Best of Breast: news for week ending 25 July 2014

The latest cancer developments from Google Alerts, with a bias towards breast cancer, for the week ending 25 July 2014.

This week’s top 2 features offer potential cures for cancer which either don’t cost very much (aspirin) or are already being used in other ways (marijuana/cannabis).

marijuana

image credit: mexicoinstitute.wordpress.com

Aspirin was originally derived from willow bark, which has been used as a painkiller since the time of Hippocrates.  Aspirin reduces inflammation, and that may play a role in inhibiting the growth of tumors — perhaps by slowing the development of new blood vessels that nourish them, or by fighting old cells that keep growing when they should be dying off. It may also inhibit estrogen production, and we know that estrogen fuels the growth of most (but not all) breast cancers.

And yet, until now, there have been no randomized trials (the gold standard of research) of aspirin use among women with breast cancer – a travesty.  The solution:  don’t wait for the boffins to rubber-stamp aspirin, just take it.

As for cannabis (or rather in its concentrated form, cannabis oil), just google cannabis oil and cancer, or Rick Simpson Oil and you’ll be overwhelmed by the number of scientific studies.  Unfortunately, unlike aspirin, cannabis oil is not available in your local friendly pharmacy, and in many countries, its use is illegal.

1.  Grandfather, 63, claims he cured his cancer with ‘Breaking Bad’ style homemade CANNABIS OIL

http://www.dailymail.co.uk/health/article-2699875/I-cured-cancer-CANNABIS-OIL.html

  • Tests late last year revealed Mike Cutler had cancerous cells in his liver
  • Worried he might die, he took to the internet to search for a cure
  • Discovered cannabis oil – and bought some of the drug to make his own
  • Claims his excruciating pain disappeared three days after taking the potion
  • And that tests a few months later showed the cancer cells had gone
  • Research published last week by scientists at the University of East Anglia found the main psychoactive ingredient in cannabis – Tetrahydrocannabinol or THC – has been shown to help combat the growth of cancerous cells.

For more information on cannabis as a treatment for cancer:  visit the Cancer Research UK website, Bud Buddies (UK source), thehealthcure.org (Netherlands source)

aspirin

  • A chemical, salicylic acid, found in willow tree has unknown cancer fighting properties and can double the survival rate among breast cancer patients, says Dr. Michelle Holmes, a researcher at Harvard Medical School.
  • Dr. Holmes studied the data collected from the long-running Nurses’ Health Study and identified almost 4,000 women suffering from breast cancer, who had undergone regular treatment, and chemotherapy.
  • She based her result on the amount of aspirin the cancer patients had consumed for other reasons such as pain or prevention of heart ailments.
  • Dr. Michelle found that women suffering from breast cancer, who took aspirin was less likely to die in comparison to those who did not take aspirin or its generic form, ASA.
  • Dr. Michelle Holmes’s study has to be backed with clinical trials and only then can we know as to how many aspirins a day should be consumed to keep breast cancer away.
  • The trial will cost the government at least $10 million and all the effort put by Dr. Holmes to convince the U.S. federal funding agencies has so far gone down waste.
  • Dr. Holmes has already been turned down four times by the agencies.
  • Disappointed that her finding is not being given the kind of attention it requires, Dr. Michelle Holmes wrote an op-ed column in the New York Times, asking readers to understand how aspirin can function as the best low-cost cancer drug that can save millions of women suffering from breast cancer in countries that cannot afford expensive therapies and treatment.

