choices - easy ways to follow: Ovarian Cancer and Us (blog)

Ovarian Cancer and Us (note: click on blog sidebar)

open access: Identifying Needs: a Qualitative Study of women’s Experiences Regarding Rapid Genetic Testing for HBOC (DNA BONus Study)

open access
Identifying Needs: a Qualitative Study of women’s Experiences Regarding Rapid Genetic Testing for Hereditary Breast and Ovarian Cancer in the DNA BONus Study 

 Results (3 key themes):

• Being “beside oneself” (eg. shock)

• Altruism and Ethical Dilemmas

•  The Need for Support and Counselling to Assist the Decision Process

   

   ...Many of the women described themselves as emotionally and mentally overloaded after their diagnosis. Being stricken by a severe disease is tough....

   ....The women’s acceptance of genetic testing was primarily motivated by the prospect of protecting their children, and particularly their daughters. This altruistic attitude is known from Hallowell’s study (Hallowell et al. 2003), which found that most women previously diagnosed with breast or ovarian cancer generated genetic information for the benefit of others.....

  
  
  

Incidence of Lymph Node Metastases in Apparent Early-Stage Low Grade Epithelial Ovarian Cancer (Review)

abstract
 Incidence of Lymph Node Metastases in Apparent Early-Stage Low-Grade Epithelial Ovarian Cancer: A Comprehensive Review.
 

Objectives: This study aimed to determine the incidence of lymph node (LN) metastases in presumed stage I-II low-grade epithelial ovarian cancer (EOC).

Methods: Eligible studies were identified from MEDLINE and EMBASE (time frame, 2015-1975), that analyzed patients with clinical or radiologic presumed early-stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as part of their surgical staging. The number and site of dissected and involved LNs and the correlation with overall outcome are analyzed. The term low grade and also the older term well differentiated were used.

Results: Thirteen of 978 identified studies were selected, and 13 of 75 studies were identified as eligible. A total of 1403 patients were analyzed in these 13 retrospective studies. The final International Federation of Gynecology and Obstetrics staging after completed surgical staging was I to II in 912 patients (65%). A total of 338 patients (24%) had grade 1 tumors whereas 473 patients (34%) had grade 2, and 502 patients (36%) had grade 3 tumors. Systematic lymphadenectomy was performed in 1159 patients (83%), whereof 1142 (82%) were pelvic and para-aortic LN dissections.

In 185 patients (13%), an upstaging from an apparent clinical stage I-II to IIIC occurred because of LN involvement: 64 (35%) of the patients had only pelvic LNs metastases, 69 (37%) had only para-aortic LNs metastasis, and 51 (28%) had both a pelvic and para-aortic LN involvement. When analyzing only the patients with low-grade (grade 1 as the old classification) presumed early-stage disease (n = 273), only 8 patients (2.9%; range, 0-6.2) were identified with LNs metastases present.

Conclusions: The incidence of occult LN metastases in apparent early-stage low-grade EOC is 2.9% in a metaanalysis of retrospective studies. Future larger-scale prospectively assessed studies with established surgical quality of the LN dissection are warranted to establish the true incidence of LN metastasis in presumed early low-grade disease.

Two Oxford research discoveries offer hope for managing ovarian cancer (Premalignant SOX2)

medical news

Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

open access
 

Highlights

• •
  Dense sequencing of an ovarian cancer identifies founder non-coding mutations .
• •
  Fallopian tube SOX2 overexpression is a common premalignant feature in ovarian cancer .
• •
  The expression of SOX2 and MYC in the fallopian tube appears mutually exclusive .
  
  

  In summary, in this study we demonstrated that SOX2 overexpression occurs in a fraction of women with BRCA1 and BRCA2 mutations prior to ovarian cancer initiation and in the majority of patients with HGSOCs irrespective of tumor stage. These findings could be exploited for filling the current gap in early detection strategies for ovarian cancer. We believe that this is the first report of the expansion of SOX2-expressing cells in the FTE of HGSOCs. This finding has important implications, as it provides a potentially powerful tool for screening for HGSOCs. Utilizing our findings as potential biomarker should take high priority.

