Étude rétrospective et mono institutionnelle des facteurs pronostiques cliniques, biologiques et génétiques des patientes mutées BRCA suivies à l'Institut Curie pour un cancer de l'ovaire

Abstract : Ovarian cancer is the fourth cause of death by cancer in France and represents 3% of women cancers. Age and general condition are linked to the stage of this disease at diagnosis, scored by FIGO staging. This FIGO staging is indeed a major prognostic factor which influences survival. Surgery at the initial stage of ovarian cancer after diagnosis, aiming for complete resection with no macroscopic residual disease, is a key element in the therapeutic care for these patients. Patients with genetic predisposition by BRCA 1/2 mutation are at higher risk of developing ovarian cancer and are more likely to show a better sensitivity to platinum based chemotherapy and a better prognosis than patients with sporadic cancer. This retrospective and monocentric study analysed 123 patients who were treated for ovarian cancer at the Curie Institute in a context of BRCA mutation. The primary objective was to analyse the several clinical, biological and genetic prognostic factors influencing the overall survival and the progression-free survival. The secondary objective was to evaluate patients who relapsed during the follow up, taking into consideration their characteristics at diagnosis, and the impact of the genetic alteration of BRCA 1 or 2 on survival. Results confirmed these prognostic factors influenced significantly the overall survival: those aged under 56 years old at diagnosis (p=0.007), a complete resection with no macroscopic residual disease (p= 0.04), as positive factors, and a FIGO III-IV at diagnosis (p= 0.02), as a negative factor. Prognostic factors influencing the survival without progression were at an advanced FIGO III-IV (p=0,000004), which was linked to a premature relapse. The absence of post-surgery residue was linked to a better survival without progression (p=0.001). On the other hand, BRCA1 mutation (p= 0.047), CA125 initially dosed over 375 UI/mL (p= 0.00001), and the timing of surgery after more than 6 cycles of neo-adjuvant chemotherapy (p= 0.042) were described as negative factors in this study. The analysis of the initial characteristics of the 70 patients who relapsed during follow-up couldn’t explain the prognosis and the reason for relapsing. A secondary analysis on BRCA genomic data shows a better prognosis on disease free survival for cases presenting a point-nonsense or frameshift alterations of BRCA genes (N=109), compared to cases known with a missense mutation (N=5, p=0.025). Despite of it being retrospective and monocentric, this study has confirmed that the prognostic factors such as age, stage FIGO, and no residual disease after surgery, as influencing factors in the overall survival and the disease-free survival of this population of selected patients. These results are going in the same direction as larger studies and meta-analyses published previously. While analysing this population of BRCA mutated patients with an ovarian cancer, no predictive factor was identified to explain the reason of a relapse event and a difference in chemo-sensitivity, considering the patients’ characteristics and their therapeutic plan at diagnosis. But this study opens a perspective for developing the interest for the different genomic alterations involved in the tumour behaviour, and the DNA repairing system. Sequencing the tumour itself could bring more information on the patients’ prognosis, even more so help predict an early relapse event.
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Victoire de Castelbajac. Étude rétrospective et mono institutionnelle des facteurs pronostiques cliniques, biologiques et génétiques des patientes mutées BRCA suivies à l'Institut Curie pour un cancer de l'ovaire. Sciences du Vivant [q-bio]. 2018. ⟨dumas-02095012⟩

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