Gene on the X-chromosome may contribute to a woman’s risk of developing ovarian cancer according to US researchers

Currently, women with a strong family history of cancer can be tested for the BRCA gene, which greatly increases a woman’s chance of developing breast cancer and ovarian cancer. Yet experts believe there may be other cases of sporadic ovarian caner that are inherited via the X chromosome females receive from their father.  Full story at BBC News 
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US researchers have used the largest familial study of ovarian cancer to argue that there exists an ovarian cancer susceptibility gene on the X-chromosome acting independently of BRCA1 and BRCA2. This observation implies that there may be many cases of seemingly sporadicovarian cancer that are actually inherited; for example, only daughters who inherit risk from their fathers. This X-linked pattern implies novel ways to prioritize families for screening even without additional testing-sisters must both be carriers or neither; fathers of women with potentially inherited ovarian cancer may receive new attention.
In addition, the scientists found evidence that other cancers affect fathers and sons in these families. Using sequencing technology, we isolated a candidate gene, MAGEC3, that may be associated with earlier onset of ovarian cancer. The further study of this gene and the X-linked pattern will require additional study.  (Author summary from PLOS Genetics)

Full reference: Eng, K. H. 2018||Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study|PLOS Genetics| https://doi.org/10.1371/journal.pgen.1007194

The article can be downloaded from PLOS here 

Related content:  Daily Telegraph  Ovarian cancer can be passed on via fathers – and it strikes younger

 

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The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma

Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors | BMC Cancer

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Image source: Haukeland universitetssjukehus – Flickr // CC BY 2.0

Aim: Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome.

Methods: A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included CA125 response, clinical benefit rate (CBR) and duration of response. Platinum-sensitivity and ER-status were evaluated as predictors of treatment response.

Results: 97 patients were included (43 T, 54 L); median age 63 years (20–92); 91% high-grade serous; median number of lines of prior chemotherapy 3 (1–8); 60% platinum-resistant, 40% platinum-sensitive; 52% ER + ve, 1% ER-ve, 47% unknown. 14 patients (6 T, 8 L) achieved a partial response, with ORR (RECIST) of 14% (T) and 15% (L). The CBR for ≥3 months was 65% (22/43) for tamoxifen and 56% (22/54) for letrozole. There was no significant difference in ORR (p = 0.99) or CBR (p = 0.14) between tamoxifen and letrozole. 22 patients (23%) had a CA-125 response with hormonal therapy (10 T – 23% and 12 L – 22%). ORR did not differ by platinum sensitivity (p = 0.42); or ER-status (positive vs unknown, p = 0.12). Responders to letrozole had longer durations of response than responders to tamoxifen (26 vs 11.5 months, p = 0.03), but equivalent disease stability duration (9.6 vs 7.2 months respectively, p = 0.11).

Conclusions: Within the constraints of a retrospective study, we identified that patients treated with letrozole had a significantly longer duration of response than those treated with tamoxifen. Treatment with either tamoxifen or letrozole is a rational treatment option for patients with ER + ve HGOC, with equivalent ORR, CBR and disease stability.

Full reference: George, A. et al. (2017) The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole. BMC Cancer. 17:456

Pre-diagnosis diet and survival after a diagnosis of ovarian cancer

The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings.

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Methods: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake.

Results: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53–0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62–0.99), fish (HR=0.74, 95% CI: 0.57–0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59–0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01–1.65, P-trend=0.03).

Conclusions: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

Full reference: Playdon, M.C. et al. (2017) Pre-diagnosis diet and survival after a diagnosis of ovarian cancer. British Journal of Cancer. 116. pp. 1627–1637

Combined oral contraceptive use before the first birth and epithelial ovarian cancer risk

Cook, L.S. et al. (2017) British Journal of Cancer. 116. pp. 265-269

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Image source: Ceridwen – commonswiki // CC BY-SA 2.0 FR

Background: Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP).

