Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases - aspects on distribution and prognosis for patients with luminal A tumours: results from a prospective randomised trial

Authors: Anna-Karin Falck, Mårten Fernö, Pär-Ola Bendahl, Lisa Rydén

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

The St Gallen surrogate molecular subtype definitions classify the oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes according to proliferation rate and/or expression of human epidermal growth factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness. Primary tumours and lymph node metastases might represent different malignant clones, but in the clinical setting only the biomarker profile of the primary tumour is used for selection of adjuvant systemic treatment. The present study aimed to classify primary breast tumours and matched lymph node metastases into luminal A, luminal B, HER2-positive and triple-negative subtypes and compare the distributions.

Methods

Eighty-five patients with available tumour tissue from both locations were classified. The distribution of molecular subtypes in primary tumours and corresponding lymph node metastases were compared, and related to 5-year distant disease-free survival (DDFS).

Results

The St Gallen molecular subtypes were discordant between primary tumours and matched lymph node metastases in 11% of the patients (p = 0.06). The luminal A subtype in the primary tumour shifted to a subtype with a worse prognostic profile in the lymph node metastases in 7 of 45 cases (16%) whereas no shift in the opposite direction was observed (0/38) (p = 0.02). All subtypes had an increased hazard for developing distant metastasis during the first 5 years after diagnosis in both primary breast tumours and matched lymph node metastases, compared with the luminal A subtype.

