Therapy-orienting testing of BRCA1 and BRCA2 germline mutations in women with ovarian cancer

BJMO - volume 9, issue 2, may 2015

K. Claes PhD, H. Denys MD, PhD, M. Huizing MD, PhD, I. Vergote MD, PhD, F. Kridelka MD, PhD, J. De Grève MD, PhD, V. Bours MD, PhD, On behalf of the BRCA Testing Working Group.

With the aim to optimally position poly-(adenosine diphosphate-ribose) polymerase inhibitors in the treatment of ovarian cancer, a panel of Belgian Experts came to a national multidisciplinary consensus: (i) germline BRCA1/2 testing should be indicated for all women with high-grade serous epithelial ovarian cancer, who are in good general condition (i.e. eligible for systemic treatment with low toxicity); BRCA1/2 mutation detection ratios being about 15–20% in this group; (ii) as the finding of a BRCA1/2 germline mutation has therapeutic implications in ovarian cancer patients, the request for therapy-orienting testing should be made as soon as possible during the course of first-line treatment. Pre-test genetic counselling is important because positive testing has implications for both the patients and their relatives, and the nature of the discussions depends on whether they take place in a therapeutic or familial context. The organisation of consultations should be coordinated in a collaborative effort between clinical geneticists, and gynaecological and medical oncologists, keeping in mind that ‘fast-track’ pre-test genetic counselling and short turnaround times are required for patients for whom the test results will have a therapeutic impact. Offering germline BRCA1/2 testing to all patients with high-grade serous epithelial ovarian cancer who are eligible for systemic treatment with low toxicity will lead to a limited increase in the number of patients eligible for this test in Belgium.

(BELG J MED ONCOL 2015;9(2):65–70)

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Prognostic factors in ductal carcinoma in situ (DCIS)

BJMO - volume 6, issue 5, october 2012

S. Altintas MD, PhD, M. Huizing MD, PhD, W. Tjalma MD, PhD

Ductal carcinoma in situ of the breast (DCIS) is a clinical entity which is discovered as microcalcifications on screening mammography, it rarely represents a palpable disease. Asymptomatic women with DCIS receive treatments that are similar to women with invasive breast cancer and therefore experience substantial psychological distress despite the fact that they have an excellent prognosis and normal life-expectancy. It is also true that, in spite of aggressive treatment approaches, some patients do recur.

In analogue with invasive breast cancer, DCIS is a heterogeneous disease with different prognostic profiles. The high incidence of DCIS and variations in its treatment with different outcomes led to the introduction of the Van Nuys Prognostic index (VNPI) developed in 1996 by Silverstein. This index is a simple decision-making tool to improve or at least standardise DCIS care and had been incorporated in our daily practice since 1997. Data on that experience were analysed. We tried to obtain a better understanding of the molecular behaviour of DCIS laesions and looked for predictive and prognostic markers associated with disease-free survival (DFS). The next step was the use of micro-array analysis with the Genomic Grade Index (GGI), based on four proliferation genes, and the proliferation index Ki-67. These two indices, which are considered to be predictive for the behaviour of invasive breast cancer, were incorporated into the VNPI. Furthermore, we looked if the tumour microenvironment might play a crucial role in local relapse of DCIS and risk of subsequent invasive disease. (BELG J MED ONCOL 2012;6:164–168)

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