Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort.

Background: False-positive results on screening mammography may affect women's willingness to return for future screening.

Objective: To evaluate the association between screening mammography results and the probability of subsequent screening.

Design: Cohort study.

Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density.

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts.

Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density.

Design, Setting, And Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data.

Burden and trajectory of social needs after breast cancer diagnosis at a safety-net hospital.

Purpose: Unmet social needs pose barriers to cancer care, contributing to adverse outcomes and health inequities. A better understanding of how social needs change after cancer diagnosis can inform more effective, equity-focused interventions.

Methods: In this study, we examined self-reported social needs at 0, 3, and 6 months after a breast cancer diagnosis in a racially diverse, multilingual sample (n = 222) enrolled in patient navigation intervention at an urban safety-net hospital.

Predicting five-year interval second breast cancer risk in women with prior breast cancer.

Background: Annual surveillance mammography is recommended for women with a personal history of breast cancer. Risk prediction models that estimate mammography failures such as interval second breast cancers could help to tailor surveillance imaging regimens to women's individual risk profiles.

Methods: In a cohort of women with a history of breast cancer receiving surveillance mammography in the Breast Cancer Surveillance Consortium in 1996-2019, we used Least Absolute Shrinkage and Selection Operator (LASSO)-penalized regression to estimate the probability of an interval second cancer (invasive cancer or ductal carcinoma in situ) in the 1 year after a negative surveillance mammogram.

Development of a novel multi‑epitope vaccine against the pathogenic human polyomavirus V6/7 using reverse vaccinology.

Background: Human polyomaviruses contribute to human oncogenesis through persistent infections, but currently there is no effective preventive measure against the malignancies caused by this virus. Therefore, the development of a safe and effective vaccine against HPyV is of high priority.

Methods: First, the proteomes of 2 polyomavirus species (HPyV6 and HPyV7) were downloaded from the NCBI database for the selection of the target proteins.

Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

Significance: Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes.

Screening Beyond the Evidence: Patterns of Age and Comorbidity for Breast, Cervical, and Colorectal Cancer Screening.

Background: Little evidence exists to guide continuation of screening beyond the recommended ages of national guidelines for breast, cervical, and colorectal cancers, although increasing age and comorbidity burden is likely to reduce the screening benefit of lower mortality.

Objective: Characterize screening after recommended stopping ages, by age and comorbidities in a large, diverse sample.

Design: Serial cross-sectional.

Supplemental magnetic resonance imaging plus mammography compared with magnetic resonance imaging or mammography by extent of breast density.

Background: Examining screening outcomes by breast density for breast magnetic resonance imaging (MRI) with or without mammography could inform discussions about supplemental MRI in women with dense breasts.

Methods: We evaluated 52 237 women aged 40-79 years who underwent 2611 screening MRIs alone and 6518 supplemental MRI plus mammography pairs propensity score-matched to 65 810 screening mammograms. Rates per 1000 examinations of interval, advanced, and screen-detected early stage invasive cancers and false-positive recall and biopsy recommendation were estimated by breast density (nondense = almost entirely fatty or scattered fibroglandular densities; dense = heterogeneously/extremely dense) adjusting for registry, examination year, age, race and ethnicity, family history of breast cancer, and prior breast biopsy.

Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights.

Immune checkpoints limit the activation of the immune system and serve an important homeostatic function but can also restrict immune responses against tumors. Inhibition of specific immune checkpoint proteins such as the B7:CD28 family members programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has transformed the treatment of various cancers by promoting the anti-tumor activation of immune cells. In contrast to these effects, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) regulates the steady state of the resting immune system and promotes homeostasis by mechanisms distinct from PD-1 and CTLA-4.

Considerations and Approaches for Cancer Immunotherapy in the Aging Host.

Advances in cancer immunotherapy are improving treatment successes in many distinct cancer types. Nonetheless, most tumors fail to respond. Age is the biggest risk for most cancers, and the median population age is rising worldwide.

Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.

Purpose: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population.

Methods: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium.

Breast Cancer Disparities and Innovations: A Focus on Kosovo.

Due to the current limited capacity to provide digital mammography-based screening to all women, and the lack of modern surgical oncology methods, mastectomy is still the predominant form of surgical treatment in many parts of the world. As such there is little incentive to detect breast cancer earlier and significant fear of treatment and outcomes continues to contribute to late presentations. Neoadjuvant chemotherapy, pre-operative breast MRI and surgical mapping techniques can combine forces to allow for more women to be treated with breast conservation, decrease fear of treatment and improve outcomes.

Phase 2 study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma.

Background: Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins.

Methods: A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m and nab-paclitaxel 125 mg/m on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.

Delivering Genetic Testing for Patients with Prostate Cancer: Moving Beyond Provider Knowledge as a Barrier to Care.

Introduction: The 2018 National Comprehensive Cancer Network guidelines for prostate cancer genetic testing expanded access to genetic services. Few studies have examined how this change has affected provider practice outside of large cancer centers.

Methods: We conducted a qualitative study of multi-disciplinary health care providers treating patients with prostate cancer at a safety-net hospital.

Proactive Immunotherapeutic Approaches against Inflammatory Breast Cancer May Improve Patient Outcomes.

Inflammatory breast cancer (IBC) is highly metastatic at the onset of the disease with no IBC-specific treatments, resulting in dismal patient survival. IBC treatment is a clear unmet clinical need. This commentary highlights findings from a recent seminal approach in which pembrolizumab, a checkpoint inhibitor against programmed cell death protein 1 (PD-1), was provided to a triple-negative IBC patient as a neoadjuvant immune therapy combined with anthracycline-taxane-based chemotherapy.

Belly Fat Weakens Immune Fitness.

Much work has been done to reduce cancer immunosuppression through inhibiting soluble proteins, surface molecules, and suppressive cells. This article shows an important role for the lipid lysophosphatidic acid, whose suppression shows promise as a novel cancer immunotherapeutic, demonstrated in ovarian cancer. See related article by Chae et al.

Patient navigator team perceptions on the implementation of a citywide breast cancer patient navigation protocol: a qualitative study.

Background: In 2018 Translating Research Into Practice (TRIP), an evidence-based patient navigation intervention aimed at addressing breast cancer care disparities, was implemented across six Boston hospitals. This study assesses patient navigator team member perspectives regarding implementation barriers and facilitators one year post-study implementation.

Methods: We conducted in-depth qualitative interviews at the six sites participating in the pragmatic TRIP trial from December 2019 to March 2021.