Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2012

01-04-2012 | Preclinical Study

The prognostic significance of B lymphocytes in invasive carcinoma of the breast

Authors: S. M. A. Mahmoud, A. H. S. Lee, E. C. Paish, R. D. Macmillan, I. O. Ellis, A. R. Green

Published in: Breast Cancer Research and Treatment | Issue 2/2012

Login to get access

Abstract

Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological factors. Higher numbers of CD20+ cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was a positive correlation between higher numbers of total CD20+ B cells and higher tumour grade (r s = 0.20, P < 0.001), ER and PgR negativity (P < 0.001), and basal phenotype (P < 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20+ cells, irrespective of location, was associated with significantly better BCSS (P = 0.037) and longer DFI (P = 0.001). In multivariate analysis, total CD20+ B cell count (HR = 0.75, 95% CI = 0.58–0.96 for BCSS and HR = 0.72, 95% CI = 0.58–0.89, for DFI), tumour size, nodal stage, grade, vascular invasion, HER-2 status, and total CD8+ T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies.
Literature
1.
go back to reference Bouaziz JD, Yanaba K, Venturi GM, Wang Y, Tisch RM, Poe JC et al (2007) Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice. Proc Natl Acad Sci USA 104(52):20878–20883PubMedCrossRef Bouaziz JD, Yanaba K, Venturi GM, Wang Y, Tisch RM, Poe JC et al (2007) Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice. Proc Natl Acad Sci USA 104(52):20878–20883PubMedCrossRef
2.
go back to reference Crawford A, Macleod M, Schumacher T, Corlett L, Gray D (2006) Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 176(6):3498–3506PubMed Crawford A, Macleod M, Schumacher T, Corlett L, Gray D (2006) Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 176(6):3498–3506PubMed
3.
go back to reference Coughlin CM, Vance BA, Grupp SA, Vonderheide RH (2004) RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy. Blood 103(6):2046–2054PubMedCrossRef Coughlin CM, Vance BA, Grupp SA, Vonderheide RH (2004) RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy. Blood 103(6):2046–2054PubMedCrossRef
4.
go back to reference Schultz KR, Klarnet JP, Gieni RS, HayGlass KT, Greenberg PD (1990) The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia. Science 249(4971):921–923PubMedCrossRef Schultz KR, Klarnet JP, Gieni RS, HayGlass KT, Greenberg PD (1990) The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia. Science 249(4971):921–923PubMedCrossRef
5.
go back to reference de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7(5):411–423PubMedCrossRef de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7(5):411–423PubMedCrossRef
6.
go back to reference Houghton AN, Uchi H, Wolchok JD (2005) The role of the immune system in early epithelial carcinogenesis: B-ware the double-edged sword. Cancer Cell 7(5):403–405PubMedCrossRef Houghton AN, Uchi H, Wolchok JD (2005) The role of the immune system in early epithelial carcinogenesis: B-ware the double-edged sword. Cancer Cell 7(5):403–405PubMedCrossRef
7.
go back to reference Bernatsky S, Ramsey-Goldman R, Clarke A (2006) Malignancy and autoimmunity. Curr Opin Rheumatol 18(2):129–134PubMedCrossRef Bernatsky S, Ramsey-Goldman R, Clarke A (2006) Malignancy and autoimmunity. Curr Opin Rheumatol 18(2):129–134PubMedCrossRef
8.
go back to reference Tomer Y, Sherer Y, Shoenfeld Y (1998) Autoantibodies, autoimmunity and cancer (review). Oncol Rep 5(3):753–761PubMed Tomer Y, Sherer Y, Shoenfeld Y (1998) Autoantibodies, autoimmunity and cancer (review). Oncol Rep 5(3):753–761PubMed
9.
go back to reference Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB et al (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4(7):e6412PubMedCrossRef Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB et al (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4(7):e6412PubMedCrossRef
10.
go back to reference Dong HP, Elstrand MB, Holth A, Silins I, Berner A, Trope CG et al (2006) NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma. Am J Clin Pathol 125(3):451–458PubMed Dong HP, Elstrand MB, Holth A, Silins I, Berner A, Trope CG et al (2006) NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma. Am J Clin Pathol 125(3):451–458PubMed
11.
