Endometrial cancer survival after breast cancer in relation to tamoxifen treatment:Pooled results from three countries

Introduction: Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer. Methods: We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: A total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P <0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P <0.0001) and age (P <0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial cancer than endometrioid patients with no tamoxifen exposure (HR = 2.11 (1.13 to 3.94)). The explanation for this latter observation is not apparent. Conclusions: Patients with endometrial cancer after breast cancer who received tamoxifen treatment for five years for breast cancer have greater endometrial cancer mortality risk than those who did not receive tamoxifen. This can be attributed to non-endometrioid histological subtypes with poorer prognosis among long term tamoxifen users

Systematic review of psychosocial factors at work and private life as risk factors for back pain

Study Design. A systematic review of observational studies. Objectives. To assess whether psychosocial factors at work and in private life are risk factors for the occurrence of back pain. Summary of Background Data. Several reviews on risk factors for back pain have paid attention to psychosocial factors. However, in none of the published reviews was a strict systematic approach used to identify and summarize the available evidence Methods. A computerized bibliographical search of several databases was performed, restricted to studies with a cohort or case-control design. A rating system was used to assess the strength of the evidence for various factors, based on the methodologic quality of the studies and the consistency of the findings. Results. Eleven cohort and two case-control studies were included in this review. Strong evidence was found for low social support in the workplace and low job satisfaction as risk factors for back pain. Insufficient evidence was found for an effect of a high work pace, high qualitative demands, low job content, low job control, and psychosocial factors in private life. Conclusions. Evidence was found for an effect of low workplace social support and low job satisfaction. However, the result for workplace social support was sensitive to slight changes in the rating system, and the effect found for low job satisfaction may be a result of insufficient adjustment for psychosocial work characteristics and physical load at work. In addition, the combined evaluation of job content and job control, both aspects of decision latitude, led to strong evidence of a role for low job decision latitude. Thus, based on this review, there is evidence for an effect of work-related psychosocial factors, but the evidence for the role of specific factors has not been established yet

Physical load during work and leisure time as risk factors for back pain

This systematic review assessed aspects of physical load during work and leisure time as risk factors for back pain. Several reviews on this topic are available, but this one is based on a strict systematic approach to identify and summarize the evidence, comparable with that applied in the clinical literature on the efficacy of intervention for back pain. A computerized bibliographical search was made of several data bases for studies with a cohort or case-referent design. Cross-sectional studies were excluded. A rating system was used to assess the strength of the evidence, based on the methodological quality of 28 cohort and 3 case-referent studies and the consistency of the findings. Strong evidence exists for manual materials handling, bending and twisting, and whole-body vibration as risk factors for back pain. The evidence was moderate for patient handling and heavy physical work, and no evidence was found for standing or walking, sitting, sports, and total leisure-time physical activity

Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer

Tamoxifen increases the risk of uterine corpus cancer. Since only few, mostly small, studies have examined prognosis of uterine corpus cancer following tamoxifen, we conducted a large retrospective cohort study to further investigate this. We examined histopathologic and immunohistochemical characteristics of 332 patients with uterine corpus cancer following breast cancer, according to tamoxifen use. Survival was examined in the same patients combined with 309 patients from a previous study with updated follow-up. Histological review of all cancers was performed. Long-term tamoxifen users showed a higher proportion of non-endometrioid tumors than non-users (32.7% vs. 17.4%, P = 0.004), especially serous adenocarcinomas and carcinosarcomas. An increased proportion of FIGO stage III and IV tumors was also observed (20.0% vs. 11.3%, P = 0.049). Within FIGO stage I, both short-term and long-term tamoxifen users showed a higher proportion of tumors limited to the endometrium than non-users (35.7% vs. 22.9%, P = 0.049 and 0.004 respectively). Uterine corpus cancers in long-term tamoxifen users were more often steroid receptor-negative (ER alpha, PRA and PRB, P = 2 years tamoxifen = 2.4; 95% CI = 1.2-4.6). In conclusion, this large study clearly shows that tamoxifen-associated tumors have less favorable histological features and a worse survival. Our results can be applied when weighing risks and benefits of tamoxifen versus other hormonal agents used in the prevention and treatment of breast cancer

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level.METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection.RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874).CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p