A summary of medical developments in Breast Cancer and Cancer for the week ending 15 August 2014.
In Best of Breast w/e 8 August 2014 it was wasp venom that was being used to fight cancer, now it’s the turn of the bee. OK, it’s not the most earth-shaking medical development, but it makes a change from the usual chemotherapy drugs.trials. And speaking of which, Item 3 examines the fact that different chemotherapy regimes have different side effects, and raises the question that we should reconsider what choices are made in selecting treatments.
Item 2A is about a purported cure using salt injected directly into tumours. Please note that this is not what it seems to be: an easy cure for cancer. The refutation is in Item 2B, and highlights the need not to jump the gun or fall prey to so-called breakthroughs. And this salt cure has nothing to do with Dr. Simoncini’s controversial work on bicarbonate of soda and tumours.
1. Bee, snake and scorpion venom could be used to fight cancer
- Bee, snake and scorpion venom could be used in fight against cancer after trials showed that the toxins can kill tumours.
- Researchers have found the poison contained in insect stings or reptile bites kills breast and skin cancer cells in the lab.
- Venom from snakes, bees and scorpions contains proteins and peptides which can attach to the walls of cancer cells.
- But it can also damage the heart and nerve cells and cause bleeding under the skin
- However, scientists have managed to encase the venom in a tiny particle which stops the poison leaking into the blood and harming the patient.
- The team identified a substance in bee venom called melittin that keeps the cancer cells from multiplying.
- Melittin is a small protein, or peptide, that is strongly attracted to cell membranes, where it can form pores that break up cells and kill them.
- Experimenting on mice, the researchers found that nanobees delivered the bee toxin melittin to tumours, while protecting other tissues from the toxin’s destructive power.
- The researchers have revealed that they tested nanobees in two kinds of mice with cancerous tumours: one mouse breed was implanted with human breast cancer cells, and the other with melanoma tumours.
- They said that after four to five injections of the melittin-carrying nanoparticles over several days, growth of the mice’s breast cancer tumours slowed by nearly 25%, and the size of the mice’s melanoma tumours decreased by 88% compared to untreated tumours.
- The research was presented at the National Meeting of the American Chemical Society in San Francisco.
For more information: Chemical and Engineering News, Volume 92 Issue 33 | p. 9 | News of The Week, Issue Date: August 18, 2014, Directing Venom To Fight Cancer
2A. Salt injection ‘kills cancer cells’
- Scientists have created a technique which can cause cancer cells to self-destruct by injecting them with salt.
- Researchers from the University of Southampton are part of an international team that has helped to create a molecule that can cause cancer cells to die by carrying sodium and chloride ions into the cells.
- Synthetic ion transporters have been created before but this is the first time researchers have demonstrated how an influx of salt into a cell triggers cell death.
- These synthetic ion transporters, described this week in the journal Nature Chemistry, could point the way to new anti-cancer drugs while also benefiting patients with cystic fibrosis.
- “This work shows how chloride transporters can work with sodium channels in cell membranes to cause an influx of salt into a cell. We found we can trigger cell death with salt.”
- Cells in the human body work hard to maintain a stable concentration of ions inside their cell membranes. Disruption of this delicate balance can trigger cells to go through apoptosis, known as programmed cell death, a mechanism the body uses to rid itself of damaged or dangerous cells.
- One way of destroying cancer cells is to trigger this self-destruct sequence by changing the ion balance in cells.
- Unfortunately, when a cell becomes cancerous, it changes the way it transports ions across its cell membrane in a way that blocks apoptosis.
- The researchers have overcome this by developing the synthetic way for transporting the ions but unfortunately this also destroys healthy cells which would have to be overcome for it to be useful in treating cancer.
For more information: Nature Chemistry(2014)doi:10.1038/nchem.2021, Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells
2B. Salt injections: not a cure for cancer
- The researchers did not inject cancer with salt, although they did create a way of getting salt inside cells (but not with a needle and syringe, as you may imagine from the headlines).
- In fact, they made two new molecules that bind to chloride and take it into cells. This increase in chloride also causes sodium to move into the cell, leading to an increase in sodium chloride.
