip to main content

Advertisement

SpringerLink
Log in

A subset of breast cancer predisposes to brain metastasis

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

This study evaluated the expression of biological markers of breast cancers with brain metastases. Eighteen paired tumors were assessed, with 42 non-brain-metastasizing breast cancers that were stained with ER, PR, HER2, CK5/6, p63, and Ki67, and were also classified into intrinsic subtypes. The expression patterns between the breast tumors with brain metastases were compared to the brain metastases and the controls. Breast cancers with brain metastases were of higher grade and showed higher incidence of lymph node metastases at initial diagnosis and higher EGFR, p63, and Ki67 expression. In the group of breast cancers with brain metastases, the brain metastases showed higher HER2, CK5/6, and Ki67 expression compared to the breast primaries. There was also a higher incidence of basal subtype and a lower incidence of luminal subtype. When tumors metastasized, changes in hormonal receptor (22%) and HER2 (6%) status were observed. We concluded that breast cancers with higher grade, lymph node involvement at diagnosis, high EGFR, p63, and Ki67 expression, and of basal subtype were at higher risk for brain metastases, and that both hormonal receptors and HER2 status may change in brain metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617

    Article  PubMed  Google Scholar 

  2. Crivellari D, Pagani O, Veronesi A, Lombardi D, Nolè F, Thürlimann B, Hess D, Borner M, Bauer J, Martinelli G, Graffeo R, Sessa C, Goldhirsch A; International Breast Cancer Study Group (2001) High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 12:353–356

    Article  PubMed  CAS  Google Scholar 

  3. Ryberg M, Nielsen D, Osterlind K, Andersen PK, Skovsgaard T, Dombernowsky P (2005) Predictors of central nervous system metastasis in patients with metastatic breast cancer. A competing risk analysis of 579 patients treated with epirubicin-based chemotherapy. Breast Cancer Res Treat 91:217–225

    Article  PubMed  Google Scholar 

  4. Abali H, Celik I (2002) High incidence of central nervous system involvement in patients with breast cancer treated with epirubicin and docetaxel. Am J Clin Oncol 25:632–633

    Article  PubMed  Google Scholar 

  5. Kosmas C, Malamos NA, Tsavaris NB, Stamataki M, Stefanou S, Gregoriou A, Rokana S, Vartholomeou M, Antonopoulos MJ (2002) Leptomeningeal carcinomatosis after major remission to taxane-based front-line therapy in patients with advanced breast cancer. J Neurooncol 56:265–273

    Article  PubMed  Google Scholar 

  6. Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer (Phila) 97:2972–2977

    Article  Google Scholar 

  7. Weil RJ, Palmieri DC, Bronder JL, Stark AM, Steeg PS (2005) Breast cancer metastasis to the central nervous system. Am J Pathol 167:913–920

    Article  PubMed  CAS  Google Scholar 

  8. Duchnowska R, Szczylik C (2005) Central nervous system metastases in breast cancer patients administered trastuzumab. Cancer Treat Rev 31:312–318

    Article  PubMed  CAS  Google Scholar 

  9. Clayton AJ, Danson S, Jolly S, Ryder WD, Burt PA, Stewart AL, Wilkinson PM, Welch RS, Magee B, Wilson G, Howell A, Wardley AM (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643

    PubMed  CAS  Google Scholar 

  10. Lee YT (1983) Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol 23:175–180

    Article  PubMed  CAS  Google Scholar 

  11. Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer (Phila) 52:2349–2354

    Article  CAS  Google Scholar 

  12. Carey LA, Ewend MG, Metzger R, Sawyer L, Dees EC, Sartor CI, Moore DT, Graham ML (2004) Central nervous system metastases in women after multimodality therapy for high risk breast cancer. Breast Cancer Res Treat 88:273–280

    Article  PubMed  Google Scholar 

  13. Evans AJ, James JJ, Cornford EJ, Chan SY, Burrell HC, Pinder SE, Gutteridge E, Robertson JF, Hornbuckle J, Cheung KL (2004) Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol 16:345–349

    Article  CAS  Google Scholar 

  14. Gonzalez-Angulo AM, Cristofanilli M, Strom EA, Buzdar AU, Kau SW, Broglio KR, Smith TL, Hortobagyi GN (2004) Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer (Phila) 101:1760–1766

    Article  Google Scholar 

  15. Miller KD, Weathers T, Haney LG, Timmerman R, Dickler M, Shen J, Sledge GW Jr (2003) Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 14:1072–1077

    Article  PubMed  CAS  Google Scholar 

  16. Maki DD, Grossman RI (2000) Patterns of disease spread in metastatic breast carcinoma: influence of estrogen and progesterone receptor status. Am J Neuroradiol 21:1064–1066