Article Outline

1. 1. Introduction
2. 2. Materials and Methods
   1. 2.1. Overall Description of the Study Design
   2. 2.2. Translational Studies
      1. 2.2.1. Ethical Approval
      2. 2.2.2. Clinical History and Sample Collection of Patient 11152
      3. 2.2.3. Precautions for Tissue Handling to Diminish the Risk of Cross Contamination of DNA
      4. 2.2.4. Section Processing for Laser Capture Microdissection
      5. 2.2.5. Macrodissection of FTE
   3. 2.3. DNA Extraction
   4. 2.4. Sequencing
      1. 2.4.1. Targeted Sequencing
      2. 2.4.2. Sanger Sequencing
      3. 2.4.3. Digital Droplet PCR
   5. 2.5. Sequencing Analysis
      1. 2.5.1. Whole Genome Sequencing
      2. 2.5.2. Performing Gene Ontology Enrichment Analysis
      3. 2.5.3. Analysis of Targeted Sequencing Data
      4. 2.5.4. Analysis of ChIP-sequence Tracks
      5. 2.5.5. Motif Analysis for the BB5 Variant
   6. 2.6. Fallopian Tubes Primary Epithelial Cell Culture
   7. 2.7. Viral Transduction
   8. 2.8. Cloning, Mutant Generation and Chicken Embryo Transfection
   9. 2.9. Chromatin Immunoprecipitation (ChIP) Assay
   10. 2.10. CRISPR Vector Construction, Cell Culture and Transfection
   11. 2.11. Immunofluorescence
   12. 2.12. Immunohistochemistry
3. 3. Results
   1. 3.1. Laparoscopy-guided Prospective Multi-region Sampling in an Ovarian Cancer Patient
   2. 3.2. Non-coding Mutations Cluster at Potential cis Regulatory Elements of Genetic Drivers of Stem Cell Differentiation
   3. 3.3. The BB5 Mutation Occurred at the Pre-neoplastic Lesion of the Tumor and Marked a Region That Was Frequently Mutated in HGSOCs
   4. 3.4. Expansion of FTE Cells Strongly Expressing SOX2 is a Feature of HGSOCs
   5. 3.5. The BB5 Region Is a Repressor of SOX2 Expression
4. 4. Discussion
5. Funding Sources
6. Conflicts of Interests
7. Contributions
8. References

Cancer drug related cardiotoxicity during breast cancer treatment + related ovarian cancer paper (Dr Yi Pan)

abstract

 Expert opinion: Despite the large number of data from Phase III trials about cardiac events incidence, there are poor evidences for detection, monitoring and management of cardiotoxicity during BC treatment. Future cardiotoxicity-oriented clinical cancer research can help to predict the risk of cardiac adverse events and improve patients’ outcome. Multidisciplinary approach as well as integration of blood biomarkers with imaging will be desirable.

• Cardiovascular Toxicity of Bevacizumab in Long-term Survival of Recurrent Ovarian Cancer: A Case Report Yi Pan (2016)
  

Class Action Lawsuit Against HPV Vaccine Filed in Japan (Gardasil & Cervarix)

Medscape

Genomics in Clinical Practice: Expect the Unexpected (2nd of 3 part series)

medscape

Pragmatic Message to Junior Doctors (eg. ethics, telling the truth)

Medscape

• Abstract and Introduction
• Doctor–Patient Relationship
• Ethical Issues Facing Junior Doctors
• Telling the Truth
• Confidentiality
• Informed Consent
• Photography
• Futile Treatment
• The Consultant is a Role Model
• Conclusion

• References

JAMA Oncology: (3) Intended Target for the Centers for Disease Control (Opiod guidelines)

JAMA Oncology (not open access articles)

 

• Intended Target of the Centers for Disease Control and Prevention Opioid Guidelines-Comment 
  

•  Intended Target of the Centers for Disease Control and Prevention Opioid Guidelines—Reply   

• Editorial | July 2016 Striving for Safe, Effective, Affordable Care for Cancer Survivors With Chronic Pain Another Kind of Moonshot

Personalized and Conscientious Medical Imaging: To Image or Not to Image

JAMA Oncology Viewpoint (open access)

Busting 5 Common Myths about FDA and Women's Health

Office on Women's Health Blog (U.S.)

