Breast Cancer: increased Survival Rates with Breast-Conserving Surgery versus Radical Mastectomy

Breast-conserving surgery led to improved cancer-specific survival in early breast cancer as compared with mastectomy, with or without radiation therapy

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The University of Utah aims to provide the best possible care, discover better treatments and train tomorrow’s health care experts.

Breast-conserving surgery led to improved cancer-specific survival in early breast cancer as compared with mastectomy, with or without radiation therapy, a large retrospective review showed.

Patients treated with breast conservation had significantly higher 5- and 10-year survival, including an 11% absolute difference from mastectomy plus radiation therapy at 10 years, according to researchers of the University of Utah.

Sources and Articles
  • Breast-Sparing Tops Mastectomy in New Analysis, MedPageToday, 20 Mar 2014
  • Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer, JAMA Surg. 1813803 2014;149(3):267-274. doi:10.1001/jamasurg.2013.3049.
  • Breast-Conserving Therapy for Triple-Negative Breast Cancer, JAMA Surg. 1793208 2014;149(3):252-258. doi:10.1001/jamasurg.2013.3037.
  • Breast-Conserving Therapy: A Viable Option for Young Women with Early Breast Cancer-Evidence from a Prospective Study, NCBI, PMID: 24599412, 2014 Mar 6
Abstract

BACKGROUND:
This study evaluated the security of breast-conserving treatment (BCT) in young patients and the effect of regional radiation therapy on young patients with 1-3 positive nodes (N+) treated with BCT.
METHODS:
In this prospective concurrent controlled study, 164 patients were defined as the BCT group, and regional radiation therapy was delivered to patients with 1-3 N+. Modified radical mastectomies (MRMs) were performed on 224 patients without regional radiation therapy.
RESULTS:
The 9-year local recurrence (LR) rate of the BCT was 7 %, compared with 3 % in the MRM group (p = 0.055). The 9-year regional recurrence (RR) rate was 6 % for the BCT group and 12 % for the MRM group (p = 0.048). The distant metastasis (DM)-free and breast cancer-specific survival rates were similar between the two groups. RR was an independent prognostic factor for DM [hazard ratio 3.27; 95 % confidence interval (CI) 1.726-6.208] and breast cancer-specific survival (hazard ratio 5.814; 95 % CI 2.690-12.568), whereas LR was not an independent prognostic factor for DM or breast cancer-specific survival.
CONCLUSIONS:
Young patients treated with BCT have a higher LR rate than that of MRM. However, LR has no detrimental effect on DM-free and breast cancer-specific survival rates, whereas RR is a strong risk factor of DM and death. Regional radiation therapy for young patients with 1-3 N+ may reduce RR and improve survival rates.

Deadly Medicines and Organized Crime: a Video Conference with Peter Gøtzsche

Prescription drugs are the third leading cause of death after heart disease and cancer

Tholduset, Helsingor, October 3, 2013

Conference with Peter Gøtzsche – Director of the Nordic Cochrane Center and Co-Founder of The Cochrane Collaboration – on the topic of his book Deadly Medicines and Organized Crime: How Big Pharma has Corrupted Healthcare.

More info and Videos
  • Video by Poet Dox, Published on 17 Oct 2013.
  • More videos via YouTube.

Novel Cancer Vaccine holds promise against Ovarian Cancer, Mesothelioma

Potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin

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A protein engineered by Massachusetts General Hospital investigators to combine a molecule targeting a tumor antigen with an immune-function stimuating protein prolonged survival in animal models of ovarian cancer and mesothelioma.

A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma. Investigators from the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center report in the Journal of Hematology & Oncology that a protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.

Read Antigen-targeting fusion protein should be less expensive, more accessible than current approaches, MGH News Release, 05/Mar/2014

A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma

Abstract

Background

Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.

Methods

Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.

Results

We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.

Conclusions

This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.

