BRCA mutation

However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches...The model demonstrated high sensitivity to cisplatin plus gemcitabine, but limited efficacy of PARPi monotherapy...The addition of anti-PD1 treatment to PARPi maintenance enhanced tumor regression and prolonged overall survival. These findings provide preclinical support for ongoing clinical trials investigating immunotherapy with PARPi as a maintenance strategy in homologous recombination-deficient PDAC.

P=N/A, N=80, Not yet recruiting, Linyi Tumor Hospital; Linyi Tumor Hospital

Initial the standard of care (SOC) treatment includes intensive cytoreductive surgery (CRS) and platinum-paclitaxel chemotherapy with/without adding anti-angiogenetic agent and/or following poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) maintenance therapy based on biomarker-guided recommendation, such as BRCA mutation and/or homologous recombination deficiency (HRD significance)...Chemoresistance may be derived from "naïve" (underlying or primary) hereditary or acquired adaption (secondary or induced), which are involved in an increasing ability to self-repairing DNA, dysregulated autophagy process and evasion of apoptosis and alternation in mitochondrial pathways as well as metabolic adaptions, changing signaling pathway for proliferation and survival, and modifying genetic and epigenetic resolution, contributing to sustaining proliferative signaling, resisting cell death, evading growth suppressor, inducing angiogenesis, activating invasion and metastases, deregulating cellular energetics, reaching cellular senescence and stemness, and epigenetic reprogramming of cancer cells. The first part is a brief review for PR-rOC, including mechanisms, and combating strategies but only limited to cytoreductive surgery for treating PR-rOC patients.

Our novel classification revealed that PARPi efficacy and prognosis varied significantly by mutation location, with the central region linked to superior outcomes compared with the N- and C-terminal regions. Comprehensive mutation profiling should guide treatment decisions to optimize outcomes in patients with BRCA-mutated ovarian cancer.

Olaparib is active in pts with MBC with gPALB2m and sBRCAm, significantly expanding the population of pts with breast cancer likely to benefit from PARP inhibitors beyond gBRCA1/2m carriers.

Codon-aware neutral modeling provides a statistical framework for distinguishing mutations that deviate from stochastic expectations and may aid in the interpretation of variants of unspecified significance. By contextualizing mutational severity relative to neutral processes, this approach offers insight into tumor evolution and may support prognostic assessment without relying on predefined gene-level neutrality.

The patient began systemic therapy with ribociclib plus letrozole, achieving radiologic improvement of the cervical lesion and abdominal disease. This case highlights the ability of ILC to recur after long latency and to metastasize to unusual gynecologic sites such as the cervix. We also review the literature on cervical recurrence from lobular carcinoma to emphasize the importance of gynecologic surveillance in breast cancer survivors and to identify areas that require further investigation.

However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making.

The findings suggest that BRCA-mutated patients may derive a survival benefit from PDS, whereas surgical timing had a limited impact on BRCA wild-type disease. This result underscores the importance of integrating molecular profiling, particularly BRCA mutation status, with surgical assessment to guide optimal and personalized treatment strategies in the PARPi era.

P2, N=81, Not yet recruiting, Onconic Therapeutics Inc.

In patients with early-stage breast cancer, heterogeneous BE and high GTC on preoperative ABUS, along with larger cancer size and BRCA mutation, was associated with worse RFS. However, BE and GTC did not affect cancer multiplicity evaluation when ABUS was used in combination with DM.

P1, N=40, Not yet recruiting, Daewoong Pharmaceutical Co. LTD.