Results: Among parous women, per year of COC use exclusively before the FFTP was associated with a 9% risk reduction (95% CI=0.86–0.96). Results were similar for high-grade serous and endometrioid/clear cell EOC. In contrast, per year of use exclusively after the FFTP was not associated with risk (aOR=0.98, 95% CI=0.95–1.02).

Conclusions: Combined oral contraceptive use before the FFTP may provide a risk reduction that remains for many years, informing possible prevention strategies.

Read the full abstract here

Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies

Cirillo. P.M. et al. International Journal of Cancer. DOI: 10.1002/ijc.30144

We tested the hypothesis that irregular menstruation predicts lower risk for ovarian cancer, possibly due to less frequent ovulation.

We conducted a 50-year prospective study of 15,528 mothers in the Child Health and Development Studies cohort recruited from the Kaiser Foundation Health Plan from 1959-1966. Irregular menstruation was classified via medical record and self-report at age 26. We identified 116 cases and 84 deaths due to ovarian cancer through 2011 via linkage to the California Cancer Registry and Vital Statistics.

Contrary to expectation, women with irregular menstrual cycles had a higher risk of ovarian cancer incidence and mortality over the 50-year follow-up. Associations increased with age (p <0.05). We observed a 2-fold increased incidence and mortality by age 70 (95% Confidence Interval (CI) = 1.1, 3.4) rising to a 3-fold increase by age 77 (95% CI = 1.5, 6.7 for incidence; 95% CI = 1.4, 5.9 for mortality). We also found a 3-fold higher risk of mortality for high-grade serous tumors (95% CI = 1.3, 7.6) that did not vary by age.

 

This is the first prospective study to show an association between irregular menstruation and ovarian cancer – we unexpectedly found higher risk for women with irregular cycles. These women are easy to identify and many may have polycystic ovarian syndrome. Classifying high-risk phenotypes such as irregular menstruation creates opportunities to find novel early biomarkers, refine clinical screening protocols and potentially develop new risk reduction strategies. These efforts can lead to earlier detection and better survival for ovarian cancer.

Read the abstract here

PARP inhibitors in ovarian cancer: Clinical evidence for informed treatment decisions

Jonathan A Ledermann and Fatima El-Khouly. British Journal of Cancer 113, S10-S16 (15 December 2015)

Ovarian cancer is the fifth leading cause of female cancer deaths in the Western world. Significant progress has been made in the treatment of patients with ovarian cancer, however, the majority of patients experience disease recurrence and new therapies are being sought for such patients. Clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment has demonstrated promising activity in this disease. Here, we review the development of PARP inhibitors and their future role in the treatment of patients with ovarian cancer. Studies of olaparib, the first PARP inhibitor to be approved in Europe and the USA, in patients with recurrent ovarian cancer have demonstrated clinical efficacy with improvements in progression-free survival. In maintenance therapy of platinum-sensitive ovarian cancer there is supporting evidence of clinical benefit from exploratory endpoints that include time to first subsequent treatment and time to second subsequent treatment. Adverse events that should be monitored following treatment with PARP inhibitors include nausea, vomiting, fatigue and anaemia. Based on the evidence presented, patients who will receive the greatest benefit from PARP inhibition are those with platinum-sensitive relapsed ovarian cancer and a BRCA mutation.

Read the abstract here

Ovarian cancer drug wins NICE approval

NICE has given the NHS the green light over a drug which can extend the lives of ovarian cancer patients.

Olaparib is particularly effective in cancers that bear specific genetic faults, and the drug has previously been rejected for routine use by the health service’s drugs rationing body.

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Cancer Research UK scientists took a leading role in the drug’s development, and trials have shown olaparib extends lives by an average of seven months compared to standard treatments.

Friday’s landmark decision will make the drug available to women who have BRCA1 or BRCA2 mutations in their tumours, and have responded to three rounds of platinum-based chemotherapy.

The initial rounds of treatment will be covered by the NHS, but women who remain on treatment after 15 months will then have the drug paid for by the manufacturer.

Read the full report via Cancer Research UK