Sources and full Research

Journal of Hematology & Oncology /content/7/1/15 2014, 7:15 doi:10.1186/1756-8722-7-15

Journée Internationale des Maladies Rares

Le Poster 2014

poster of journée internationale des maladies rares
Depuis 2001, la Plateforme Maladies Rares est un lieu qui rassemble une centaine de salariés et de nombreux bénévoles, mobilisés pour faire avancer le combat contre les maladies rares et améliorer la vie des personnes malades et de leurs familles.

Lisez le post: Ensemble pour mieux accompagner les malades, journée des maladies rares.

Le Distilbène DES, maladie rare, en savoir plus

Has Big Pharma hijacked the European Health Research Budget?

Pharmaceutical research is a legitimate use of public money. This is not the first time researchers across Europe have taken issue with the priorities of the European Union’s health research programme

a paper by Michael J Galsworthy, Leonardo Palumbo, Martin McKee

mike galsworthy
Mike Galsworthy: Science by day, poetry by night. Tweets mainly on EU & UK science policy, politics, open data – and occasionally poetry/arts stuff.

The European Commission has just launched its new €80 billion 7-year science fund Horizon 2020. Separately, the Commission has been negotiating five joint-technology initiatives cofinanced by a range of industries. However, the source of matching funds within Horizon 2020 has been unclear.

Now it emerges that one joint technology initiative, the Innovative Medicines Initiative 2 (IMI2), cofunded by the European Federation of Pharmaceutical Industries and Associations, is promised €1·7 billion, not from the Excellent Science (basic research) nor the Industrial Leadership pillars of Horizon 2020, but exclusively from the third pillar, Societal Challenges – specifically the €7·4 billion Health, Demographic Change and Wellbeing stream designed for public health and health services research. An additional €683 million ring-fenced for clinical trials means that 25–32% of health and demographic change research funds are dedicated to drug development.

Pharmaceutical research is a legitimate use of public money. As its name suggests, the IMI2 is the successor to IMI1, which received €1 billion in public funds and was proclaimed as “the world’s largest public-private partnership in health”. However, the source and size of IMI2 funds are alarming. In 2012, the US National Institutes of Health came in for criticism when they decided to divert just 2% of their US$31 billion annual budget on a scheme to speed up drug development. This is not the first time researchers across Europe have taken issue with the priorities of the European Union’s health research programme.

In late 2013, the Commission published its first work programme for health in Horizon 2020. This publication caused immediate consternation, with four of Europe’s leading health organisations expressing, in a letter to the Commissionner, how they were “deeply concerned about the balance of priorities” as the programme focused primarily on biotechnology and personalised medicine, and reiterating the importance of prevention and promotion programmes, tackling social inequalities, providing faster and joined-up services, and improving health-care delivery.

So how did the joint-technology initiatives win these funds without observers of European science policy knowing? First, despite their size, they were never mentioned in the detailed Horizon 2020 breakdowns circulated widely. Second, their finalisation took place separately from the Horizon 2020 negotiations in the European Council, with no meaningful consultation with wider stakeholders. In the same way that hefty donations with strings attached distort spending by WHO,6 the European pharmaceutical industry can use a fraction of its €27 billion annual spend on research and development to leverage public subsidy, seemingly without the wider research community present to offer counterarguments.

Arguments by organisations seeking greater transparency of IMI2 through the European Parliament’s Industry, Research and Energy Committee have been rebuffed because of increases in “administrative burden …undermining competitiveness”. The scale of IMI2 and use of societal challenges funds to pay for it can expect to attract considerable controversy. ”

Sources
  • TheLancet, PDF Downloads, March 19 2014
  • Mike @mikegalsworthy ‘s tweet, 19 Mar 2014

The Development of Cervical and Vaginal Adenosis as Result of Diethylstilbestrol Exposure in Utero

Women pre-natally exposed to DES develop abnormalities that can lead to cancer

Abstract

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Women exposed to diethylstilbestrol (DES) in utero develop abnormalities, including cervical and vaginal adenosis that can lead to cancer.

Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed with DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenosis are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models can be used to study the development of DES-induced anomalies, focusing on cervicovaginal adenoses, and discusses its molecular pathogenesis.

