Breast cancer accounts for nearly 1 in 3 cancers diagnosed in U.S. women [2]. In October 2010, the National Breast Cancer Coalition (NBCC) called for a vaccine for breast cancer with a deadline of 2020. Almost a year later, GE’s healthymagination initiative has also focused on breast cancer with a target of 2020.

Modeled after GE’s ecomagination challenge, which resulted in over 5,000 submitted ideas and $134 million in investments and partnerships by GE, the new healthymagination challenge focuses on improving early detection of breast cancer at the molecular level. GE’s first healthymagination Challenge is an open call to action for oncology researchers, businesses, students, and healthcare innovators. Through the Challenge, GE and its venture capital partners will award up to $100 million to fund the best ideas to improve breast cancer diagnostics. The are several goals to the Challenge:

1. Improve early breast cancer detection and allow for more accurate diagnosis
2. Better understand tumors associated with triple negative breast cancer, which is less responsive to standard treatments and is typically more aggressive
3. Better understand the molecular similarities between breast cancer and other solid tumors

Jeff Immelt, CEO and Chairman, GE, said [3]:

We envision a day when cancer is no longer a deadly disease. When you add our cutting edge cancer detection technologies to the innovative ideas of our new partners, it’s a powerful formula for tackling cancer and helping doctors and researchers improve care.

In partnership with O’Reilly Media, the effort will also feature a special focus on data (CEO and founder, Tim O’Reilly, is an advocate for using data science to spur innovation). A series of code-a-thons or “data challenges” will be held to engage the data science community in finding new applications for breast cancer data.

To enable analysis and further accelerate innovation, GE is also investing in the development of a first-in-kind “super database” that will consolidate clinical, pathology, therapy and outcomes data. The database will be available in collaboration with leading cancer research organizations, as well as NGO and government groups, starting with relevant cancer data from GE’s Medical Quality Improvement Consortium (MQIC); Clarient, a cancer diagnostics and GE Healthcare Company; The Premier healthcare alliance; and the U.S. Department of Health & Human Services.

In addition, Immelt also said that GE will invest $1 billion over the next five years on research and development programs to expand its suite of advanced technologies and solutions for cancer detection and treatment. At the September event, GE presented several new technologies:

1. GE SenoCase, a new concept in mobile mammography that will deliver breast cancer screening capabilities to millions of women around the world who lack access to existing screening options
2. GE PET Tracer, a new Positron Emission Tomography (PET) tracer technology in development that will inform doctors if cancer treatments are working, very early in the course of treatment, by measuring new blood vessel formation in tumors
3. GE SenoBright Contrast Enhanced Spectral Mammography (CESM), a technique that helps radiologists localize a known or suspected breast cancer lesion

Lastly, GE announced a three-year partnership with Susan. G Komen for the Cure to forge first-in-kind programs that bring the latest breast cancer technologies to more women in the United States and around the world. Initially, these programs will run in Wyoming (one of the most rural states in the U.S.), Saudi Arabia and China.

GE will publicly track progress against this cancer initiative at healthymagination.com.

References

1. GE Launches New Commitment to Accelerate Cancer Fight: Integrated Tech Portfolio and Collaboration with Doctors and Researchers to Deliver Better Care to 10M Patients by 2020. GE reports. 2011 Sep 15.
2. Breast Cancer Facts & Figures 2011-2012. American Cancer Society. Accessed 2011 Nov 17.
3. GE and Partners Aim to Speed Fight Against Cancer, Starting with Breast Cancer. Healthymagniation press release. 2011 Sep 15.

In December 2010, VBI researchers discovered a four-nucleotide repeat (AAAG) in the estrogen-related receptor gamma (ESRRG) gene, which indicates an individual’s genetic susceptibility to breast cancer [2]. Longer DNA sequences of the repetitive microsatellite were much more likely to be present in breast cancer patients than healthy volunteers; patients with a greater number of copies of the repeat in the promoter region of the ESRRG gene have a 3-fold higher cancer susceptibility rate than those who do not.

In the present study, instead of focusing on a single gene, the scientists created a design for a new DNA microarray that allowed them to measure the over 2 million microsatellites in the human genome in a single experiment. They evaluated the global microsatellite content in the genomes of 72 cancer, cancer-free, and high risk patient and cell line samples.

A unique, reproducible and statistically significant motif of 18 pattern-specific microsatellite families was identified in germline and tumor DNA from breast cancer patients but not in germline DNA of cancer-free patients or in breast cancer patients with BRCA1 or BRCA2 mutations.

