Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174

Σάββατο 5 Ιανουαρίου 2019

Neratinib in HER2-Positive Breast Cancer Patients.

Neratinib in HER2-Positive Breast Cancer Patients.

Ann Pharmacother. 2019 Jan 04;:1060028018824088

Authors: Paranjpe R, Basatneh D, Tao G, De Angelis C, Noormohammed S, Ekinci E, Abughosh S, Ghose R, Trivedi MV

Abstract
OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib in human epidermal growth factor receptor (HER2)+ breast cancer (BC).
DATA SOURCES: A PubMed search was performed using the term neratinib between September 12, 2018, and November 21, 2018. References of published articles and reviews were also assessed for additional information.
STUDY SELECTION AND DATA EXTRACTION: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib were evaluated.
DATA SYNTHESIS: Neratinib, an irreversible inhibitor of HER1, HER2, and HER4, is Food and Drug Administration approved for the extended adjuvant treatment of stage I-III HER2+ BC to follow trastuzumab-based therapy. A phase III study has demonstrated statistically significant improvement in 5-year disease-free survival rate (90.2 vs 87.7; hazard ratio = 0.73, 95% CI = 0.57-0.92, P = 0.0083). Its most common adverse effect is diarrhea, observed in more than 90% of patients. The incidence of grade 3/4 diarrhea (~40%) is reduced by half with loperamide prophylaxis, which is recommended for the first 8 weeks of neratinib therapy. Other common adverse reactions are nausea and fatigue. The patients need to be monitored for liver function tests and drug interactions with acid-reducing agents, CYP3A4 inhibitors/inducers, and P-glycoprotein substrates with narrow therapeutic window. Relevance to Patient Care and Clinical Practice: American Society of Clinical Oncology and National Comprehensive Cancer Network clinical guidelines suggest the use of neratinib for extended adjuvant therapy following 1-year trastuzumab in stage I to III HER2+ BC. Diarrhea remains a clinically significant but manageable adverse event.
CONCLUSION: Neratinib significantly improves treatment outcomes and has manageable toxicity in stage I to III HER2+ BC patients.

PMID: 30607980 [PubMed - as supplied by publisher]

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Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU.

Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU.

Clin Drug Investig. 2019 Jan 03;:

Authors: Dhillon S

Abstract
Neratinib (Nerlynx®) is an oral, irreversible pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor of HER1, HER2 and HER4. Neratinib therapy for 12 months significantly reduced the risk of invasive disease recurrence or death relative to placebo at both 2 and 5 years post-randomization in the pivotal ExteNET trial in women with early-stage HER2-positive breast cancer who had completed adjuvant trastuzumab. Subgroup analyses showed that patients with hormone receptor (HRc)-positive disease derived greater benefit with neratinib than patients with HRc-negative disease, and patients who initiated neratinib within 1 year of completing trastuzumab had better outcomes than those who started treatment 1-2 years after trastuzumab. This led to the approval of neratinib in the EU as extended adjuvant therapy for patients with early-stage HRc-positive, HER2-positive breast cancer and who are less than 1 year from completion of prior adjuvant trastuzumab-based therapy. It is the first agent of its class to be approved in the EU in this setting. As with other tyrosine kinase inhibitors, diarrhoea, which was manageable with antidiarrhoeal prophylaxis and/or dose modifications, was the most common any-grade or grade ≥ 3 treatment-emergent adverse event with neratinib. Thus, current evidence indicates that neratinib provides a valuable option to reduce the risk of recurrence in this setting and has been included in the updated ESMO patient guide as an extended adjuvant therapy for some patients.

PMID: 30607817 [PubMed - as supplied by publisher]

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TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort.

TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort.