For more information:  New York Times, May 19, 2014, A Cancer Treatment in Your Medicine Cabinet? and Journal of Clinical Oncology, doi:10.1200/JCO.2009.22.7918,  Aspirin Intake and Survival After Breast Cancer

3.  Total darkness at night is key to tamoxifen effectiveness

http://www.independent.ie/irish-news/health/darkness-key-to-breast-treatment-30458710.html

  • Being exposed to light at night makes breast cancer resistant to the widely used hormonal therapy tamoxifen.
  • Such exposure shuts off night time production of the hormone melatonin, according to researchers at Tulane University in New Orleans, in the US.
  • Their study, published in the journal Cancer Research, suggests that this hormone is “vital” to the success of the drug in treating breast cancer.
  • The researchers examined the role of melatonin on the effectiveness of tamoxifen in fighting human breast cancer cells implanted in rats.
  • However, researchers found that in tests on rats, a melatonin hormone supplement during the night could overcome this.
  • The study did not identify how much light exposure it would take to suppress this production. “We think it could be as little as the amount of light that comes in the bedroom window from a street light.”
  • The researchers cautioned against patients supplementing naturally produced melatonin. “Melatonin is produced by our bodies exclusively during darkness at night, and taking melatonin supplements at the wrong time of day would potentially disrupt the circadian [sleep-wake cycle] system, particularly the natural melatonin cycle, which may, in itself, impair breast cancer responsiveness to tamoxifen.”
  • “Our levels of melatonin are not determined by sleep, as many people think.
  • “It is actually the darkness that is important. During the night, if you sleep in a brightly lit room, your melatonin levels may be inhibited; however, if you are in the dark but cannot sleep, your melatonin levels will rise normally.”

For more information:  Cancer Research Journal, 2014; doi: 10.1158/0008-5472.CAN-13-3156, Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

4.  Antioxidants may ‘cancel out’ breast cancer from meat: Diet supplements remove extra dangers of regularly eating processed meat

http://www.dailymail.co.uk/health/article-2697968/Pill-cancel-breast-cancer-meat-Diet-supplements-remove-extra-dangers-regularly-eating-ham-bacon-sausages-study-claims.html

  • French scientists examined the case histories of 4,684 middle-aged women who took part in a trial between 1994 and 2007.
  • Half the participants were given a daily capsule containing vitamins C and E plus zinc, selenium and beta carotene. The other half were given a placebo.
  • In total, 190 of the women went on to develop breast cancer.
  • The new research, at the University of Sorbonne Paris Cite, re-evaluated the data to take into account meat consumption.
  • The study said a high processed meat intake was associated with an increased breast cancer risk in the placebo group, but not in those taking supplements, adding: ‘This suggests that supplemental and possibly dietary antioxidants may counteract the potential pro-carcinogenic effects of processed meat.’
  • In the placebo group, those who ate above-average amounts of processed meat were around 2.5 times more at risk of cancer – even when other variables such age, weight, smoking, drinking, exercise and family cancer history were taken into consideration.
  • For more information:  Int. J. Epidemiol. (2014), doi: 10.1093/ije/dyu134, Prospective association between red and processed meat intakes and breast cancerrisk: modulation by an antioxidant supplementation in the SU.VI.MAX randomized controlled trial.

5.  Malaria drug could prevent liver cancer

http://www.telegraph.co.uk/health/healthnews/10978915/Malaria-drug-could-prevent-liver-cancer.html

  • Chloroquine, a derivative of quinine, is a cheap and safe drug available from most pharmacists and is the medication of choice for travellers visiting the tropics.
  • Now scientists at University College London have found that it can also prevent liver cancer in a discovery which could prevent thousands of deaths a year and give hope to hundreds of thousands of people at risk of developing the disease.
  • ‘Chloroquine works by switching off two proteins (Toll-like proteins 7 and 9), which are thought to be turned on when liver cells die, triggering chronic inflammation, which stops cells regenerating properly, and causes cancer.
  • When a liver is badly scarred through cirrhosis, caused by drinking too much alcohol or hepatitis, the damaged organ attempts to regenerate itself but cannot reproduce properly and so creates cancerous cells.
  • The researchers found that the drug prevented cancer occurring in 80 per cent of cases. It also shrank tumours.
  • Although the research has so far only been conducted on mice and rats, the team are hopeful the success will be repeated in clinical trials on humans.