go back to reference Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT (2008) Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res 14(16):5220–5227PubMedCrossRef Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT (2008) Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res 14(16):5220–5227PubMedCrossRef
12.
go back to reference Kuroda H, Tamaru J, Sakamoto G, Ohnisi K, Itoyama S (2005) Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast. Virchows Arch 446(1):10–14PubMedCrossRef Kuroda H, Tamaru J, Sakamoto G, Ohnisi K, Itoyama S (2005) Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast. Virchows Arch 446(1):10–14PubMedCrossRef
13.
go back to reference Hansen MH, Nielsen HV, Ditzel HJ (2002) Translocation of an intracellular antigen to the surface of medullary breast cancer cells early in apoptosis allows for an antigen-driven antibody response elicited by tumor-infiltrating B cells. J Immunol 169(5):2701–2711PubMed Hansen MH, Nielsen HV, Ditzel HJ (2002) Translocation of an intracellular antigen to the surface of medullary breast cancer cells early in apoptosis allows for an antigen-driven antibody response elicited by tumor-infiltrating B cells. J Immunol 169(5):2701–2711PubMed
14.
go back to reference Hansen MH, Nielsen H, Ditzel HJ (2001) The tumor-infiltrating B cell response in medullary breast cancer is oligoclonal and directed against the autoantigen actin exposed on the surface of apoptotic cancer cells. Proc Natl Acad Sci USA 98(22):12659–12664PubMedCrossRef Hansen MH, Nielsen H, Ditzel HJ (2001) The tumor-infiltrating B cell response in medullary breast cancer is oligoclonal and directed against the autoantigen actin exposed on the surface of apoptotic cancer cells. Proc Natl Acad Sci USA 98(22):12659–12664PubMedCrossRef
15.
go back to reference Lee AH, Happerfield LC, Bobrow LG, Millis RR (1997) Angiogenesis and inflammation in invasive carcinoma of the breast. J Clin Pathol 50(8):669–673PubMedCrossRef Lee AH, Happerfield LC, Bobrow LG, Millis RR (1997) Angiogenesis and inflammation in invasive carcinoma of the breast. J Clin Pathol 50(8):669–673PubMedCrossRef
16.
go back to reference Nzula S, Going JJ, Stott DI (2003) Antigen-driven clonal proliferation, somatic hypermutation, and selection of B lymphocytes infiltrating human ductal breast carcinomas. Cancer Res 63(12):3275–3280PubMed Nzula S, Going JJ, Stott DI (2003) Antigen-driven clonal proliferation, somatic hypermutation, and selection of B lymphocytes infiltrating human ductal breast carcinomas. Cancer Res 63(12):3275–3280PubMed
17.
go back to reference Coronella JA, Spier C, Welch M, Trevor KT, Stopeck AT, Villar H et al (2002) Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast. J Immunol 169(4):1829–1836PubMed Coronella JA, Spier C, Welch M, Trevor KT, Stopeck AT, Villar H et al (2002) Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast. J Immunol 169(4):1829–1836PubMed
18.
go back to reference Lee AH, Happerfield LC, Millis RR, Bobrow LG (1996) Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast. Br J Cancer 74(5):796–801PubMedCrossRef Lee AH, Happerfield LC, Millis RR, Bobrow LG (1996) Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast. Br J Cancer 74(5):796–801PubMedCrossRef
19.
go back to reference Tedder TF, Engel P (1994) CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 15(9):450–454PubMedCrossRef Tedder TF, Engel P (1994) CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 15(9):450–454PubMedCrossRef
20.
go back to reference Stashenko P, Nadler LM, Hardy R, Schlossman SF (1980) Characterization of a human B lymphocyte-specific antigen. J Immunol 125(4):1678–1685PubMed Stashenko P, Nadler LM, Hardy R, Schlossman SF (1980) Characterization of a human B lymphocyte-specific antigen. J Immunol 125(4):1678–1685PubMed
21.
go back to reference Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005) The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun 8:140–174PubMedCrossRef Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005) The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun 8:140–174PubMedCrossRef
22.
go back to reference Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340–350PubMedCrossRef Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340–350PubMedCrossRef
23.