Fam Cancer. 2019 Jan 03;:

Authors: Bakhuizen JJ, Hogervorst FB, Velthuizen ME, Ruijs MW, van Engelen K, van Os TA, Gille JJ, Collée M, van den Ouweland AM, van Asperen CJ, Kets CM, Mensenkamp AR, Leter EM, Blok MJ, de Jong MM, Ausems MG

Abstract
Early-onset breast cancer may be due to Li-Fraumeni Syndrome (LFS). Current national and international guidelines recommend that TP53 genetic testing should be considered for women with breast cancer diagnosed before the age of 31 years. However, large studies investigating TP53 mutation prevalence in this population are scarce. We collected nationwide laboratory records for all young breast cancer patients tested for TP53 mutations in the Netherlands. Between 2005 and 2016, 370 women diagnosed with breast cancer younger than 30 years of age were tested for TP53 germline mutations, and eight (2.2%) were found to carry a (likely) pathogenic TP53 sequence variant. Among BRCA1/BRCA2 mutation negative women without a family history suggestive of LFS or a personal history of multiple LFS-related tumours, the TP53 mutation frequency was < 1% (2/233). Taking into consideration that TP53 mutation prevalence was comparable or even higher in some studies selecting patients with breast cancer onset at older ages or HER2-positive breast cancers, raises the question of whether a very early age of onset is an appropriate single TP53 genetic testing criterion.

PMID: 30607672 [PubMed - as supplied by publisher]

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Efficacy and safety of dasatinib with trastuzumab and paclitaxel in first line HER2-positive metastatic breast cancer: results from the phase II GEICAM/2010-04 study.

Efficacy and safety of dasatinib with trastuzumab and paclitaxel in first line HER2-positive metastatic breast cancer: results from the phase II GEICAM/2010-04 study.

Breast Cancer Res Treat. 2019 Jan 03;:

Authors: Ocana A, Gil-Martin M, Antolín S, Atienza M, Montaño Á, Ribelles N, Urruticoechea A, Falcón A, Pernas S, Orlando J, Montero JC, Escudero MJ, Benito S, Caballero R, Carrasco E, Rojo F, Pandiella A, Ruiz-Borrego M

Abstract
BACKGROUND: An important proportion of HER2-positive metastatic breast cancer patients do not respond to trastuzumab. The combination of dasatinib and trastuzumab has shown to be synergistic in preclinical models.
METHODS: We conducted a phase II trial combining dasatinib 100 mg once daily with trastuzumab 2 mg/kg and paclitaxel 80 mg/m2 weekly. Primary objective was objective response rate (ORR) and secondary included safety, other efficacy parameters and pharmacodynamics in tumour tissue, blood samples and skin biopsies.
RESULTS: From June 2013 to December 2015, 29 patients were included. Median number of cycles was 12 (1-49). Only 6 patients discontinued due to adverse events. ORR was 79.3% (95% CI 60.3-92), clinical benefit rate 82.8% (95% CI 64.2-94.2). Median time to progression 23.9 months (95% CI 14.9-not reached [NR]), median progression-free survival 23.9 months (95% CI 10.3-NR). No grade 4 toxicity was seen. Grade 3 toxicities included: ejection fraction decrease, neutropenia, hyponatremia, fatigue and sensory neuropathy and one left ventricular systolic dysfunction. Phosphorylated (p)-SRC was reduced in peripheral blood mononuclear cells. Phosphorylated SRC, ERK and AKT were also reduced in epidermal keratinocytes.
CONCLUSIONS: Dasatinib can be safely combined with trastuzumab and paclitaxel. The combination is active with an ORR of almost 80%.
TRIAL REGISTRATION: NCT01306942, EudraCT 2010-023304-27.

PMID: 30607629 [PubMed - as supplied by publisher]

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PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis.

PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis.

J Breast Cancer. 2018 Dec;21(4):382-390

Authors: Seo Y, Park YH, Ahn JS, Im YH, Nam SJ, Cho SY, Cho EY

Abstract
Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers.
Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients.
Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016).
Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

PMID: 30607159 [PubMed]

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Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration associated with cognitive affective syndrome in a patient with breast cancer: a case report and literature review.

Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration associated with cognitive affective syndrome in a patient with breast cancer: a case report and literature review.

Curr Oncol. 2018 Dec;25(6):e585-e591

Authors: Le May M, Dent S

Abstract
Breast cancer is the most common cancer in women, with 15%-25% of those tumours overexpressing the human epidermal growth factor receptor 2 (her2), which is associated with more aggressive disease. On rare occasions, patients present with a paraneoplastic syndrome months to years before their cancer diagnosis. Paraneoplastic cerebellar degeneration (pcd) is associated with fewer than 1% of cancers and is strongly associated with breast and gynecologic malignancies. Anti-Yo antibody is the antibody most frequently identified with the syndrome, and it is associated with a very poor prognosis. Recent studies have implicated a relationship between overexpression of her2 and anti-Yo-mediated pcd. Current pcd treatments include tumour removal, chemotherapy, targeted therapy, and immune-suppressive treatments. Outcomes of pcd are typically poor, and no guidelines for treatment currently exist. Early recognition followed by rapid initiation of treatment remains the cornerstone of therapy. Here, we present a case of anti-Yo-antibody pcd secondary to estrogen and progesterone receptor-negative, her2-positive breast cancer. Despite treatment with mastectomy, chemotherapy, and her2-targeted therapy, no significant neurologic improvement was achieved, and cerebellar cognitive affective syndrome subsequently developed.

PMID: 30607127 [PubMed - in process]

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miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2.

miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2.

Pathol Res Pract. 2018 Dec 24;:

Authors: Chen F, Qi S, Zhang X, Wu J, Yang X, Wang R

Abstract
Oral squamous cell carcinomas (OSCCs) are one of the most ubiquitous malignancies the world over, and are accompanied by a high mortality. microRNAs (miRNAs) have increasingly garnered attention with regards to the roles they play in initiation and progression of various kinds of cancers, including OSCC. It has been reported, that miR-23a-3p promotes the development of tumors for prostate cancer, gastric cancer and gliomas. The functions of miR-23a-3p in OSCC however, remain unclear. In this study, fibroblast growth factor 2 (FGF2) is revealed as a direct target of miR-23a-3p, based on luciferase assays and immunoblotting. The expression of miR-23a-3p and FGF2 were found to be significantly downregulated and upregulated in OSCC tissues respectively. This indicates a reverse correlation between miR-23a-3p and FGF2 levels. Using in vitro approaches we ascertained that miR-23a-3p might contribute to the inhibition of growth and inhibition through increasing apoptosis in OSCC cells; while an inhibitor of miR-23a-3p could reverse this effect. Examination of a clinical cohort of OSCC patients suggested that reduced expression of miR-23a-3p is correlated with more advanced cancerous stage and poorer differentiation of OSCC cell. Additionally, a survival analysis and the Cox-hazard regression model showed that higher levels of miR-23a-3p can be used reliably for prognosis of OSCC patients. This study indicates that miR-23a-3p might suppress tumor proliferation, invasion and promote apoptosis of OSCC by targeting FGF2. miR-23a-3p has the potential to be used as prognostic indicator, and could be exploited as a therapeutic reagent for OSCC in the future.

PMID: 30606659 [PubMed - as supplied by publisher]

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The value of magnetic resonance imaging in esophageal carcinoma: Tool or toy?

The value of magnetic resonance imaging in esophageal carcinoma: Tool or toy?

