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LiFE re
Literature for ENYGO
Hereditary ovarian cancer (BRCA1/2 mutation, genetic counselling,
management)
Editor Sara Giovannoni
Descriptive summary
PARP inhibitors:
1. D omchek et al. published a subgroup analysis of Study 42 (phase
II) including gBRCA1/2 mutated, heavily pre-treated ovarian cancer
patients. In these 193 patients, the ORR on olaparib monotherapy was
34 %, and median DoR was 7.9 months. This study confirms the notable
antitumour activity in this population and is comparable to the results for 2. L heureux published the results of two web-based surveys performed
all ovarian cancer patients in Study 42.
2. C hoi et al. identified a microRNA, miR-622 that regulates the expression
of the ku-complex and suppresses NHEJ during S-phase. Consistent
with this effect, over-expression of miR-622 rescues the HR-deficiency
of BRCA1 mutant ovarian tumour lines and induces resistance to PARP
inhibitors and platinum-based drugs.
3. M oudry et al. investigated the role of TOPB1 (Topoisomerase Iβ-binding
protein) and PARP inhibitor sensitivity. TOPBP1 seems to be crucial in
HR repair and is involved in sensitizing human ovarian cancer cells to
olaparib. These findings are important in order to predict the response to
PARP inhibitors and to develop new molecular target agents.
4. D u et al. demonstrated that the receptor kinase c-Met may increase the
efficacy of PARP by phosphorylation of PARP1 at Tyr907. PARP1 pY907
increases PARP1 enzymatic activity and reduces binding to a PARP
inhibitor, thereby rendering cancer cells resistant to PARP inhibition. The carriers with and without a diagnosis of ovarian cancer published by
combination of c-Met and PARP1 inhibitors synergised to suppress the
growth of breast cancer cells in vitro and xenograft tumour models. So
far there are no data on ovarian cancer, but PARP1Py907 may predict
tumour resistance to PARP inhibitors and treatment with both c-Met and
PARP inhibitors may be beneficial in patients with high c-Met expression
who do not respond to PARP inhibition alone.
5. T wo interesting reviews summarise the evidence of PARP inhibitors in
ovarian cancer (Drew Y, BJC; Ledermann JA BJC).
Hereditary ovarian cancer/prevention/counselling:
1. H artmann recently published an interesting review about the role of
risk-reducing surgery in hereditary breast and ovarian cancer. A woman’s
age is highly relevant to her risk of breast or ovarian cancer. For ovarian
cancer, BRCA1 carriers have an average cumulative risk by the age of
80 of 45 %, and BRCA2 carriers of 12 %. Current guidelines recommend
RRSO for both mutation carriers between 35 and 40 years. However,
BRCA 2 carriers tend to develop ovarian cancer later (1 % at the age
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International Journal of Gynecological Cancer, Volume 26, Supplement #1
OVARIAN CANCER
of 50) and the authors think that the procedure can be delayed until
approximately 45 years of age in in those patients. Salpingectomy alone
is still an investigational approach. And even if most of the studies
have shown a risk-reducing effect of RRSO on breast cancer risk later
in life, most of the studies are prone to bias and the authors of this
review recommend some caution in counselling these patients. Women
should be informed about the expected effects (i.e., increased risk of
osteoporosis, cardiovascular disease and possible cognitive decline) and
management options for symptoms.
by the Gynecologic Cancer InterGroup (GCIG). The study highlights the
need for collaborative efforts to devise international guidelines around
BRCA1/2 testing in ovarian cancer to ensure consistent BRCA1/2 scree-
ning practices are adopted.
3. The new NCCN Guidelines for Genetic/Familial High-Risk Assessment:
Breast and Ovarian provide recommendations for genetic testing, coun-
selling and management for hereditary cancer syndromes.
4. S ermijn et al. studied the impact of an interventional counselling proce-
dure in families with BRCA gene mutation. Informing relatives directly
nearly doubles the number of relatives tested and is psychologically
safe.
Treatment of infertility in BRCA carrier patients:
A matched case-control study of 941 pairs of BRCA1 or BRCA2 mutation
Gronwald et al. suggested that infertility treatment does not significantly
increase the risk of ovarian cancer in these women.
Survival/BRCA mutation status:
The ten-year survival data from 1,421 Canadian patients published by
Kotsopulos and Rosen in January 2016, showed no association between
survival and BRCA mutation status. The initial survival advantage among
women with BRCA mutations may reflect a higher initial sensitivity of
BRCA carriers to chemotherapy, but this response does not predict long-
term survival. The authors suggest that differences in statistical modelling
may explain the discrepancies between studies published to date. The
strongest predictor of long-term survival is status of no residual disease at
resection.
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