    PubMed  CAS  Google Scholar 

  17. Samaan NA, Buzdar AU, Aldinger KA, Schultz PN, Yang KP, Romsdahl MM, Martin R (1981) Estrogen receptor: a prognostic factor in breast cancer. Cancer (Phila) 47:554–560

    Article  CAS  Google Scholar 

  18. Tsuda H, Takarabe T, Hasegawa F, Fukutomi T, Hirohashi S (2000) Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases. Am J Surg Pathol 24:197–202

    Article  PubMed  CAS  Google Scholar 

  19. Rakha EA, Putti TC, Abd El-Rehim DM, Paish C, Green AR, Powe DG, Lee AH, Robertson JF, Ellis IO (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208:495–506

    Article  PubMed  CAS  Google Scholar 

  20. Laakso M, Tanner M, Nilsson J, Wiklund T, Erikstein B, Kellokumpu-Lehtinen P, Malmström P, Wilking N, Bergh J, Isola J (2006) Basoluminal carcinoma: a new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin Cancer Res 12:4185–4191

    Article  PubMed  CAS  Google Scholar 

  21. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374

    Article  PubMed  CAS  Google Scholar 

  22. Gaedcke J, Traub F, Milde S, Wilkens L, Stan A, Ostertag H, Christgen M, von Wasielewski R, Kreipe HH (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20:864–870

    Article  PubMed  CAS  Google Scholar 

  23. Yonemori K, Tsuta K, Shimizu C, Hatanaka Y, Hashizume K, Ono M, Nakanishi Y, Hasegawa T, Miyakita Y, Narita Y, Shibui S, Fujiwara Y (2008) Immunohistochemical profiles of brain metastases from breast cancer. J Neurooncol 90:223–228

    Article  PubMed  Google Scholar 

  24. Hicks DG, Short SM, Prescott NL, Tarr SM, Coleman KA, Yoder BJ, Crowe JP, Choueiri TK, Dawson AE, Budd GT, Tubbs RR, Casey G, Weil RJ (2006) Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 30:1097–1104

    PubMed  Google Scholar 

  25. Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer (Phila) 107:696–704

    Article  Google Scholar 

  26. Grupka NL, Lear-Kaul KC, Kleinschmidt-DeMasters BK, Singh M (2004) Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status. Arch Pathol Lab Med 128:974–979

    PubMed  CAS  Google Scholar 

  27. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology (Oxf) 19:403–410

    Article  CAS  Google Scholar 

  28. Boogerd W (1996) Central nervous system metastasis in breast cancer. Radiother Oncol 40:5–22

    Article  PubMed  CAS  Google Scholar 

  29. DiStefano A, Yong Yap Y, Hortobagyi GN, Blumenschein GR (1979) The natural history of breast cancer patients with brain metastases. Cancer (Phila) 44:1913–1918

    Article  CAS  Google Scholar 

  30. Posner JB (1977) Management of central nervous system metastases. Semin Oncol 4:81–91

    PubMed  CAS  Google Scholar 

  31. Cairncross JG, Kim JH, Posner JB (1980) Radiation therapy for brain metastases. Ann Neurol 7:529–541

    Article  PubMed  CAS  Google Scholar 

  32. Lee SS, Ahn JH, Kim MK, Sym SJ, Gong G, Ahn SD, Kim SB, Kim WK (2008) Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat 111:523–530

    Article  PubMed  Google Scholar 

  33. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500

    Article  PubMed  CAS  Google Scholar 

  34. Hines SL, Vallow LA, Tan WW, McNeil RB, Perez EA, Jain A (2008) Clinical outcomes after a diagnosis of brain metastases in patients with estrogen- and/or human epidermal growth factor receptor 2-positive versus triple-negative breast cancer. Ann Oncol 19:1561–1565

    Article  PubMed  CAS  Google Scholar 

  35. Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, Crivellari D, Fey MF, Murray E, Pagani O, Simoncini E, Castiglione-Gertsch M, Gelber RD, Coates AS, Goldhirsch A; International Breast Cancer Study Group (IBCSG) (2006) Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17:935–944

    Article  PubMed  CAS  Google Scholar 

  36. Stemmler HJ, Kahlert S, Siekiera W, Untch M, Heinrich B, Heinemann V (2006) Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer. Breast 15:219–225

    Article  PubMed  CAS  Google Scholar 

  37. Shmueli E, Wigler N, Inbar M (2004) Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 40:379–382

    Article  PubMed  CAS  Google Scholar 

  38. Stemmler HJ, Heinemann V (2008) Central nervous system metastases in HER-2-overexpressing metastatic breast cancer: a treatment challenge. Oncologist 13:739–750