Conclusion

The classification according to the St Gallen molecular subtypes in primary tumours and matched lymph node metastases, implicates a shift to a more aggressive subtype in synchronous lymph node metastases compared to the primary breast tumour. The selection of systemic adjuvant therapy might benefit from taking the molecular subtypes in the metastatic node into account.
Appendix
Available only for authorised users
Literature
1.
Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ: Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009, 20 (8): 1319-1329. 10.1093/annonc/mdp322.CrossRefPubMedPubMedCentral
2.
EBCTCG 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 (9472): 1687-1717.CrossRef
3.
Joensuu H, Pylkkanen L, Toikkanen S: Long-term survival in node-positive breast cancer treated by locoregional therapy alone. Br J Cancer. 1998, 78 (6): 795-799. 10.1038/bjc.1998.581.CrossRefPubMedPubMedCentral
4.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 2000, 406 (6797): 747-752. 10.1038/35021093.CrossRefPubMed
5.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98 (19): 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
6.
Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS, et al: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009, 101 (10): 736-750. 10.1093/jnci/djp082.CrossRefPubMedPubMedCentral
7.
Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, Cheang MC, Gelmon K, Nielsen TO, Blomqvist C, 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 (5): e1000279-10.1371/journal.pmed.1000279.CrossRefPubMedPubMedCentral
8.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10 (16): 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
9.
Callagy G, Cattaneo E, Daigo Y, Happerfield L, Bobrow LG, Pharoah PD, Caldas C: Molecular classification of breast carcinomas using tissue microarrays. Diagn Mol Pathol. 2003, 12 (1): 27-34. 10.1097/00019606-200303000-00004.CrossRefPubMed
10.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ: Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011, 22 (8): 1736-1747. 10.1093/annonc/mdr304.CrossRefPubMedPubMedCentral
11.
Brouckaert O, Laenen A, Vanderhaegen J, Wildiers H, Leunen K, Amant F, Berteloot P, Smeets A, Paridaens R, Christiaens MR, et al: Applying the 2011 St Gallen panel of prognostic markers on a large single hospital cohort of consecutively treated primary operable breast cancers. Ann Oncol. 2012, 23 (10): 2578-2584. 10.1093/annonc/mds062.CrossRefPubMed
12.
Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D: Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann Oncol. 2010, 21 (6): 1254-1261. 10.1093/annonc/mdp427.CrossRefPubMed
13.
Lindstrom LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, Hatschek T, Skoog L, Bergh J: Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012, 30 (21): 2601-2608. 10.1200/JCO.2011.37.2482.CrossRefPubMed
14.
Jensen JD, Knoop A, Ewertz M, Laenkholm AV: ER, HER2, and TOP2A expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer. Breast Cancer Res Treat. 2012, 132 (2): 511-521. 10.1007/s10549-011-1610-3.CrossRefPubMed
15.
Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF, Albarracin C, Meric-Bernstam F, Woodward W, Theriault RL, et al: Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009, 20 (12): 1953-1958. 10.1093/annonc/mdp263.CrossRefPubMedPubMedCentral
16.
Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, et al: Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012, 30 (6): 587-592. 10.1200/JCO.2010.33.5232.CrossRefPubMed
17.
Falck AK, Ferno M, Bendahl PO, Ryden L: Does analysis of biomarkers in tumor cells in lymph node metastases give additional prognostic information in primary breast cancer?. World J Surg. 2010, 34 (7): 1434-1441. 10.1007/s00268-010-0499-z.CrossRefPubMed
18.
D’Andrea MR, Limiti MR, Bari M, Zambenedetti P, Montagutti A, Ricci F, Pappagallo GL, Sartori D, Vinante O, Mingazzini PL: Correlation between genetic and biological aspects in primary non-metastatic breast cancers and corresponding synchronous axillary lymph node metastasis. Breast Cancer Res Treat. 2007, 101 (3): 279-284. 10.1007/s10549-006-9300-2.CrossRefPubMed
19.
Strien L, Leidenius M, von Smitten K, Heikkila P: Concordance between HER-2 and steroid hormone receptor expression between primary breast cancer, sentinel node metastases, and isolated tumor cells. Pathol Res Pract. 2010, 206 (4): 253-258. 10.1016/j.prp.2009.12.006.CrossRefPubMed
20.
Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, Clemons MJ: Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases?. Ann Oncol. 2009, 20 (9): 1499-1504. 10.1093/annonc/mdp028.CrossRefPubMedPubMedCentral
21.
Feng Y, Sun B, Li X, Zhang L, Niu Y, Xiao C, Ning L, Fang Z, Wang Y, Cheng J, et al: Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients. Breast Cancer Res Treat. 2007, 103 (3): 319-329. 10.1007/s10549-006-9385-7.CrossRefPubMed
22.
Falck AK, Bendahl PO, Chebil G, Olsson H, Ferno M, Ryden L: Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years’ follow-up. Breast Cancer Res Treat. 2013, 140 (1): 93-104. 10.1007/s10549-013-2617-8.CrossRefPubMed
23.
Houssami N, Macaskill P, Balleine RL, Bilous M, Pegram MD: HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? Insights through meta-analysis. Breast Cancer Res Treat. 2011, 129 (3): 659-674. 10.1007/s10549-011-1632-x.CrossRefPubMed
24.
Ryden L, Haglund M, Bendahl PO, Hatschek T, Kolaric A, Kovacs A, Olsson A, Olsson H, Strand C, Ferno M: Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer: a national survey performed at pathology departments in Sweden. Acta Oncol. 2009, 48 (6): 860-866.PubMed
25.
Dybdal N, Leiberman G, Anderson S, McCune B, Bajamonde A, Cohen RL, Mass RD, Sanders C, Press MF: Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat. 2005, 93 (1): 3-11. 10.1007/s10549-004-6275-8.CrossRefPubMed
26.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007, 131 (1): 18-43.PubMed
27.
Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S: American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 2010, 6 (4): 195-197. 10.1200/JOP.777003.CrossRefPubMedPubMedCentral
28.
Klintman M, Bendahl PO, Grabau D, Lovgren K, Malmstrom P, Ferno M: The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer. Mod Pathol. 2010, 23 (2): 251-259. 10.1038/modpathol.2009.167.CrossRefPubMed
29.
Ahlin C, Aaltonen K, Amini RM, Nevanlinna H, Fjallskog ML, Blomqvist C: Ki67 and cyclin A as prognostic factors in early breast cancer. What are the optimal cut-off values?. Histopathology. 2007, 51 (4): 491-498. 10.1111/j.1365-2559.2007.02798.x.CrossRefPubMed
30.
Romero Q, Bendahl PO, Klintman M, Loman N, Ingvar C, Ryden L, Rose C, Grabau D, Borgquist S: Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies. BMC Cancer. 2011, 11: 341-10.1186/1471-2407-11-341.CrossRefPubMedPubMedCentral
31.
Deyarmin B, Kane JL, Valente AL, van Laar R, Gallagher C, Shriver CD, Ellsworth RE: Effect of ASCO/CAP guidelines for determining ER status on molecular subtype. Ann Surg Oncol. 2013, 20 (1): 87-93. 10.1245/s10434-012-2588-8.CrossRefPubMed
32.
Thompson AM, Jordan LB, Quinlan P, Anderson E, Skene A, Dewar JA, Purdie CA: Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast Cancer Res. 2010, 12 (6): R92-10.1186/bcr2771.CrossRefPubMedPubMedCentral
33.
Chebil G, Bendahl PO, Idvall I, Ferno M: Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer–clinical associations and reasons for discrepancies. Acta Oncol. 2003, 42 (7): 719-725. 10.1080/02841860310004724.CrossRefPubMed
34.
SBCCG: Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. Swedish Breast Cancer Cooperative Group. J Natl Cancer Inst. 1996, 88 (21): 1543-1549.CrossRef
35.
Ryden L, Jonsson PE, Chebil G, Dufmats M, Ferno M, Jirstrom K, Kallstrom AC, Landberg G, Stal O, Thorstenson S, et al: Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005, 41 (2): 256-264. 10.1016/j.ejca.2004.06.030.CrossRefPubMed
Metadata
Title
St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases - aspects on distribution and prognosis for patients with luminal A tumours: results from a prospective randomised trial
Authors
Anna-Karin Falck
Mårten Fernö
Pär-Ola Bendahl
Lisa Rydén
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-558

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Concurrent chemoradiotherapy with tomotherapy in locally advanced non-small cell lung cancer: a phase i, docetaxel dose-escalation study, with hypofractionated radiation regimen

Research article

High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer

Research article

Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer

Research article

Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide

Research article

Axin gene methylation status correlates with radiosensitivity of lung cancer cells

Research article

A case–control study on the association between bladder cancer and prior bladder calculus
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits