Heather J. Agnew

Metabolic Syndrome and the Risk of Breast, Endometrial, and Ovarian Cancer among Postmenopausal Women in the UK Biobank

Abstract Background: There is some evidence that metabolic syndrome (MetS) is associated with postmenopausal breast and gynecologic cancer. However, results from previous studies have been inconsistent and varied by the definition of MetS used. Methods: Using data from the UK Biobank, the association between MetS, according to three definitions, and the risk of breast, endometrial, and ovarian cancer was assessed among postmenopausal women with serologic biomarker data. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI), adjusting for a range of confounders. Results: In total, 4,791 breast cancers, 820 endometrial cancers, and 582 ovarian cancers were diagnosed. For all definitions, MetS was associated with a higher risk of breast cancer (harmonized definition; HR, 1.11; 95% CI, 1.04–1.19) and endometrial cancer (harmonized definition; HR, 2.18; 95% CI, 1.86–2.55) but not ovarian cancer (harmonized definition; HR, 1.08; 95% CI, 0.88–1.31). Assessment of the individual MetS components revealed that only abdominal obesity was consistently associated with breast cancer, whereas all components were associated with a higher risk of endometrial cancer. Conclusions: In this cohort, MetS and all MetS components were individually associated with a higher risk of endometrial cancer, but only abdominal obesity was consistently associated with an increased risk of breast cancer. No associations were observed between MetS and ovarian cancer risk. Impact: These findings underline the need for further mechanistic research to clarify potential causal relationships and to better inform public health strategies to address the increasing obesity-related cancer burden, particularly endometrial cancer in postmenopausal women.

Patient and clinician priorities for information on treatment outcomes for advanced ovarian cancer: a Delphi exercise

Patients with advanced ovarian cancer face a range of treatment options, and there is unwarranted variation in treatment decision-making between UK providers. Decision support tools that produce data on treatment outcomes as a function of individual patient characteristics, would help both patients and clinicians to make informed, preference- and values-based choices. However, data on treatment outcomes to include in such tools are lacking. Following a literature review, a questionnaire was designed for use in a Delphi process to establish which treatment outcomes are important to both patients and clinicians in decision-making for treatment for advanced ovarian cancer. Patient and clinician panels were established. Following 2 Delphi rounds, consensus was achieved for 7/11 items in the patient panel and 8/11 items in the clinician panel. Consensus across both panels was achieved for inclusion of both overall survival and progression free survival as important items in the decision-making process, although there remained differences of opinion as to whether these should be presented as relative or absolute values. Information needs for treatment decision-making in ovarian cancer differ between and within patient and clinician groups. Whilst overall survival and progression free survival are universally accepted as important data items, decision support tools will need to be nuanced to allow presentation of a range of outcomes and associated probabilities, and in a range of formats, that can be tailored to the preferences of clinician and patients.

Leading causes of death after a diagnosis of endometrial cancer: a systematic review and meta-analysis

Despite curative treatment, an endometrial cancer (EC) diagnosis is associated with an elevated risk of death compared with age-matched women in the general population. This study aimed to quantify their risk of death from EC, cardiovascular disease, and other causes. A systematic review of Medline, Embase, and CENTRAL databases was performed to February 2024. Studies reporting cause of death after a diagnosis of EC were included. Mortality rates and 95% CIs were calculated using a random-effects model. Heterogeneity was assessed through visual inspection of forest plots and the I In total, 22 studies including 323,551 participants were analyzed and 102,711 (31.7%) died within 20 years of diagnosis, 62.6% (n = 64,155) from non-EC causes. In the 12 studies that reported cardiovascular death, 24.6% of participants (n = 24,309) died from cardiovascular disease. Those with local disease at presentation were more likely to die from non-EC causes than those with advanced disease at presentation (48.9% vs 13.5%). A total of 2 studies reported cause of death by ethnicity; overall, Black individuals were more likely to die than individuals of White or Other ethnicities (40.8% vs 27.9% vs 18.9%). Deaths related to non-EC causes, including cardiovascular disease, overtook EC-specific deaths >5 years after diagnosis. Significant heterogeneity was noted, despite sub-group analyses, and the findings were based on very low certainty evidence. Individuals with a history of EC are at increased risk of death from other causes. Oncology follow-up appointments provide the ideal opportunity to optimize cardiovascular risk factors to reduce preventable deaths. Future research needs to reflect the global majority.

Gynecological malignancies and obesity

The global pandemic of obesity has had a significant impact on gynecological malignancies, most notably endometrial cancer. It has resulted in worldwide increases in the incidence of endometrial cancer and a change in patient demographics, resulting in more diagnoses than ever before being made in pre-menopausal women, who are often keen to pursue fertility-sparing treatments. Obesity increases the risk of gynecological cancers by creating a pro-carcinogenic environment of unopposed estrogen, hyperinsulinemia, and chronic inflammation. It can present both a diagnostic challenge and strongly influence management decisions, including the practicalities of performing surgery, increase anesthetic risks, and alter response rates to adjuvant and medical therapies. Obesity may also influence endometrial cancer mortality and certainly contributes to poorer overall survival due to an excess of deaths related to cardiovascular disease. Weight loss may well, therefore, be the key to the prevention of gynecological cancers and their recurrence.