Asia Pac J Clin Oncol. 2019 Jan 04;:

Authors: Zhu Y, Fu L, Jing W, Guo D, Chen Y, Kong L, Yu J

Abstract
Currently, the use of magnetic resonance imaging (MRI) in patients with esophageal carcinoma is limited. However, the quality of MRI for esophageal carcinoma continues to improve and the importance of MRI in patients with esophageal carcinoma has been gradually recognized. Compared with endoscopic ultrasound and computed tomography applied in T and N staging, MRI has now achieved excellent results after the imaging technique has been optimized. We review the literature on MRI and discuss the future of MRI in esophageal carcinoma. While the role of MRI in staging, tumor volume target delineation and evaluation for preoperative chemoradiotherapy, prognosis and recurrence is still evolving. The application of MRI in esophageal carcinoma has a bright future and potential to improve precision of T and N staging as well as treatment delivery.

PMID: 30609237 [PubMed - as supplied by publisher]

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Multimodal Management of Congenital Orbital Malignant Rhabdoid Tumor: Review of Literature and Report of a Rare Case.

Multimodal Management of Congenital Orbital Malignant Rhabdoid Tumor: Review of Literature and Report of a Rare Case.

J Pediatr Hematol Oncol. 2018 Dec 31;:

Authors: Biswas A, Kumar R, Bakhshi S, Sen S, Sharma MC

Abstract
BACKGROUND: Malignant rhabdoid tumor (MRT) is a rare and aggressive tumor with a dismal prognosis. It commonly arises in the brain (65%), soft tissues (26%), and the kidney (9%). Primary orbital involvement is extremely rare. Although it has been mostly described in children below 2 years old, presentation at birth is sparsely reported.
OBSERVATION: We have described a case of congenital orbital MRT, who presented with rapidly progressive right-sided proptosis and was initially treated with subtotal resection and postoperative chemotherapy with ICE (Ifosfamide, Carboplatin, Etoposide) regimen. On local progression the child was treated with palliative radiotherapy (20 Gy) to the right orbit and second-line chemotherapy with VAC (Vincristine, Adriamycin, Cyclophosphamide) regimen. Unfortunately he died due to progressive disease 4 months after the initial diagnosis.
CONCLUSIONS: This report highlights the importance of awareness of orbital MRT as a differential diagnosis of rapidly progressing proptosis in the neonatal period. This tumor is often refractory to conventional multimodality treatment and more intensive and innovative treatment approaches are clearly needed in future.

PMID: 30608492 [PubMed - as supplied by publisher]

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Radiation-induced nausea and vomiting: a comparison between MASCC/ESMO, ASCO, and NCCN antiemetic guidelines.

Radiation-induced nausea and vomiting: a comparison between MASCC/ESMO, ASCO, and NCCN antiemetic guidelines.

Support Care Cancer. 2019 Jan 03;:

Authors: McKenzie E, Zaki P, Raman S, Olson R, McFarlane T, DeAngelis C, Chan S, Pidduck W, Razvi Y, Bushehri A, Chow E

Abstract
PURPOSE: Radiation-induced nausea and vomiting (RINV) can affect 50-80% of patients undergoing radiotherapy and negatively impacts quality of life. This review aimed to compare the most recent RINV antiemetic guidelines produced by the Multinational Association for Supportive Care in Cancer (MASCC), the European Society of Clinical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Future improvements to the guidelines and the need for further research in RINV were also discussed.
METHODS: Antiemetic guidelines produced by MASCC/ESMO, ASCO, and NCCN were examined to identify similarities, differences, and inadequacies within the guidelines.
RESULTS: Areas of dissension within the guidelines include the addition of dexamethasone to moderate-risk antiemetic regimens, the prophylactic treatment of RINV in the low-risk categories, and the appropriate treatment for breakthrough emesis. The guidelines are in accordance that high-risk radiotherapy regimens should be treated prophylactically with a serotonin receptor antagonist and for those undergoing concurrent chemotherapy and radiotherapy, antiemetic treatment should be prescribed according to the emetic risk associated with their respective chemotherapy regimen. Low- and minimal-risk recommendations are based on low-level evidence and informal consensus.
CONCLUSION: RINV is a frequent and distressing side effect of radiotherapy and requires further research to establish effective antiemetic guidelines and ensure optimal treatment outcomes.