- Scientists already knew that increasing the level of salt within a cell would cause the cell to die, but wanted to know why.
- The researchers found that increasing the salt level within normal and cancer cells in the laboratory caused cell death through one of the natural mechanisms, called the “caspase-dependent pathway”.
- This is a different pathway for cell death than the ones currently triggered by cancer drugs. The researchers hope this knowledge can be used to develop new drugs to treat cancer.
- It is important to note that they have only done this in cells in a laboratory, not in any humans or other living creatures.
3. Breast Cancer Chemotherapy Varies Widely: Study Raises Questions About Early Treatment Choices
- Last month, the Journal of Clinical Oncology reported that six chemotherapy regimens commonly given to patients with early-stage breast cancer vary widely in their side effects.
- The researchers found that some drug combinations are more likely to lead to hospitalization than others.
- The finding, while hardly surprising, points to the value of patients and doctors having fuller discussions about chemotherapy choices.
- An accompanying editorial emphasizes that because most patients are likely to live for a long time after initial therapy for breast cancer, and options abound, chemotherapy decisions should be more granular than is typical in practice.
- TAC and AC + T were associated with the highest risk of hospitalization in patients younger than age 65 years.
- Among patients older than age 65 years, all regimens (aside from dose-dense AC + P) were associated with a higher risk of hospitalization than TC.
- Results may be affected by selection biases where less aggressive regimens are offered to frailer patients.
For more information: (1) Journal of Clinical Oncology, May 27, 2014 JCO.2013.49.3676, Risk of Hospitalization According to Chemotherapy Regimen in Early-Stage Breast Cancer (2) JCO July 1, 2014 vol. 32no. 19 1990-1993, Enhancing Therapeutic Decision Making When Options Abound: Toxicities Matter
4. Cancer should be classified by genetic and molecular type, say scientists
- Doctors usually classify cancer by where its point of origin in the body is: Lung cancer, breast cancer, brain cancer.
- However, a new research study published on August 7 in the journal Cell shows that there may be a more accurate way to diagnose cancer: the genetics of the disease itself.
- The research study was done at the University of California, San Francisco.
- One in ten cancers could be diagnosed more accurately based on genetic makeup, they suggested.
- The researchers also said that if we changed the diagnosis of cancer to be based on genetics, it could revolutionize treatment in the future.
- There have already been studies that suggest cancer should be defined by features at the genetic and molecular level. For example, Medical News Today recently reported another TCGA study that found four distinct molecular subtypes of stomach cancer.
- But in this latest study – the largest genomic study of cancer – the researchers found even across tissue types (for instance, breast, bladder and kidney), what we currently regard as different cancers have tumors that are more similar at the molecular and genetic level than at the tissue level.
- The study also confirms known differences in subtypes of breast cancer but reveals a surprising finding in that basal-like breast cancers – also known as triple-negative breast cancer – are actually a class of their own. These cancers are very aggressive and more common in African-American and younger women.
- Even though these basal-like cancers may arise in the breast, the study shows that at the molecular level they are more like ovarian cancers and cancers of squamous cell origin than other breast cancer subtypes.
- He believes this study and future repeats will improve design of clinical trials by helping to identify patients more likely to respond to new treatments based on the genomic reclassification of their tumors.
- Many more cancer types will be reclassified; possibly as much as 30 to 50 percent.
For more information: Cell, 7 August 2014, DOI: 10.1016/j.cell.2014.06.049, Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin
5. Aspirin may help halt spread of breast cancer
- An Irish-funded study has found that women who have been prescribed aspirin regularly, before being diagnosed with breast cancer, are less likely to have cancer that spreads, than women not on prescription aspirin.
- The study examined data from more than 2,700 women with various stages of breast cancer.
- It found that aspirin may reduce death from breast cancer by preventing the cancer spreading to the lymph nodes.
- Our study was observational and these results do not mean that women should start taking aspirin as a precautionary measure. Aspirin can have serious side-effects.