go back to reference Rakha EA, Putti TC, Abd El-Rehim DM, Paish C, Green AR, Powe DG et al (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208(4):495–506PubMedCrossRef Rakha EA, Putti TC, Abd El-Rehim DM, Paish C, Green AR, Powe DG et al (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208(4):495–506PubMedCrossRef
24.
go back to reference 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 19(5):403–410PubMedCrossRef 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 19(5):403–410PubMedCrossRef
25.
go back to reference Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20(6):479–489PubMedCrossRef Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20(6):479–489PubMedCrossRef
26.
go back to reference Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef
27.
go back to reference Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24(1):41–47PubMedCrossRef Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24(1):41–47PubMedCrossRef
28.
go back to reference McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072PubMedCrossRef McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072PubMedCrossRef
29.
go back to reference Camp RL, Charette LA, Rimm DL (2000) Validation of tissue microarray technology in breast carcinoma. Lab Invest 80(12):1943–1949PubMedCrossRef Camp RL, Charette LA, Rimm DL (2000) Validation of tissue microarray technology in breast carcinoma. Lab Invest 80(12):1943–1949PubMedCrossRef
30.
go back to reference Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Lee AHS, Ellis IO et al (2011) An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res Treat 127(1):99–108 Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Lee AHS, Ellis IO et al (2011) An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res Treat 127(1):99–108
31.
go back to reference Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO (2008) Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol 39(6):857–865PubMedCrossRef Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO (2008) Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol 39(6):857–865PubMedCrossRef
32.
go back to reference Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS et al (2011) Tumor-infiltarting CD8+ lymphocytes predicts clinical outcome in breast cancer. J Clin Oncol 29(15):1949-1955 Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS et al (2011) Tumor-infiltarting CD8+ lymphocytes predicts clinical outcome in breast cancer. J Clin Oncol 29(15):1949-1955
33.
go back to reference Cox DR (1972) Regression models and life-tables. J R Stat Soc Series B Stat Methodol 34(2):187–220 Cox DR (1972) Regression models and life-tables. J R Stat Soc Series B Stat Methodol 34(2):187–220
34.
go back to reference Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252–7259PubMedCrossRef Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252–7259PubMedCrossRef
35.
go back to reference Dolled-Filhart M, McCabe A, Giltnane J, Cregger M, Camp RL, Rimm DL (2006) Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome. Cancer Res 66(10):5487–5494PubMedCrossRef Dolled-Filhart M, McCabe A, Giltnane J, Cregger M, Camp RL, Rimm DL (2006) Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome. Cancer Res 66(10):5487–5494PubMedCrossRef
36.
go back to reference Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671PubMedCrossRef Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671PubMedCrossRef
37.
go back to reference Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32PubMedCrossRef
38.
go back to reference Rakha EA, El-Rehim DA, Paish C, Green AR, Lee AH, Robertson JF et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149–3156PubMedCrossRef Rakha EA, El-Rehim DA, Paish C, Green AR, Lee AH, Robertson JF et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149–3156PubMedCrossRef
39.
go back to reference Marsigliante S, Biscozzo L, Marra A, Nicolardi G, Leo G, Lobreglio GB et al (1999) Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer Lett 139(1):33–41PubMedCrossRef Marsigliante S, Biscozzo L, Marra A, Nicolardi G, Leo G, Lobreglio GB et al (1999) Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer Lett 139(1):33–41PubMedCrossRef
40.
go back to reference Naukkarinen A, Syrjanen KJ (1990) Quantitative immunohistochemical analysis of mononuclear infiltrates in breast carcinomas—correlation with tumour differentiation. J Pathol 160(3):217–222PubMedCrossRef Naukkarinen A, Syrjanen KJ (1990) Quantitative immunohistochemical analysis of mononuclear infiltrates in breast carcinomas—correlation with tumour differentiation. J Pathol 160(3):217–222PubMedCrossRef
