Amplification of HSD17B1 and ERBB2 in primary breast cancer

Estrogens play a crucial role in the development of breast cancer. Estradiol can be produced in the breast tissue in situ , and one of the enzymes involved in this process is 17 β -hydroxysteriod dehydrogenase (17 β -HSD) type 1 that catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17 β -HSD type 1 ( HSD17B1 ) is located at 17q12–21, close to the more studied ERBB2 and BRCA1 . The aim of this study was to investigate if HSD17B1 shows an altered gene copy number in breast cancer. We used real-time PCR and examined 221 postmenopausal breast tumors for amplification of HSD17B1 and ERBB2 . In all, 32 tumors (14.5%) showed amplification of HSD17B1 and 21% were amplified for ERBB2 . Amplification of the two genes was correlated ( P =0.00078) and in 14 tumors (44%) with amplification of HSD17B1 , ERBB2 was co amplified. The patients with amplification in at least one of the genes had a significantly worse outcome than patients without ( P =0.0059). For estrogen receptor (ER)-positive patients who received adjuvant tamoxifen, amplification of HSD17B1 was related to decreased breast cancer survival ( P =0.017), whereas amplification of ERRB2 was not. Amplification of HSD17B1 might be an indicator of adverse prognosis among ER-positive patients, and possibly a mechanism for decreased benefit from tamoxifen treatment.