Kristina Lindemann

Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study

We examined the relationship of body mass index (BMI), diabetes and smoking to endometrial cancer risk in a cohort of 36 761 Norwegian women during 15.7 years of follow-up. In multivariable analyses of 222 incident cases of endometrial cancer, identified by linkage to the Norwegian Cancer Registry, there was a strong increase in risk with increasing BMI (P-trend <0.001). Compared to the reference (BMI 20–24 kg m−2), the adjusted relative risk (RR) was 0.53 (95% confidence interval (CI): 0.19–1.47) for BMI<20 kg m−2, 4.28 (95% CI: 2.58–7.09) for BMI of 35–39 kg m−2 and 6.36 (95% CI: 3.08–13.16) for BMI⩾40 kg m−2. Women with known diabetes at baseline were at three-fold higher risk (RR 3.13, 95% CI: 1.92–5.11) than those without diabetes; women who reported current smoking at baseline were at reduced risk compared to never smokers (RR 0.55, 95% CI: 0.35–0.86). The strong linear positive association of BMI with endometrial cancer risk and a strongly increased risk among women with diabetes suggest that any increase in body mass in the female population will increase endometrial cancer incidence.

Long-Term Outcomes After Pelvic Radiation for Early-Stage Endometrial Cancer

PURPOSE This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer. PATIENTS AND METHODS Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups. RESULTS After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15). CONCLUSION We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.

Serum lipids and endometrial cancer risk: results from the HUNT-II study.

Obesity is a major risk factor for endometrial cancer. Still, the association of obesity‐related metabolic factors, such as serum lipids and lipoprotein levels, is unclear. We prospectively examined the association of serum levels of triglycerides, total cholesterol, low‐density lipoprotein cholesterol, non–high‐density lipoprotein (non‐HDL), and HDL cholesterol with endometrial cancer risk among 31,473 women. During 9 years of follow‐up, 100 cases of endometrial cancer were identified by linkage to the Cancer Registry of Norway. There was a positive association of serum triglyceride levels with endometrial cancer risk. Comparing the highest to the lowest quartile of triglycerides, the age‐adjusted hazard ratio was 2.34 (95% CI: 1.04–5.28), and further adjustment for body mass index attenuated the association (hazard ratio 1.79, 95% CI: 0.79–4.05). For total serum cholesterol, low‐density lipoprotein cholesterol and HDL cholesterol there were no associations with endometrial cancer risk, either without or after adjustment for body mass index. Serum triglyceride levels were positively associated with the risk of endometrial cancer, and some of the association seems to be attributable to obesity. Apart from higher estrogen levels produced in adipose tissue, mechanisms more specifically related to triglycerides may also be involved in endometrial cancer. Further prospective studies on this subject are needed to better understand the association of blood lipids with endometrial cancer risk.

Body mass index and the risk of meningioma, glioma and schwannoma in a large prospective cohort study (The HUNT Study)

Background:Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS).Methods:In a large population study (The Nord–Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma.Results:A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0–25) of follow-up. In obese women (BMI ⩾30 kg m−2), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97–2.92, P-trend=0.05) than in the reference group (BMI 20–24.9 kg m−2), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ⩾25 kg m−2) with the risk of schwannoma (HR=0.48, 95% CI: 0.23–0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup.Conclusion:These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk.

Endometrial cancer incidence trends in Norway during 1953-2007 and predictions for 2008-2027

Endometrial cancer is the most common cancer of the female genital tract in Western countries. Monitoring the incidence is important for health care planning and the identification of risk factors. We present an age‐period‐cohort analysis of incidence trends of endometrial cancer in Norway from 1953 to 2007 and compare the incidence trends with those in 3 other Nordic countries. Based on the observed trends, we have predicted endometrial cancer rates in Norway in 2015 and 2025. In women at postmenopausal age (≥55 years), the annual incidence increase was 2.1% (95% CI: 0.9%, 3.4%) from 1988 to 1997 and 1.7% (95% CI: 0.6%, 2.8%) from 1998 to 2007. In younger women, there was an annual reduction of 0.6% (95% CI: −2.3%, 2.2%) from 1988 to 1997, followed by an annual increase of 1.7% (95% CI: −0.4%, 3.9%) from 1998 to 2007. The secular changes are likely to reflect both cohort and period effects. Our prediction estimates by 2025 suggest an incidence increase in the range of 50 to 100%, relative to the observed incidence in 2005. There has been a strong and consistent incidence increase in endometrial cancer in the Nordic countries over the last 50 years. The increase has been most pronounced in postmenopausal women, but in the last decade, rates have increased also in women younger than 55 years. The prediction for the next 20 years suggests that endometrial cancer rates will dramatically increase unless effective preventive strategies are implemented.

Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)

BackgroundWe evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.MethodsWe performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients.ResultsRecruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated.ConclusionTreatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.Trial registrationTrial identification number (Clinical Trials.gov): NCT01965080.Nordic Society of Gynecological Oncology: NSGO–EC–0302.EudraCT number: 2004-001103-35.

Minimal residual disease in breast cancer and gynecological malignancies: phenotype and clinical relevance.

