1 in 69 women will develop ovarian cancer in her lifetime
Objectives To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.
Design Observational diagnostic study using prospectively collected clinical and ultrasound data.
Setting 24 ultrasound centres in 10 countries.
Participants Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.
Main outcome measures Histological classification and surgical staging of the mass.
Results The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.
Conclusions The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.
Sources and more information:
Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study, The BMJ 2014;349:g5920, 15 October 2014.
New test to distinguish between ovarian tumours, NHS Choices, October 16 2014.
New test ‘helps identify best ovarian cancer treatment’, BBC News Health, October 16 2014.
Association of skirt size and postmenopausal breast cancer risk in older women: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening
Objectives Several studies suggest that overall and central-obesity are associated with increased breast cancer (BC) risk in postmenopausal-women. However, there are no studies investigating changes of central obesity and BC. We report on the association of BC risk with self-reported skirt size (SS; waist-circumference proxy) changes between 20s and postmenopausal-age.
Design Prospective cohort-study.
Setting UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) involving the nine trial centres in England.
Participants Postmenopausal-women aged >50 with no known history of BC prior to or on the day of completion of the study-entry questionnaire.
Interventions At recruitment and at study entry, women were asked to complete a questionnaire. Women were followed-up via ‘flagging’ at the NHS Information Centre in England and the Hospital Episode Statistics.
Main outcome-measure Time to initial BC diagnosis.
Results Between 2 January 2005 and 1 July 2010, 92 834 UKCTOCS participants (median age 64.0) completed the study-entry questionnaire. During median follow-up of 3.19 years (25th–75th centile: 2.46–3.78), 1090 women developed BC. Model adjusted analysis for potential confounders showed body mass index (BMI) at recruitment to UKCTOCS (HR for a 5 unit change=1.076, 95% CI 1.012 to 1.136), current SS at study entry (HR=1.051; 95% CI 1.014 to 1.089) and change in SS per 10 years (CSS) (HR=1.330; 95% CI 1.121 to 1.579) were associated with increased BC risk but not SS at 25 (HR=1.006; 95% CI 0.958 to 1.056). CSS was the most predictive singe adiposity measure and further analysis including both CSS and BMI in the model revealed CSS remained significant (HR=1.266; 95% CI 1.041 to 1.538) but not BMI (HR=1.037; 95% CI 0.970 to 1.109).
Conclusions CSS is associated with BC risk independent of BMI. A unit increase in UK SS (eg, 12–14) every 10-years between 25 and postmenopausal-age is associated with postmenopausal BC risk by 33%. Validation of these results could provide women with a simple and easy to understand message.
Strengths and limitations of this study
To the best of our knowledge, this is the first study investigating the association between central obesity using skirt size (SS) as a proxy and breast cancer risk. Between 25 and postmenopausal age, an increase in SS by one unit every decade increased the risk of postmenopausal breast cancer by 33% while decrease in SS was associated with lowering of risk.
Our prospective cohort-study includes 94 000 women with comprehensive follow-up through data linkage to multiple national databases.
There is a possibility of underestimation of self-reported SS. However, if current SS at study entry is uniformly underestimated then there is merely rescaling of CSS so that the strength of the association is unaffected. Furthermore, recall bias of the SS at 25 maybe a limitation but unless this inability in reporting is systematically related to future breast cancer, measurement error can only result in underestimating the strength of the true association between CSS and breast cancer risk.
Given that obesity is now emerging as a global epidemic, from a public health prospective these findings are significant as they provide women with a simple and easy to understand message.
Sources and More Information:
Association of skirt size and postmenopausal breast cancer risk in older women: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), BMJ Open 2014;4:e005400 doi:10.1136/bmjopen-2014-005400, 24.09.2014.
Skirt size increase ups breast cancer risk, NHS Choices, Cancer, September 25 2014.
There are three predominant cancers that affect women – breast, ovarian and womb cancer. Of the three, ovarian cancer is of the greatest concern as it is usually diagnosed only at an advanced stage due to the absence of clear early warning symptoms. Successful treatment is difficult at this late stage, resulting in high mortality rates. Ovarian cancer has increased in prevalence in Singapore as well as other developed countries recently. It is now the fifth most common cancer in Singapore amongst women, with about 280 cases diagnosed annually and 90 deaths per year..
Identifying Ovarian Cancer Earlier
Bioinformatics Analysis to Develop Personalised Treatment
Read AstarHQ Press Release, A*STAR scientists make breakthroughs in ovarian cancer research, August 08, 2014.
Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures,LandesBioScience, 30 May 2014.
Lgr5 marks stem/progenitor cells in ovary and tubal epithelia, NatureCellBiology, 06 July 2014.
Studies have shown that a person’s genes can cause an increased risk in breast and ovarian cancer
Studies have shown that a person’s genes can cause an increased risk in breast and ovarian cancer. This infographic shows the chromosomal mutations and the risk they can pose. According to the National Cancer Institute, studies have shown that inherited mutations in the BRCA1 and BRCA2 genes account for 5-10 percent of all breast cancers and 15 percent of all ovarian cancers. While genetic testing is encouraged only for those who have a family history of breast or ovarian cancer, education and awareness are important to early detection and treatment. How can a better understanding of the cause of these genetic mutations help further the cause of finding a cure for cancer?
The authors describe a 15-year-old girl with small cell carcinoma of the ovary whose maternal grandmother had been taking DES while she was pregnant with the patient’s mother.
This case, while anecdotal, suggests that a transgenerational history of DES exposure should be noted, and that granddaughters with persistent abdominal pain even during childhood may need evaluation for genital tract abnormalities.
Ovarian carcinoma in an adolescent with transgenerational exposure to diethylstilbestrol, NCBI, PMID: 12902917, 2003 Aug;25(8):635-6.
Full text – Clinical and Laboratory Observations Volume 25 – Issue 8, Lippincott Williams & Wilkins, pp 635-636 2003.
Full text – A case of small cell carcinoma of the ovary hypercalcemic variant in a teenager, ScienceDirect, S2211338X12000622 2012.
Potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin
A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma. Investigators from the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center report in the Journal of Hematology & Oncology that a protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.
Read Antigen-targeting fusion protein should be less expensive, more accessible than current approaches, MGH News Release, 05/Mar/2014
A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma
Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.
Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.
We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.
This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.
Sources and full Research
Journal of Hematology & Oncology /content/7/1/15 2014, 7:15 doi:10.1186/1756-8722-7-15