- We still need to identify exactly how aspirin may prevent breast cancer from spreading to the lymph nodes; which women, or types of breast cancer are most likely to benefit from taking aspirin; as well as what the optimum doses might be.
- The Irish study’s finding comes just a week after research in Britain suggested that taking aspirin every day for 10 years could save tens of thousands of people from dying of cancer.
- However, the same research also said that for every 17 people likely to avoid death by cancer, four others are likely to die from heart, stroke and stomach ulcers linked to long-term use of aspirin.
For more information: 1. Annals of Oncology (2014) doi:10.1093 /annonc/mdu225, Estimates of benefits and harms of prophylactic use of aspirin in the general population; Annals of Oncology; 2. Cancer Res August 1, 201474; 4065, doi: 10.1158/0008-5472. CAN-13-2679, Recent Prediagnostic Aspirin Use, Lymph Node Involvement, and 5-Year Mortality in Women with Stage I–III Breast Cancer: A Nationwide Population-Based Cohort Study
6. ‘Metal detector for cancer’ helps doctors spot tumours instantly by listening to the cells
- Surgeons now able to detect mutant cells by listening to them
- Detectors use a probe hooked up to an audio device with headphones
- Surgeons now able to hear if cancer is present after removing a tumour
For more information: School of Digital Media Technology at Birmingham City University, http://www.bcu.ac.uk/tee/news/groundbreaking-new-research-will-allow-instant-cancer-diagnosis
7. Premenopausal Breast Cancer: Potential New Treatment Standard Is Emerging
- After effective resection of hormone receptor–positive breast cancer in premenopausal women, recurrence is less likely among those treated with ovarian function suppression (OFS) along with exemestane rather than tamoxifen, according to a combined analysis of two large studies called TEXT and SOFT.
- Previously confined to use in postmenopausal women, now adjuvant exemestane combined with OFS “provides a new treatment option” in the premenopausal setting.
For more information: N Engl J Med 2014; 371:107-118 July 10, 2014 DOI: 10.1056/ NEJMoa1404037, Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer
8. Nanoparticles could help deliver a killer blow to cancer
- Nanotherapy is showing promise as a means to target chemotherapy, kill tumour cells by heating or enhance the effectiveness of radiotherapy.
- “The reason chemotherapy doesn’t always work is because you can’t give enough of it without exposing the body to too many toxins,” explains Jack Hoopes of the Norris Cotton Cancer Centre in New Hampshire. “So you can’t get enough drug into the tumour to be effective. I think what nanotechnology offers is the ability to target things to individual cancer cells and that’s the future of cancer therapy.”
- Nanoparticles are typically between 3 and 200 nanometres across, allowing them to be injected directly into the tumour for more accessible cancers, or injected in close proximity in combination with antibodies that target cancer cells.
- The unique architecture of tumours’ blood supply makes it easy for them to absorb nanoparticles. There are “fenestrations” or gaps in the walls of blood vessels that opened up when the tumours formed, says Helen Townley of the Department of Engineering Science at Oxford University.
- “Instead of having a nice continuous sheet of cells as you see in normal blood vessels, the arrangement is very rapid, chaotic and disorganised. These gaps are up to 300nm, so as long as our nanoparticles are smaller than that, they’re going to leave the blood vessel and enter the tumour.”
- Once the nanoparticles are inside the tumour they’re likely to stay there, she says. Normal tissue is drained by lymph vessels, but tumour tissue lacks this efficient drainage system
- The main aim has been to use nanoparticles to increase chemotherapy doses but researchers have been increasingly looking at additional means of destroying tumours or slowing their growth.
- Hoopes’s group uses iron oxide nanoparticles coated with biocompatible substances.
- Once inside the tumour, the iron oxide nanoparticles can be heated using an alternating magnetic field, killing it with little damage to the surrounding tissue.
- Researchers at Oxford University have been looking at titanium nanoparticles as a means of enhancing the effectiveness of radiotherapy.
- When the particles are excited by x-rays they generate high concentrations of reactive oxygen species – chemically reactive molecules that cause significant damage to cell structures leading to cell death.
