Part II: consensus statements and expert recommendations for BRCA-associated breast cancer in the Asia-Pacific region: clinical management.

Introduction: Existing guidelines have practical gaps in decision and treatment sequencing for BRCA germline pathogenic variant breast cancers. This paper aims to develop clinical-practice consensus guidelines to address these gaps in the clinical management of BRCA germline pathogenic variants-associated breast cancer in the Asia-Pacific region.

Methods: An expert panel of 16 medical oncologists, geneticists, and breast cancer surgeons from the Asia-Pacific region arrived at 25 statements.

Part I: consensus statements and expert recommendations for -negative early breast cancer in the Asia-Pacific region: diagnosis and risk assessment.

Introduction: In the Asia-Pacific region, there is increasing contention on the practical challenges involved in managing human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). This modified Delphi consensus explores gaps in genetic counselling (GC) and genetic testing (GT), and clinical risk assessment for -negative eBC.

Methods: An expert panel of 16 Asia-Pacific medical oncologists, geneticists, and breast cancer surgeons arrived at 33 statements.

Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial.

Importance: Gynecological clear cell cancers (CCCs) are aggressive malignant neoplasms with low response rate to chemotherapy. The treatment of patients with metastatic disease remains an area of significant unmet need.

Objective: To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade using nivolumab and ipilimumab in advanced gynecological CCCs.

Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma: the Asian cohort of the AtTEnd/ENGOT-EN7 trial.

Objective: This post-hoc analysis of the AtTEnd trial explored differences in the prognostic characteristics and in the efficacy of atezolizumab between Asians and non-Asians.

Methods: The role of Asian race was evaluated on progression-free survival (PFS) using Cox-models and on time to appearance of new lesions using Fine and Gray models.

Results: From October 2018 to February 2022, 549 patients were randomized, of whom, 20.

Impact of exercise on sexual health, body image, and therapy-related symptoms in women with metastatic breast cancer: The randomized controlled PREFERABLE-EFFECT trial.

The understanding and treatment of sexual health problems, impaired body image, and other non-life threatening but burdensome symptoms of women with metastatic breast cancer (mBC) is still insufficient. We studied the factors associated with such symptoms and investigated whether these problems could be alleviated by a structured exercise intervention. In the multinational PREFERABLE-EFFECT study, 355 women with mBC were randomly assigned to usual care (n = 178) or a 9-month supervised exercise program (n = 177).

Diagnostic Potential of Ga-NeoB PET/CT with Estrogen Receptor- and Progesterone Receptor-Positive Breast Cancer Undergoing Staging or Restaging for Metastatic Disease.

F-FDG PET/CT has low sensitivity for estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer. By contrast, gastrin-releasing peptide receptor is overexpressed in ER/PR-positive breast cancer. This study assessed the diagnostic potential of Ga-NeoB PET/CT in staging or restaging metastatic ER/PR-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Patients' and doctors' preferences in early-stage triple-negative breast cancer treatment in Asia-Pacific: a multi-territory discrete choice experiment using a cross-sectional survey.

Objectives: This study aimed to assess preferences of patients and doctors regarding treatment attributes for early-stage triple-negative breast cancer (eTNBC) in the Asia-Pacific region.

Design: A discrete choice experiment (DCE) by cross-sectional survey was conducted with patients and doctors. Key attributes relevant to eTNBC treatment decision-making were verified through a consultative process with clinical experts.

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis.

Background: Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma.

Methods: We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma.

Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population.

Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia.

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design.

Background: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 () in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.

Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.

Background: MLH1 epimutation is characterised by constitutional monoallelic MLH1 promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of MLH1 epimutation CRCs were used to classify germline MLH1 promoter variants of uncertain significance and MLH1 methylated early-onset CRCs (EOCRCs). Genome-wide DNA methylation and somatic mutational profiles of tumours from two germline MLH1: c.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

Aim: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme.

Methods And Results: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups.

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means.

Results of PD-L1 Analysis of Women Treated with Durvalumab in Advanced Endometrial Carcinoma (PHAEDRA).

Women with advanced endometrial carcinoma (EC) with mismatch repair (MMR) deficiency have improved outcomes when treated with immune checkpoint inhibitors; however, additional biomarkers are needed to identify women most likely to respond. Scores for programmed death ligand 1 (PD-L1), immunohistochemical staining of tumor (TC+), immune cells (IC+) and presence of tumor-associated immune cells (ICP) on MMR deficient (n = 34) and proficient (n = 33) EC from women treated with durvalumab in the PHAEDRA trial (ANZGOG1601/CTC0144) (trial registration number ACTRN12617000106336, prospectively registered 19 January 2017) are reported and correlated with outcome. Receiver operating characteristic (ROC) analyses and area under the ROC curve were used to determine optimal cutpoints.

Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study.

Background: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VOpeak), and prevent cardiac dysfunction.

Methods: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52).

The role of depression and other psychological factors in work ability among breast cancer survivors in Australia.

Objective: Identifying modifiable factors affecting work ability among cancer survivors is important. The primary aim of the present study was to examine the effects of depression and related psychological factors on work ability among breast cancer survivors in Australia.

Methods: In this cross-sectional electronic and postal survey, Australian breast cancer survivors were investigated.

Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior.

Purpose: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS).

Methods: Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment.

Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial.

Background: In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)-mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).

Methods: A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression.

Pilot study of an online training program to increase genetic literacy and communication skills in oncology healthcare professionals discussing BRCA1/2 genetic testing with breast and ovarian cancer patients.

The increasing use of genetic testing for BRCA1/2 and other pathogenic variants in the management of women with breast and ovarian cancer necessitates increased genetic literacy in oncology healthcare professionals. This pilot study aimed to evaluate an online training program to increase genetic literacy and communication skills in Australian oncology healthcare professionals tasked with discussing and coordinating mainstream genetic testing with breast and ovarian cancer patients. A training website with embedded videos was developed.

Communicating polygenic risk scores in the familial breast cancer clinic.

Objective: To describe the communication of polygenic risk scores (PRS) in the familial breast cancer setting.

Methods: Consultations between genetic healthcare providers (GHP) and female patients who received their PRS for breast cancer risk were recorded (n = 65). GHPs included genetic counselors (n = 8) and medical practitioners (n = 5) (i.