Relationship of histologic grade and histologic subtype with oncotype Dx recurrence score; retrospective review of 863 breast cancer oncotype Dx results

Abstract

Purpose

Oncotype Dx (ODx) is a multigene assay that is prognostic and predictive in estrogen receptor (ER) positive early breast cancer. ODx recurrence score (RS) is reported to be histologic grade dependent. Relationship of RS with breast cancer histologic subtypes is unknown. This study was designed to assess the relationship of histologic subtype with RS. Histologic grade dependence of RS was also investigated.

Methods

Results of consecutive ODx tests (1/2007–7/2016) from two institutions were reviewed. Histologic subtypes (in: Lakhani et al., WHO classification, IARC Press, Lyon, 2012), combined Nottingham histologic grade, age and tumor size were recorded from pathology reports. Univariate and multivariate analysis was performed to investigate the relationship between RS and ODx risk categories and histologic subtypes, grade, age and tumor size.

Results

RS was grade dependent. RS of grade 1 and grade 2 tumors were significantly lower than grade 3 tumors. There was no high-risk grade 1 tumor. In favorable histologic subtypes there was no high-risk tumor. Mean RS of grade 1 lobular tumors was significantly higher than grade 1 ductal tumors. Using newer ODx cut-offs, 5 grade 1 tumors were reclassified as high risk (RS > 25) and grade 3 lobular tumors showed significantly higher rate of reclassification as high-risk than grade 3 ductal tumors. In a multivariate analysis, only grade showed a significant positive correlation with RS. Adding dichotomous histologic subtyping (favorable vs. non-favorable) to grade further improved correlation with RS.

Conclusions

The Oncotype Dx result is impacted by histologic grade and histologic subtype. Tumors with favorable histologic subtypes and histologic grade 1 tumors do not have high-risk RS. High RS in a grade 1 tumor or in a tumor with favorable histology is unusual that warrants further investigation. Invasive lobular carcinomas rarely show high-risk RS. Histologic grade and histologic subtype should be considered while ordering ODx testing.

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Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy

Abstract

Purpose

Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study.

Methods

We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters.

Results

Low levels of percent rhythm (HR:2.59, 95% CI 1.50–4.72), double amplitude (HR:2.70, 95% CI 1.51–4.85), and mesor (HR: 2.48, 95% CI 1.44–4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02–5.69) and double amplitude (HR:2.49, 95% CI 1.05–5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant.

Conclusions

This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

http://ift.tt/2B9qMRb

A case of long-survival insulinoma with multiple neuroendocline tumour type 1 controlled by multimodal therapy

Abstract

Insulinomas with multiple neuroendocrine tumour type 1 (MEN1) sometimes have metachronous or recurrent tumours. However, the treatment for these tumours is controversial, and published reports regarding multimodal therapy for insulinomas are limited. We report a 73-year-old woman with recurrent insulinoma with MEN1 successfully controlled by multimodal therapy. She had several complications, and poor performance status. Her hypoglycaemia did not improve after 6-month octreotide LAR; as such, she underwent enucleation of the pancreatic tumour. Within 7 years after the first operation, she underwent four succeeding surgeries for recurrent tumours. Her medications during follow-up were octreotide-LAR and Everolimus. Insulinoma can be managed through various treatment options. Medical treatment includes octreotide-LAR and Everolimus, while surgical approach includes enucleation and pancreaticoduodenectomy. Some tumours, particularly those that are MEN1, can recur repeatedly. Thus, several treatments are needed to control them. We highlight the importance of multimodal therapy, including repeated surgery, for the control of the disease.

http://ift.tt/2ByDCZR

Functional outcome after hand replantation in Guatemala

Abstract

Amputations of a traumatic origin are very frequent in developing countries, in the case of Guatemala these are a result of work accidents very closely related to poor work conditions existing for manual workers, as well as social violence and the lack of security that governs society. The present case shows a patient that suffered a left hand amputation at wrist level. Amputated hand was transported swiftly and in adequate conditions, maintaining cold chain at all times until arrival at Hospital for replantation. After 14 months, patient has evolved satisfactorily and obtained functional result of the hand.

