Ovarian Cancer

Ovarian cancer is a devastating disease which affects the primary reproductive organs for females. At birth the ovaries are rendered as body tissue, until very sophisticatedly, once a female reaches puberty and matures physically, so do her ovaries.^1,2

Despite advances in treatment, ovarian cancer is one of the most common female cancers³ and one of the most common causes of death from cancer in women worldwide.⁴ The goals of front-line therapy have always been to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission - yet currently ~70% of patients relapse within three years of initial treatment.^5,6,7,8

These statistics show there is still much to be done for women with ovarian cancer and that there needs to be a clear and accessible understanding of the latest scientific advancements and novel therapies. At AstraZeneca we have focused our attention in this area. Our aim is to help improve the outcomes of these patients and our ambition is to one day eliminate cancer as a cause of death.

The functions of the ovaries – small but powerful

To understand ovarian cancer, we must first understand the evolving role of the ovaries. One function only starts at puberty; the ovaries secrete reproductive hormones, the most commonly known being oestrogen and progesterone, to drive the reproductive cycle and develop physical female characteristics. When a female goes through menopause, usually in her 40s or 50s, the ovaries stop producing as much oestrogen and no longer release an egg each month,^9,10 and the menstrual cycle stops.

The amount of hormone secreted therefore changes not only throughout the menstrual cycle but also across a lifespan. There is also disparity in ovarian cancer across the ages; although younger women can develop ovarian cancer, it usually affects women who have reached menopause,¹¹ with over two-thirds of diagnoses being in women aged 55 and above.¹²

Why is the survival rate still so low?

There’s a reassuring link between rapid diagnosis of ovarian cancer and improved survival.¹³ Cancer progresses through four stages of development, from early (stages 1-2) to late (stages 3-4) and once it has become ‘advanced’, it may have spread from the ovaries to other parts of the body and can be more challenging to control.^8,13

Two thirds of women are currently diagnosed with late-stage disease, when the cancer has already spread beyond ovaries, making it harder to treat, and greatly reducing survival. Despite this clear correlation between rapid diagnosis and survival, most ovarian cancers are diagnosed at a late stage^14,15 – but why?

Part of the complexity comes from recognising early symptoms so that the cancer can be diagnosed at an early stage. Symptoms are non-specific, meaning they can often go unnoticed or may be misdiagnosed for another illness until the cancer is advanced.^3,16  It is important to remember that the four most common symptoms, listed here, may also not indicate the presence of cancer.

Another reason is that unlike other cancers, there is still no reliable and effective screening method for ovarian cancer,^2,17 further delaying the ability to diagnose it. It is known that certain lifestyle¹⁸ and medical factors do indicate an increased risk of developing ovarian cancer which go beyond age, such as a lack of parity, endometriosis or a family history of ovarian, breast, or colorectal cancer.^3,19  Beyond physical characteristics and lifestyle factors, a woman’s genetic makeup can also influence her risk of developing ovarian cancer.

Genetic pathways and gene mutations - have you HRD about them?

Every cell in the body suffers from DNA damage and undergoes a repair process in order to function normally.²⁰ The Homologous Recombination Repair (HRR) pathway is just one genetic pathway which produces proteins, such as BRCA1/2, among others, to carry out this repair process via double-stranded breaks. PARPs [poly(ADP-Ribose) Polymerases] are an example of a family of enzymes vital to another genetic pathway, to repair single-stranded DNA breaks.^20,21 This DNA damage response (DDR) shines a light on the connection between gene mutation and ovarian cancer.

HRD stands for Homologous Recombination Deficiency, a lack of functional components in one or more of the DNA repair pathways and a common trait of cancer cells, which have a high genetic mutation rate. One example is BRCA. Both men and women possess BRCA1 and BRCA2 proteins which when functioning normally, act as tumour suppressors.^22,23 Their role within the HRR pathway is to repair cell damage and prevent them from growing and dividing too quickly – mutated BRCA genes result in abnormal cells which grow uncontrollably²⁴ and are just one of many HRDs.

You can find out more about the DDR, HRD and other molecules involved here.

What is the importance of testing at diagnosis?

Genetic testing allows both clinicians and patients to make an informed decision when it comes to the treatment they receive. Conducting testing prior to or at the point of diagnosis can be important in improving patient care and enabling access to certain targeted therapies.²⁵ By understanding the heritability of a woman’s cancer (if the mutation she possesses can be inherited), a patient’s family can also understand their risk of developing the disease – understanding the full picture has important implications for cancer risk assessment and prevention among relatives.²³

What does this mean for treatment?

It’s one thing to know the link between genetic mutations and cancer development, another to leverage the science and target genetic vulnerability in order to optimise treatment. Targeted therapy for advanced ovarian cancer hinges on understanding the repair pathways and exploiting HRD by targeting PARPs. By inhibiting PARPs, the cells cannot repair single-stranded DNA breaks through its normal way and must rely on other pathways (such as HRR) to do so. Because cancer cells have HRD, there are already fewer functional pathways; for BRCA mutations, there are fewer HRR pathways. This means cellular damage goes beyond the point of repair and results in cell death. Thus, the growth of abnormal cells is prevented.²⁰

Our understanding of how to exploit HRD is evolving. We will continue our research in this pathway to further our understanding of how treatment options and combinations can potentially help achieve the best possible outcome.

