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Identification of intermediate risk breast cancer patients with1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis
Sahlgrens Acad, Sweden .
Karolinska Institute, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
2013 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 22, no 5, 643-649 p.Article in journal (Refereed) Published
Abstract [en]

Background: According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. less thanbrgreater than less thanbrgreater thanAim: Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. less thanbrgreater than less thanbrgreater thanMaterial and methods: Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. less thanbrgreater than less thanbrgreater thanResults: A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/mu gDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p andlt; 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Coxs proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. less thanbrgreater than less thanbrgreater thanConclusion: By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 22, no 5, 643-649 p.
Keyword [en]
Intermediate risk breast cancer, Apoptosis, Proliferation, Tamoxifen, Survival
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-100030DOI: 10.1016/j.breast.2013.07.043ISI: 000324516800011OAI: oai:DiVA.org:liu-100030DiVA: diva2:659438
Note

Funding Agencies|Swedish State under the LUA (Sahlgrenska University Hospital, Gothenburg)|VGFOUREG-75911|King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg|2009:49|Swedish Cancer Foundation||Swedish Research Council||

Available from: 2013-10-25 Created: 2013-10-25 Last updated: 2017-12-06

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Arnesson, Lars-GunnarStål, Olle

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Division of Clinical SciencesFaculty of Health SciencesDepartment of Surgery in LinköpingDepartment of Oncology
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