http://ift.tt/2B2o9QT

Histoplasmosis hepatitis after orthotopic liver transplantation

Abstract

Histoplasmosis is an endemic mycosis in the Ohio and Mississippi River valleys and can cause disseminated infection in immunocompromised hosts. Disseminated histoplasmosis is often respiratory in nature and most cases in transplant patients occur within 2 years post-transplantation. A 32-year-old male on mycophenolate and tacrolimus who underwent an orthotopic liver transplantation 10 years prior presented with generalized body aches, fevers, mild congestion, dysuria and elevated transaminases. Liver biopsy revealed epithelioid granulomas with narrow-based budding yeast, suggesting histoplasma. Liver involvement in disseminated histoplasmosis is well characterized however the disease is usually pulmonary in origin. Only three other case reports describe isolated granulomatous hepatitis, and this is the first to our knowledge to occur in a liver transplant allograft. A high index of suspicion is essential for diagnosis and prompt treatment of histoplasmosis in transplant patients considering their immunocompromised state.

http://ift.tt/2BytGQ7

Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors

Abstract

Purpose

This project was undertaken to examine the association between dietary intake of soy or cruciferous vegetables and breast cancer treatment-related symptoms among Chinese-American (CA) and Non-Hispanic White (NHW) breast cancer survivors.

Methods

This cross-sectional study included 192 CA and 173 NHW female breast cancer survivors (stages 0–III, diagnosed between 2006 and 2012) recruited from two California cancer registries, who had completed primary treatment. Patient-reported data on treatment-related symptoms and potential covariates were collected via telephone interviews. Dietary data were ascertained by mailed questionnaires. The outcomes evaluated were menopausal symptoms (hot flashes, night sweats, vaginal dryness, vaginal discharge), joint problems, fatigue, hair thinning/loss, and memory problems. Associations between soy and cruciferous vegetables and symptoms were assessed using logistic regression. Analyses were further stratified by race/ethnicity and endocrine therapy usage (non-user, tamoxifen, aromatase inhibitors).

Results

Soy food and cruciferous vegetable intake ranged from no intake to 431 and 865 g/day, respectively, and was higher in CA survivors. Higher soy food intake was associated with lower odds of menopausal symptoms (≥ 24.0 vs. 0 g/day, OR 0.51, 95% CI 0.25, 1.03), and fatigue (≥ 24.0 vs. 0 g/day, OR 0.43, 95% CI 0.22, 0.84). However, when stratified by race/ethnicity, associations were statistically significant in NHW survivors only. Compared with low intake, higher cruciferous vegetable intake was associated with lower odds of experiencing menopausal symptoms (≥ 70.8 vs. < 33.0 g/day, OR 0.50, 95% CI 0.25, 0.97) in the overall population.

Conclusions

In this population of breast cancer survivors, higher soy and cruciferous vegetable intake was associated with less treatment-related menopausal symptoms and fatigue.

http://ift.tt/2ydIP3d

Internal herniation through lesser omentum hiatus and gastrocolic ligament with malrotation: a case report

Internal herniation through lesser omentum hiatus and gastrocolic ligament with malrotation is extremely rare. This type of internal hernia has rarely been described before. Preoperative diagnosis is difficult...

http://ift.tt/2BUTAJT

A review of the value of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): N.A. Nixon, M.B. Hannouf, S. Verma
The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the survival benefits gained by new treatments have been undeniably substantial. It is important to assess the financial value of these therapies for decision making at both the societal and individual level. This information is key for managing resources in resource-limited health care systems, while at the same time supporting patient decision-making and conversations between patient and physicians on cost versus benefit. In this article, we perform a systematic review of cost-effectiveness analyses that have been completed to date on HER2-targeted agents, focussing on those that correlate with standard of care therapy. Our discussion also highlights potential strategies to overcome several limitations associated with measuring value for anticancer drugs.



