nach oben

Erschienen in:

01.01.2009 | Epidemiology

Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive

verfasst von: Ben Van Calster, Isabelle Vanden Bempt, Maria Drijkoningen, Nathalie Pochet, Jiqiu Cheng, Sabine Van Huffel, Wouter Hendrickx, Julie Decock, Huei-Jean Huang, Karin Leunen, Frederic Amant, Patrick Berteloot, Robert Paridaens, Hans Wildiers, Erik Van Limbergen, Caroline Weltens, Dirk Timmerman, Toon Van Gorp, Ann Smeets, Walter Van den Bogaert, Ignace Vergote, Marie-Rose Christiaens, Patrick Neven

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

Aims To examine the frequency of axillary lymph node (ALN) invasion of operable breast cancers by their combined oestrogen receptor (ER), progesterone receptor (PR) and HER-2 status. Methods 2227 recently operated cases in one centre were retrieved from the Multidisciplinary Breast Centre database and stratified according to their combined immunohistochemical (IHC) expression of ER/PR/HER-2 status. An equivocal HER-2 status was further analysed by Fluorescence in situ Hybridisation (FISH). The following 6 groups were considered: ER⁻PR⁻HER-2⁻ (NNN; triple negative), ER⁻PR⁻HER-2⁺ (NNP), ER⁺PR⁻HER-2⁻ (PNN), ER⁺PR⁻HER-2⁺ (PNP), ER⁺PR⁺HER-2⁻(PPN), ER⁺PR⁺HER-2⁺ (PPP; triple positive). For ALN, the following variables were tested in uni- and multivariate models: age at diagnosis (years), tumour size (mm), tumour grade, ER, PR, HER-2 and the combined steroid receptor and HER-2 status. Likelihood ratio χ²-tests were used for univariate analysis and logistic regression for multivariate analysis. Results Triple positive tumours had a higher likelihood of being ALN positive than others (56.2% versus 35.7%; P < 0.0001). Univariate logistic regression also withheld age, size, grade and HER-2 as predictors of ALN involvement. Final multivariate logistic regression revealed age, size, grade and PPP versus non-PPP to be independent predictors of ALN involvement; the odds ratio (OR) and 95% CI for PPP versus non-PPP tumours was 2.169 (1.490–3.156). Conclusion Our data provide insight into the natural history of triple positive breast carcinomas. Such tumours are more likely ALN positive than those with another steroid receptor and HER-2 status. How these findings correlate with breast cancer prognosis remains to be investigated.

Esteva FJ, Hortobagyi GN (2004) Prognostic molecular markers in early breast cancer. Breast Cancer Res 6:109–118PubMedCrossRef

Akiyama T, Sudo C, Ogawara H et al (1986) The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232:1644–1646PubMedCrossRef

Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2 oncogene. Science 235:177–182PubMedCrossRef

Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2 proto-oncogene in human breast and ovarian cancer. Science 244:707–712PubMedCrossRef

Paik S, Hazan R, Fisher ER et al (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112PubMed

Ross JS, Fletcher JA, Linette GP et al (2003) The HER-2 gene and protein in breast cancer 2003: biomarker and target of therapy. Rev Oncologist 8:307–325CrossRef

Elledge RM, Allred DC (2004) Clinical aspects of estrogen and progesterone receptors. In: Harris JR, Lippman ME, Morrow M et al (eds) Diseases of the breast (ed 3). Lippincott Williams and Wilkins, Philadelphia, PA, pp 603–617

Saphner T, Tormey DC, Gray R (1996) Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 14:2738–2746PubMed

Grann VR, Troxel AB, Zojwalla NJ, Jacobson JS, Hershman D, Neugut AI (2005) Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer 103:2241–2251PubMedCrossRef

10.

Bardou V-J, Arpino G, Elledge RM et al (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 21:1973–1979PubMedCrossRef

11.

Zeillinger R, Kury F, Czerwenka K et al (1989) HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer. Oncogene 4:109–114PubMed

12.

Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Kato S, Endoh H, Masuhiro Y et al (1995) Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270:1491–1494CrossRef

13.

Lee AV, Cui X, Oesterreich S (2001) Cross-talk among estrogen receptor, epidermal growth factor, and insulin-like growth factor signaling in breast cancer. Review Clin Cancer Res 7:4429–4435 (Suppl 12)

14.

Konecny G, Pauletti G, Pegram M et al (2003) Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 95:142–153PubMedCrossRef

15.

Huang HJ, Neven P, Drijkoningen M et al (2005) Association between tumour characteristics and HER-2 by immunohistochemistry in 1362 women with primary operable breast cancer. J Clin Pathol 58:611–616PubMedCrossRef

16.

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 (Review)PubMedCrossRef

17.

Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCrossRef

18.

Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423PubMedCrossRef

19.

Fan C, Oh DS, Wessels L et al (2006) Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 355:560–569PubMedCrossRef

20.

Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtype and survival in the Carolina breast cancer study. JAMA 295:2492–2502PubMedCrossRef

21.

Fisher B (1977) Biological and clinical considerations regarding the use of surgery and chemotherapy in the treatment of primary breast cancer. Cancer 40(Suppl1):574–587PubMedCrossRef

22.

Dunnwald LK, Rossing MA, Li CI (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 9:R6PubMedCrossRef

23.

Elston EW, 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 19:403–410PubMedCrossRef

24.

Hosmer DW, Lemeshow S (2000) Applied logistic regression (2nd ed). Wiley, New York

25.

Sterne JA, Davey Smith G (2001) Sifting the evidence—what’s wrong with significance tests. Br Med J 322:226–231CrossRef

26.

Ravdin PM, De Laurentiis M, Vendely T, Clark GM (1994) Prediction of axillary lymph node status in breast cancers by prognostic indicators. J Natl Cancer Inst 86:1771–1775PubMedCrossRef

27.

Gajdos C, Tartter PI, Bleiweiss IJ (1999) Lymphatic invasion, tumor size, and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers. Ann Surg 220:692–696CrossRef

28.

Gann PH, Colilla SA, Gapstur SM, Winchester DJ, Winchester DP (1999) Factors associated with axillary lymph node metastasis from breast carcinoma. Cancer 86:1511–1519PubMedCrossRef

29.

Silverstein MJ, Skinner KA, Lomis TJ (2001) Predicting axillary nodal positivity in 2282 patients with breast carcinoma. World J Surg 25:767–772PubMedCrossRef

30.

Chua B, Ung O, Taylor R, Boyages J (2001) Frequency and predictors of axillary lymph node metastases in invasive breast cancer. ANZ J Surg 71:723–728PubMedCrossRef

31.

Viale G, Zurrida S, Maiorano E et al (2005) Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Cancer 103:492–500PubMedCrossRef

32.

Patani NR, Dwek MV, Douek M (2007) Predictors of axillary lymph node metastasis in breast cancer: a systemic review. Eur J Surg Oncol 33:409–419PubMedCrossRef

33.

Revillion F, Bonneterre J, Peyrat JP (1998) ERBB2 oncogene in human breast cancer and its clinical significance. Rev Eur J Cancer 34:791–808CrossRef

34.

Bartlett JM, Ellis IO, Dowsett M et al (2007) Human epidermal growth factor receptor 2 status correlates with lymph node involvement in patients with estrogen receptor (ER)-negative, but with grade in those with ER-positive early-stage breast cancer suitable for cytotoxic chemotherapy. J Clin Oncol 25:4423–4430PubMedCrossRef

35.

Taucher S, Rudas M, Mader RM et al (2003) Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer 98:2547–2553PubMedCrossRef

36.

Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRef

37.

Shou J, Massarweh S, Osborne CK et al (2004) Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 96:926–935PubMed

38.

Pritchard KI, Shepherd LE, O’Malley FP et al (2006) HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354:2103–2111PubMedCrossRef

39.

Mackey JR, Kaufman B, Clemens M et al (2006) Trastuzumab prolongs progressive-free survival in hormone-dependent and HER-2 positive metastatic breast cancer. Breast Cancer Res Treat 100 S1:S5–Abstr 3

40.

Lange CA, Richer JK, Shen T et al (1998) Convergence of progesterone and epidermal growth factor signaling in breast cancer. Potentiation of mitogen-activated protein kinase pathways. J Biol Chem 273:31308–31316PubMedCrossRef

41.

Schneider J, Pollan M, Tejerina A, Sanchez J, Lucas AR (2003) Accumulation of uPA-PAI-I complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer. Brit J Cancer 88:96–101PubMedCrossRef

42.

Lockwood CJ (2001) Regulation of plasminogeen activator inhibitor I expression by interaction of epidermal growth factor with progestin during decidualization of human endometrial stromal cells. Am J Obstet Gynecol 184:798–804PubMedCrossRef

43.

Russell KS, Hung M-C (1992) Transcriptional repression of the neu protooncogene by estrogen stimulated estrogen receptor. Cancer Res 52:6624–6629PubMed

44.

Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL (1989) HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7:1120–1128PubMed

45.

Borg A, Baldetorp B, Ferno M et al (1991) ERBB2 amplification in breast cancer with a high rate of proliferation. Oncogene 6:137–143PubMed

46.

McCann AH, Dervan PA, O’Regan M et al (1991) Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. Cancer Res 51:3296–303PubMed

47.

Allred DC, Clark GM, Tandon AK et al (1992) HER-2 in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 10:599–605PubMed

48.

Love RR, Duc NB, Havighurst TC et al (2003) HER-2 overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer. J Clin Oncol 21:453–457PubMedCrossRef

49.

Peiro G, Adrover E, Aranda FI et al (2007) Prognostic implication of HER-2 status in steroid receptor positive, lymph node negative breast carcinoma. Am J Clin Path 127:780–786PubMedCrossRef

50.

Saal LH, Holm K, Maurer M et al (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65:2554–2559PubMedCrossRef

51.

Foulkes WD, Brunet JS, Stefansson IM et al (2004) The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 64:830–835PubMedCrossRef

Titel: Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive
verfasst von: Ben Van Calster
Isabelle Vanden Bempt
Maria Drijkoningen
Nathalie Pochet
Jiqiu Cheng
Sabine Van Huffel
Wouter Hendrickx
Julie Decock
Huei-Jean Huang
Karin Leunen
Frederic Amant
Patrick Berteloot
Robert Paridaens
Hans Wildiers
Erik Van Limbergen
Caroline Weltens
Dirk Timmerman
Toon Van Gorp
Ann Smeets
Walter Van den Bogaert
Ignace Vergote
Marie-Rose Christiaens
Patrick Neven
Publikationsdatum: 01.01.2009
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-9914-7

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive

Abstract

Neu im Fachgebiet Onkologie

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2009

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Joint effects of body size, energy intake, and physical activity on breast cancer risk

Expression of Bmi-1 protein in tumor tissues is associated with favorable prognosis in breast cancer patients

Increase in response rate by prolonged treatment with neoadjuvant letrozole

Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study

Is chemotherapy necessary for premenopausal women with lower-risk node-positive, endocrine responsive breast cancer? 10-year update of International Breast Cancer Study Group Trial 11-93

Neu im Fachgebiet Onkologie

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Update Onkologie