(patient engagement - short survey) Do you feel nervous before a hospital visit? - Sunnybrook Hospital

Sunnybrook Hospital (plus short survey)

 

What Happens When Underperforming Big Ideas in Research Become Entrenched? Viewpoint

JAMA (partial view)

This Viewpoint provides evidence for the dominance of the narrative that a combination of subcellular biology knowledge coupled with information technology will lead to improvements in health care and human health being published among biomedical funding and journal publications; discusses themes embedded in the narrative to show that this approach has failed; and proposes a reevaluation of the way forward in biomedical research.

For several decades now the biomedical research community has pursued a narrative positing that a combination of ever-deeper knowledge of subcellular biology, especially genetics, coupled with information technology will lead to transformative improvements in health care and human health. In this Viewpoint, we provide evidence for the extraordinary dominance of this narrative in biomedical funding and journal publications; discuss several prominent themes embedded in the narrative to show that this approach has largely failed; and propose a wholesale reevaluation of the way forward in biomedical research.

First Page Preview

View Large

Validating a standardized laparoscopy curriculum for gynecology residents: a randomized controlled trial

abstract

Conclusion

Participation in a comprehensive simulation-based training curriculum for gynecologic laparoscopy leads to a superior improvement in knowledge and technical performance in the operating room compared with conventional residency training.

Host response to synthetic mesh in women with mesh complications

abstract

Conclusion

In women with complications, mesh induces a proinflammatory response that persists years after implantation. The increase in MMP-9 in mesh explants that were removed for exposure indicates degradation; the positive association between interleukin-10 and M2 macrophages in mesh explants that are removed for pain is consistent with fibrosis.

Staging for low malignant potential ovarian tumors: a global perspective

abstract
 

Objective

We describe current evidence for staging low malignant potential ovarian tumors and their conformity to current consensus guidelines and practice from an international perspective.

Data Sources

A search of MEDLINE, EMBASE, and SCOPUS databases was conducted for articles published between January 1990 and April 2015.

Study Eligibility Criteria

Studies on low malignant potential ovarian tumors that evaluated the prognostic value of disease stage, staging vs no staging, complete vs incomplete staging, or discrete components of staging were eligible. Studies that described only crude survival rates were excluded.

Study Appraisal and Synthesis Methods

Eligible studies were categorized according to their outcome (disease stage, staging procedure, or discrete staging elements). Data were abstracted using a standard form. Inconsistencies on data abstraction were resolved by consensus among the authors. Risk of bias was assessed using the Newcastle-Ottawa Scale.

Results

Of 1116 studies, 702 were excluded for irrelevance and 364 for not meeting inclusion criteria. Nine studies were excluded for describing crude survival rates without a comparative conclusion. We found that studies supporting the value of defining disease stage or staging procedures (mostly conducted in northern Europe) included more patients than studies that did not find disease stage or staging useful (predominantly from North America, 4072 vs 3951). Disease stage correlated with survival in 13 of 25 studies, whereas none of the studies that evaluated the value of staging found it beneficial (9 studies, 1979 patients). Studies that evaluated isolated components of staging found no benefit to these procedures. Regional guidelines and consensus reviews drew conclusions based on a limited number of studies that generally originated from the same region.

Conclusions

Although the correlation of stage with survival was mixed, performing staging procedures for low malignant potential ovarian tumors is not supported by the best available evidence. Guidelines in support of staging based their recommendations on a few regional studies and conflict with better-quality data that do not support staging procedures. An international consensus statement is needed to standardize the surgical management of low malignant potential ovarian tumors.

Genetic profiling increases cancer treatment options, Sanford Health study finds

Medical News 

Optimizing Genotype Matched Clinical Trial (GMCT) accrual in a community oncology program (COP) - solid tumors

Abstracts | link ASCO

Optimizing Genotype Matched Clinical Trial (GMCT) accrual in a community oncology program (COP).

