CD8 + lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

Breast Cancer Research

Volumn 14, Issue 2, 2012, Pages

  Liu, Shuzhen ^a   Lachapelle, Jonathan ^b   Leung, Samuel ^a   Gao, Dongxia ^a   Foulkes, William D ^b,c,d   Nielsen, Torsten O ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN RECEPTOR; VASCULOTROPIN RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERBB2 PROTEIN, HUMAN; TUMOR MARKER;

ADULT; AGED; ARTICLE; BREAST CANCER; CANCER PATIENT; CANCER SPECIFIC SURVIVAL; CD8+ T LYMPHOCYTE; DISEASE SEVERITY; FEMALE; FOLLOW UP; GROUPS BY AGE; HUMAN; IMMUNOHISTOCHEMISTRY; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; PROGNOSIS; TISSUE MICROARRAY; BREAST TUMOR; COHORT ANALYSIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; KAPLAN MEIER METHOD; METABOLISM; MIDDLE AGED; MORTALITY; MULTIVARIATE ANALYSIS; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL; TUMOR ASSOCIATED LEUKOCYTE;

BREAST NEOPLASMS; CD8-POSITIVE T-LYMPHOCYTES; COHORT STUDIES; FEMALE; FOLLOW-UP STUDIES; HUMANS; KAPLAN-MEIER ESTIMATE; LYMPHOCYTES, TUMOR-INFILTRATING; MIDDLE AGED; MULTIVARIATE ANALYSIS; PROGNOSIS; RECEPTOR, ERBB-2; TUMOR MARKERS, BIOLOGICAL;

EID: 84862784272     PISSN: 14655411     EISSN: 1465542X     Source Type: Journal    
DOI: 10.1186/bcr3148     Document Type: Article

References (69)

