Updated 16 September 2014
The weekly summary of medical news developments for Breast Cancer and Cancer for the week ending 21 August 2014.
This post focuses on screening. Call it coincidence, but there were three articles on different ways to screen for breast cancer, this week. The first is a trial into using dogs to sniff out breast cancer. I’ve covered dogs being used to sniff out cancer in previous posts, but this time, scientists are finally testing this on breast cancer. Perhaps one day the gold standard in screening could be a golden labrador!
Item number 2 is a study that shows that MRIs are more accurate than ultrasound and mammogram in detecting recurrent tumours. I wonder how MRIs compare to Pet-CTs in terms of radiation exposure. There is no ionizing radiation in an MRI. The dose for a typical PET-CT scan is 25 mSv for a 70-kg person. The dose for a mammogram is 0.4 to 0.7 mSv. The PET-CT gives 625 times more radiation. CT scans alone produce 7 mSV, 10 to 15 times the dose of a mammogram.
Did you know that four PET-CT scans in one year puts you at twice the total annual dose allowed to nuclear power plant workers? In a healthy person, that might not be an issue, but people with cancer have a compromised immune system, and that level of radiation might cause further mutations.
The question is: how sensitive is MRI compared to PET-CTs in detecting cancer? And why aren’t doctors using MRIs?
Update 16 September 2014: With thanks to reader Rebecca Coady for posting a comment on how to mitigate the damage caused by radiation: one suggestion is to have an intranvenous vitamin C infusion of 25g. Or check out the Life Extension website for more information on radiation, body scans, Pet-CTs, and ways to minimise the damage caused by radiation.
1. Dogs to be used to detect breast cancer in new research trial
- Women at high risk of breast cancer could be screened for the disease by simply breathing into a tube which is then sniffed by a specially trained dog, in a new clinical trial after UK scientists found the animals are highly accurate at detecting other cancers.
- The animals working for Medical Detection Dogs in Buckinghamshire have already been shown to be more reliable at detecting prostate cancer than current blood tests, with 93 per cent accuracy when sniffing urine samples.
- The results of the prostate cancer trial were published in the British Medical Journal and other reputable scientific publications so now the team are moving on to breast cancer.
- Dr Claire Guest, a behavioural psychologist and founder of the charity, said her dog Daisy alerted her to her own breast cancer when they were working on the prostate cancer trial.
- Daisy has worked on 6,000 urine samples and has been found to be 93 per cent reliable in detecting prostate cancer.
- Now six other dogs will be trained to sniff for breast cancer in breath samples for the new trial, which has already begun.
- The best four will taken forward and tested in the trial using samples from 1,500 women.
- It is thought the dogs, which can detect scent in one part per trillion, are sniffing out volatile substances given off by cancerous cells.
- “If proven it would have a significant impact on what we consider possible in the diagnosis of cancer.
- “High risk young women, who are too young for routine, regular mammograms could breathe into a tube every six months and find out quickly and painlessly if they have cancer.”
- In the long-term it is hoped the substances that the dogs are detecting can be identified and electronic noses created to pick them up.
For more information: http://medicaldetectiondogs.org.uk/breast.html:
— In an additional study in 2006, McCulloch et al. also tested the dog’s ability to distinguish exhaled breath samples of 31 breast cancer patients from those of the 83 healthy controls. Dog handlers and experimental observers were blinded to the identity of breath samples, obtained from subjects not previously encountered by the dogs during the training period. Among breast cancer patients and controls, sensitivity was 0.88 and specificity 0.98. However there were some limitations in the design of this study and number of subjects included and further work is needed with peer reviewed publication to support this finding.
See also British Medical Journal, BMJ 2004;329:712–5, Olfactory detection of human bladder cancer by dogs: proof of principle study
2. Study: MRI Better Detects Recurrent Breast Cancer
- Single-screening breast magnetic resonance imaging (MRI) detects 18.1 additional cancers after negative findings with mammography and ultrasonography (US) per 1,000 women with a history of breast cancer, according to a study published in the August issue of Radiology.
- The researchers found that MRI detected 11 additional cancers (18.1 cancers per 1,000 women).
- “Our data suggest that women with a history of BCT for breast cancer may be appropriate candidates for breast MRI screening in view of the high detection yield for T1 invasive cancers, acceptable PPV,” the authors write.
For more information: Radiology, August 2014, DOI: http://dx.doi.org/10.1148/ radiol.14131893, Breast MR Imaging Screening in Women with a History of Breast Conservation Therapy
3. Cancer fears prompt call to cut hospitals’ CT scan radiation levels
- Radiation doses used in CT hospital scanners to diagnose injuries and diseases should be reduced to the lowest possible level, to avoid potential harm, a government advisory body has warned.
- The Committee on Medical Aspects of Radiation in the Environment (Comare) – originally set up to investigate radiation emissions from the Sellafield nuclear plant – says one adult in 2,000 (or one child in 1,000) who has an abdominal scan, which subjects a patient to the highest amount of radiation, will develop a new cancer as a result.
