In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China

BackgroundTo characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.MethodsThe China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).ResultsThere were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p < 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).ConclusionOur findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.

Survival in Women with De Novo Metastatic Breast Cancer: A Comparison of Real-World Evidence from a Publicly-Funded Canadian Province and the United States by Insurance Status

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute’s SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77–1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95–54.59) and 55.54% (49.49–61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25–41.37) and 40.53% (36.20–44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.

Assessment of Role of Platelet Aggregation in Metastatic Breast Cancer Patients

Background: To assess role of platelet aggregation in metastatic breast cancer patients.Methods:40 cases (Group I) of metastatic breast cancer patients and equal number of healthy control (Group II) subjects were included. Platelet aggregation studies in vitro using ADP and Thrombin were performed using an optical aggregometer. Detection of platelet aggregation was done by Chrono log series 490 dual and four channel optical aggregometer systems.Results:There were 4 subjects in group I and 12 in group II having ADP <60, 26 subjects in group I and 28 in group II with ADP 61-72 and 10 subjects in group I with ADP >72. Low thrombin <58 was seen in 8 in group II, normal thrombin between 61-72 was seen among 11 in group I and 32 in group II and high thrombin >82 among 29 in group I respectively. Amongst patients with normal platelet count, 14 patients had platelet aggregation with ADP in the normal range and 4 patients had platelet aggregation with ADP in the lower range. In patients with high platelet count, 12 showed aggregation in the normal range, and 10 patients showed aggregation in the higher range which was statistically significant (P< 0.05) (Table III, Graph II).Conclusion: Platelet aggregation has an important part to play in the tumor metastasis of breast cancer patients.

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.

Systemic HER3 ligand-mimicking bioparticles cross the blood–brain barrier reducing intracranial triple-negative breast cancer growth

Triple-negative breast cancer (TNBC) lacks selective biomarkers targeted by current clinical therapies and often metastasizes to the brain. Crossing the blood-brain barrier (BBB) and reaching intracranial tumors is a clinical challenge contributing to poor prognoses for patients. The human epidermal growth factor receptor HER3 has emerged as a biomarker of metastasis and may provide a means of therapeutically targeting TNBC. We have developed HER3-targeted biological particles (bioparticles) that exhibit systemic homing to resistant and metastatic breast tumors. Here we show that HER3 is expressed on the brain endothelium and can mediate the passage of bioparticles across the BBB and into intracranial TNBC. Our findings show that the extravasation of systemic bioparticles in mice and in human induced pluripotent stem cell-based BBB chips corresponds to HER3 levels. Furthermore, systemically delivered bioparticles carrying tumoricidal agents reduced the growth of intracranial TNBC in mice and exhibited improved therapeutic profile compared to current therapies.

Successful surgical treatment of intractable post-radiation rectal bleeding

Patients will typically present symptoms of chronic post-radiation colitis and proctitis 8-12 months after finishing their treatment. Endoscopic methods play the main role the treatment of bleeding caused by post-radiation colitis and proctitis. Surgical treatment is required for remained approximately 10% of patients. Here we present a 64 year old female with metastatic breast cancer, who was referred to us for intractable rectal bleeding. Total colonoscopy and rigid rectosigmoidoscopy revealed proctitis, rectal and sigmoidal telangiectasis, multiple necrotic ulcers between 15 to 30 cm from the anal verge, and also huge ishemic ulcer with patchy necrotic areas about 10 cm from the anal verge. This abnormal irradiated part was resected and then mucosectomy of the remnant rectum, both transabdominally and transanally was done. We performed pull-through technique of normal proximal colon to anal region through the remnant rectal wall and finally did coloanal anastomosis. Diverting stoma was not made because of anastomosis in anal region. With this technique we can achieve benefits such as avoidance of harsh dissection in a frozen pelvis and its consequences, we can avoid intra-abdominal anastomosis, there is no need to a diverting stoma and, most important of all, definite bleeding control.

SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.