PMID: 30607675 [PubMed - as supplied by publisher]

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A common Chk1-dependent phenotype of DNA double-strand break suppression in two distinct radioresistant cancer types.

A common Chk1-dependent phenotype of DNA double-strand break suppression in two distinct radioresistant cancer types.

Breast Cancer Res Treat. 2019 Jan 03;:

Authors: Dinkelborg PH, Wang M, Gheorghiu L, Gurski JM, Hong TS, Benes CH, Juric D, Jimenez RB, Borgmann K, Willers H

Abstract
PURPOSE: Triple-negative breast cancers (TNBC) are often resistant to treatment with ionizing radiation (IR). We sought to investigate whether pharmacologic inhibition of Chk1 kinase, which is commonly overexpressed in TNBC, preferentially sensitizes TNBC cells to IR.
METHODS: Ten breast cancer cell lines were screened with small molecule inhibitors against Chk1 and other kinases. Chk1 inhibition was also tested in isogenic KRAS mutant or wild-type cancer cells. Cellular radiosensitization was measured by short-term and clonogenic survival assays and by staining for the DNA double-strand break (DSB) marker γ-H2AX. Radiosensitization was also assessed in breast cancer biopsies using an ex vivo assay. Aurora B kinase-dependent mitosis-like chromatin condensation, a marker of radioresistance, was detected using a specific antibody against co-localized phosphorylation of serine 10 and trimethylation of lysine 9 on histone 3 (H3K9me3/S10p). Expression of CHEK1 and associated genes was evaluated in TNBC and lung adenocarcinoma.
RESULTS: Inhibition of Chk1 kinase preferentially radiosensitized TNBC cells in vitro and in patient biopsies. Interestingly, TNBC cells displayed lower numbers of IR-induced DSBs than non-TNBC cells, correlating with their observed radioresistance. We found that Chk1 suppressed IR-induced DSBs in these cells, which was dependent on H3K9me3/S10p-a chromatin mark previously found to indicate radioresistance in KRAS mutant cancers. Accordingly, the effects of Chk1 inhibition in TNBC were reproduced in KRAS mutant but not wild-type cells. We also observed co-expression of genes in this Chk1 chromatin pathway in TNBC and KRAS mutant lung cancers.
CONCLUSIONS: Chk1 promotes an unexpected, common phenotype of chromatin-dependent DSB suppression in radioresistant TNBC and KRAS mutant cancer cells, providing a direction for future investigations into overcoming the treatment resistance of TNBC.

PMID: 30607635 [PubMed - as supplied by publisher]

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Myelodysplastic syndrome from theoretical review to clinical application view.

Myelodysplastic syndrome from theoretical review to clinical application view.

Oncol Rev. 2018 Jul 04;12(2):397

Authors: Mohammad AA

Abstract
Myelodysplastic syndromes (MDS), called ineffective hematopoiesis is indicated by bone marrow failure and tendency to acute myeloid leukemia transformation. Since the disease is more common in elderly with non- hematology co-morbidities, the research for less toxic and curative novel agents is essential. More than 12 years without new Food and Drug Administration approved drugs in MDS management through the whole course, only 5 drugs. We summarized the basic data in diagnosis, treatment guidelines and future direction.

PMID: 30607219 [PubMed]

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A little help from my friends: social support in palliative rehabilitation.

A little help from my friends: social support in palliative rehabilitation.

