Epithelial ovarian cancer is a rare but “insidious” disease, which is usually diagnosed at an advanced stage and often recurs. However, the improvement of diagnostic methods, molecular identification and treatment strategies by specialized treatment groups has significantly improved the prognosis of this disease with excellent results.

“Key” in dealing with patients, personalized treatment

The modern trend in the treatment of malignancies is the individualization of treatment, in order to adapt it to the specific characteristics of the disease of each individual patient.

The histological type, the burden and the stage of the disease, the result of the surgical intervention, the patient’s symptoms, the possible comorbidities and the general clinical condition, as well as the molecular identity of the tumor determined through genetic testing.

It is of crucial importance that these decisions are made in the context of an Oncology Council consisting of specialized therapeutic groups in Centers with relevant experience in dealing with this disease.

New medicines for patients

PARP inhibitors are the new drugs in our therapeutic quiver. The best known PARP inhibitors are Olaparib, Niraparib, Rucaparib, Veliparib, Talazoparib, etc. They are available in pill form and have a satisfactory safety profile with side effects usually well managed by patients. Already in our country they are used and provided by E.O.P.Y.Y. with specific conditions and criteria Olaparib and Niraparib with excellent results.

Gene control & PARP inhibitors

A. Detection of BRCA mutation in healthy women

After many years of research, two dominant genes were identified, BRCA1 and BRCA2, which when damaged make the person carrying this damage vulnerable to developing ovarian, breast and/or other organ cancer at some point in their life.
Therefore, for healthy women with a hereditary history positive for the above diseases, genetic counseling is recommended, in order to undergo genetic testing, which is carried out with a blood test (or saliva in some centers). This is absolutely useful information for the healthy woman who is a carrier of the mutation, so that she can receive specific instructions for the prevention of cancer related to the above gene lesions. This information is equally useful for direct blood relatives, since the probability for each 1st degree relative to carry the mutation is 50%.
B. Hereditary ovarian cancer & PARP inhibitors

For women diagnosed with epithelial ovarian cancer, having a BRCA mutation is also a therapeutic opportunity. Specifically, the BRCA genes are responsible for recognizing and repairing DNA damage through a mechanism called homologous recombination, which they control. Homologous recombination is used by both normal and cancer cells to repair their DNA damage. The therapeutic goal is for the cancer cell to fail to repair its damage and die, a process facilitated by an error in homologous recombination.
Inherited mutations in the BRCA1 & 2 genes are found in 15-20% of patients with epithelial ovarian cancer. Especially for patients with a diagnosis of poorly differentiated serous cancer, the percentage is much higher. These mutations are the backdoor of the cancer cell since new drugs called PARP inhibitors block the repair of damage to the cancer’s own DNA, resulting in its apoptosis.

C. Non-hereditary ovarian cancer & PARP inhibitors

Non-hereditary (sporadic) ovarian cancer is clearly more common. In the cases of patients with sporadic cancer, the gene test in the blood is negative, however there is a possibility of finding a BRCA mutation in the cancer cell. These mutations are rarer and affect less than 10% of ovarian cancer patients. But PARP inhibitors remain equally effective in sporadic cases. In other words, the cancer cell cannot recognize whether the error in its DNA is intrinsic (inherited) or acquired, while remaining just as vulnerable to the PARP inhibitor as long as it bears the stamp of the BRCA mutation.

D. Single mutations & PARP inhibitors

Through clinical observation it was found that PARP inhibitors remained effective drugs even in cases of patients with negative gene control for BRCA mutation (both in cancer tissue and in blood). This phenomenon was attributed to the fact that homologous recombination is not only controlled by the BRCA genes, but also by a number of other genes. Research has shown that an error in some of the genes that control homologous recombination is associated with varying degrees of response to PARP inhibitors. In this way, an additional percentage of women benefiting from these new drugs was identified.

E. Gene instability & PARP inhibitors

The most important development of the last three years is recognition of gene instability as a predictive indicator of response to PARP inhibitors. The realization that the identification of single mutations favors only a few cases of patients and even at great administrative cost has led to the creation of platforms that study the biological impact of all these gene lesions rather than the individual causes that caused it.

Current guideline recommendations

On a practical level, ideally all women newly diagnosed with epithelial ovarian cancer should undergo genetic testing for BRCA mutations and/or genetic instability (GIS).

The recommendation of genetic testing at diagnosis is a common point of all known scientific bodies. Obviously, the implementation of the recommendations varies around the world depending on the respective health system, the possibility of carrying out the examination and the way it is reimbursed. It should be noted that EOPYY contributes to covering the cost of hereditary BRCA mutation for patients with epithelial ovarian cancer, but not GIS screening.

It is written by
Dr. Ioannis Syrios
Pathologist – Oncologist
Scientific Associate HEALTH