These 18 pattern-specific microsatellite families suggest a new mechanism disrupting the genome in cancer patients and may represent a new breast cancer risk biomarker.

The repetitive motifs were also more pronounced in the germlines and tumors of colon cancer tumor patients (3/6 samples) and microsatellite unstable colon cancer cell lines. Although there were only 9 colon cancer samples, it suggests a more general role for microsatellites in the genome. The pattern on the microarray serves as the biomarker that can measure the amount of risk an individual has for developing cancer in the future.

Harold “Skip” Garner, VBI executive director who leads the institute’s Medical Informatics and Systems Division, explained:

We have now arrived at a new biomarker — an indicator that could be used to evaluate the amount of risk that you have for developing cancer in the future. This is part of an effort to understand their (microsatellite) role in the genome and then proceed on directly towards something that is of utility in the clinic. What just came out in our paper is a description of the technology that allows us to very quickly and efficiently and inexpensively measure these two million places using a uniquely designed microarray … It’s the pattern on that microarray that provides us the information we need.

You can watch an interview with Dr. Garner discussing the research and its future implications below:

References

1. Galindo et al. Sporadic breast cancer patients’ germline DNA exhibit an AT-rich microsatellite signature. Genes Chromosomes Cancer. 2011 Apr;50(4):275-83. doi: 10.1002/gcc.20853. Epub 2011 Jan 14.
   View abstract
2. Genetic Biomarker for Risk of Breast Cancer Identified in “Junk” DNA. Biomarker Commons. 2010 Dec 20.

On one side, you have critics of the FDA accusing them of rationing healthcare while on the other side, you have comparative effectiveness research showing that there’s no statistically meaningful difference in the survival of patients receiving Avastin plus chemotherapy compared to chemotherapy alone.

What is Comparative Effectiveness Research?

Traditional clinical research typically evaluates the effectiveness of a single method for preventing, diagnosing or treating health conditions compared to no intervention. Comparative effectiveness research compares two or more different methods. This is done using clinical trial data, analyses of claims records, systematic reviews of biomedical literature or computer modeling.

The aim of comparative effectiveness research is to improve health outcomes by developing evidence-based information on the effectiveness of treatments relative to other options and disseminating that information to patients, providers and healthcare decision-makers.

Over the past decade, there has been some federal funding for comparative effectiveness research, principally through the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ). Funding was dramatically increased when, in 2009, the American Recovery and Reinvestment Act allocated $1.1 billion for comparative effectiveness research.

The PPACA builds on the economic recovery package to support and direct research comparing patient treatments. The PPACA establishes a new Patient Centered Outcomes Research Institute (PCORI) responsible for the identification, prioritization and execution of comparative effectiveness research.

The issue surrounding Avastin

And that brings us to the issue surrounding the use of Avastin.

Avastin (bevacizumab) is a targeted monoclonal antibody that prevents tumors from creating and maintaining their own blood supply. Tumors can’t grow without oxygen and nutrients from blood. Avastin doesn’t cure cancer; it averts and/or reduces the spread of cancer-causing cells.

Avastin blocks a protein called vascular endothelial growth factor (VEGFA and VEGFB), which plays an important part in the formation of blood vessels, a process called angiogenesis. In addition to metastatic breast cancer, Avastin has also been approved for metastatic colorectal cancer, non-small cell lung cancer, metastatic kidney cancer and glioblastoma.

In 2008, the FDA granted accelerated approval for Avastin to be used in combination with paclitaxel chemotherapy for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. The approval was based on a phase III study (the E2100 study) of 722 patients with metastatic breast cancer randomly assigned to receive Avastin with paclitaxel chemotherapy or paclitaxel alone. A doubling in progression-free survival was observed in patients who received Avastin in combination with paclitaxel chemotherapy compared to patents who recieved paclitaxel alone [1].

Note however that this result doesn’t mean that women taking Avastin lived longer. A doubling in progression-free survival simply means that it took twice as long for the tumor to progress. In fact, there was no increase in overall survival. Moreover, those women who received Avastin experienced a higher overall incidence of toxicities as well as more severe toxicities.

A second phase III trial, the (Avastin plus Docetaxel) AVADO trial, investigated the benefits of combining Avastin with a different chemotherapy, docetaxel, in over 700 previously untreated patients HER2-negative locally recurrent or metastatic breast cancer [2]. In the primary analysis (data cut-off point: October 2007; median follow-up of 10.2 months), treatment with Avastin significantly increased progression-free survival compared to patients who received docetaxel chemotherapy alone [3]. However, more recent analysis of the patient population evaluating overall survival (data cut off point: April 2009; median follow-up of 25 months) failed to define a statistically meaningful benefit [4].