Curr Oncol. 2018 Dec;25(6):358-365

Authors: Rutkowski NA, Lebel S, Richardson K, Mutsaers B, Chasen M, Feldstain A

Abstract
Background: Social support has been shown to buffer some difficulties of living with advanced cancer. The Palliative Rehabilitation Program (prp) was an interdisciplinary outpatient program offering post-treatment palliative rehabilitation to patients with advanced cancer. Social support was directly integrated into the program. The aim of the present study was to examine the types and sources of social support that patients found most beneficial.
Methods: Twelve patients participated in 30-minute semi-structured interviews. Thematic content analysis was used to explore the social support experiences of those patients in the prp. Patients were eligible to participate in the interview if they had completed the 8-week prp, spoke English, and did not have cognitive or auditory impairments affecting their ability to participate.
Results: The main sources of support reported by participants were team members and spouse, family, or close friends; peers attending the program; and spiritual beliefs. Social support varied based on sex and age, such that, compared with women, men reported relying less on social support, and the supportive needs of younger (≤50 years of age) and older participants differed. Team members were endorsed as frequently as family as social support.
Discussion: Emotional support was endorsed with the greatest frequency. The members of the interdisciplinary care team were also providers of emotional and informational support for patients, bolstering the support received from caregivers. Widowed or divorced women might rely on health care providers more readily than do married men, who chose their wives as support. Future rehabilitation programs might consider the importance of an interdisciplinary team, the formal integration of caregivers, and the incorporation of spirituality to meet the unique supportive needs of patients with advanced cancer.

PMID: 30607109 [PubMed - in process]

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Impact of Comorbidities and Age on Cause-Specific Mortality in Postmenopausal Patients with Breast Cancer.

Impact of Comorbidities and Age on Cause-Specific Mortality in Postmenopausal Patients with Breast Cancer.

Oncologist. 2019 Jan 03;:

Authors: Derks MGM, van de Velde CJH, Giardiello D, Seynaeve C, Putter H, Nortier JWR, Dirix LY, Bastiaannet E, Portielje JEA, Liefers GJ

Abstract
BACKGROUND: The aim was to study the impact of comorbidities and age on breast cancer mortality, taking into account competing causes of death.
SUBJECTS, MATERIALS, AND METHODS: Cohort analysis of Dutch and Belgian patients with postmenopausal, early hormone receptor-positive breast cancer included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. This is a randomized controlled trial of patients who had completed local treatment with curative intent and were randomized to receive exemestane for 5 years, or sequential treatment of tamoxifen followed by exemestane for a duration of 5 years. Patients were categorized by number of comorbidities (no comorbidities, 1-2 comorbidities, and >2 comorbidities) and age (<70 years and ≥70 years). Main outcome was breast cancer mortality considering other-cause mortality as competing event; cumulative incidences were calculated using the Cumulative Incidence Competing Risk Methods, and the Fine and Gray model was used to calculate the effect of age and comorbidities for the cause-specific incidences of breast cancer death, taking into account the effect of competing causes of death.
RESULTS: Overall, 3,159 patients were included, of which 2,203 (69.7%) were aged <70 years and 956 (30.3%) were aged ≥70 years at diagnosis. Cumulative incidence of breast cancer mortality was higher among patients ≥70 without comorbidities (22.2%, 95% CI, 17.5-26.9) compared with patients <70 without comorbidities (15.6%, 95% CI, 13.6-17.7, reference group), multivariable subdistribution hazard ratio (sHR) 1.49 (95% CI, 1.12-1.97, p = .005) after a median follow-up of 10 years. Use of chemotherapy was lower in older patients (1%, irrespective of the number of comorbidities) compared with younger patients (50%, 44%, and 38% for patients with no, 1-2, or >2 comorbidities, p < .001).
CONCLUSION: Older patients without comorbidities have a higher risk of dying due to breast cancer than younger counterparts, even when taking into account higher competing mortality, while use of chemotherapy in this group was low. These findings underline the need to take into account comorbidities, age, and competing mortality in the prognosis of breast cancer for accurate decision making.
IMPLICATIONS FOR PRACTICE: Older patients without comorbidity are at increased risk of dying from breast cancer, despite a higher other-cause mortality. This study shows that including age and comorbidity for the assessment of breast cancer mortality and other-cause mortality is indispensable for treatment decision making in older patients. Future prognostic tools for breast cancer prognosis should incorporate these items as well as risk of toxicity of adjuvant chemotherapy to adequately predict outcomes to optimize personalized treatment for older patients with early breast cancer.

