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
2013 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 22, no 5, 643-649 p.Article in journal (Refereed) Published
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.
Intermediate risk breast cancer, Apoptosis, Proliferation, Tamoxifen, Survival
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-100030DOI: 10.1016/j.breast.2013.07.043ISI: 000324516800011OAI: oai:DiVA.org:liu-100030DiVA: diva2:659438
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||2013-10-252013-10-252014-03-25