A third phase III trial, the RIBBON-1 trial, evaluated chemotherapy (assigned at the discretion of a physician: either a taxane, an anthracycline or capecitabine) with or without Avastin for first-line treatment of stage IV HER2-negative locally recurrent or metastatic breast cancer [5]. Avastin plus capecitabine compared with placebo plus capecitabine, and Avastin plus taxane or anthracycline versus placebo plus a taxane or anthracycline significantly improved progression-free survival but had no effect on overall survival.

In both the AVADO and RIBBON-1 trials, women receiving Avastin had an increased risk of death; 0.8% of women in AVADO and 1.2% of women in RIBBON-1 died from side effects thought to be related to Avastin [6].

A fourth phase III trial, the RIBBON-2 trial, which evaluated the efficacy and safety of Avastin in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer also significantly improved progression-free survival but failed to show statistically significant improvement of overall survival [4].

Thus, Avastin reproducibly increases progression-free survival but, on average, doesn’t keep women with metastatic breast cancer alive any longer than chemo alone.

Exceptions to the rule

The survival benefit identified in the four studies described above is an average, not an absolute. Avastin does increase overall survival in some patients. One of those patients is Christi Turnage, a registered nurse and breast-cancer survivor from Madison, Mississippi. Turnage started an online petition in the hopes of convincing the FDA to maintain the breast cancer indication for Avastin. Her son Josh wrote about the family’s fight in a plea to the FDA:

We did have a small bit of hope, though. Even though there’s not yet a cure for cancer, a new medicine — Avastin — had just been approved by the FDA, to be used in conjunction with chemotherapy. After just four treatments of medicine, all signs of cancer had left. My mom’s doctor couldn’t even find a trace of it.

In January 2009, my mom had her last chemotherapy treatment. Since then, she’s only been on Avastin. Twenty months later, she remains cancer free.

The problem with Avastin is that doctors don’t know which patients will respond favorably in terms of overall survival. In the majority of patients, Avastin increases progression-free survival but has no effect on overall survival.

When the FDA started discussing the possibility of withdrawing the indication for Avastin, critics of the agency accused them of rationing healthcare, claiming that it was Avastin’s high cost (as much as $100,000 a year), not its limited benefit, that the FDA cared about.

Although the issue clearly revolves around Avastin’s survival benefit, the FDA should be concerned about costs. Healthcare costs endanger U.S. financial stability. Simply ignoring the skyrocketing costs of healthcare and focusing exclusively on the treatment benefits, however small — in this case the average survival benefit is zero — will have a devastating effect on the U.S. economy.

Our opinion

Avastin should be placed in a restricted-access program so that patents already on the drug and benefiting from it can maintain access to it. Pharmacogenomics should be used to identify the best candidate patient population and a subsequent study should then be undertaken to determine biomarkers that have clinical utility in measuring the efficacy of Avastin in those patients. Several candidate biomarkers have already been described, including tumor and plasma VEGF, circulating E-selectin, ICAM 1 and VCAM1 [7].

We consider this a realistic and rational approach to provide effective, personalized therapy while simultaneously managing healthcare costs.

Indeed, patient advocacy organizations called for the use of personalized medicine stratetiges back in August to keep Avastin on the market for those who are most likely to benefit from the disease [8-9]:

We recognize the benefits of Avastin overall are modest for women with metastatic breast cancer. However, we do know that for some women, Avastin offers a greater benefit — but we do not yet know how to determine which patients will experience greater benefits. We have much more to learn about the drug and how individual patients respond to the drug, such as why some women receive greater benefit while others do not. Moving into the world of personalized medicine, cancer treatments will be more tailored to the characteristics of patients’ individual tumors. Yet, due to the current state of the science, we don’t always know which patients will benefit most before a drug is made commercially available. As with all medicines, we encourage a thoughtful discussion between a woman and her doctor that carefully considers the benefits and the risks. FDA approval is not a requirement for a doctor to prescribe a drug. However, the panel’s decision could limit the so-called “off-label” use of Avastin for metastatic breast cancer — or ovarian cancer, for which Avastin is currently prescribed off label — if third party payers refuse to cover the cost of treatment.