1. Tsuta K, Ishii G, Kim E, Shiono S, Nishiwaki Y, Endoh Y, Kodama T, Nagai K, Nagai K. Primary lung adenocarcinoma with massive lymphocyte infiltration. Am J Clin Pathol 2005, 123:547-552. 10.1309/APKQ4Q9D52GNLR8W, 15743751.
2. Canna K, McArdle PA, McMillan DC, McNicol AM, Smith GW, McKee RF, McArdle CS. The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer 2005, 92:651-654. 10.1038/sj.bjc.6602419, 2361875, 15700032.
3. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003, 348:203-213. 10.1056/NEJMoa020177, 12529460.
4. Clemente CG, Mihm MC, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996, 77:1303-1310. 10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5, 8608507.
5. Furihata M, Ohtsuki Y, Sonobe H, Araki K, Ogata T, Toki T, Ogoshi S, Tamiya T. Prognostic significance of simultaneous infiltration of HLA-DR-positive dendritic cells and tumor infiltrating lymphocytes into human esophageal carcinoma. Tohoku J Exp Med 1993, 169:187-195. 10.1620/tjem.169.187, 8248911.
6. Jass JR. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol 1986, 39:585-589. 10.1136/jcp.39.6.585, 499954, 3722412.
7. Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, Salvadori B, Colnaghi MI, Rilke F. Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 1997, 3:817-819.
8. Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001, 61:5132-5136.
9. Schondorf T, Engel H, Lindemann C, Kolhagen H, von Rucker AA, Mallmann P. Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours. Cancer Immunol Immunother 1997, 44:88-96. 10.1007/s002620050360, 9177470.
10. Ben-Hur H, Cohen O, Schneider D, Gurevich P, Halperin R, Bala U, Mozes M, Zusman I. The role of lymphocytes and macrophages in human breast tumorigenesis: an immunohistochemical and morphometric study. Anticancer Res 2002, 22:1231-1238.
11. Leong PP, Mohammad R, Ibrahim N, Ithnin H, Abdullah M, Davis WC, Seow HF. Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunol Lett 2006, 102:229-236. 10.1016/j.imlet.2005.09.006, 16246429.
12. Schillaci R, Salatino M, Cassataro J, Proietti CJ, Giambartolomei GH, Rivas MA, Carnevale RP, Charreau EH, Elizalde PV. Immunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+ response involving Fas/Fas ligand cytotoxic pathway. J Immunol 2006, 176:3426-3437.
13. Dobrzanski MJ, Reome JB, Hylind JC, Rewers-Felkins KA. CD8-mediated type 1 antitumor responses selectively modulate endogenous differentiated and nondifferentiated T cell localization, activation, and function in progressive breast cancer. J Immunol 2006, 177:8191-8201.
14. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005, 353:2654-2666. 10.1056/NEJMoa051424, 16371631.
15. Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR. Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 2006, 48:692-701. 10.1111/j.1365-2559.2006.02410.x, 16681685.
16. Yakirevich E, Izhak OB, Rennert G, Kovacs ZG, Resnick MB. Cytotoxic phenotype of tumor infiltrating lymphocytes in medullary carcinoma of the breast. Mod Pathol 1999, 12:1050-1056.
17. Rakha EA, Aleskandarany M, El-Sayed ME, Blamey RW, Elston CW, Ellis IO, Lee AH. The prognostic significance of inflammation and medullary histological type in invasive carcinoma of the breast. Eur J Cancer 2009, 45:1780-1787. 10.1016/j.ejca.2009.02.014, 19286369.
18. Matkowski R, Gisterek I, Halon A, Lacko A, Szewczyk K, Staszek U, Pudelko M, Szynglarewicz B, Szelachowska J, Zolnierek A, Kornafel J. The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer. Anticancer Res 2009, 29:2445-2451.
19. Carlomagno C, Perrone F, Lauria R, de Laurentiis M, Gallo C, Morabito A, Pettinato G, Panico L, Bellelli T, Apicella A. Prognostic significance of necrosis, elastosis, fibrosis and inflammatory cell reaction in operable breast cancer. Oncology 1995, 52:272-277. 10.1159/000227472, 7777238.
20. Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E, Syrjanen K. Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 1992, 28A:859-864.
21. Camp BJ, Dyhrman ST, Memoli VA, Mott LA, Barth RJ. In situ cytokine production by breast cancer tumor-infiltrating lymphocytes. Ann Surg Oncol 1996, 3:176-184. 10.1007/BF02305798, 8646519.
22. Liu F, Lang R, Zhao J, Zhang X, Pringle GA, Fan Y, Yin D, Gu F, Yao Z, Fu L. CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat 2011, 130:645-655. 10.1007/s10549-011-1647-3, 21717105.
23. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011, 29:1949-1955. 10.1200/JCO.2010.30.5037, 21483002.
24. Baker K, Lachapelle J, Zlobec I, Bismar TA, Terracciano L, Foulkes WD. Prognostic significance of CD8(+) T lymphocytes in breast cancer depends upon both oestrogen receptor status and histological grade. Histopathology 2011, 58:1107-1116.
25. Eden P, Ritz C, Rose C, Ferno M, Peterson C. 'Good Old' clinical markers have similar power in breast cancer prognosis as microarray gene expression profilers. Eur J Cancer 2004, 40:1837-1841. 10.1016/j.ejca.2004.02.025, 15288284.
26. Nimeus-Malmstrom E, Ritz C, Eden P, Johnsson A, Ohlsson M, Strand C, Ostberg G, Ferno M, Peterson C. Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy. Eur J Cancer 2006, 42:2729-2737. 10.1016/j.ejca.2006.06.031, 17023159.
27. Cleator S, Ashworth A. Molecular profiling of breast cancer: clinical implications. Br J Cancer 2004, 90:1120-1124. 10.1038/sj.bjc.6601667, 2409657, 15026788.
28. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005, 365:1687-1717. Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
29. Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience?. Nat Rev Clin Oncol 2010, 7:683-692. 10.1038/nrclinonc.2010.154, 20877296.
30. Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P, Birnbaum D. How basal are triple-negative breast cancers?. Int J Cancer 2008, 123:236-240. 10.1002/ijc.23518, 18398844.
31. Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 2008, 14:1368-1376. 10.1158/1078-0432.CCR-07-1658, 18316557.
32. Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, Cheang MC, Gelmon K, Nielsen TO, Blomqvist C, Heikkila P, Heikkinen T, Nevanlinna H, Akslen LA, Begin LR, Foulkes WD, Couch FJ, Wang X, Cafourek V, Olson JE, Baglietto L, Giles GG, Severi G, McLean CA, Southey MC, Rakha E, Green AR, Ellis IO, Sherman ME, Lissowska J, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 2010, 7:e1000279. 10.1371/journal.pmed.1000279, 2876119, 20520800.
33. Bertucci F, Finetti P, Rougemont J, Charafe-Jauffret E, Cervera N, Tarpin C, Nguyen C, Xerri L, Houlgatte R, Jacquemier J, Viens P, Birnbaum D. Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res 2005, 65:2170-2178. 10.1158/0008-5472.CAN-04-4115, 15781628.
34. Bertucci F, Finetti P, Cervera N, Charafe-Jauffret E, Mamessier E, Adelaide J, Debono S, Houvenaeghel G, Maraninchi D, Viens P, Charpin C, Jacquemier J, Birnbaum D. Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res 2006, 66:4636-4644. 10.1158/0008-5472.CAN-06-0031, 16651414.
35. Mouawad R, Spano JP, Khayat D. Lymphocyte infiltration in breast cancer: a key prognostic factor that should not be ignored. J Clin Oncol 2011, 29:1935-1936. 10.1200/JCO.2011.35.4845, 21482993.
36. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010, 141:39-51. 10.1016/j.cell.2010.03.014, 20371344.
37. Cheang MC, Treaba DO, Speers CH, Olivotto IA, Bajdik CD, Chia SK, Goldstein LC, Gelmon KA, Huntsman D, Gilks CB, Nielsen TO, Gown AM. Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival. J Clin Oncol 2006, 24:5637-5644. 10.1200/JCO.2005.05.4155, 17116944.
38. Lohrisch C, Jackson J, Jones A, Mates D, Olivotto IA. Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer. J Clin Oncol 2000, 18:2828-2835.
39. Liu S, Chia SK, Mehl E, Leung S, Rajput A, Cheang MC, Nielsen TO. Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients. Breast Cancer Res Treat 2010, 119:53-61. 10.1007/s10549-009-0318-0, 19205877.
40. Chia S, Norris B, Speers C, Cheang M, Gilks B, Gown AM, Huntsman D, Olivotto IA, Nielsen TO, Gelmon K. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol 2008, 26:5697-5704. 10.1200/JCO.2007.15.8659, 19001334.
41. 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. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004, 10:5367-5374. 10.1158/1078-0432.CCR-04-0220, 15328174.
42. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS, Perou CM, Ellis MJ, Nielsen TO. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009, 101:736-750. 10.1093/jnci/djp082, 2684553, 19436038.
43. Gatza ML, Lucas JE, Barry WT, Kim JW, Wang Q, Crawford MD, Datto MB, Kelley M, Mathey-Prevot B, Potti A, Nevins JR. A pathway-based classification of human breast cancer. Proc Natl Acad Sci USA 2010, 107:6994-6999. 10.1073/pnas.0912708107, 2872436, 20335537.
44. Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol 2007, 8:R157. 10.1186/gb-2007-8-8-r157, 2374988, 17683518.
45. Teschendorff AE, Caldas C. A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer. Breast Cancer Res 2008, 10:R73. 10.1186/bcr2138, 2575547, 18755024.
46. Reyal F, van Vliet MH, Armstrong NJ, Horlings HM, de Visser KE, Kok M, Teschendorff AE, Mook S, van't Veer L, Caldas C, Salmon RJ, van de Vijver MJ, Wessels LF. A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer. Breast Cancer Res 2008, 10:R93. 10.1186/bcr2192, 2656909, 19014521.
47. Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, Lehr HA, Hengstler JG, Kolbl H, Gehrmann M. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 2008, 68:5405-5413. 10.1158/0008-5472.CAN-07-5206, 18593943.
48. Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, Delorenzi M, Piccart M, Sotiriou C. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 2008, 14:5158-5165. 10.1158/1078-0432.CCR-07-4756, 18698033.
49. Calabro A, Beissbarth T, Kuner R, Stojanov M, Benner A, Asslaber M, Ploner F, Zatloukal K, Samonigg H, Poustka A, Sultmann H. Effects of infiltrating lymphocytes and estrogen receptor on gene expression and prognosis in breast cancer. Breast Cancer Res Treat 2009, 116:69-77. 10.1007/s10549-008-0105-3, 18592372.
50. Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007, 9:R65. 10.1186/bcr1771, 2242660, 17910759.
51. Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, Tallet A, Chabannon C, Extra JM, Jacquemier J, Viens P, Birnbaum D, Bertucci F. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat 2011, 126:407-420. 10.1007/s10549-010-0897-9, 20490655.
52. Sabatier R, Finetti P, Mamessier E, Raynaud S, Cervera N, Lambaudie E, Jacquemier J, Viens P, Birnbaum D, Bertucci F. Kinome expression profiling and prognosis of basal breast cancers. Mol Cancer 2011, 10:86. 10.1186/1476-4598-10-86, 3156788, 21777462.
53. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 2009, 16:91-102. 10.1016/j.ccr.2009.06.018, 2778576, 19647220.
54. Teschendorff AE, Gomez S, Arenas A, El-Ashry D, Schmidt M, Gehrmann M, Caldas C. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules. BMC Cancer 2010, 10:604. 10.1186/1471-2407-10-604, 2991308, 21050467.
55. Whitford P, Mallon EA, George WD, Campbell AM. Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer. Br J Cancer 1990, 62:971-975. 10.1038/bjc.1990.419, 1971553, 2124138.
56. Georgiannos SN, Renaut A, Goode AW, Sheaff M. 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 2003, 134:827-834. 10.1016/S0039-6060(03)00292-7, 14639362.
57. Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 2006, 90:1-50.
58. Pedersen AE, Stryhn A, Justesen S, Harndahl M, Rasmussen S, Donskov F, Claesson MH, Pedersen JW, Wandall HH, Svane IM, Buus S. Wildtype p53-specific antibody and T-cell responses in cancer patients. J Immunother 2011, 34:629-640. 10.1097/CJI.0b013e3182281381, 21989411.
59. Svane IM, Pedersen AE, Johansen JS, Johnsen HE, Nielsen D, Kamby C, Ottesen S, Balslev E, Gaarsdal E, Nikolajsen K, Claesson MH. Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers. Cancer Immunol Immunother 2007, 56:1485-1499. 10.1007/s00262-007-0293-4, 17285289.
60. Hansen MH, Nielsen H, Ditzel HJ. 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 2001, 98:12659-12664. 10.1073/pnas.171460798, 60110, 11606714.
61. Apetoh L, Tesniere A, Ghiringhelli F, Kroemer G, Zitvogel L. Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies. Cancer Res 2008, 68:4026-4030. 10.1158/0008-5472.CAN-08-0427, 18519658.
62. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008, 8:59-73. 10.1038/nri2216, 18097448.
63. Zitvogel L, Apetoh L, Ghiringhelli F, Andre F, Tesniere A, Kroemer G. The anticancer immune response: indispensable for therapeutic success?. J Clin Invest 2008, 118:1991-2001. 10.1172/JCI35180, 2396905, 18523649.
64. Del Campo AB, Carretero J, Aptsiauri N, Garrido F. Targeting HLA class I expression to increase tumor immunogenicity. Tissue Antigens 2012, 79:147-154. 10.1111/j.1399-0039.2011.01831.x, 22309256.
65. Putti TC, El-Rehim DM, Rakha EA, Paish CE, Lee AH, Pinder SE, Ellis IO. Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. Mod Pathol 2005, 18:26-35. 10.1038/modpathol.3800255, 15332092.
66. Wernicke M, Roitman P, Manfre D, Stern R. Breast cancer and the stromal factor. The 'prometastatic healing process' hypothesis. Medicina (B Aires) 2011, 71:15-21.
67. Schraml P, Kononen J, Bubendorf L, Moch H, Bissig H, Nocito A, Mihatsch MJ, Kallioniemi OP, Sauter G. Tissue microarrays for gene amplification surveys in many different tumor types. Clin Cancer Res 1999, 5:1966-1975.
68. Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Kochli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi OP, Sauter G. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 2001, 159:2249-2256. 10.1016/S0002-9440(10)63075-1, 1850582, 11733374.
69. Alexe G, Dalgin GS, Scanfeld D, Tamayo P, Mesirov JP, DeLisi C, Harris L, Barnard N, Martel M, Levine AJ, Ganesan S, Bhanot G. High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates. Cancer Res 2007, 67:10669-10676. 10.1158/0008-5472.CAN-07-0539, 18006808.