Subcategory: 

Access to Care/Care Delivery

Category: 

Health Services Research and Quality of Care

Meeting: 

2016 ASCO Annual Meeting

Session Type and Session Title: 

This abstract will not be presented at the 2016 ASCO Annual Meeting but has been published in conjunction with the meeting.

Abstract Number: 

e18036

Citation: 

J Clin Oncol 34, 2016 (suppl; abstr e18036)

Author(s): 

Steven Francis Powell, Elie G. Dib, Jonathan Scott Bleeker, Michael D. Keppen, Miroslaw Mazurczak, Keely Marie Hack, Mark Mutuota Gitau, Preston D. Steen, Shelby A. Terstriep, John Reynolds, Jayan Nair, Megan L Landsverk, Chun-Hung Chan, Paul A. Thompson, Christie Ellison, Lora Jane Black, James M. Ford, Anu G. Gaba; Sanford Health, Sioux Falls, SD; Sanford Health, Roger Maris Cancer Center, Fargo, ND; Roger Maris Cancer Center, Fargo, ND; Sanford Roger Maris Cancer Center, Fargo, ND; Sanford Health, Bismarck, ND; Sanford Health, Bemidji, MN; Stanford University School of Medicine, Stanford, CA; Sanford Health, Fargo, ND

Abstract Disclosures

Abstract: 

Background: While molecular profiling (MP) is becoming widely accessible, clinician understanding may be a barrier to GMCT enrollment. MP programs at academic medical centers report GMCT enrollment rates at 5-17% of eligible patients. To advance precision medicine, this process must be adapted to serve COPs.  
Methods: We performed a prospective MP study (NCT02416518) at Sanford Health, a predominantly rural health care system with 4 participating COP sites. The primary outcome of the study was feasibility of testing in this setting. Secondary outcomes included correlating GMCT enrollment, impact on treatment decisions, and patient outcomes. Eligible patients included those with incurable solid tumor malignancies that had progressed on ≥ 1 prior line of therapy or had no standard first-line treatment options available, an ECOG PS of ≤ 1, adequate organ function, and recent tissue biopsy ( ≤ 14 weeks) available for MP. MP was performed using FoundationOne. A weekly, video conferenced genomic tumor board (GTB), composed of COP providers, reviewed each case for actionable alterations (AAs) and provided recommendations to the treating physician. Results: From June 2014-Dec 2015, 145 patients signed consent to participate in the prospective MP study. 120 patients were eligible for testing and 109 had reviewable MP results. Reasons for failure to complete MP included: insufficient tissue (n = 8), decline in clinical status (n = 2), and withdrawal of consent (n = 1). 99 (90.8%) of those with reviewable results had at least one AA that was felt to have a rational therapeutic option based on GTB review. Of those with an AA, 39 (39.4%) were treated based on their MP findings. 16 (16.2%) of those with an AA enrolled in GMCTs. 7 (7.1%) were treated with FDA approved on-label drug and 16 (16.2%) were treated with FDA approved off-label drug. Patient outcomes are being tracked in accordance with the corresponding GMCTs and for those treated with off-label drug.  
Conclusions: Development of a system-wide MP program in the community is feasible and can optimize accrual to GMCTs. This program will be adapted to enrich patient enrollment into rapidly emerging GMCTs available through the National Cancer Institute (NCI) and industry. Clinical trial information: NCT02416518

Strategies for Improving Surgical Care: When Is Regionalization the Right Choice?

abstract/partial view

This Viewpoint considers 3 nuances of the policy debate regarding the regionalization of high-risk surgery by restricting care to high-volume centers of excellence.

Regionalizing high-risk surgery by restricting care to high-volume centers of excellence is a quality-improvement strategy with intuitive appeal. Decades of research have shown that the highest-volume hospitals have better outcomes for major surgery.¹ Accordingly, 3 prominent medical centers—Dartmouth-Hitchcock Medical Center, Johns Hopkins Medicine, and the University of Michigan—recently announced a “volume pledge” to restrict their own facilities and surgeons from performing any of 10 selected procedures unless they meet volume criteria.^2,3 Apart from a voluntary pledge, other policy approaches to regionalization have included the refusal to reimburse low-volume facilities (as Medicare currently does for solid-organ transplants) and tiered insurance benefits (ie, reducing out-of-pocket payments at high-volume hospitals).