For more information:  Liver International, DOI: 10.1111/liv.12626, Effect of Toll-Like Receptor 7 and 9 Targeted Therapy to Prevent the Development of Hepatocellular Carcinoma

6.  Breast tissue growth protein may promote cancer

http://www.healthcanal.com/cancers/53236-breast-tissue-protein-may-promote-cancer.html

  • Scientists for the first time describe the function of a protein called Par3L, that may play a role in promoting cancer.
  • Par3L is very similar to another protein, Par3, which functions as a polarity protein. That means it helps determine the “top-bottom” orientation of cells, including the adult stem cells that give rise to new epithelial tissues throughout the body, including the breast.
  • Epithelial cells line the ducts that produce milk in the breast, and pump it to the nipples. Normal growth of breast tissue occurs during each menstrual cycle, and during pregnancy and lactation. However, the biological role of Par3L itself was completely unknown.
  • Par3L is present specifically in mammary stem cells, and at the growing tips of mammary ducts.
  • If the gene for Par3L is deleted or “knocked down,” mammary stem cells in the mouse die, and mammary tissue doesn’t grow.
  • Huo discovered the mechanism: Normally Par3L “puts the brakes” on another polarity protein called LKB1, which suppresses mammary tissue growth. LKB1 is an important regulator of growth — loss of LKB1 can cause cancer in several organs, including the breast, but too much LKB1 can kill cells.
  • Without Par3L to tamp down the activity of this protein, LKB1 becomes over-active and stem cells quickly die. If, on the other hand, Par3L is overexpressed, it acts as a “tumor promoter” by shutting down LKB1 and promoting uncontrolled growth, not only in the breast but in other tissues.
  • Eighty percent of all human cancers and all breast cancers arise from epithelial tissues. “There’s a lot of evidence that stem cells are the cells of origin of breast cancer,” he said, but “there’s still much that we don’t understand about the mammary stem cells themselves.

For more information:  Nature Cell Biology, 16, 529–537 (2014) doi:10.1038/ncb2969, The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance

7.  Researchers ID Possible Protein target for Early-Stage Breast Cancer Immunotherapy

http://au.ibtimes.com/articles/559735/20140721/targets-immunotherapy-early-stage-breast-cancer.htm#.U9UaS4FdW5I

  • PD-L1 is a protein that plays an important role in suppressing immune response, and in cancer, it may allow tumors to evade immune attack.
  • The study demonstrated that about 60 percent of early-stage breast cancers have PD-L1 expression, and a subset of these cancers also have large numbers of tumor infiltrating lymphocytes.
  •  High levels of lymphocytes and PD-L1 predicted for better survival, suggesting a beneficial role for the immune system in at least partially controlling these cancers.
  • Yale Cancer Center researchers used a new molecular analysis tool to accurately detect the level of an important target for immunotherapy in early-stage breast cancers.
  • The diagnostic test, using RNAScope, measures the amount of PD-L1 (programmed death ligand 1) mRNA in routine formalin-fixed cancer tissues and is devoid of many of the technical issues that plague antibody-based detection methods that have yielded conflicting results in the past.
  • PD-L1 is the target of several novel immune stimulatory therapies in clinical trials.
For more information:  Journal of Clinical Cancer Research, March 19, 2014; doi:10.1158/1078-0432.CCR-13-2702, In situ Tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas

8.  Structure of protein vital to cancer development is mapped

http://www.medicalnewstoday.com/articles/279823.php

  • A major breakthrough has been made by scientists who have successfully managed to map out the structure of a complicated protein that is regarded to be one of the most important in cell division.
  • A team from the UK comprised of members of The Institute of Cancer Research, London, and the Medical Research Council Laboratory of Molecular Biology, Cambridge, have produced the world’s first detailed images of the anaphase-promoting complex (APC/C).
  • The APC/C is important as it is involved with a range of vital tasks within the process of cell division, mitosis.
  • During mitosis, a cell duplicates itself, pulling apart its chromosomes into two separate daughter cells.
  • Mitosis occurs in animals and plants alike.It is during cell division that cancer rears its ugly head, hijacking the process in order to make hundreds of copies of harmful cancer cells.
  • Every subunit of the APC/C bonds and meshes with other units during different points of the cell cycle.
  • This bonding allows the APC/C to control several mitotic processes, such as the initiation of DNA copying, the separation of chromosomes and cytokinesis, the splitting of one cell into two.
  • New cancer drugs that could be developed in light of this research would target binding sites, disrupting these processes to hopefully prevent cancer cells from dividing or even kill them completely.
For more information: Nature(2014)doi:10.1038/nature13543, Molecular architecture and mechanism of the anaphase-promoting complex 
Fibroadenoma

