The Trend of Dental Check-Up And Incidence of Dental Complications Following The Use of Bone Modifying Agents In Patients With Metastatic Breast And Prostate Cancer: Analysis of Data From The Korean National Health Insurance Service

Purpose: Bone-modifying agents (BMAs) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMAs is associated with adverse dental events including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the rate of preoperative dental surveillance to reduce the incidence of adverse dental events including MRONJ after BMA treatment in patients with bone metastasis from breast and prostate cancer. Methods: Data, including age, cancer diagnosis, administered BMAs, and adverse dental events during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. Results: Of the 15357 patients who received BMAs, 1706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-ups increased from 4.4% in 2007 to 16.7% in 2019. Referral for dental check-up was more frequent in clinics and primary hospitals than in tertiary hospitals, and from the departments of internal medicine and urology than from the department of general surgery, regardless of the patient's health insurance status. After BMA treatment, 3328 patients (21.6%) developed adverse dental events, including tooth extraction (73.0%), abscess (16.9%), acute periodontitis (5.3%), acute pericoronitis (2.6%), and MRONJ (2.2% of 3328, 0.5% of 15357). Conclusions: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental treatment before the initiation of BMAs.

Cytomorphological spectrum of metastatic bone tumors: Experience at a tertiary care center

Objectives: Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. Fine-needle aspiration cytology (FNAC) provides reasonably accurate pre-operative diagnosis in vast majority of cases. This study aims to elicit the cytomorphological detail of various metastatic bone tumors. Material and Methods: A total of 109 cases of tumors metastatic to bone have been included in this study. The details of the cases were available from the archives of the department of cytology. May Grunwald Giemsa and hematoxylin and eosin stained smears were studied and examined for the cytomorphological spectrum. Cell block and immunohistochemistry tests were done, wherever feasible. Results: Among 109 patients, the mean age was 54.52 years. There was male preponderance with 90 males and 19 females. The most common site of metastases was in the vertebra (82 cases), and 76 cases were in the dorsolumbar region. The most common type of tumor metastasizing was adenocarcinoma. Conclusion: FNAC is a very useful, economical procedure. There are characteristic cytological features of the metastatic lesions and the basic diagnostic categorization of the malignant tumors is possible on FNAC. Regarding the primary source clinical history, radiological features of the primary tumor, if any, and immunocytochemistry may be needed.

Disparities in Disease-Specific Remaining Life Expectancy Among Medicare Beneficiaries in the United States

Racial and geographic disparities in life expectancy (LE) in the US are a persistent problem. We used 5% Medicare Claims for 2000-2017 to investigate the patterns of remaining LE (RLE) in the U.S. with the highest and the lowest LE. RLEs in race-/ethnicity specific populations aged 65+ were calculated in patients with specific diseases and in the total population using the area under the Kaplan-Meier estimator. The Cox model was used to investigate the effect of state-specific residence on total LE and RLE. Between-the-states differences in RLE were most pronounced for cerebrovascular disease, atherosclerotic heart disease, breast and prostate cancer. RLE was the lowest for lung cancer and sepsis, followed by Alzheimer’s disease, dementia, pneumonia, and heart failure. RLE for myocardial infarction and cerebrovascular disease decreased over time, while for renal failure, diabetes, atherosclerotic heart disease, and cancers of breast and prostate RLE increased.

Pre-clinical validation of a novel pan-cancer CAR-T cell immunotherapy against nfP2X7

Chimeric antigen receptor (CAR)-T immunotherapy is a novel treatment that genetically modifies the patient’s own T cells to target and kill malignant cells. CAR-T cells demonstrated robust clinical activity against certain B-cell malignancies. However, identification of tumour-specific antigens expressed on multiple cancer types, especially on solid cancers, remains a major challenge. P2X purinoceptor 7 (P2X7) is an ATP gated cation channel that forms homotrimers and heterotrimers at the cell surface. When functioning normally, it controls ion transport in response to ATP. A dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from a range of tissues, while being undetectable on healthy cells. We generated prototype nfP2X7-targeting human CAR-T cells, which demonstrated effective antigen-specific cytotoxicity against twelve solid cancer types including breast, prostate, lung, colorectal, brain and skin in vitro. In preclinical xenograft mouse models of aggressive breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibited robust anti-tumour efficacy. These data indicate CAR-T cells targeting nfP2X7 have potential as a novel broad-spectrum cancer immunotherapy for solid tumours in humans.

Family history of breast cancer is associated with elevated risk of prostate cancer: evidence for shared genetic risks

Introduction: Although breast and prostate cancers arise in different organs and are more frequent in the opposite sex, multiple studies have reported an association between their family history. Analysis of single nucleotide polymorphism data, based on distant relatives, has revealed a small positive genetic correlation between these cancers explained by common variants. The estimate of genetic correlation based on close relatives reveals the extent to which shared genetic risks are explained by both common and rare variants. This estimate is unknown for breast and prostate cancer. Method: We estimated the relative risks, heritability, and genetic correlation of breast cancer and prostate cancer, based on the Minnesota Breast and Prostate Cancer Study, a family study of 141 families ascertained for breast cancer. Results: Heritability of breast cancer was 0.34 (95% credible interval: 0.23-0.49) and 0.65 (95% credible interval: 0.36-0.97) for prostate cancer, and the genetic correlation was 0.23. In terms of odds ratios, these values correspond to a 1.3 times higher odds of breast cancer among probands, given that the brother has prostate cancer. Conclusion: This study shows the inherent relation between prostate cancer and breast cancer; an incident of one in a family increases the risk of developing the other. The large difference between estimates of genetic correlation from distant and close relatives, if replicated, suggests that rare variants contribute to the shared genetic risk of breast and prostate cancer. However, the difference could steam from genotype-by-family effects shared between the two types of cancers.

Erratum: Barsasella et al. Sleep Quality among Breast and Prostate Cancer Patients: A Comparison between Subjective and Objective Measurements. Healthcare 2021, 9, 785

The authors wish to make the following erratum to this paper [...]

Mechanisms, Diagnosis and Treatment of Bone Metastases

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients’ quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells

H2A.J is a poorly studied mammalian-specific variant of histone H2A. We used immunohistochemistry to study its localization in various human and mouse tissues. H2A.J showed cell-type specific expression with a striking enrichment in luminal epithelial cells of multiple glands including those of breast, prostate, pancreas, thyroid, stomach, and salivary glands. H2A.J was also highly expressed in many carcinoma cell lines and in particular, those derived from luminal breast and prostate cancer. H2A.J thus appears to be a novel marker for luminal epithelial cancers. Knocking-out the H2AFJ gene in T47D luminal breast cancer cells reduced the expression of several estrogen-responsive genes which may explain its putative tumorigenic role in luminal-B breast cancer.