References

1. Miller et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76.
   View abstract
2. D. Miles et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J. Clin. Oncol. 2008;26(155)(Suppl): LBA1011.
3. Avastin improves survival in advanced breast cancer. Pharma Strategy Blog. 2008 Jun 2.
4. Avastin for breast cancer shines in PFS but not overall survival. Pharma Times. 2009 Dec 4.
5. Robert et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J. Clin. Oncol. 2009;27(155)(Suppl): 1005.
6. FDA Advisory Committee Recommends against Bevacizumab for Metastatic Breast Cancer. NCI Cancer Bulletin. 2010 Jul 27.
7. Yang SX. Bevacizumab and breast cancer: current therapeutic progress and future perspectives. Expert Rev Anticancer Ther. 2009 Dec;9(12):1715-25.
   View abstract
8. Statement on Avastin. Susan G. Komen for the Cure. 2010 Aug 17.
9. Ovarian Cancer National Alliance and Susan G. Komen for the Cure Appeal to FDA and Key Lawmakers on Avastin Issue. Ovarian Cancer National Alliance. 2010 Aug 12.

Since 1991, the National Breast Cancer Coalition — an influential disease lobbying organization — has promoted evidence-based medicine and focused its public policy advocacy on legislative priorities that encompass three primary goals: increased funding for breast cancer research, improved access to quality breast cancer care and clinical trials, and expanded influence of breast cancer advocates wherever and whenever breast cancer decisions are made.

Last month, the National Breast Cancer Coalition (NBCC) launched the Breast Cancer Deadline 2020 — a call to action for policymakers, researchers, breast cancer advocates and other stakeholders to end the disease by January 1st, 2020.

In what some might call an unrealistic goal, the NBCC has drawn a line in the sand. Clearly, however, the NBCC has had it with the status quo, declaring that more of the same will not end breast cancer [1]:

More than 40 years and billions of dollars have not ended breast cancer. It has, however, created a robust cancer industry that thrives on raising awareness and producing drugs, screening devices and genetic tests. It has also created an academic system that generates hundreds of thousands of articles about breast cancer and builds careers for thousands. Although there is no doubt individual researchers sincerely want to end breast cancer, every system is perfectly designed to achieve the results it gets. The current system is perfectly designed to be lucrative, cautious and incremental.

Breast cancer research takes place within many disciplines, including laboratory science, clinical research, epidemiology, social sciences, and health services research. Generally, research organizations do strive for excellence and prioritize in order to make significant progress in their work. However, there are conflicting agendas that can hinder progress. Pursuit of fame and profit can take the emphasis away from achieving genuine advances for women. Emphasis on research for its own sake limits the avenues for application. Reluctance to include patient and advocate perspectives in research means that issues critical to those living with breast cancer and at risk are neglected, which results in less productive or useful research.

Breast cancer research over the decades has produced elegant science and thousands of important research papers, but little that has had a big impact on patients or those at risk. It is possible for researchers to gain significant acclaim for their work, and to be judged highly successful by the scientific world’s measurement, without having helped a single patient. The system rewards safe ideas and discourages innovative ones that might lead to the big breakthroughs in prevention and treatment. The infrastructure of breast cancer research is to keep things moving along as they have been and to reward people for doing safe, low-impact work. These obstacles are not scientific challenges but rather organizational and systematic dysfunctions. These are problems with solutions.

The NBCC is doing more than just setting a deadline. They have outlined an action plan to get there.

The NBCC has hosted catalyst meetings for more than a decade, bringing together a unique combinations of expert perspectives, including advocates, policy makers, physicists, geneticists, healthcare providers, economists, mathematicians and epidemiologists. The NBCC is now expanding its catalyst meetings to address important questions that are often overlooked but could have a dramatic impact on ending breast cancer; the NBCC will assist in the development of collaborations to design and implement strategies to answer them. The first initiative is the development of a preventive breast cancer vaccine.

A breast cancer vaccine

Cancer vaccines are designed to strengthen the body’s natural defenses by stimulating the immune system to recognize and attack existing cancer cells. There is a model for the NBCC’s approach: human papilloma virus (HPV). Key to this strategy and the challenge for researchers will be the identification of molecular mechanisms shared among the various breast cancer subtypes that cause the disease. A breast cancer vaccine may be closer than you think. A report in Nature Medicine earlier this year reported an experimental vaccine that prevented breast cancer in mouse models [2].

Dr. Kathy Miller from Sound Medicine — a weekly talk radio show produced by the Indiana University School of Medicine and WFYI Public Radio — recently interviewed the researcher who led the study, immunologist Dr. Vincent Tuohy. You can listen to the interview at Sound Medicine.

The National Breast Cancer Coalition (NBCC) is determined to end breast cancer and is committed to the challenges necessary to overcome whatever barriers are in the way. What do you think? Check out BreastCancerDeadline2020.org and choose your side.