A stained histopathology slide of a fibroadenoma when viewed under low-power magnification, showing the mix of epithelial (dark) and stromal (light) cells. Credit: Singapore General Hospital

9.  Scientists discover genetic cause of fibroadenomas in women

http://medicalxpress.com/news/2014-07-scientists-genetic-common-breast-tumours.html

  • Fibroadenomas are the most common benign breast tumours in women of reproductive age, affecting millions of women  each year.
  • Frequently discovered in clinical workups for breast cancer diagnosis and during routine breast cancer screening, clinicians often face of challenge of distinguishing fibroadenomas from breast cancer.
  • A team of scientists in Singapore used advanced DNA sequencing technologies to identify a critical gene called MED12 that was repeatedly disrupted in nearly 60% of fibroadenoma cases.
  • The team’s findings have also deepened the conceptual understanding of how tumours can develop.
  • Like most breast tumours including breast cancers, fibroadenomas consist of a mixed population of different cell types, called epithelial cells and stromal cells.
  • However, unlike breast cancers where the genetic abnormalities arise from the epithelial cells, the scientists, using a technique called laser capture microdissection (LCM), showed that the pivotal MED12 mutations in fibroadenomas are found in the stromal cells.

For more information: Nature Genetics, doi:10.1038/ng.3037, Exome sequencing identifies highly recurrentMED12 somatic mutations in breast fibroadenoma

10.  Gene changes in breast cancer cells pinpointed with new computational method

http://medicalxpress.com/news/2014-07-gene-breast-cancer-cells-method.html

  • Computer scientists at Carnegie Mellon University, working with high-throughput data generated by breast cancer biologists at Lawrence Berkeley National Laboratory, have devised a computational method to determine how gene networks are rewired as normal breast cells turn malignant and as they respond to potential cancer therapy agents.
  • The researchers were able to identify different signaling networks with just three microarrays for each of five cell states—normal, malignant and three types of reverted cells.
  • Though the reverted cells looked physically normal in culture, their signaling pathways differed not only from the malignant cells, but also the normal cells.
  • In fact, each had distinctly different signaling pathways depending on what drug had been used to treat them, as each compensated for the effects of the drugs in different ways.
  • In the case of cells that had been treated with MMP inhibitors, the researchers could see how the rewired signaling pathways had created compensatory signaling which would cause them to resist the drug—an effect that would explain why cancer patients receiving MMP inhibitors in clinical trials show either poor survival or no survival benefit.

For more information:  PLOS Computational Biology, July 24, 2014, DOI: 10.1371/journal.pcbi.1003713, Network Analysis of Breast Cancer Progression and Reversal Using a Tree-Evolving Network Algorithm

11.  Study identifies genes linked to breast cancer in East Asian women

http://medicalxpress.com/news/2014-07-genes-linked-breast-cancer-east.html

  • A new study in East Asian women has identified three genetic changes linked to an increased risk of breast cancer.
  • “We found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk and we identified a possible association with a fourth gene locus.  Two of those sequence changes are in parts of the genome that regulate the expression of nearby genes.”
  • ARRDC3 and PRC1 genes were previously linked to breast cancer growth and poor survival in breast cancer patients, respectively. The role of ZC3H11A in breast cancer is unknown.
  • For more information:  Nature Genetics(2014)doi:10.1038/ng.3041, Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

 