First Page Preview

View Large

MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib

open access
 

Conclusions

MK-2206 shows promise as a chemosensitization agent in BRCA-deficient EOC and merits clinical investigation in this patient population.

ASCO: Always screen cancer survivors for chronic pain

ASCO: Always screen cancer survivors for chronic pain

 Vitals

Key clinical point: Screen all survivors of adult cancers for chronic pain at every visit.

Major finding: An estimated 14 million adults with a history of cancer are living in the United States alone, and the prevalence of chronic pain related to their malignancy is reported to be as high as 40%.

Data source: The first ASCO clinical practice guideline for managing chronic pain in survivors of adult cancers.

Disclosures: This work was supported by ASCO. Dr. Paice reported having no relevant financial disclosures; some of her associates reported financial ties to industry.

FDA updates warning label for systemic fluoroquinolones (eg. cipro...)

FDA updates warning label for systemic fluoroquinolones

 Avelox; Cipro, both standard and extended release; Factive; Levaquin; and ofloxacin are the fluoroquinolones currently approved by the FDA for systemic use. Their active ingredients are moxifloxacin, ciprofloxacin, gemifloxacin, levofloxacin, and ofloxacin, respectively.

 As a result, health care providers should reserve systemic fluoroquinolones for patients who have no other treatment options for any of the following conditions: acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTIs). The FDA also said that, for some serious bacterial infections, the benefits of fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option.

(ureter) Template-based lymphadenectomy reduces the risk of regional lymph node recurrence among patients with upper/middle ureteral cancer

abstract:
Template-based lymphadenectomy reduces the risk of regional lymph node recurrence among patients with upper/middle ureteral cancer

Background

Our previous nonrandomized prospective study showed that template-based lymphadenectomy improved survival among patients with renal pelvic cancer but not among patients with ureteral cancer. However, regional node sites vary according to the tumor’s location in relation to the ureter. Therefore, this retrospective study examined the therapeutic role of lymphadenectomy for ureteral cancer according to tumor location.

Methods

Between January 1988 and September 2015, we performed nephroureterectomy for 154 patients with nonmetastatic urothelial carcinoma of the ureter at two Japanese institutions. The tumors’ locations were classified as the lower ureter or the upper/middle ureter (before the cranial crossing of the common iliac artery). The appropriate regional nodes were identified based on our previous mapping study. Dissection was classified as complete lymphadenectomy (all regional sites were dissected), incomplete lymphadenectomy (not all sites were dissected), or no lymphadenectomy. We focused the analyses on patients with ≥pT2 disease to clarify the effect of the lymphadenectomy.

Results

Among the 48 patients with upper/middle ureteral cancer, recurrence-free and cancer-specific survival were significantly higher in the complete lymphadenectomy group (vs. the incomplete or no lymphadenectomy groups). However, there were no differences in recurrence-free and cancer-specific survivals among the 56 patients with lower ureteral cancer. In the patients with upper/middle ureteral cancer, multivariate analysis revealed that template-based lymphadenectomy was independently associated with a reduced risk of cancer-specific mortality.

Conclusions

Template-based lymphadenectomy has a therapeutic benefit for treating patients with upper/middle ureteral cancer but not for treating patients with lower ureteral cancer.

Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with/w/o CDKN2A

abstract:
Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations 
 

The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequencing data to examine 24 putative PC-related genes in 43 PC patients with and 23 PC patients without germline CDKN2A mutations and 1001 controls. For each gene and the four pathways in which they occurred, we tested whether PC patients (overall or CDKN2A+ and CDKN2A− cases separately) had an increased number of rare nonsynonymous variants. Overall, we identified 35 missense variants in PC patients, 14 in CDKN2A+ and 21 in CDKN2A− PC cases. We found nominally significant associations for mismatch repair genes (MLH1, MSH2, MSH6, PMS2) in all PC patients and for ATM, CPA1, and PMS2 in CDKN2A− PC patients. Further, nine CDKN2A+ and four CDKN2A− PC patients had rare potentially deleterious variants in multiple PC-related genes. Loss-of-function variants were only observed in CDKN2A− PC patients, with ATM having the most pathogenic variants. Also, ATM variants (n = 5) were only observed in CDKN2A− PC patients with a family history that included digestive system tumors. Our results suggest that a subset of PC patients may have increased risk because of germline mutations in multiple PC-related genes.

Causality and chance in the origins of cancer (video)

video (7:37min)
 IARC 50th Anniversary Conference. ecancer

Dr George Davey Smith - University of Bristol, Bristol, UK

Dr Smith speaks with ecancertv at IARC 2016 about cancer causes and causality.
Addressing public perceptions of luck as a determining factor for developing cancer in the lifetime, he notes the interrelatedness of confounding factors including diet and lifestyle, which may in turn be further enhanced by genetic predispositions.

video: Germline mutations influence risk and recovery throughout life

video (6:49 min)

 IARC 50th Anniversary Conference

Dr Stephen Chanock - United States National Cancer Institute, Bethesda, USA

Dr Chanock speaks with ecancertv at IARC 2016 about increased risk of cancer passed down through heritable genetic mutations.
Weighing genomics against the influence of environmental factors, Dr Chanock discusses a patients' polygenic risk score.
Accurate scoring and stratification may not only reflect patient susceptibility to disease, but also predict which treatments would be best tolerated and overall wellbeing.

Presentation of Benefits and Harms in US Cancer Screening and Prevention Guidelines: Systematic Review

Medscape
 J Natl Cancer Inst. 2016;108(6)

 Conclusions:
Sixty-nine percent of cancer prevention and screening recommendation statements either did not quantify benefits and harms or presented them in an asymmetric manner. Improved presentation of benefits and harms in guidelines would better ensure that clinicians and patients have access to the information required for making informed decisions.

Government listing of clinical trials doesn't offer patient costs

medical news

Nov 6-8 conference notice/program Schedule - Society to Improve Diagnosis in Medicine

 
 

Program Schedule
 

Registration Now Open

Register now for the Diagnostic Error in Medicine 9th International Conference. This year we will continue to evaluate the existing knowledge and explore paths From IOM to Action. Online registration is now open. Make plans to join us November 6-8, 2016 at the Loews Hollywood Hotel in Hollywood, CA.

Download the Program Guide, and explore the complete program for education, keynote speakers, registration and more! 

Submit an Abstract

The Society to Improve Diagnosis in Medicine is soliciting proposals for oral and poster abstracts to be presented at the Diagnostic Error in Medicine 9th International Conference. Submissions should fall into one of the following three categories: scientific abstract, applied innovations and/or clinical vignette.
The deadline to submit your abstract for consideration is Friday, July 29.

BRCA 1185delAG mutation - Ashkenazi Jewish women - (sundry search results) -

BRCA1185delAG mutation

Commentary (partial view) - BRCA1 loses the ring but lords over resistance

JCI 
 

First published July 25, 2016 - More info

Commentary
 

See the related articles BRCA1^185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1 and RING domain–deficient BRCA1 promotes PARP inhibitor and platinum resistance.

Germline breast cancer 1 (BRCA1) variants are associated with a high risk of breast and ovarian cancers. Many BRCA1-mediated cancers are initially responsive to platinum-based therapy; however, resistance commonly develops. The BRCA1^185delAG mutation is common in the Ashkenazi Jewish population and has been thought to result in loss of function due to the introduction of a stop codon in the 5′ region of the BRCA1 transcript. Two studies in this issue of the JCI reveal that the BRCA1^185delAG mutation results in the production of BRCA1 that lacks the N-terminal really interesting new gene (RING) domain. RING-less BRCA1 was shown to directly mediate chemoresistance, while maintaining some homologous recombination function. These results provide important insight into BRCA1 function and indicate that other truncated proteins could arise through similar alterations in codon usage.