- “Essentially you can treat any tumour with radiotherapy if you can turn [the power] up high enough,” Townley says.
- “But you’ve got this therapeutic index which is the balance between damaging healthy tissue and damaging the tumour tissue.
- If we can get the nanoparticles into tumours where normally you wouldn’t be able to crank the radiation up high enough without severely harming the patient, we have the potential for a lower dose or a shorter course of treatment.”
- Her group has also developed microparticles for another technique called chemoembolisation.
- The microparticles – which are about a thousand times bigger than nanoparticles – block the blood supply carrying food and oxygen to the tumour, causing the cancerous tissue to die.
- Nanoparticles attached to the bigger particles also deliver chemotherapy to the site of the tumour.
- So far the researchers have applied their techniques in preclinical studies looking at lung cancer in mice.
- While lung cancer survival rates in humans have almost doubled over the past 20 years, the disease remains one of the deadliest common cancers in the UK, with five-year survival rates of less than 10% for both men and women.
For more information: (1) http://cancer.dartmouth.edu/about_us/newsdetail/65737/, (2) http://www.begbroke.ox.ac.uk/Academic/ResearchGroups/HelenTownley.php
9. How breast cancer usurps the powers of mammary stem cells
- A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex.
- While having a child reduces a woman’s risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy.
- The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.
- During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland.
- These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child.
- Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.
- The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors.
- The researchers focused on a family of cell surface receptor proteins called integrins that act as key communications conduits, ultimately zeroing in on the role of one member of this family called beta-3 integrin.
- Also known as CD61, it was already linked to metastasis and resistance to cancer drugs.
- This property may be to blame for the more aggressive nature of beta3-expressing breast cancer cells.
- This normal pathway ends up contributing to the progression of cancer.
For more information: Developmental Cell, Volume 30, Issue 3, 11 August 2014, Pages 251–252, A Role for β3-Integrins in Linking Breast Development and Cancer
10. Discovered: new way of predicting cancer-free survival in breast cancer patients
- UNIVERSITY of Queensland researchers have discovered a way of predicting cancer-free survival in breast cancer patients and identified a new treatment target.
- The researchers found that breast cancer patients with a particular genetic ‘signature’ are more likely to survive without their cancer spreading.
- The team also identified a protein that could be targeted by cancer drugs.
- Tissue samples from over 100 breast cancer patients were analysed and it was discovered that those with low levels of the enzyme PRMT2 had a better chance of surviving without their cancer metastasising.
- This enzyme has the ability to affect hundreds of genes so we also examined these genes and the proteins they produce.
- One of these proteins, RORγ, is a druggable protein, meaning it appears to be a good target for treatment.
- This discovery suggests in future doctors will be able to more confidently predict outcomes in some breast cancer patients, and subsequently improve treatment regimes.
For more information: Molecular Endocrinology, DOI: http://dx.doi.org/10.1210/me.2013-1403, PRMT2 and RORγ Expression Are Associated With Breast Cancer Survival Outcomes
11. Tumor-infiltrating lymphocytes predicted outcomes in triple-negative breast cancer
- Stromal lymphocytic infiltration significantly and independently predicted outcomes in patients with triple-negative breast cancer treated with adjuvant chemotherapy, according to an analysis of data from two randomized phase 3 trials.
- Most of the 481 evaluable cancers has stromal TILs (80%), whereas 15% had intraepithelial TILs.
- Median follow-up was 10.6 years. Researchers found that higher stromal TILs scores were associated with a better overall prognosis. Specifically, every 10% increase in stromal TILs correlated with a 19% decreased risk for death (P=.01), an 18% decreased risk for distant recurrence (P=.04), and a 14% decreased risk for recurrence or death (P=.02).
- Multivariable analysis showed stromal TILs were independent prognostic markers of DFS, distant recurrence-free interval and OS.
For more information: Journal of Clinical Oncology, July 28, 2014, doi:10.1200/ JCO.2013.55.0491, Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
12. Study shines new light on genetic alterations of Luminal B subtype breast cancer
- Researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine have uncovered new information about the genetic alterations that may contribute to the development of a subtype breast cancer typically associated with more aggressive forms of the disease and higher recurrence rates.