PMID: 30606886 [PubMed - as supplied by publisher]

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T-Cell Lymphopenia in Patients with Advanced Thyroid Carcinoma Is Associated with Poor Prognosis.

T-Cell Lymphopenia in Patients with Advanced Thyroid Carcinoma Is Associated with Poor Prognosis.

Oncologist. 2019 Jan 03;:

Authors: Rabold K, Gielen PR, Kers-Rebel ED, Netea MG, Smit JWA, Adema GJ, Netea-Maier RT

Abstract
BACKGROUND: Aggressive forms of thyroid carcinoma (TC) show an abundant infiltration of immune cells, and this correlates with prognosis. However, little is known about circulating immune cell levels in advanced TC.
OBJECTIVE: Investigate T-cell and myeloid-derived suppressor cell (MDSC) levels in peripheral blood of patients with advanced TC and correlate them with survival.
METHODS: T cells and MDSCs were quantified by flow cytometry in peripheral blood from nine patients with advanced TC and nine healthy volunteers.
RESULTS: No significant differences in MDSC or regulatory T-cell levels were detected between patients with TC and healthy controls. CD3, CD4, and CD8 T-cell levels were significantly lower in patients with TC. CD3 and CD4 T-cell levels further decreased in patients with survival of less than 1 month.
CONCLUSION: These data suggest that T-cell lymphopenia in patients with TC indicates an aggressive tumor behavior and might influence therapeutic choices in the future. Restoring T-cell levels may become a potential therapeutic option within the multitarget approaches.

PMID: 30606882 [PubMed - as supplied by publisher]

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Methylation of the first exon in the erythropoietin receptor gene does not correlate with its mRNA and protein level in cancer cells.

Methylation of the first exon in the erythropoietin receptor gene does not correlate with its mRNA and protein level in cancer cells.

BMC Genet. 2019 Jan 03;20(1):1

Authors: Fecková B, Kimáková P, Ilkovičová L, Szentpéteriová E, Macejová M, Košuth J, Zulli A, Debeljak N, Hudler P, Jašek K, Kašubová I, Kubatka P, Solár P

Abstract
BACKGROUND: Erythropoietin receptor (EPOR) is a functional membrane-bound cytokine receptor. Erythropoietin (EPO) represents an important hematopoietic factor for production, maturation and differentiation of erythroid progenitors. In non-hematopoietic tissue, EPO/EPOR signalization could also play cytoprotective and anti-apoptotic role. Several studies identified pro-stimulating EPO/EPOR effects in tumor cells; however, numerous studies opposed this fact due to the usage of unspecific EPOR antibodies and thus potential absence or very low levels of EPOR in tumor cells. It seems that this problem is more complex and therefore we have decided to focus on EPOR expression at several levels such as the role of methylation in the regulation of EPOR expression, identification of possible EPOR transcripts and the presence of EPOR protein in selected tumor cells.
METHODS: Methylation status was analysed by bisulfite conversion reaction, PCR and sequencing. The expression of EPOR was monitored by quantitative RT-PCR and western blot analysis.
RESULTS: In this study we investigated the methylation status of exon 1 of EPOR gene in selected human cancer cell lines. Our results indicated that CpGs methylation in exon 1 do not play a significant role in the regulation of EPOR transcription. However, methylation status of EPOR exon 1 was cell type dependent. We also observed the existence of two EPOR splice variants in human ovarian adenocarcinoma cell line - A2780 and confirmed the expression of EPOR protein in these cells using specific A82 anti-EPOR antibody.
CONCLUSION: We outlined the methylation status of all selected cancer cell lines in exon 1 of EPOR gene and these results could benefit future investigations. Moreover, A82 antibody confirmed our previous results demonstrating the presence of functional EPOR in human ovarian adenocarcinoma A2780 cells.