12.  Hormones after breast cancer: Not fuel for the fire after all? New study suggests a safe and effective role for bio-identical hormones in treating postmenopausal breast cancer

http://medicalxpress.com/news/2014-07-hormones-breast-cancer-fuel.html

  • Scientists set out to explore a radical and counterintuitive hypothesis: Could an optimal choice of hormones lead to improved survival factors and quality of life, enough to outweigh any negative effect on tumor recurrence?
  • Radical—because current standard of practice considers hormone treatment of any type absolutely contraindicated following hormone-receptor-positive breast cancer.
  • Counterintuitive— because estrogen-blocking aromatase inhibitors, a nearly opposite treatment, are the current adjuvant treatment for women after hormone-sensitive breast cancer.
  • In the experiments, the researchers used the same type of hormones present in the body, because bioidentical hormones have been shown to possess a more positive risk-benefit profile than molecularly altered hormones.
  • In the landmark Women’s Health Initiative study, a negative risk-benefit profile was seen with oral equine estrogens plus oral synthetic medroxyprogesterone acetate (PremPro), an older drug combination that continues to dominate the market in English-speaking countries.
  • Estradiol and progesterone delivered non-orally were selected for the experiments in part because of an extensive literature indicating more favorable outcomes.
  • The results showed that the right combination of hormone treatments reduced the risk of osteoporosis and cardiovascular disease, undesirable health effects associated with estrogen deficiency following menopause.
  • Adding a little testosterone helped even more.
  • Estrogen, progesterone, and testosterone, together (E plus P plus T treatment) was associated with greater physical activity, improved cognition, and better cardiovascular and bone health in the mouse model, and demonstrated the potential significance of hormone treatment in postmenopausal women.
  • Giving any sort of estrogen after hormone-sensitive breast cancer would generally be considered “throwing fuel on the fire.” But the results were counterintuitive: tumor growth was reduced the most by E plus P plus T treatment. Long term, only in one group—the lowest-dose E plus P group—did addition of hormones result in tumor volumes slightly worse than in the control animals, noted Lakshmanaswamy.
  • “In this study, the aromatase inhibitor did indeed reduce recurrence as expected. However, recurrence rates in the aromatase inhibitor group bounced back up after the 5-year-equivalent treatment period, and the overall improved health outcomes in the hormone groups meant a trend towards greater survival in those groups. Even more notably, two of the regimens were even better than the aromatase inhibitor at preventing tumor growth.”
  • To date, epidemiological plus animal and laboratory evidence combined suggest that though the recurrence picture is complicated, the majority of women post-breast-cancer will do better on optimized hormones than on anti-hormones, because of better global outcomes.
  • V. Craig Jordan, OBE, PhD, DSc, a scientist specializing in medications that treat and prevent breast cancer at the Lombardi Comprehensive Cancer Center, Georgetown University, considers the study an intriguing contribution to a scientific area now receiving a lot of interest.
  • Jordan is widely considered the “father” of tamoxifen, a selective estrogen receptor modulator (SERM) that changed the field of breast cancer treatment.
  • He also proved the anti-cancer effects of raloxifene, another SERM that blocks the effects of estrogen in breast tissue.
  • He now studies how cancer cells can be killed by estrogen after being super-sensitized to it by those very same estrogen-blocking drugs.
  • The results of this study are consistent with those found in his lab. “This paper has all of the right results for the tumor and the right results for the mouse. It all lines up as far as I’m concerned.” The only downside, according to Jordan, is the four-month treatment period for the mice—when women are treated for decades, and tumors are “clever and can change in a heartbeat.” “Things happen short term in labs all the time; it’s a very hard sell to go from experiments to outside the lab,” he said.
  • The four-month period for mice was designed to be equivalent to five years in a woman’s lifespan, and is the same time period used in aromatase inhibitor pre-approval studies. But the trend is towards ever-longer treatment periods with aromatase inhibitors, ten years or more, despite impacts on quality of life.

For more information: Reproductive Biology and Endocrinology 2014, 12:66 DOI: 10.1186/1477-7827-12-66, The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model

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