RING domain–deficient BRCA1 promotes PARP inhibitor and platinum resistance

JCI - open access

also:
 See the related Commentary beginning on page 2802.

BRCA 1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1

JCI - open access

also:
See the related Commentary beginning on page 2802.

(2 research items) BRCA1 mutations in breast and ovarian cancer can predict treatment resistance - Medical News Today

Medical News

Adapted Media Release

July 25, 2015/6

---

Mutations in the BRCA1 gene are one of the most common risk factors for breast and ovarian cancers. Although tumors that harbor BRCA1 mutations initially respond well to cancer treatments, many tumors eventually become less responsive. This month, two studies in the JCI investigated the mechanisms underlying the treatment resistance associated with some BRCA1 mutations, and the findings provide information that may help predict which treatments will be effective in women with breast and ovarian cancer.
A team led by Jos Jonkers at the Netherlands Cancer Institute discovered that a mouse harboring an analog of the cancer-associated human BRCA1 mutation, BRCA1184delAG, expresses a BRCA1 protein that is missing a structural component called a RING domain. Loss of the RING domain predicted poor treatment responses in both mouse and human mammary tumors. Neil Johnson's lab at the Fox Chase Cancer Center examined treatment resistance in breast cancer cells expressing the same BRCA1185delAG mutation and determined that the RING-deficient BRCA1 protein was also responsible for loss of sensitivity to certain types of cancer treatments. These findings identify specific BRCA1 mutations that are more likely to develop therapy resistance, which may lead to more accurate predictions and personalized treatments for breast and ovarian cancers.

Articles:

BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1, Rinske Drost, Kiranjit K. Dhillon, Hanneke van der Gulden, Ingrid van der Heijden, Inger Brandsma, Cristina Cruz, Dafni Chondronasiou, Marta Castroviejo-Bermejo, Ute Boon, Eva Schut, Eline van der Burg, Ellen Wientjens, Mark Pieterse, Christiaan Klijn, Sjoerd Klarenbeek, Fabricio Loayza-Puch, Ran Elkon, Liesbeth van Deemter, Sven Rottenberg, Marieke van de Ven, Dick H.W. Dekkers, Jeroen A.A. Demmers, Dik C. van Gent, Reuven Agami, Judith Balmaña, Violeta Serra, Toshiyasu Taniguchi, Peter Bouwman, and Jos Jonkers, JCI, doi: 10.1172/JC170196, published 25 July 2016.

RING domain-deficient BRCA1 promotes PARP inhibitor and platinum resistance, Yifan Wang, John J. Krais, Andrea J. Bernhardy, Emmanuelle Nicolas, Kathy Q. Cai, Maria I. Harrell, Hyoung H. Kim, Erin George, Elizabeth M. Swisher, Fiona Simpkins, and Neil Johnson, JCI, doi: 10.1172/JC187033, published 25 July 2016.

To be in pain (or not): a computer enables outpatients to inform their physician

abstract

Background In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control.

Patients and methods At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate–severe) pain. Differences were tested with the χ² test.

Results During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001).

Conclusion Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain.

Clinical trial number Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324).

A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer (MSH6)

BMC Cancer | Full Text

 In addition, within the recent published IMPACT series [7], patients with a history of Lynch Syndrome were not included for analysis..... Our report, albeit small, contributes to the literature in this field. Important publications arguing for an increased risk for prostate cancer with Lynch Syndrome are appropriately cited in our report.

 

Voluntary Recall for 30 Bakery Products (small metal fragments)

Recalls, Market Withdrawals, & Safety Alerts

Correspondence: Impact of Depression in Patients Undergoing HiPEC With Cytoreductive Surgery

open access

 The recent article by Low et al⁵ noted that patients with preoperative depressive symptoms had significantly increased risks of 30-day morbidity and 30-day readmission following hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS). Although the study strongly highlights the importance of psychologic assessment in patients with cancer who are scheduled for surgery, some statistical aspects of the study should be clarified to draw conclusions regarding the prognostic impact of preoperative depression.