Treatment falls into active and maintenance therapy. Active treatment includes surgery, chemotherapy and radiotherapy and maintenance therapy typically follows one round of active treatment. When a woman with ovarian cancer is in remission, she may have no treatment or otherwise undergo maintenance therapy to control the cancer.^26,27 Age may influence such treatment options.²⁸

Our approach

As leading pioneers, AstraZeneca has a portfolio of approved and potential treatment for advanced ovarian cancer including in newly diagnosed patients. Through our research, we have made progress in increasing the time that women can live without disease progression and improving quality of life. Our approach is based on using ground-breaking science to further our understanding of targeted therapy within ovarian cancer, focusing on patients with HRD and transferring our learnings to the wider patient population and paving the way to achieve the best possible outcomes for progression-free and overall survival.

Although progress has been made to understand the disease and novel therapies, there is still a very long way to go to expose the threat of ovarian cancer and help save more lives. Improvements in earlier diagnosis and accelerated access to the best available diagnostic testing and medicines are achievable goals which could help save countless lives.

Addressing the gaps in ovarian cancer care

As a founding member of the Ovarian Cancer Commitment (OCC), together with our partners European Society of Gynaecological Oncology (ESGO) and the European network of Gynaecological Cancer Advocacy Groups (ENGAGe), we have a bold ambition to improve the experience and survival of people living with ovarian cancer.

The OCC provides a platform for partners to pledge their commitment and implement tangible actions. We aim to increase membership of partner organisations as the initiative evolves, to reflect and address remaining gaps in the care of those with ovarian cancer across the globe.

Olivia: A unique digital support resource to help guide ovarian cancer patients

Olivia, the Digital Patient Pathway developed by the Ovarian Cancer Commitment, is a comprehensive resource to help address the needs of everyone affected by ovarian cancer. Olivia truly is a single source of information on ovarian cancer, with educational articles, video stories and a directory of resources. From a dedicated section for those who are newly diagnosed with ovarian cancer to an interactive pathway for those receiving and recovering from treatment, supporting them at every stage of their experience.

Olivia is currently available in several languages with further languages coming soon to eliminate any barriers for those seeking information. Visit Olivia for guidance and support throughout your ovarian cancer experience.

Shedding light on the need for rapid diagnosis in ovarian cancer

The second initiative launched under the OCC umbrella is ‘Don’t Overlook: A Specialist Care Initiative’, designed to increase awareness of the symptoms of ovarian cancer and the benefits of specialist care for those living with the disease and accelerate access to centralised specialist care.

By launching ‘Don’t Overlook’, we aim to shine a light on the gaps in ovarian cancer care, urge women and physicians not to overlook ovarian cancer and upskill Patient Advocacy Groups and Primary Care Physicians.

References

1. Livescience. Ovaries: Facts, Function and Disease. Available at https://www.livescience.com/58862-ovary-facts.html. Accessed May 2024.
2. Patni R. Screening for Ovarian Cancer: An Update. Journal of Mid-Life Health. 2019;10(1), pp.3-5.
3. World Health Organization. IARC. Cancer Today: Absolute numbers, Incidence, Females, in 2022. Available at: https://gco.iarc.fr/today/en/dataviz/bars?mode=cancer&sexes=2&key=total&group_populations=1&types=0. Accessed May 2024.
4. World Health Organization. IARC. Cancer Today: Absolute numbers, Mortality, Females, in 2022. Available at: https://gco.iarc.fr/today/en/dataviz/bars?mode=cancer&sexes=2&key=total&group_populations=1&types=1. Accessed May 2024.
5. Ovarian Cancer Research Alliance. Recurrence. Available at https://ocrahope.org/patients/about-ovarian-cancer/recurrence/. Accessed May 2024.
6. Nag, S, et al. Maintenance therapy for newly diagnosed epithelial ovarian cancer– a review. Journal of Ovarian Research. 2022;15:88.
7. Elyashiv O, et al. Frontline maintenance treatment for ovarian cancer. Curr Oncol Rep. 2021;23(8):97.
8. NHS Choices. 2022. Treatment Ovarian Cancer. Available at https://www.nhs.uk/conditions/ovarian-cancer/treatment/. Accessed May 2024. 
9. WebMD. 2021. Menopause? Available at https://www.webmd.com/menopause/guide/menopause-basics#:~:text=Their%20ovaries%20also%20make%20the,after%20the%20age%20of%2040. Accessed May 2024.
10. NHS Choices (2018). Menopause Overview. Available at: https://www.nhs.uk/conditions/menopause/. Accessed May 2024.
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20. Bohen S, et al. DNA Damage Response –An Emerging Target for Groundbreaking Cancer Therapies. European Oncology & Haematology. 2018;14(Suppl 1):2-7.
21. Pascal J. The comings and goings of PARP-1 in response to DNA damage. DNA Repair. 2018;71:177–182.
22. Bonadio R, et al. Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (Sao Paulo). 2018 Aug 20;73(suppl 1):e450s.
23. National Cancer Institute. (2019). BRCA1 and BRCA 1: Cancer Risk and Genetic Testing. Available at http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed May 2024. 
24. Ovarian Cancer Action. What Are Genetic Mutations? Available at http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed May 2024.
25. Ngoi NYL, et al. The role of homologous recombination deficiency testing in ovarian cancer And its clinical implications: do we need it? ESMO Open Cancer Horizons. 2021;6(3):1-12.
26. Force. Ovarian Cancer Treatment. Available at https://www.facingourrisk.org/understanding-brca-and-hboc/information/cancertreatment/ovarian-treatment/basics/maintenance-therapy-ovarian-cancer.php. Accessed May 2024.
27. Cancer Council Queensland - Active Treatment. Available at https://cancerqld.org.au/glossary/active-treatment/. Accessed May 2024.
28. Van Walree IC, et al. Treatment decision-making in elderly women with ovarian cancer: an age-based comparison. Int J Gynecol Cancer. 2019;29(1):158-165.