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Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

Large B-cell lymphomas, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma, are treated with combination chemoimmunotherapy at diagnosis. Patients who have a relapse with chemotherapy-sensitive disease may be treated with high-dose…

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A Milestone for CAR T Cells

More than 7 years have passed since the regression of advanced lymphoma was first reported in a patient who had undergone the infusion of T cells engineered to express a chimeric antigen receptor (CAR) targeting the CD19 antigen expressed on the surface of both normal and malignant B cells.…

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Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

Diffuse large B-cell lymphoma, the most common non-Hodgkin's lymphoma, is successfully treated in about two thirds of patients with rituximab-based immunochemotherapy. When current frontline immunochemotherapy fails, high-dose chemotherapy with autologous stem-cell transplantation can lead to…

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A Milestone for CAR T Cells

More than 7 years have passed since the regression of advanced lymphoma was first reported in a patient who had undergone the infusion of T cells engineered to express a chimeric antigen receptor (CAR) targeting the CD19 antigen expressed on the surface of both normal and malignant B cells.…

http://ift.tt/2yWsX8S

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

Large B-cell lymphomas, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma, are treated with combination chemoimmunotherapy at diagnosis. Patients who have a relapse with chemotherapy-sensitive disease may be treated with high-dose…

http://ift.tt/2yVYck9

Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

Diffuse large B-cell lymphoma, the most common non-Hodgkin's lymphoma, is successfully treated in about two thirds of patients with rituximab-based immunochemotherapy. When current frontline immunochemotherapy fails, high-dose chemotherapy with autologous stem-cell transplantation can lead to…

http://ift.tt/2ycc1ra

A Milestone for CAR T Cells

More than 7 years have passed since the regression of advanced lymphoma was first reported in a patient who had undergone the infusion of T cells engineered to express a chimeric antigen receptor (CAR) targeting the CD19 antigen expressed on the surface of both normal and malignant B cells.…

http://ift.tt/2yWsX8S

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

Large B-cell lymphomas, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma, are treated with combination chemoimmunotherapy at diagnosis. Patients who have a relapse with chemotherapy-sensitive disease may be treated with high-dose…

http://ift.tt/2yVYck9

Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

Diffuse large B-cell lymphoma, the most common non-Hodgkin's lymphoma, is successfully treated in about two thirds of patients with rituximab-based immunochemotherapy. When current frontline immunochemotherapy fails, high-dose chemotherapy with autologous stem-cell transplantation can lead to…

http://ift.tt/2ycc1ra

[Fertility preservation in oncology].

Related Articles

[Fertility preservation in oncology].

Bull Cancer. 2017 Dec 05;:

Authors: Chaput L, Grémeau AS, Vorilhon S, Pons H, Chabrot C, Grèze V, Pouly JL, Brugnon F

Abstract
Since the improvement of cancer diagnosis and treatment, survival rates of these patients increase. Gonadal damages are frequent consequences of cancer treatments with different evidence of impaired fertility. In this context, fertility preservation should be proposed to patients exposed to potentially gonadotoxic treatments. Different preservation approaches may be proposed depending on patient age, sex, cancer type and type of treatment. The indications of fertility preservation depend on sexual maturity. In young girls, ovarian cortex cryopreservation is the only technique feasible in order to preserve their reproductive potential. Vitrification of oocytes which needs ovarian stimulation or oocytes in vitro maturation is becoming more commonly performed for pubertal women to preserve their fertility. Ovarian cortex freezing could be offered to emergency fertility preservation of adult female cancer patients. In prepubertal boys, testicular tissue cryopreservation is the only line treatment for fertility preservation. For future use, various approaches are being evaluated such as spermatogonial stem cell injection or in vitro maturation. Cryopreservation of spermatozoa is, today, an established and successful technique for male adults. When there are no spermatozoa in ejaculate, sperm can be retrieved after treatment of testicular biopsy. The French bioethics law clearly indicates that fertility preservation should be proposed to patients exposed to potentially gonadotoxic treatment. Today, many approaches are possible. Fertility preservation indications are based on multidisciplinary consultations within platforms for the fertility preservation in order to optimize the patient care.

