BRCA1 promoter methylation

We believe that BRCA1/2 methylation alone or combined with other biomarkers in a clinical setting is expected to change the scenery in prognosis and predicting treatment response in multiple cancer types and is worthy of further attention. The quantitative BRCA1 promoter methylation assessment might predict treatment response in PARPi and analysis of BRCA1/2 methylation in liquid biopsy might define patient subgroups at different time points that may benefit from PARPi. Finally, we suggest a pipeline that could be implemented in liquid biopsy to aid precision pharmacotherapy in BRCA-associated tumors.

BRCA1 and BRCA2 methylation was significant and correlated with decreased survival in patients with operable pancreatic cancer. A larger cohort of patients is required to further explore the potential of these findings as well as to investigate whether BRCA1/2 methylation in plasma could serve as a potential prognostic biomarker in pancreatic cancer.

Conclusions HRD positive, defined as GIS score >9, may be an appropriate threshold to predict the likelihood of response to PARPi in prostate cancer. Prospective, and large sample clinical trials will be needed to confirm our findings.

In this proof-of-concept study, O did not show clinically nor statistically significant antitumor activity in pretreated aTNBC pts with BRCA1/2-meth. Clinical trial information: NCT03205761. >*7 pts had ≥3 CT lines.

P2, N=11, Completed, Spanish Breast Cancer Research Group | Active, not recruiting --> Completed

P2, N=11, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=34 --> 11 | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

We found no evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1 and BRCA2 in patients with pancreatic cancer. This study reveals that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.

P2, N=34, Recruiting, Spanish Breast Cancer Research Group | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

Remarkably, a considerable subset of germline BRCA-negative EOCs showed somatic methylation and, likely, HRD. A subpopulation of women with BRCA methylation, even without BRCA mutations, could potentially benefit from PARP-inhibitors; further clinical studies are needed to clarify the predictive role of somatic BRCA methylation of PARP-therapy response.

P2, N=34, Recruiting, Spanish Breast Cancer Research Group | Trial completion date: May 2020 --> Dec 2020 | Trial primary completion date: May 2020 --> Dec 2020

Fifty-eight articles including 19,084 individuals met full eligibility criteria. We observed that the frequency of BRCA1 gene promoter methylation was higher in breast cancer tissues compared with normal tissues, and the prognostic analysis suggested that BRCA1 gene promoter methylation was significantly associated with poor overall survival and poor disease-free survival. This study also verified that there was no statistically significant difference in the methylation frequency of BRCA1 gene promoter between peripheral blood and tumor tissues in breast cancer patients, which suggests that the detection of BRCA1 promoter methylation in peripheral blood may be a non-invasive and rapid way to monitor the occurrence breast cancer.

P2, N=34, Recruiting, Spanish Breast Cancer Research Group | Trial completion date: Jan 2020 --> May 2020 | Trial primary completion date: Dec 2019 --> May 2020