Because polychlorinated biphenyls (PCBs) are thought to cause endocrine disruption, we examined 438 adolescent boys from a birth cohort in the Faroe Islands, where PCB exposures are elevated. We measured PCBs and p,p′-dichlorodiphenyldichloroethylene (DDE) in cord blood and in serum from clinical examination at age 14. Higher prenatal PCB exposure was associated with lower serum concentrations of both luteinizing hormone (LH) and testosterone. In addition, sex hormone binding globulin (SHBG) was positively associated with both prenatal and concurrent PCB exposures. The PCB-SHBG association was robust to covariate adjustment. In a structural equation model, a doubling in prenatal PCB exposure was associated with a decrease in LH of 6% (p = 0.03). Prenatal exposure to PCB and DDE showed weak, non-significant inverse associations with testicular size and Tanner stage. DDE was highly correlated with PCB and showed slightly weaker associations with the hormone profile. These findings suggest that delayed puberty with low serum-LH concentrations associated with developmental exposure to non dioxin-like PCBs may be due to a central hypothalamo-pituitary mechanism.

Epidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR-inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments. The aim is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review was conducted in accordance to the PRISMA guidelines. Literature searches were conducted to identify publications exploring correlations between EGFR/EGFR-ligands in serum/plasma of breast cancer patients and prognostic/predictive outcome measures. Sixteen publications were eligible for inclusion. Twelve studies evaluated EGFR, whereas five studies evaluated one or more of the EGFR-ligands. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced breast cancer, especially in patients with estrogen and/or progesterone receptor positive tumors. The prognostic and predictive value of EGFR and EGFR-ligands in blood has only been investigated in highly selected subsets of breast cancer patients and most studies were small. This is the first systematic review evaluating the utility of EGFR and EGFR-ligands as predictive and prognostic biomarkers in blood in breast cancer. Further exploration in large well-designed studies is needed.

Background The epidermal growth factor receptor (EGFR) system is involved in cancer pathogenesis and serves as an important target for multiple cancer treatments. EGFR and its ligands epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF), betacellulin (BTC), amphiregulin (AREG) and transforming growth factor α (TGF-α) have potential applications as prognostic or predictive serological biomarkers in cancer. The aim was to establish EGFR and EGFR ligand reference intervals in healthy women. Methods EGFR and EGFR ligands were measured in serum from 419 healthy women aged 26–78 years. The need for age partitioned reference intervals was evaluated using Lahti’s method. EGFR and EGF were analyzed using ELISA assays, whereas HB-EGF, BTC, AREG and TGF-α were analyzed using the highly sensitive automated single molecule array (Simoa) enabling detection below the lower reference limit for all six biomarkers. Results Reference intervals for EGFR and the EGFR ligands were determined as the 2.5th and 97.5th percentiles. All six biomarkers were detectable in all serum samples. For EGFR, EGF, HB-EGF and TGF-α, reference intervals were established for women <55 years and for women >55 years, whilst common reference intervals were established for AREG and BTC including women aged 26–78 years. Conclusions Age specific reference intervals were determined for EGFR, EGF, HB-EGF, BTC, AREG and TGF-α.

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