Abstract
The US FDA has recently granted approval for the marketing and use of a new biomarker test for ovarian cancer. The combination of tests examining levels of HE4 and CA125 with the Risk of Ovarian Malignancy Algorithm (ROMA™), developed at the Women and Infants Hospital of Rhode Island (Providence, RI, USA), promises high accuracy and specificity when determining the risk of ovarian cancer in both pre- and postmenopausal women. The new tool may help overcome issues such as distinguishing between benign and malignant pelvic mass and identifying individuals with a high likelihood of malignancy who would benefit from surgery.
“Combining ROMA with the biomarkers HE4 and CA125 is an excellent triage tool to identify women at high risk for ovarian cancer, allowing for accurate triage of these patients to the most qualified physicians and centers for their care.”
Presently, testing serum CA125 levels is favored when monitoring patients with ovarian cancer; however, the test is unable to detect all types of ovarian cancer and has limited sensitivity and specificity. Currently, three quarters of patients are not diagnosed until they are in an advanced stage of the disease.
Speaking to Women's Health, Richard G Moore, lead author of the study, from Brown University (Providence, RI, USA), commented that “Less than 50% of women diagnosed with ovarian cancer are initially operated on by a gynecologic oncologist, despite several studies showing improved outcomes and survival for women who have their surgeries carried out by gynecologic oncologists and at centers familiar with this disease. Combining ROMA with the biomarkers HE4 and CA125 is an excellent triage tool to identify women at high risk for ovarian cancer, allowing for accurate triage of these patients to the most qualified physicians and centers for their care. Hopefully with better triage tools such as ROMA we can increase the number of women receiving their care with specialists trained to manage this disease, resulting in better outcomes and improved survival.”
The FDA clearance was based upon prospective, double-blind, multicenter trials, which found that the combined HE4 and CA125 algorithm resulted in 95% of epithelial ovarian cancers being correctly classified as high risk. Moore stated that “We have performed two national validation trials, one in a high-risk population and the second in a low-risk population, with very similar results. The later trial led the FDA, 2 weeks ago, to clear ROMA and HE4 for clinical use in the USA.” Serum HE4 and CA125 levels were measured pre-operatively in 472 patients, allowing the ROMA score to be calculated. In the postmenopausal group a sensitivity and specificity of 92.3 and 76.0% were attained, respectively, whilst in the premenopausal group the sensitivity was 100%, with a specificity of 74.2%.
Further commenting to Women's Health, Moore added “ROMA is an excellent tool for physicians (i.e., general obstetrics and gynecologists, family practitioners and internists, surgeons) to use for the risk assessment of a woman who presents with an ovarian cyst or pelvic mass. Women determined to be at high risk for a malignancy can be appropriately referred to a gynecologic oncologist and women found to be at low risk can safely stay in their communities with the physician that knows them best and where they have the support of their family.”
Paul Tohey, President and CEO of Fujirebio Diagnostics (Malvern, PA, USA), the manufacturers of the algorithm, believes that “With this increased ability to improve referral patterns, as well as a price that is comparable to CA125 testing, the healthcare costs involved with cancer diagnosis and treatment should decrease significantly.”
Source: Moore RG, Miller MC, Disilvestro P et at. Evaluation of the diagnostic accuracy of the Risk of Ovarian Malignancy Algorithm in women with a pelvic mass. Obstet. Gynecol. 118(2 Pt 1), 280–288 (2011).
Study finds premenopausal hormones are not linked to lower risk of heart disease in women
Researchers at Johns Hopkins University School of Medicine (Baltimore, MD, USA) have performed a modeling study which demonstrated that aging and not hormonal changes caused by the menopause increase women's risk of cardiovascular death. The findings may have implications for the assessment of heart health in premenopausal women, who are currently believed to be at negligible risk of heart attack. Dhananjay Vaidya, from Johns Hopkins University School of Medicine and leader of the study, commented that, whilst menopause has an effect on risk of other diseases, such as breast cancer, “What we believe is going on [here] is that the cells of the heart and arteries are aging like every other tissue in the body and that is why we see more and more heart attacks every year as women age. Aging itself is an adequate explanation and the arrival of menopause with its altered hormonal impact does not seem to play a role.”
“Special attention should be paid to heart health in women due to their overall lifetime risk, not just after the time of menopause.”
The team analyzed longitudinal mortality statistics from people born in England, Wales and the USA between 1916 and 1945. These were split into three cohorts, each representing 9 years and followed between 1950 and 2000. They found that, at the time of menopause, there was no deviation from the steady curve that is expected from aging. This has implications for physicians; Vaidya comments “Special attention should be paid to heart health in women due to their overall lifetime risk, not just after the time of menopause.”
