Ovarian Cancer:
Non-Specific Signs, BRCA & PARP Inhibitors

1. What is ovarian cancer?

Ovarian cancer is a malignant tumour that develops in the ovaries. According to current knowledge, the most common and most dangerous type, high-grade serous carcinoma, often does not start in the ovary itself at all but at the end of the fallopian tube, and spreads early within the abdomen. It mainly affects women after the menopause; inherited forms tend to occur earlier.^¹,²

Ovarian cancer is much less common than breast cancer, but in most of those affected it is only discovered at an advanced stage, when tumour deposits have already formed on the lining of the abdomen (peritoneum). That is the main reason why it is one of the most serious gynaecological cancers — and why it is worth taking new abdominal symptoms seriously.^²

2. Types and stages

“Ovarian cancer” covers several types of tumour that differ in how they behave and how they are treated. Cancers of the fallopian tube and the peritoneum are so closely related that they are treated in the same way.^³

• High-grade serous carcinoma — the most common type. It grows quickly but usually responds well to platinum-based chemotherapy at first. BRCA changes are found particularly often in this type.
• Low-grade serous carcinoma — grows more slowly and responds less well to chemotherapy.
• Endometrioid and clear cell carcinoma — more often linked to endometriosis, and often discovered at earlier stages.
• Mucinous carcinoma — rare; it has to be distinguished from secondary tumours from elsewhere, for example the bowel.
• Borderline tumours, germ cell and sex cord-stromal tumours — special types that sometimes affect young women and are treated differently, often in a way that preserves fertility.

3. Symptoms: why it is so often noticed late

The ovaries lie deep in the pelvis, with plenty of space around them. A tumour can grow there for a long time without pressing on anything. When symptoms do appear, they are non-specific — they resemble indigestion or an irritable bladder:^¹

• A bloated abdomen and a growing waistline, often together with weight loss — your trousers feel tight even though you have not put on weight. The cause can be fluid in the abdomen (ascites).
• Feeling full quickly and a sense of fullness, loss of appetite, nausea.
• Abdominal or pelvic pain, pressure in the pelvis.
• A frequent urge to pass urine or changed bowel habits, for example new constipation.
• Bleeding after the menopause — less common, but always needs to be checked.
• Breathlessness due to fluid in the chest, or severe tiredness with advanced disease.

4. Causes, risk factors and BRCA

Why ovarian cancer develops is not fully understood. Factors that raise or lower the risk are known:^¹,³

• Inherited genetic changes — above all in the BRCA1 and BRCA2 genes, less often in RAD51C, RAD51D or BRIP1, and in Lynch syndrome, which also favours bowel cancer. The risk is markedly increased in carriers.^⁴
• Family history — ovarian cancer in a relative or several cases of breast cancer, especially at a young age or in men.
• Age — the risk rises after the menopause.
• Endometriosis — a slightly increased risk of certain types.
• Never having been pregnant and a long period of ovulation; also excess weight.

Other protective factors are pregnancy and breastfeeding. Tying or removing the fallopian tubes also lowers the risk, which is why removal of the fallopian tubes is sometimes offered during abdominal surgery that is planned anyway, once a woman’s family is complete.^³

5. Diagnosis and early detection

Early detection: an honest assessment

There is no effective screening programme for ovarian cancer. In large studies, regular examinations with ultrasound and the blood marker CA-125 in women without symptoms did not prevent any deaths, but triggered many false alarms and unnecessary operations. The IGeL-Monitor, a German service that assesses self-pay health services, therefore rates ovarian ultrasound for cancer screening, which is offered as a self-pay service, as “negative”.^³,⁵ Separate recommendations apply to women with an inherited risk (see section 9).

If cancer is suspected

• Pelvic examination and transvaginal ultrasound: the ultrasound shows the size and structure of a change; certain features point more towards benign or malignant.
• CA-125 in the blood: often raised, but not conclusive — endometriosis, fibroids, your period or liver and peritoneal diseases can also raise the level.
• CT of the chest and abdomen: shows how far it has spread and helps with planning the operation.
• Surgery as the diagnosis: ovarian cancer is usually confirmed by tissue examination during or after the operation. A needle biopsy through the abdominal wall of what appears to be an early tumour is avoided, because it can spread tumour cells.
• Genetic and tumour tests: according to the guideline, all patients with ovarian cancer should be offered testing for inherited BRCA changes. In addition, the tumour tissue is tested for BRCA and for so-called homologous recombination deficiency (HRD) — important for maintenance therapy.