- The committee said the risk remains low – the exposure is the same as 4.5 years of natural background radiation – and has to be set against the advantages of swift and accurate patient diagnosis.
- But Comare chairman Alex Elliott said the use of CT scans is rapidly increasing. There were 1m CT scans a year in England in the 1990s. There are now around 5m a year, rising at around 10% a year with no sign of levelling off.
For more information: Committee on Medical Aspects of Radiation in the Environment
(COMARE), Sixteenth report, Patient radiation dose issues resulting from the use of CT in the UK
4. No two tumour cells in a single patient have an identical genome
- The latest study of breast cancer at the University of Texas shows that no two tumour cells in a single patient have an identical genome.
- The researchers say their findings, published in Nature, have important implications for the diagnosis and treatment of breast cancer.
- The team used a new DNA sequencing approach called Nuc-seq to study mutations in thousands of cells in individual patients.
- They discovered a huge range of genetic changes taking place, at a rate that differed between types of cancer: in hormone-sensitive “oestrogen receptor positive” breast cancer the mutation rate remained constant as the cancer developed, while in “triple negative” tumours (which are not responsive to hormone treatment) the mutation rate rose.
- An important question about chemotherapy is whether resistant mutations already exist in a few rare cells in the tumour before treatment begins or whether they arise through natural selection as the cancer evolves during therapy.
- Our data suggest that a large number of diverse mutations are likely to be pre-existing in the tumour prior to chemotherapy.
- Therefore we expect that measuring genomic diversity may also have prognostic value in identifying which patients will develop resistance to chemotherapy.
For more information: Nature512,155–160(14 August 2014), doi:10.1038/nature13600, Clonal evolution in breast cancer revealed by single nucleus genome sequencing
5. Novel Gene DP103 Predicts Both Breast Cancer Relapse and Response to Chemotherapy
- Scientists have made it easier to predict both breast cancer relapses and responses to chemotherapy, through the identification of a unique gene.
- The newly found marker could help doctors classify each breast cancer patient and customise a treatment regimen that is more effective.
- Scientists uncovered a gene, DP103, which is activated in metastatic breast cancer. DP103 acts as a master regulator, which expresses two sets of unfavourable proteins – one leads to metastasis and the other causes patients to be unresponsive to chemotherapy.
- Consequently, doctors can predict the probability of metastasis by examining the levels of DP103 in breast cancer patients.
- The same gene could also be used to predict whether a patient would respond to chemotherapy.
- “Doctors are unable to tell if a breast cancer patient will respond to chemotherapy until six months after the treatment has been prescribed. It is very worrisome as the ones who are not responsive to chemotherapy usually also suffer relapses due to metastasis.
- This DP103 gene that we found explains the link and will facilitate doctors in selecting suitable treatments for different cases of breast cancer.
- In addition, the study revealed that reducing the levels of DP103 could contain the cancer, shrink the tumour and make patients more amenable to chemotherapy.
- All the findings in the study have been validated with samples of breast cancer patients from Singapore, Canada, China and the USA.
- Most cancer deaths occur when the disease spreads, or metastasizes, from the original tumor site to a distant location.
- In breast cancer patients, metastasis to the brain can occur months or years after seemingly successful treatment of the primary tumor.
- Now Memorial Sloan Kettering researchers have found that a protein called cathepsin S may play a key role in the spread of breast cancer to the brain.
- A complex interplay between breast cancer cells and certain surrounding cells called macrophages induces both cell types to secrete increased levels of cathepsin S, an enzyme that promotes the cancer cells’ ability to metastasize.
- In mice with brain metastases, the cathepsin S gene was significantly overexpressed. Interestingly, the tumor cells produced more cathepsin S at the beginning of metastasis and then tapered production, in parallel with a progressive increase in macrophage cathepsin S levels within the brain.
- The reciprocal relationship suggests that breast cancer cells become equipped for metastasis through the two-way signaling between tumor cells and macrophages in the microenvironment.
- The interplay between the two cell types takes place both at the primary tumor location and at the metastatic site in the brain.
- The researchers showed that cathepsin S enables the cancer cells to penetrate through the blood-brain barrier, a densely packed vascular structure that protects the brain from most large molecules in the blood.
- Cathepsin S is a protease, a type of enzyme that degrades proteins.
- The researchers found that cathepsin S cleaves a protein called (JAM)-B, which normally helps hold cells in the blood-brain barrier together.
- The higher levels of cathepsin S presumably negate (JAM)-B’s effect and allow the cancer cells to penetrate the barrier.
7. Leukemia drug shows promise for skin, breast and other cancers
- A leukemia drug called dasatinib shows promise for treating skin, breast and several other cancers, according to researchers at Loyola University Chicago Stritch School of Medicine.
- Dasatinib fights leukemia by checking the uncontrolled growth of cancer cells.
- But when used against other cancer cells, researchers found, the drug employs a different strategy: It causes the cells to clump together, thus preventing them from migrating. Without the ability to migrate, cancer cells cannot metastasize.