    Article  PubMed  Google Scholar 

  39. Pestalozzi BC, Brignoli S (2000) Trastuzumab in CSF. J Clin Oncol 18:2349–2351

    PubMed  CAS  Google Scholar 

  40. Lin NU, Winer EP (2007) Brain metastases: the HER2 paradigm. Clin Cancer Res 13:1648–1655

    Article  PubMed  CAS  Google Scholar 

  41. Sainsbury JR, Farndon JR, Needham GK, Malcolm AJ, Harris AL (1987) Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1: 1398–1402

    PubMed  CAS  Google Scholar 

  42. Tsutsui S, Ohno S, Murakami S, Kataoka A, Kinoshita J, Hachitanda Y (2003) Prognostic value of the combination of epidermal growth factor receptor and c-erbB-2 in breast cancer. Surgery (St. Louis) 133:219–221

    Article  Google Scholar 

  43. Nicholson S, Sainsbury JR, Halcrow P, Chambers P, Farndon JR, Harris AL (1989) Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer. Lancet 1:182–185

    Article  PubMed  CAS  Google Scholar 

  44. Luck AA, Evans AJ, Green AR, Rakha EA, Paish C, Ellis IO (2008) The influence of basal phenotype on the metastatic pattern of breast cancer. Clin Oncol 20:40–45

    Article  CAS  Google Scholar 

  45. Mobbs BG, Fish EB, Pritchard KI, Oldfield G, Hanna WH (1986) Estrogen and progesterone receptor content of primary and secondary breast carcinoma: influence of time and treatment. Eur J Cancer Clin Oncol 23:819–826

    Article  Google Scholar 

  46. Santinelli A, Pisa E, Stramazzotti D, Fabris G (2008) HER-2status discrepancy between primary breast cancer and metastatic sites: impact on target therapy. Int J Cancer 122:99–104

    Google Scholar 

  47. Masood S, Bui MM (2000) Assessment of Her-2/neu overexpression in primary breast cancers and their metastatic lesions: an immunohistochemical study. Ann Clin Lab Sci 30:259–265

    PubMed  CAS  Google Scholar 

  48. Shimizu C, Fukutomi T, Tsuda H, Akashi-Tanaka S, Watanabe T, Nanasawa T, Sugihara K (2000) c-erb B2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol 73:17–20

    Article  PubMed  CAS  Google Scholar 

  49. Kamby C, Rasmussen BB, Kristensen B (1989) Oestrogen receptor status of primary breast carcinomas and their metastases. Relation to pattern of spread and survival after recurrence. Br J Cancer 60:252–257

    Article  PubMed  CAS  Google Scholar 

  50. Li BD, Byskosh A, Molteni A, Duda RB (1994) Estrogen and progesterone receptor concordance between primary and recurrent breast cancer. J Surg Oncol 57:71–77

    Article  PubMed  CAS  Google Scholar 

  51. Lear-Kaul KC, Yoon HR, Kleinschmidt-DeMasters BK, McGavran L, Singh M (2003) Her-2/neu status in breast cancer metastases to the central nervous system. Arch Pathol Lab Med 127: 1451–1457

    PubMed  CAS  Google Scholar 

  52. Elyse EL, Eleanor LG, Deborah AB, Robbin B, Sue H (2005) Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat 90:62–70

    Google Scholar 

  53. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23:7721–7735

    Article  PubMed  CAS  Google Scholar 

  54. Zidan J, Dashkovsky I, Stayerman C, Basher W, Cozacov C, Hadary A (2005) Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93:552–556

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, China

    Mu-min Shao

  2. Key Laboratory of Breast Cancer Prevention and Terapy, Tianjin Medical University, Ministry of Education and Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Jun Liu & Yun Niu

  3. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China

    Joaquim S. Vong, Anthony W.H. Chan, Philip C.W. Lui & Gary M. Tse

  4. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Barbara Germin & Ping Tang

  5. Breast Center, Union Hospital, Hong Kong, China

    Bonita K.B. Law

  6. Department of Pathology, Singapore General Hospital, Singapore, Singapore

    Puay-Hoon Tan

Authors
  1. Mu-min Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joaquim S. Vong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barbara Germin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ping Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anthony W.H. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Philip C.W. Lui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bonita K.B. Law
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Puay-Hoon Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gary M. Tse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary M. Tse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shao, Mm., Liu, J., Vong, J.S. et al. A subset of breast cancer predisposes to brain metastasis. Med Mol Morphol 44, 15–20 (2011). https://doi.org/10.1007/s00795-010-0495-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-010-0495-2

Key words

Search

Navigation