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ObjectiveTo present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer.MethodsSystematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation.ResultsBecause of its low sensitivity (50–62% for early stage epithelial ovarian cancer) and limited specificity (94–98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery.ConclusionsAt present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.

Cardiorespiratory fitness is an independent risk factor for cardiovascular disease and shortened life expectancy in breast cancer survivors. This randomised controlled trial (n = 153) was designed for patients with a physically inactive lifestyle prediagnosis and concurrently referred to adjuvant chemotherapy. We compared two 12-week exercise interventions aimed at physiological and patient-reported outcomes (cardiorespiratory fitness, muscle strength, metabolic markers, physical activity, pain, fatigue), including a 39-week follow-up. A supervised hospital-based moderate to high intensity group exercise intervention was compared to an instructed home-based individual pedometer intervention. The two 12-week interventions included oncologists’ recommendations and systematic health counselling. Outcomes were measured at baseline and week 6, 12 and 39. Primary outcome cardiorespiratory fitness declined significantly during chemotherapy and was restored in both interventions at follow-up. The interventions effectively engaged breast cancer patients in sustaining physical activities during and following adjuvant treatment. A composite metabolic score improved significantly. Positive cardiorespiratory fitness responders had improved clinical effects on fatigue, pain and dyspnoea versus negative responders. We conclude that a loss of cardiorespiratory fitness among physically inactive breast cancer patients may be restored by early initiated interventions and by adapting to physical activity recommendations, leading to a decreased cardiovascular risk profile in breast cancer survivors.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI −7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI −9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI −9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker–guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy.

Cancer antigen 125 (CA125) is used to monitor tumor burden among patients with advanced serous epithelial ovarian cancer. The purpose is to compare the monitoring performance of seven previously proposed criteria. The CA125 assessment criteria were applied to simulated datasets. We investigated the ability to provide information on CA125 increments as well as their robustness against false positive signals. For baseline concentrations above cut-off, the best performing criterion was based on a confirmed increment ≥2.5-times the nadir concentration. For baseline concentrations below cut-off, the best performing criterion was based on a confirmed increment from ≤ cut-off to >two-times cut-off. Computer simulation models may be useful for a preclinical validation of criteria to be investigated in clinical trials.