PMID: 30606107 [PubMed - in process]

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Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer.

Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer.

Acta Oncol. 2019 Jan 03;:1-12

Authors: Wendt C, Margolin S

Abstract
INTRODUCTION: Heritage is the most important risk factor for breast cancer. About 15-20% of breast cancer is familial, referring to affected women who have one or more first- or second-degree relatives with the disease. The heritable component in these families is substantial, especially in families with aggregation of breast cancer with low age at onset. Identifying breast cancer susceptibility genes: Since the discovery of the highly penetrant autosomal dominant susceptibility genes BRCA1 and BRCA2 in the 1990s, several more breast cancer genes that confer a moderate to high risk of breast cancer have been identified. Furthermore, during the last decade, advances in genomic technologies have led to large scale genotyping in genome-wide association studies that have identified a considerable amount of common low penetrance loci. In total, the high risk genes, BRCA1, BRCA2, TP53, STK11, CD1 and PTEN account for approximately 20% of the familial risk. Moderate risk variants account for up to 5% of the inherited familial risk. The more than 180 identified low-risk loci explain 18% of the familial risk. Altogether more than half of the genetic background in familial breast cancer remains unclear. Other genes and low risk loci that explain a part the remaining fraction will probably be identified. Clinical aspects and future perspectives: Definitive clinical recommendations can be drawn only for carriers of germline variants in a limited number of high and moderate risk genes for which an association with breast cancer has been established. Future progress in evaluating previously identified breast cancer candidate variants and low risk loci as well as exploring new ones can play an important role in improving individual risk prediction in familial breast cancer.

PMID: 30606073 [PubMed - as supplied by publisher]

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[Application and prospect of artificial intelligence in cancer diagnosis and treatment].

[Application and prospect of artificial intelligence in cancer diagnosis and treatment].

Zhonghua Zhong Liu Za Zhi. 2018 Dec 23;40(12):881-884

Authors: Shen TL, Fu XL

Abstract
Artificial intelligence is a man-made device that simulates intellectual work such as human thinking and judgment. There are many successful applications of artificial intelligence in the fields of medicine, healthcare, agriculture, education, finance, service, news and machinery. Intelligent computer hospital management systems, intelligent medical diagnostic expert systems and intelligent surgical robots have revolutionized the medical field. Therefore, the attentions which are paid to artificial intelligence in cancer diagnosis and cancer treatment are on the rise. Some breakthroughs have also been made in the application of imaging diagnosis, pathological diagnosis, oncology surgery, oncology radiotherapy, drug development and cancer screening. Artificial intelligence is gradually changing the traditional medical model, which is a future direction and trend of human medical development. Here, we delineate the concept and development of artificial intelligence, and its application and prospect in the diagnosis and treatment of malignant tumors.

PMID: 30605975 [PubMed - in process]

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Editorial Board

Publication date: 15 March 2019

Source: Behavioural Brain Research, Volume 360

Author(s):

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Pulmonary Sarcoidosis: A Pictorial Review

Publication date: Available online 4 January 2019

Source: Seminars in Ultrasound, CT and MRI

Author(s): Arya M. Iranmanesh, Lacey Washington

Abstract

Sarcoidosis is a multisystem granulomatous process that most commonly involves the lungs. Radiographic findings consistent with sarcoidosis are important to the diagnosis of this disease, as no specific diagnostic test for sarcoidosis exists. The classic imaging manifestations of sarcoidosis are related to granulomatous involvement along the lymphatic pathways within the lungs, granulomatous involvement of lymph nodes, and fibrosis at the sites of previous inflammation. These findings sometimes take atypical forms. Additional manifestations of sarcoidosis are caused by involvement of the bronchi and bronchioles, the pulmonary arteries, and the heart. Fungal colonization may also occur. A range of thoracic imaging manifestations of sarcoidosis is illustrated to facilitate the diagnosis of this common, multifaceted disease.

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