These results were contrary to those discovered in men, where heart mortality risk for men below the age of 45 years increased by 30% per year, slowing to 5% per year after the age of 45 years. It is postulated this difference may be caused by the different effects of aging on telomere length in the cells of men and women.
Source: Vaidya D, Becker DM, Bittner V, Mathias RA, Ouyang P. Aging, menopause, and ischaemic heart disease mortality in England, Wales, and the United States: modelling study of national mortality data. BMJ 343(2), d5170 (2011).
Study suggests survival rate is no different for young women undergoing breast conservation therapy or mastectomy
A team from the University of Maryland Marlene and Stewart Greenbaum Cancer Center (Baltimore, MD, USA) have demonstrated that the choice between breast conservation therapy (BCT) and mastectomy does not alter survival rates in young women with early-stage breast cancer. Recently, a rise in the number of mastectomies undertaken, probably caused by concerns regarding cancer recurrence, has been observed.
Steven J Feigenberg, from the University of Maryland Medical System and senior author of the study, believes that “These findings are very significant for young women with early-stage breast cancer who might choose to have a mastectomy in the hope of improving their outcome. This study confirms that BCT is a safe, effective treatment option and will not have a detrimental effect on survival.”
About the Bulletin Board
The Bulletin Board highlights some of the most important events and research in the field of women's health. If you have newsworthy information, please contact:
Louise Rishton, Commissioning Editor, Women's Health, Future Medicine Ltd, Unitec House, London, N3 1QB, UK
Women under the age of 40 years are often at higher risk of cancer reoccurrence, and previous studies have implied that women choosing BCT have a higher chance of recurrence. However, previous studies did not analyze the effect of treatment choice on survival rates. The current study involved a retrospective analysis on data from almost 15,000 women from the Surveillance, Epidemiology and End Results (SEER) registry. Of the women, who were aged between 20 and 39 years, 45% chose breast conservation surgery while 55% opted for mastectomy. The median follow-up was 6 years; 5-year survival rate was 92.5% for those who selected BCT, and 91.9% for those who selected mastectomy. The results were confirmed by performing a matched pair analysis on a smaller group of patients.
“This large analysis breaks new ground in advancing what we know about how to treat young women with early-stage breast cancer. It will most certainly help young women and their doctors to better understand the most appropriate treatment options…”
E Albert Reece, Dean of the Maryland School of Medicine, commented that “This large analysis breaks new ground in advancing what we know about how to treat young women with early-stage breast cancer. It will most certainly help young women and their doctors to better understand the most appropriate treatment options and make decisions based on what's best for each patient.”
Sources: Mahmood U, Morris CG, Neuner GA et al. Comparing survival with breast-conservation therapy or mastectomy in the management of young women with early-stage breast cancer. Presented at: 2011 Breast Cancer Symposium. San Francisco, CA, USA, 9–11 September 2011; University of Maryland Medical Center Press release: www.umm.edu/news/releases/breast-conservation-therapy.htm
IUD use could halve the risk of cervical cancer
A research group from the Virus and Cancer research group at Institute d'Investigació Biomèdice de Bellvitge (IDIBELL, Barcelona, Spain) have recently published results that contradict the popular belief that IUDs may increase the risk of cervical cancer. The group analyzed ten case–control studies and 16 human papillomavirus (HPV) prevalence surveys and discovered that IUD use appears to be associated with a significantly decreased risk of squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma.
The researchers analyzed international data from two studies performed by the International Agency for Research on Cancer (Lyon, France) and the Institut Català d'Oncologia (Barcelona, Spain). IUD use, while not affecting the risk of HPV infection, appeared to result in a 44% reduction in the likelihood of squamous cell carcinoma and a 54% reduction in the likelihood of adenocarcinoma and adenosquamous carcinoma. The length of IUD use did not appear to significantly alter the risk of cervical cancer, with the protective effect remaining after 10 years of use. The findings were adjusted for relevant covariates including number of Papanicolaou smears and number of sexual partners.
The authors comment that “The associations found in our study strongly suggest that IUD use does not modify the likelihood of prevalent HPV infection, but might affect the likelihood of HPV progression to cervical cancer.” They note a possible explanation for the protective effect of IUDs may be that the device may trigger cellular immunity via processes such as induction of chronic mucosal inflammation. It is also suggested that insertion or removal of the device may destroy precancerous lesions.
Source: Castellsagué X, Díaz M, Vaccarella S et al. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies. Lancet Oncol. 12(11), 1023–1031 (2011).