Article Text

Download PDFPDF

64 Can chemotherapy change tumor BRCA status and affect susceptibility to treatment?
Free
  1. M D’Indinosante,
  2. C Marchetti,
  3. R Ergasti,
  4. A Pietragalla,
  5. G Scambia and
  6. A Fagotti
  1. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A.Gemelli IRCCS, Italy

Abstract

Introduction Ovarian cancer (OC) development in BRCA-heterozygotes is due to somatic inactivation of the remaining BRCA-allele. For patients with a long history of systemic treatment, secondary tumor mutations are described in the literature, leading to a possible change in the response to the therapy. The objective of our study was to assess whether short-time chemotherapy can cause BRCA-molecular changes in the tumor.

Material Retrospective single-institutional study on HGSOC patients who had at least double tumor BRCA assessment during chemotherapy.

Results A total of 19 paired-tumor-BRCA (t-BRCA) were identified between January-2017 and December-2018 among HGSOC patients treated at primary diagnosis or recurrence.

Primary tumor BRCA assessment showed somatic wild-type variant (s-WT) in 14/19 (73.7%), pathogenic-variant (PVs) in 4/19 (21.0%) and variant of uncertain-significance (s-VUS) in 1/19 (5.3%). Twelve patients (63.2%) received second tumor BRCA assessment at time of interval-debulking-surgery (IDS) (Group A) and 7 patients (36.8%) at time of secondary cytoreductive surgery (Group B). Treatment consisted of standard carboplatin and taxol. Six (31.6%) cases received additional Bevacizumab or PARP-i. The median number of cycles was 3 (range: 3–4) for Group A and 6 (5–7) for Group B.

No reversal of tumor BRCA status was observed between two consecutive samplings.

Conclusion In a small cohort of HGSOC patients there is no plasticity of somatic BRCA-status after few cycles of standard chemotherapy. These results need to be confirmed in a larger sample-size and compared with those obtained after long biological treatments.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.