In breast cancer, about 35% of patients without any clinical signs of overt distant metastases already have disseminated tumor cells in bone marrow aspirates at the time of primary therapy. A significant prognostic impact of these disseminated tumor cells has been shown by many international studies: patients with tumor cells in their bone marrow have a significantly worse prognosis than those without them. Even in malignancies where the skeletal system is not a preferred location for distant metastasis, such as ovarian cancer, early presence of minimal residual disease (MRD) is correlated with poor patient outcome. Thus, besides analysis of the primary tumor, detection of MRD can be used for assessment of patient prognosis and for prediction or monitoring of response to systemic therapy. Disseminated tumor cells are also the targets for novel tumor biological therapy approaches such as specific antibody-based therapies against target cell-surface antigens such as HER2, Ep-CAM (17-1A), and uPA-R. In breast cancer, a first antibody-based tumor therapy against HER2 (Herceptin) has already been approved for clinical use in recurrent disease. However, patient selection for such tumor biological therapies becomes rather difficult due to phenotype changes, which may manifest themselves as differences between primary lesion and disseminated tumor cells. Therefore, not only identification of disseminated tumor cells but even more so their characterization at the protein and gene levels have become increasingly important. In conclusion, characterization of tumor biological properties of disseminated tumor cells allows identification of patients with breast cancer or gynecological malignancies at risk for relapse who are likely to benefit from systemic treatment and/or novel tumor biological therapy approaches.

The impact of BMI on subgroups of uterine cancer.

Background:Obesity increases the risk of uterine cancer, but results by histological type have differed.Methods:We followed 36 755 women for 17.8 years for uterine cancers.Results and conclusion:Body mass index (BMI) was positively associated with uterine cancers as a whole, particularly for endometrioid adenocarcinomas, for which the relative risk for very obese women (BMI: ⩾40 kg m−2) compared with lean (BMI: 20–24 kg m−2) women, was 11.1 (95% confidence interval: 5.2–23.8).

Poor concordance between CA-125 and RECIST at the time of disease progression in patients with platinum-resistant ovarian cancer: analysis of the AURELIA trial.

BACKGROUND Data on CA-125 as a predictor of disease progression (PD) in ovarian cancer come predominantly from patients with platinum-sensitive disease receiving chemotherapy alone. We assessed concordance between CA-125-defined and RECIST-defined PD using data from the Gynecologic Cancer InterGroup (GCIG) randomized phase III AURELIA trial in platinum-resistant ovarian cancer (PROC). PATIENTS AND METHODS Patients with PROC were randomized to receive single-agent chemotherapy with or without bevacizumab. PD by CA-125 was defined according to GCIG criteria (except that confirmatory CA-125 measurement was not required). This exploratory analysis included patients with RECIST PD and a CA-125 reading ≤28 days before and ≤21 days after RECIST-defined PD. RESULTS Of 218 eligible patients, only 94 (43%, 95% confidence interval 36% to 50%) had concordant RECIST and CA-125 PD status (42% in the chemotherapy-alone arm; 45% in the bevacizumab combination arm, P = 0.6). There was no evidence of CA-125-defined PD in the remaining 124 patients despite PD according to imaging. There were no significant differences in baseline characteristics between patients with PD defined by both RECIST and CA-125 and those with RECIST-only PD. CA-125 was even less sensitive in detecting PD in patients with early (<8 weeks after randomization) compared with later RECIST-defined PD (69% versus 53%, respectively, not meeting CA-125 criteria; P = 0.053). There was no significant difference in survival after PD in patients with concordant PD by RECIST and CA-125 versus those with PD only by RECIST. We validated our findings in an independent study population of PROC. CONCLUSIONS In this platinum-resistant population, PD was typically detected earlier by imaging than by CA-125, irrespective of bevacizumab treatment. Disease status by CA-125 at the time of PD was not prognostic for overall survival. Regular radiologic assessment as well as symptom benefit assessment should be considered during PROC follow-up.

Body mass index, diabetes and survival after diagnosis of endometrial cancer: A report from the HUNT-Survey

OBJECTIVE We studied the association of body mass index (BMI) and diabetes with all-cause death and endometrial cancer-specific death among women with endometrial cancer (EC). METHODS Included were 337 women in the Health Surveys in North-Trøndelag, Norway who were followed from EC diagnosis to death or end of follow-up, 30th June 2012. Risks of death associated with BMI and diabetes were estimated as hazard ratios (HRs) with 95% confidence intervals (95% CI). The risks of EC-specific death were estimated as sub-HRs, after adjustment for competing causes of death. We also studied the risk of death associated with diabetes in women with BMI<25kg/m(2) and in women with BMI≥25kg/m(2). RESULTS During the median follow-up time of 6.7years, 166 women (49.3%) died. Diabetes increased the risk of all-cause death (HR 2.14, 95% CI: 1.26-3.63) and endometrial cancer-specific death (SHR, 2.62, 95% CI: 1.07-6.43) after adjustment for age, histological type and stage of EC. BMI was not associated with risk of all-cause or EC-specific death. The increased risk of both all-cause death and EC specific death in diabetic women seemed to be more pronounced in women with BMI<25kg/m(2) (HR 6.35, 95% CI: 1.90-21.14) compared to women with BMI>25kg/m(2) (HR 1.80, 95% CI: 0.98-3.33). CONCLUSIONS Diabetes, but not BMI, was associated with increased risk of all-cause death and death from EC. The increased risk of death associated with diabetes seemed to be most pronounced in women with BMI<25kg/m(2).