- While expressing the estrogen receptor, the luminal B breast cancers usually have higher tumor grade, larger tumor size, and poor prognosis, with most cases difficult to treat by endocrine therapy.
- “We wanted to gain a deeper understanding about the genetic alterations underlying this particular form of breast cancer, because we do not know about what malfunctions potentially cause this form to be more aggressive.”
- In the study, Wang and colleagues identified a particular gene fusion on the estrogen receptor itself (hybrid gene formed from two previously separate genes) that was preferentially present in a subset of samples of tumors that were luminal B and ER-positive.
- The fusion was a result of rearrangements in the estrogen receptor gene called ESR1 and another neighboring gene called CCDC170.
- Rearrangement in the genes causes the disruption of the transfer of information.
- In a majority of cases this fusion seems to be generated by a tandem duplication of the genetic material spanning the ESR1 and CCDC170 genes.
- The aggressive luminal B subtype of breast cancer is a heterogeneous and complex disease.
- In the era of precision medicine, the current study emphasizes the importance and promise of integrative genomic research methodologies.
- This approach can identify genetic aberrations that may drive the development and progression of these aggressive tumors and that may guide more personalized effective therapeutic strategies.
For more information: Nature Communications, 5, Article number: 4577 doi: 10.1038/ ncomms5577, Recurrent ESR1–CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers
13. Women with multiple endocrine neoplasia type 1 gene mutation more predisposed to breast cancer
- Women with a rare gene mutation and associated hereditary endocrine disease are at an increased risk for breast cancer, according to a letter published in the August 7 issue of the New England Journal of Medicine.
- The rare disease is known as multiple endocrine neoplasia type 1, or MEN1, and is caused by germline mutations in the MEN1 tumor-suppressor gene.
- MEN1 patients are susceptible to various benign and malignant tumors, such as parathyroid tumors, duodenopancreatic neuroendocrine tumors, and pituitary adenomas.
- Now, an international team of researchers has discovered that female patients with MEN 1 are also more likely to have breast cancer than members of the general population. In addition, they tend to develop breast cancer at a much younger age.
For more information: N Engl J Med 2014; 371:583-584 August 7, 2014 DOI: 10.1056/NEJMc1406028, Breast-Cancer Predisposition in Multiple Endocrine Neoplasia Type 1
14. Biphosphonates may not protect osteoporotic women from breast cancer
- Osteoporosis drugs known as bisphosphonates may not protect women from breast cancer as had been thought, according to a new study led by researchers at UC San Francisco (UCSF).
- The drugs’ protective effect was widely assumed after several observational studies showed that women who took them were less likely to get breast cancer.
- But when researchers assessed the effect of two of the most widely used osteoporosis drugs – sold under the brand names, Fosamax and Reclast – in two large randomized clinical trials, neither drug protected women with osteoporosis from getting breast cancer. The results were published August 11, 2014, in JAMA Internal Medicine.
- The researchers said the link found in the previous observational studies between taking the drugs and having a lower incidence of breast cancer may be due to a third factor, low estrogen.
- Since having low estrogen both weakens bones and protects against most breast cancers, the women most likely to be prescribed drugs for osteoporosis are usually also at lower risk for breast cancer.
For more information: JAMA Intern Med. Published online August 11, 2014. doi:10.1001/ jamainternmed.2014.3634, Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer
15. Preventing chemotherapy resistance in triple negative breast cancer
- ‘Triple-negative’ breast cancer can sometimes be more aggressive, and has limited treatment options
- In addition, breast tumours can sometimes become resistant to chemotherapy drugs used to treat them
- Paclitaxel, or Taxol, is a chemotherapy drug used to treat triple‑negative breast cancer
- Researchers have recently found that a protein, when overproduced in breast tumours, increases resistance to chemotherapy
- Dr Murphy has found that another protein interacts with this overproduced protein
- She believes that they work together to make breast tumours resistant to chemotherapy drugs like paclitaxel
- In this project, Dr Murphy will study in more detail how the two proteins work together to cause resistance to chemotherapy, using triple-negative breast cancer cells grown in the lab
- Dr Murphy will also measure the amounts of both proteins in samples of tumours donated by people with triple-negative breast cancer
- This will tell her whether these two proteins could be used to predict which breast tumours might become resistant to chemotherapy drugs
16. Colgate Total Ingredient Linked to Hormones, Cancer Spotlights FDA Process
- The chemical triclosan has been linked to cancer-cell growth and disrupted development in animals.