PMID: 29221621 [PubMed - as supplied by publisher]

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[Nomograms in routine clinical practice: Methodology, interest and limitations].

Related Articles

[Nomograms in routine clinical practice: Methodology, interest and limitations].

Bull Cancer. 2017 Dec 05;:

Authors: Filleron T, Chaltiel L, Jouve E, Cabarrou B, Gilhodes J, Lusque A, Mery E, Dalenc F, Martinez A

Abstract
In order to help the clinician, mathematical models including several clinical and pathological variables are proposed in the literature with the aim to predict the occurrence of an event of interest. Nomograms allow individual prognosis for each patient. When they are developed, validated and correctly used, nomograms can provide important information for patients' care. But, despite the strong interest in nomograms in oncology, statistical methodologies used remain unknown from the medical community. This paper presents the major steps in the development, the validation and the clinical use of nomograms. Examples are given to illustrate these different points and the limits of this methodology. Finally, guidelines on the use of nomograms are proposed for clinicians.

PMID: 29221620 [PubMed - as supplied by publisher]

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Discussion on Raposo et al

Publication date: Available online 23 November 2017
Source:Seminars in Oncology
Author(s): Chand Khanna




http://ift.tt/2AbJVhq

Mind the Graph. Foregone Health Gains in Lung Cancer

Publication date: Available online 6 December 2017
Source:Seminars in Oncology
Author(s): Laird Cameron, Richard Sullivan, Brendan Luey, Ben Solomon




http://ift.tt/2AHIvwj

Newcastle Disease Virus (NDV) co-expressing IL7 and IL15 modified tumor cells as a vaccine for cancer immunotherapy

Abstract

IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro. Then, the antitumor effects of tumor vaccine modified with recombinant virus were tested in the murine tumor models. We observed strong antitumor responses induced by LX/IL(15+7)-modified tumor cells both in prophylaxis and therapeutic models. Although the tumor-infiltrating CD4⁺ T cells and CD8⁺ T cells were both increased, the antitumor activity of the tumor vaccine modified with LX/IL(15+7) was dependent on CD8⁺ T cells. Taken together, our data strongly indicated that tumor vaccine modified with NDV strain LX/IL(15+7) is a promising agent for cancer immunotherapy.

This article is protected by copyright. All rights reserved.

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Regulation of c-MYC transcriptional activity by transforming growth factor-beta 1-stimulated clone 22

Abstract

C-MYC stimulates cell proliferation through the suppression of cyclin-dependent kinase (CDK) inhibitors including P15 (CDKN2B) and P21 (CDKN1A). It also activates E-box-mediated transcription of various target genes including telomerase reverse transcriptase (TERT) that is involved in cellular immortality and tumorigenesis. Transforming growth factor-beta 1 (TGF-β1)-stimulated clone 22 (TSC-22/TSC22D1) encodes a highly conserved leucine zipper protein that is induced by various stimuli, including TGF-β. TSC-22 inhibits cell growth in mammalian cells and in Xenopus embryos. However, underlying mechanisms of growth inhibition by TSC-22 remain unclear. Here, we show that TSC-22 physically interacts with c-MYC to inhibit the recruitment of c-MYC on the P15 (CDKN2B) and P21 (CDKN1A) promoters, effectively inhibiting c-MYC-mediated suppression of P15 (CDKN2B) and also P21 (CDKN1A) promoter activities. On the other hand, TSC-22 enhances c-MYC-mediated activation of the TERT promoter. Additionally, the expression of TSC-22 in embryonic stem cells inhibits cell growth without affecting its pluripotency-related gene expression. These results indicate that TSC-22 differentially regulates c-MYC-mediated transcriptional activity to regulate cell proliferation.

This article is protected by copyright. All rights reserved.

