High expression of stromal PDGFR beta is associated with reduced benefit of tamoxifen in breast cancer

• Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFR beta is an important regulator of fibroblasts. Experimental studies have linked PDGFR beta-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFR beta-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFR beta, which was not observed in the group with high stromal PDGFR beta. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFR beta as a marker related to tamoxifen benefit in early breast cancer.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

breast cancer

tamoxifen

tumour stroma

PDGFR beta

term-follow-up

growth-factor

tumor microenvironment

adjuvant

tamoxifen

receptor expression

resistance

chemotherapy

fibroblasts

sensitivity

inhibition

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)