- US regulators are reviewing whether it’s safe to put in soap, cutting boards and toys. Consumer companies are phasing it out.
- Minnesota voted in May to ban it in many products.
- At the same time, millions of Americans are putting it in their mouths every day, by way of a top-selling toothpaste that uses the antibacterial chemical to head off gum disease –Colgate-Palmolive Co.’s Total.
- Total is safe, Colgate says, citing the rigorous Food and Drug Administration process that led to the toothpaste’s 1997 approval as an over-the-counter drug.
- A closer look at that application process, however, reveals that some of the scientific findings Colgate put forward to establish triclosan’s safety in toothpaste weren’t black and white — and weren’t, until this year, available to the public.
- Colgate’s Total application included 35 pages summarizing toxicology studies on triclosan, which the FDA withheld from view. The agency released the pages earlier this year in response to a lawsuit over a Freedom of Information Act request. Later, following inquiries from Bloomberg News, the FDA put the pages on its website.
- The pages show how even with one of the U.S.’s most stringent regulatory processes — FDA approval of a new drug — the government relies on company-backed science to show products are safe and effective.
- Among the pages were studies showing fetal bone malformations in mice and rats. Colgate said the findings weren’t relevant.
- Viewed through the prism of today’s science, such malformations look more like a signal that triclosan is disrupting the endocrine system and throwing off hormonal functioning, according to the three scientists.
For more information: FDA drug approval package for Colgate Total, July 11, 1997
17. New ways to treat hormone receptor-positive breast cancer
- Up to 80% of breast cancers overproduce the oestrogen receptor (ER), and many also overproduce the progesterone receptor (PR), which drive the growth of tumours.
- ‘Anti-hormone’ drugs exist to halt the growth of these cancers, by blocking the activity of these hormone receptors, but sometimes the cancer can become resistant to these drugs.
- ER or PR are overproduced in the cells of up to 80% of breast tumours and once activated cause the cancer cells to multiply, driving tumour growth. They do this by binding to the DNA in places that have specific genetic codes, and activating genes that cause the cell to multiply and survive.
- Scientists will create short pieces of DNA in the lab which could act as ‘decoys’, mimicking the parts of DNA that ER or PR would normally bind to.
- These could then be used like drugs to block ER or PR from binding to the breast cancer cell’s DNA, and so prevent them from driving the growth of breast cancer.
- Scientists will test whether ER and PR bind to these fragments, and study what effect they have on breast cancer cells grown in the lab.
For more information: http://www.keele.ac.uk/pressreleases/2014/newwaystotreathormonereceptor-positivebreastcancer.html
18. Gut bacteria can predict colon cancer
- A new study published in Cancer Prevention Research, a journal published by the American Association for Cancer Research, shows that analyzing the bacteria in the colon was more successful at screening patients for precancerous adenomatous polyps and signs of colorectal cancer than fecal occult blood testing.
- The researchers were able to find unique microbiome signatures for each group. When they additionally factored in age and race, risk factors for colon cancer and precancerous polyps, they were able to increase prediction of precancerous adenomatous polyps by 4.5 times the amount of just the bacteria alone. When they additionally factored in BMI, another risk factor for colon cancer, they improved the accuracy of prediction by 5.4 times.
- The study found that analyzing microbiome signatures in the gut together with fecal occult blood tests, age, race, and BMI was significantly better than analyzing for fecal occult blood tests alone.
For more information: Cancer Prevention Research, Published Online August 7, 2014; doi:10.1158/1940-6207.CAPR-14-0129, The Human Gut Microbiome as a Screening Tool for Colorectal Cancer