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Down-regulation of 15-PGDH by interleukin-1 beta from activated macrophages leads to poor prognosis in pancreatic cancer

Abstract

Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE₂). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC. Here, we showed that interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, down-regulates 15-PGDH expression in PDAC cells and that IL-1β expression was inversely correlated with 15-PGDH levels in frozen PDAC tissues. We also found that activated macrophages produced IL-1β and reduced 15-PGDH expression in PDAC cells. Furthermore, the number of CD163-positive tumor-associated macrophages (TAMs) was shown to be inversely correlated with 15-PGDH levels in PDAC cells by immunohistochemical staining of 107 PDAC samples. Finally, we demonstrated that low 15-PGDH expression was significantly associated with advanced tumors, presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC patients. Our results indicate that IL-1β derived from TAMs suppresses 15-PGDH expression in PDAC cells, resulting in poor prognosis of PDAC patients.

This article is protected by copyright. All rights reserved.

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via IFTTT

Newcastle Disease Virus (NDV) co-expressing IL7 and IL15 modified tumor cells as a vaccine for cancer immunotherapy

Abstract

IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro. Then, the antitumor effects of tumor vaccine modified with recombinant virus were tested in the murine tumor models. We observed strong antitumor responses induced by LX/IL(15+7)-modified tumor cells both in prophylaxis and therapeutic models. Although the tumor-infiltrating CD4⁺ T cells and CD8⁺ T cells were both increased, the antitumor activity of the tumor vaccine modified with LX/IL(15+7) was dependent on CD8⁺ T cells. Taken together, our data strongly indicated that tumor vaccine modified with NDV strain LX/IL(15+7) is a promising agent for cancer immunotherapy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2kgOOiy

Regulation of c-MYC transcriptional activity by transforming growth factor-beta 1-stimulated clone 22

Abstract

C-MYC stimulates cell proliferation through the suppression of cyclin-dependent kinase (CDK) inhibitors including P15 (CDKN2B) and P21 (CDKN1A). It also activates E-box-mediated transcription of various target genes including telomerase reverse transcriptase (TERT) that is involved in cellular immortality and tumorigenesis. Transforming growth factor-beta 1 (TGF-β1)-stimulated clone 22 (TSC-22/TSC22D1) encodes a highly conserved leucine zipper protein that is induced by various stimuli, including TGF-β. TSC-22 inhibits cell growth in mammalian cells and in Xenopus embryos. However, underlying mechanisms of growth inhibition by TSC-22 remain unclear. Here, we show that TSC-22 physically interacts with c-MYC to inhibit the recruitment of c-MYC on the P15 (CDKN2B) and P21 (CDKN1A) promoters, effectively inhibiting c-MYC-mediated suppression of P15 (CDKN2B) and also P21 (CDKN1A) promoter activities. On the other hand, TSC-22 enhances c-MYC-mediated activation of the TERT promoter. Additionally, the expression of TSC-22 in embryonic stem cells inhibits cell growth without affecting its pluripotency-related gene expression. These results indicate that TSC-22 differentially regulates c-MYC-mediated transcriptional activity to regulate cell proliferation.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jEbwSc

Down-regulation of 15-PGDH by interleukin-1 beta from activated macrophages leads to poor prognosis in pancreatic cancer

Abstract

Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE₂). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC. Here, we showed that interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, down-regulates 15-PGDH expression in PDAC cells and that IL-1β expression was inversely correlated with 15-PGDH levels in frozen PDAC tissues. We also found that activated macrophages produced IL-1β and reduced 15-PGDH expression in PDAC cells. Furthermore, the number of CD163-positive tumor-associated macrophages (TAMs) was shown to be inversely correlated with 15-PGDH levels in PDAC cells by immunohistochemical staining of 107 PDAC samples. Finally, we demonstrated that low 15-PGDH expression was significantly associated with advanced tumors, presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC patients. Our results indicate that IL-1β derived from TAMs suppresses 15-PGDH expression in PDAC cells, resulting in poor prognosis of PDAC patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2khuKwJ