scholarly journals Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zuzana Cierna ◽  
Bozena Smolkova ◽  
Dana Cholujova ◽  
Paulina Gronesova ◽  
Svetlana Miklikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Immunological Tolerance ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Increased Risk ◽  
Plasma Cytokines ◽  
Multifunctional Molecules ◽  
Circulating Cytokines

AbstractProgrammed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as a proxy for non-invasive identification of sensitive prognostic biomarkers reflecting tumour and its microenvironment. Immunohistochemistry was used to measure PD-L1 expression in tumour tissue sections of 148 chemonaïve breast cancer (BC) patients. The panel of 51 cytokines was analysed using multiplex bead arrays. High PD-L1 expression in tumours was associated with shorter progression-free survival (HR 3.25; 95% CI 1.39–7.61; P = 0.006) and low circulating levels of three multifunctional molecules; VEGF, TNF-β and IL-15 (P = 0.001). In multivariate analysis, patients with low VEGF had 4.6-fold increased risk of PD-L1 overexpression (P = 0.008), present in 76.5% of patients with all these three cytokines below the median (vs. 35.6% among the others; P = 0.002). The area under the curve value of 0.722 (95% CI 0.59–0.85; P = 0.004) shows that this combination of cytokines has a moderate ability to discriminate between PD-L1 high vs. PD-L1 low patients. Plasma cytokines, therefore, could serve as potential non-invasive biomarkers for the identification of high-risk BC cases.

ER, PR & HER2 Receptor status in recurrent breast cancer: Its relation to age & time of recurrence

2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Younger Patients ◽  
Receptor Status ◽  
Increased Risk ◽  
Neoplastic Lesions ◽  
Recurrent Breast

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore

2021 ◽  
pp. jmedgenet-2020-107471
Author(s):  
Pei Sze Ng ◽  
Rick ACM Boonen ◽  
Eldarina Wijaya ◽  
Chan Eng Chong ◽  
Milan Sharma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rare Variants ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Dna Double Strand Breaks ◽  
Functional Impact ◽  
Missense Variants ◽  
Increased Risk

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

scholarly journals Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel C. Beachler ◽  
Cynthia de Luise ◽  
Aziza Jamal-Allial ◽  
Ruihua Yin ◽  
Devon H. Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Pulmonary Embolism ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Elevated Risk ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Serious Infections

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

Buparlisib in Kombination mit Tamoxifen: Rationale für zielgerichtete Therapie bei PIK3CA-mutiertem metastasierten Mammakarzinom bestätigt

2021 ◽  
pp. 1-3
Author(s):  
Carlota Claussen ◽  
Maggie Banys-Paluchowski
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Pik3ca Mutation ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Open Label ◽  
Pik3ca Mutations ◽  
Hormone Receptor Positive ◽  
Pi3k Inhibition

The PIKTAM study evaluated the efficacy and safety of the PI3K inhibitor buparlisib in combination with tamoxifen in hormone receptor-positive (HR+), HER2-negative advanced breast cancer patients after failure of prior endocrine therapy. In this open-label, single-arm phase II trial, 25 patients were enrolled in 11 sites in Germany. Patients were stratified according to PIK3CA mutation status (tissue and cfDNA from serum samples) and/or loss of PTEN expression. Patients received buparlisib (100mg) and tamoxifen (20mg) once daily on a continuous schedule (28-day cycle) until progression or unacceptable toxicity. Primary endpoint was overall 6-month progression-free survival (PFS) rate. Key secondary endpoints included the 6-month PFS rate in subpopulations, PFS, overall survival, overall response rate (ORR), disease control rate (DCR), and safety. Overall, the 6-month PFS rate was 33.3% (n/N = 7/21, one-sided 95% CI 16.8–100) and median PFS was 6.1 (CI 2.6–10.6) months. The ORR and DCR were 12.5% and 44%. The PIK3CA-mutated subgroup consistently showed the highest 6-month PFS rate (62.5%, n/N = 5/8), median PFS (8.7 months), ORR (40%), and DCR (80%). No new safety signals emerged. Most common adverse events were gastrointestinal disorders (56%), psychiatric/mood disorders (48%), skin rash/hypersensitivity (44%), cardiovascular (40%), and hepatic (32%) events. The trial was prematurely terminated due to the substantially altered risk – benefit profile of buparlisib. Nevertheless, PIK3CA mutations emerged as a clinically feasible and useful biomarker for combined PI3K inhibition and endocrine therapy in patients with HR+ breast cancer. Further biomarker – stratified studies with isoform – specific PI3K inhibitors are warranted. EudraCT No: 2014–000599–24.

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