Treatment belongs in a centre with experience in ovarian cancer surgery; this has been shown to improve results. For the first consultation, the guide Preparing for a doctor’s appointment will help.^³

6. Treatment: surgery and chemotherapy

Treatment rests on two pillars: surgery that is as complete as possible and platinum-based chemotherapy. The most important factor for the prognosis that can be influenced is whether no visible tumour remains at the end of the operation.^³

To put it honestly: even after successful first treatment, advanced ovarian cancer comes back in many women. It is then often treated for years like a chronic illness, with changing therapies. Which steps suit you is decided by the treatment team together with you at the tumour board; a second opinion is expressly your right.^³

7. PARP inhibitors and maintenance therapy

PARP inhibitors are tablets that block one of the cell’s repair systems. Tumour cells whose second repair system is already impaired by a BRCA change or HRD can then no longer repair their DNA and die. They are used as maintenance therapy once the tumour has responded to platinum-based chemotherapy.^³,⁶

To put it honestly: the benefit of PARP inhibitors is clearest with a BRCA mutation — here they considerably extend the time without relapse. Without a BRCA mutation and without HRD, the advantage is much smaller, and a gain in survival has not been reliably shown. This belongs openly in the weighing-up against side effects and the burden of a daily tablet over months to years.^³

8. Side effects and interactions

Between chemotherapy, infusions, maintenance tablets and supportive medicines, it is easy to lose track. The most important points according to the Summaries of Product Characteristics:^⁶

• Paclitaxel: can trigger allergic reactions, which is why you are given medicines such as dexamethasone and antihistamines beforehand. Hair loss and tingling in the hands and feet (polyneuropathy) are common, and the tingling does not always go away completely.
• Carboplatin: lowers blood counts and causes nausea; medicines such as ondansetron on a fixed schedule help to prevent it. After many cycles, for example at relapse, allergic reactions become more frequent.
• PARP inhibitors: nausea, tiredness and anaemia are common, and with niraparib also a drop in platelets and raised blood pressure. That is why the blood count is checked closely at first. Rarely, disorders of blood formation develop (MDS, leukaemia).
• Bevacizumab: often raises blood pressure and can cause protein in the urine; wound healing and the bowel wall become more vulnerable. Measuring at home is worthwhile; see Measuring blood pressure correctly.
• Mirvetuximab soravtansine: can damage the eyes; eye examinations and preventive eye drops are mandatory.

The dose of PARP inhibitors is often adjusted or briefly paused because of side effects — that is decided by the treatment team, not by the patient herself. According to the Summary of Product Characteristics, a missed tablet is not made up; you simply carry on at the next regular time.^⁶ Herbal preparations and supplements belong on the plan as well; see Herbal medicines.

9. BRCA in the family: genetic testing and preventive surgery

If a BRCA change is found in you, it does not only affect your own treatment: parents, brothers and sisters and children have a 50 per cent chance of having inherited it. Genetic counselling, for example at a centre of the German Consortium for Hereditary Breast and Ovarian Cancer, clarifies who can be tested and what a result means.^⁴

• Preventive removal of the ovaries and fallopian tubes — for healthy BRCA carriers, the most effective measure against ovarian cancer. It is recommended once family planning is complete, usually somewhat earlier with BRCA1 than with BRCA2.
• The consequence: early menopause — before the natural menopause, the operation brings on hot flushes, sleep problems and a higher risk of osteoporosis. Hormone replacement therapy until around the age of natural menopause is possible for many carriers without breast cancer and is discussed individually.
• Keep an eye on your breasts — BRCA changes also increase the risk of breast cancer. For carriers there is an intensified early detection programme at specialist centres.
• Ultrasound does not replace surgery — regular ultrasound and CA-125 checks do not reliably lower the risk of death, even in high-risk women.

10. Follow-up care, the menopause and everyday life

Follow-up care is there to treat symptoms and late effects and to detect a relapse. In the first few years, appointments take place every few months, later less often. How often CA-125 and imaging are used is decided individually by the centre; according to studies so far, a relapse that is detected only by a rising marker cannot automatically be treated better.^³

• Menopausal symptoms — after the operation, the menopause starts abruptly if it had not already happened. Whether hormones are an option depends on the tumour type; for many types, it is possible after counselling.
• Protect your bones — the loss of oestrogen and cortisone during chemotherapy put a strain on the bones; exercise, vitamin D and, if necessary, a bone density scan make sense; see osteoporosis.
• Prevent blood clots — keep moving, drink enough and know the warning signs; see thrombosis and pulmonary embolism.
• Eating after bowel surgery — smaller meals, chew well and avoid foods that cause wind at first. Dietary advice helps if parts of the bowel have been removed.
• Exhaustion and mental health — cancer-related fatigue, fear of relapse and questions about sex are common. Psycho-oncological counselling, rehabilitation and self-help groups are part of care.

Ovarian cancer stays with many women for years — with phases without treatment, maintenance tablets and further treatment. A complete medication plan that also includes supportive medicines and preparations for menopausal symptoms makes every conversation with the hospital, your GP practice and the pharmacy easier.

Chemo, maintenance, follow-up — under control with brite

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