Sources

NCBI, PMC3443265, Oct 2012 The Development of Cervical and Vaginal Adenosis as a Result of Diethylstilbestrol Exposure In Utero.

More DES DiEthylStilbestrol Resources

Review of Valproate and Related Substances and their Use in Pregnant Women – EU Medicines Agency

Women to be better informed of risks of valproate use in pregnancy and need for contraception

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Latest news from the European Medicines Agency, the European Union agency responsible for the evaluation and supervision of medicines.

The European Medicines Agency has started a review of valproate and related substances and their use in pregnant women.

Valproate medicines are used for treating epilepsy and bipolar disorder. It has been known for some time that using anti-epileptic medicines in pregnant women increases the risk of birth defects in their children and that valproate medicines may be associated with a higher risk of certain birth defects than other anti-epileptic medicines. It has also been known that development may be delayed in children born to women who were treated with valproate medicines during pregnancy. The product information for valproate medicines in the EU contains information on their use during pregnancy.

The review of valproate medicines has been requested by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) following the publication of new studies suggesting that in some children problems in development, which can include autism, may be long-lasting. The MHRA also noted that there was a need to update the product information of these medicines to bring them in line with current evidence.

The European Medicines Agency will now review the available data on the benefits and risks of valproate and related substances and issue an opinion on the use of these medicines in pregnant women. ”

Sources European Union Medicines Agency Press ReleasePDF

Introducing “Testing Treatments Interactive”

Promoting Better Research for Better HealthCare, 2014

Sir Iain Chalmers explains why fair tests of the effects of treatments can improve healthcare.

More information

Why Americans are Over-Medicated

Pill Nation: why it’s likely to stay like that

Pill Nation 4, image of US drugs stats
Pill Nation : why it’s likely to stay like that

American is a nation of pill poppers. Nearly 13 prescriptions were prescribed per man, woman, and child last year. We’re one of only two countries in the world who allow direct-to-consumer Rx advertising; and Rx have slowly grown to be the third highest medical cost. Welcome to the pill nation.
Sources and full article on TheNursingBible and Janice_Flahiff on WordPress.

Find More Information:

All our posts about AEDsbig pharmaDESdoctorsdrug money,drugsEx Pharma Rx Drug Pusher Confessions – Gwen Olsen, the FDAmedical representativesSSRIsthalidomidevalproate. See more infographics.

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Les priorités de travail de l’ANSES pour 2014

Les enfants et les pesticides

L’Anses présente ses priorités de travail pour 2014

Enfants
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L’Agence présente ce jour son programme de travail pour l’année 2014, élaboré à l’issue d’un processus de consultation avec les ministères et les parties prenantes. Les deux priorités de l’#ANSES pour 2014 sont les enfants et les #pesticides.

Certaines populations sont particulièrement vulnérables aux agents présents dans leur environnement, leur alimentation ou les produits de consommation. C’est en particulier le cas des enfants, c’est la raison pour laquelle l’Anses a décidé de mettre l’accent en 2014 sur les travaux spécifiques concernant les risques auxquels les enfants peuvent être exposés : risques liés à l’usage d’appareils radioélectriques (veille-bébés, tablettes, consoles 3D, talkies-walkies, etc.), substances chimiques présentes dans les jouets, composition des aliments des tout-petits ou contaminants auxquels ils sont susceptibles d’être exposés par l’alimentation, autant de sujets autour desquels se concentreront les efforts des experts de l’Agence afin de mieux protéger cette population sensible.

Pesticides

L’Anses continue par ailleurs à s’investir sur la question des expositions aux pesticides des travailleurs agricoles et des riverains. En 2014, l’Agence publiera plusieurs avis et rapports sur la caractérisation de ces expositions, ainsi que sur l’efficacité des vêtements et équipements de protection individuelle. Ces rapports se baseront sur des travaux d’un groupe d’experts dédié à une meilleure connaissance des expositions réelles aux pesticides, auxquels s’ajoutent les travaux menés dans le cadre de la réglementation européenne et les résultats d’une expertise collective récente de l’Inserm.

En savoir plus