World Ovarian Cancer Day: “20 Years of BRCA”

Friday, 8 May 2015

20 Years of BRCA in Ovarian Cancer

Ovarian cancer has the lowest survival rate of all female cancers and is responsible for 140,000 deaths annually1. It is the 5th most commonly diagnosed cancer in women in Europe2, yet symptoms often go unnoticed which delays diagnosis. Over half of cases are diagnosed at an advanced stage, by which time the patient has a poor prognosis3.

Greater understanding of the implication of BRCAm status and its significance in hereditary breast and ovarian cancer has led to increased opportunity for prevention as well as encouraging scientific innovation in the field of personalised treatments.

BRCA: A brief history

Two genes are most commonly associated with an increased risk of developing early onset (before age 50) breast and ovarian cancer – BRCA1 and BRCA24 . While the overall lifetime risk for developing ovarian cancer is 1.3% in the general population, 39% of women with BRCA1 and 11-17% of women with BRCA2 mutations will be diagnosed with the disease by age 705. An estimated 15% of ovarian cancers are linked to BRCA1 and BRCA2 mutations5.

The first evidence of the BRCA1 gene and its link to breast and ovarian cancer was provided by Mary-Claire King and her lab in 19906. At the time of her discovery, the idea of a hereditary link to breast or ovarian cancer was radical and went against mainstream thinking. However, her discovery triggered a race to identify and isolate the specific gene, which was identified in 1994.

Shortly after the discovery of BRCA1, the BRCA2 gene was identified in 1994 by Professor Michael Stratton and Dr. Richard Wooster of the Institute of Cancer Research in the UK. Using DNA samples from Icelandic families affected by several cases of breast cancer, the researchers compared the sequence of the entire gene in families affected by breast cancer to those of healthy women, finding mistakes only in the gene from affected families7.

BRCA: From the lab to the clinic

Identification of BRCA status can be used to better understand an individual’s ovarian cancer and, ultimately, the most appropriate treatment path. Patients are consented for BRCA testing by oncology clinicians, including nurses working in the ovarian cancer field.  When a patient is found to have a BRCA mutation, relatives can also be referred for testing, enabling them to make important health care choices, such as whether to undergo monitoring or risk reducing surgery8.

Due to the familial implications, prognostic and predictive significance, and the high rates of BRCA mutation in ovarian cancer patients, a growing number of national guidelines recommend that BRCA testing be carried out for ovarian cancer patients9,10,11. However, although emerging technologies have significantly increased the availability of BRCA testing, there is still a shortfall in testing rates across the world12.

Fortunately, greater awareness in the role of the BRCA genes in hereditary breast and ovarian cancer has been seen in clinics, driven significantly by media coverage around Angelina Jolie’s decision to undergo a risk-reducing double mastectomy in 2013, and the removal of her ovaries and fallopian tubes in 2015, due to her positive BRCA mutation status – which researchers have dubbed ‘The Jolie Effect’13.

Conclusions

Ovarian cancer is a devastating disease. Despite improved patient outcomes and a greater understanding of the role of BRCA mutations in this disease, there is currently no reliable screening method to detect ovarian cancer and symptoms often go unnoticed. Patient awareness is our best defence against ovarian cancer.

World Ovarian Cancer Day is celebrated annually on the 8th May, and aims to educate and raise awareness around ovarian cancer and its risk factors. For more information, please see www.ovariancancerday.org

References:

1. World Ovarian Cancer Day. About ovarian cancer. Available at: http://ovariancancerday.org/about-ovarian/

2. Cancer Research UK. Ovarian cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/ovary/incidence/uk-ovarian-cancer-incidence-statistics

3.Cancer Research UK: Statistics and outlook for ovarian cancer. Available at: http://www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/treatment/statistics-and-outlook-for-ovarian-cancer

4. Pruthi S, et al. Identification and management of women with BRCA mutations or hereditary predisposition for breast and ovarian cancer. Mayo Clinic Proceedings. 2010;85:1111‒1120.

5. National Cancer Institute. BRCA1 and BRCA2: Cancer Risk and Genetic Testing. http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA.

6. Hall JM et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990;250:1684-9.

7. Cancer Research UK. Tracking down the BRCA genes (Part 2). Available at: http://scienceblog.cancerresearchuk.org/2012/02/29/high-impact-science-tracking-down-the-brca-genes-part-2/

8. Gadzicki D, et al. Genetic testing for familial/hereditary breast cancer – comparison of guidelines and recommendations from the UK, France, the Netherlands and Germany. J Community Genet. 2011;2:53-69.

9. NICE Guideline. Familial breast cancer: Classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. June 2014. Available at: http://www.nice.org.uk/guidance/cg164/chapter/recommendations

10. US Preventive Services. BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing. 2013. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing

11. Australian Government. Clinical Practice Recommendations. September 2011. Available at: http://guidelines.canceraustralia.gov.au/guidelines/high_risk_ovarian/ch01s03.php

12. Levy DE, et al. Underutilization of BRCA1/2 testing to guide breast cancer treatment: black and Hispanic women particularly at risk. Genet Med. 2011;13:349-55.

13. Evans et al. (2014) The Angelina Jolie effect: how high celebrity profile can have a major impact on provision of cancer related services. Breast Cancer Research. 16:442.