41.
go back to reference Stewart TH, Heppner GH (1997) Immunological enhancement of breast cancer. Parasitology 115(Suppl):S141–S153PubMedCrossRef Stewart TH, Heppner GH (1997) Immunological enhancement of breast cancer. Parasitology 115(Suppl):S141–S153PubMedCrossRef
42.
go back to reference Rohrer JW, Barsoum AL, Dyess DL, Tucker JA, Coggin JH Jr (1999) Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes. J Immunol 162(11):6880–6892PubMed Rohrer JW, Barsoum AL, Dyess DL, Tucker JA, Coggin JH Jr (1999) Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes. J Immunol 162(11):6880–6892PubMed
43.
go back to reference Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34):5373–5380PubMedCrossRef Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34):5373–5380PubMedCrossRef
44.
go back to reference Bilik R, Mor C, Hazaz B, Moroz C (1989) Characterization of T-lymphocyte subpopulations infiltrating primary breast cancer. Cancer Immunol Immunother 28(2):143–147PubMedCrossRef Bilik R, Mor C, Hazaz B, Moroz C (1989) Characterization of T-lymphocyte subpopulations infiltrating primary breast cancer. Cancer Immunol Immunother 28(2):143–147PubMedCrossRef
45.
go back to reference Georgiannos SN, Renaut A, Goode AW, Sheaff M (2003) The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators. Surgery 134(5):827–834PubMedCrossRef Georgiannos SN, Renaut A, Goode AW, Sheaff M (2003) The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators. Surgery 134(5):827–834PubMedCrossRef
46.
go back to reference Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E et al (1992) Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 28A(4–5):859–864PubMedCrossRef Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E et al (1992) Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 28A(4–5):859–864PubMedCrossRef
47.
go back to reference Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H et al (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13):5405–5413PubMedCrossRef Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H et al (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13):5405–5413PubMedCrossRef
48.
go back to reference Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR (2006) Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 48(6):692–701PubMedCrossRef Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR (2006) Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 48(6):692–701PubMedCrossRef
49.
go back to reference Lee AHS (2008) Inflammation and vascularity in carcinoma of the breast. University of Cambridge, Cambridge Lee AHS (2008) Inflammation and vascularity in carcinoma of the breast. University of Cambridge, Cambridge
50.
go back to reference Balch CM, Riley LB, Bae YJ, Salmeron MA, Platsoucas CD, von Eschenbach A et al (1990) Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg 125(2):200–205PubMedCrossRef Balch CM, Riley LB, Bae YJ, Salmeron MA, Platsoucas CD, von Eschenbach A et al (1990) Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg 125(2):200–205PubMedCrossRef
51.
go back to reference Lee YT, Sheikh KM, Quismorio FP Jr, Friou GJ (1985) Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis. Breast Cancer Res Treat 6(1):57–65PubMedCrossRef Lee YT, Sheikh KM, Quismorio FP Jr, Friou GJ (1985) Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis. Breast Cancer Res Treat 6(1):57–65PubMedCrossRef
52.
go back to reference Coronella-Wood JA, Hersh EM (2003) Naturally occurring B-cell responses to breast cancer. Cancer Immunol Immunother 52(12):715–738PubMedCrossRef Coronella-Wood JA, Hersh EM (2003) Naturally occurring B-cell responses to breast cancer. Cancer Immunol Immunother 52(12):715–738PubMedCrossRef
Metadata
Title
The prognostic significance of B lymphocytes in invasive carcinoma of the breast
Authors
S. M. A. Mahmoud
A. H. S. Lee
E. C. Paish
R. D. Macmillan
I. O. Ellis
A. R. Green
Publication date
01-04-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-011-1620-1

Other articles of this Issue 2/2012

Breast Cancer Research and Treatment 2/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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