- Dasatinib (trade name, Sprycel) is approved for certain types of leukemia. It targets a protein called BCR-ABL that fuels the growth of cancer cells.
- BCR-ABL is similar to a protein called Fyn that’s found in other malignancies, including breast, brain, pancreatic, skin and head-and-neck cancers.
- Fyn is associated with cell-cell adhesion and cell migration.
- Denning and colleagues found that applying dasatinib to cancer cells in the laboratory caused the cells to clump together, and also prevented the cells from migrating.
- They found similar results with breast cancer cells. While dasatinib did not eliminate Fyn, it inhibited the protein’s activity.
For more information: Molecular Carcinogenesis, 29 JUN 2014, DOI: 10.1002/ mc.22190, Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell–cell adhesion
See also: Cancer Letters, Volume 283, Issue 2, Pages 143–151, October 8, 2009, Src inhibitor dasatinib inhibits growth of breast cancer cells by modulating EGFR signaling
8. New protein could affect Vitamin A cancer therapy
- A protein that is present in nearly every cancer could prevent the Vitamin A cancer therapy from being effective, a new study has revealed.
- Researchers at Virginia Commonwealth University (VCU) Massey Cancer Center set out to discover why some cancer patients did not respond well to the retinoic acid (a subtype of vitamin A) drug treatment that is used to help prevent the reoccurrence of numerous forms of cancer.
- The retinoic acid therapy works by activating retinoid X receptors (RXR), which control the level of cancerous cell growth and development.
- After performing copious investigations over a number of years into the unexplained resistance of the treatment, scientists found that the protein known as AEG-1 binds to the RXR, interfering with the regulation of cell growth and instead encouraging the development of tumours.
- In an attempt to counteract this, it was revealed that by blocking the production of AEG-1, retinoic acid was able to successfully destroy liver cancer cells.
For more information Cancer Res August 15, 201474; 4364, AEG-1 Regulates Retinoid X Receptor and Inhibits Retinoid Signaling
9. New Study Tests Lotion To Treat Radiation Dermatitis in Breast Cancer Patients
- Irving, Texas based Reata Pharmaceuticals has announced enrollment of its first patient in a Phase 2 dose-ranging study examining the safety, tolerability, and efficacy of the company’s RTA 408 Lotion versus vehicle for prevention and treatment of radiation dermatitis in breast cancer patients for whom radiation therapy (RT) is recommended.
- Radiation dermatitis is a complication experienced by a majority of patients receiving radiation therapy for cancer.
- RT can damage the cellular structures in the skin and cause pain, ulceration, necrosis, and fibrosis of exposed skin tissues.
- Free radicals produced during cancer radiotherapy often lead to dermatitis, with the degree of insult to body tissues ranging from mild erythema to moist desquamation and ulceration.
- Radiation dermatitis usually manifests within one to four weeks after initiation of RT and can result in delays in or failure to complete RT, limiting the dose effect of RT, which can negatively affect treatment outcomes.
- Currently there are no approved agents for the prevention of radiation-induced dermatitis.
- The researchers observe that this toxicity can be dose-limiting and promote chronic complications, such as fibrosis and wound recurrence.
- The purpose of the study reported was to evaluate if RTA 408, a synthetic triterpenoid that potently activates the antioxidative transcription factor Nrf2 and inhibits the proinflammatory transcription factor nuclear factor-kappa b (NF-kB), could protect skin from radiation-induced dermatitis.
- The coauthors note that dose-dependent improvements in the appearance of skin were also manifestly visible, with RTA 408 at 1.0% eliciting a normal macroscopic appearance by the end of the treatment period on day 40, including substantial hair regrowth.
- Moreover, they report that 1.0% RTA 408 markedly reduced epidermal and collagen thickening, prevented dermal necrosis and completely alleviated skin ulcers.
- These improvements were associated with significant increases in Nrf2 target genes and significant decreases in NF-kB target genes, concluding that together these data indicate that RTA 408 represents a potentially promising experimental therapy for the treatment of radiation-induced dermatitis.
10. Following A Mastectomy, 58% Of Breast Cancer Survivors Do Not Choose Breast Reconstruction
- A study conducted by Memorial Sloan-Kettering revealed that less than 42 percent of women choose breast reconstruction following their mastectomy.
- Of the 485 women, 24.8 percent underwent immediate breast reconstruction and 16.8 percent had delayed reconstruction: 41.6 percent total.
- Common reasons for not choosing breast reconstruction were the desire to avoid additional surgery (48.5 percent), fear of breast implants (36.3 percent), and feeling reconstruction was not important (33.8 percent).
- Nearly a quarter of these women felt concerned reconstruction might interfere with the detection of later cancer.
- Among the factors linked to choosing against reconstruction were being black, a lower education level, being older, a major coexisting illness, and chemotherapy.
For more information: JAMA Surgery, http://archsurg.jamanetwork.com/article.aspx?doi=10.1001/jamasurg.2014.548, Patient Perspectives on Breast Reconstruction Following Mastectomy