References

1. Breast Cancer Deadline: Why Now? National Breast Cancer Coalition whitepaper. 2010 Sep 20.
2. Jaini et al. An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nat Med. 2010 Jul;16(7):799-803. Epub 2010 May 30.
   View abstract

Over 200,000 American women will be diagnosed with invasive breast cancer this year [1]. Health Dialog’s decision aid for early-stage breast cancer helps empower women with the information they need to answer tough questions and make informed decisions when they face a breast cancer diagnosis. The company’s decision aids are currently offered to over 20 million individuals through the health plans that the company works with and also at various physician practice demonstration sites through the Foundation for Informed Medical Decision Making.

Facing the decisions

Women diagnosed with early-stage breast cancer face many decisions. The quality of a decision can be measured by the extent to which the treatment reflects the goals of the patient (i.e. what is most important to an informed patient). A recent study that surveyed breast cancer survivors and providers for three types of breast cancer treatment decisions — surgery, reconstruction and adjuvant chemotherapy, and hormone therapy — identified 38 facts (11–14 per decision) and 27 goals (8–10 per decision) relevant to each treatment decision [2].

These facts and goals are reflected in Health Dialog’s breast cancer decision aid Early-Stage Breast Cancer: Choosing Your Surgery. The program is just one of Health Dialog’s many Shared Decision Making initiatives that has been nationally recognized.

Health Dialog is a private, wholly-owned subsidiary of Bupa, a global provider of healthcare services. Health Dialog helps healthcare payors improve healthcare quality while reducing overall costs. Company offerings include health coaching for medical decisions, chronic conditions, and wellness; population analytic solutions; and consulting services. Health Dialog helps individuals participate in their own healthcare decisions, develop more effective relationships with their physicians, and live healthier, happier lives.

Early-stage breast cancer: choosing your surgery

Health Dialog’s decision aid Early Stage Breast Cancer: Choosing Your Surgery provides patient-friendly explanations of medical terms, comparisons of the treatment choices, photos and diagrams, many videos, and a printable booklet, covering everything from how to read a pathology report to illustrating what a patient can expect from different types of surgeries.

The decision aid explains what breast cancer is, the local and systemic treatments for breast cancer, and choices for surgery: mastectomy or lumpectomy with radiation. It describes each of the surgeries and what to expect after the procedure is done, including possible side effects.

The decision aid helps patients make decisions by comparing and contrasting treatments, asking personal, reflective questions about the choices, and suggesting questions to ask the doctor. In addition, the tool includes photos of how women look after lumpectomy or mastectomy, after breast reconstruction surgery, and in some cases after surgery on the other breast to match the results of a breast reconstruction.

The section on working with your doctor defines “shared decision-making” and provides video interviews with women who were involved in their treatment decisions. Lastly, something we particularly like here at Highlight HEALTH, all the research that supports the decision aid is listed and linked to abstracts published at the National Library of Medicine.

According to Jan Maurer, MD, Vice President and Medical Director at Health Dialog [3]:

Facing a breast cancer diagnosis is an intimidating situation that thousands of women unfortunately experience every month. Research shows that women participating in their treatment decisions are more confident in facing the experiences that come with the diagnosis. This decision aid is designed to strengthen the conversations between patients and physicians and help empower women to make informed decisions about their breast cancer treatment.

You can explore the decision aid at www.healthdialog.com/go/BCAM. You can also get there by going to www.healthdialog.com and, at the bottom of the page under “Raising Awareness,” clicking on “Visit HealthCrossroads.com.”

References

1. Cancer Facts & Figures 2010. American Cancer Society. 2010.
2. Lee et al. Development of instruments to measure the quality of breast cancer treatment decisions. Health Expect. 2010 Sep;13(3):258-72. Epub 2010 Jun 9.
   View abstract
3. Health Dialog Makes Decision Aid Available for Breast Cancer Awareness Month. Health Dialog. 2010 Oct 5.

Breast Cancer Awareness Month — also referred to as National Breast Cancer Awareness Month (NBCAM) — is an annual international health campaign organized by major breast cancer charities every October to increase awareness of the disease and raise funds for research into its cause, prevention and cure. The campaign also offers information and support to those affected by breast cancer.

In 2010, the American Cancer Society estimates that 207,090 women will be diagnosed with invasive breast cancer, approximately 54,010 women will be diagnosed with carcinoma in situ (CIS; the earliest non-invasive form of breast cancer), and approximately 39,840 women will die from breast cancer [1]. Indeed, breast cancer is the second leading cause of cancer death in women, following lung cancer.

In 1975, a woman had a 1 in 11 chance of developing invasive breast cancer some time in her life — today, the chance is even greater at 1 in 8. Although the risk has increased, deaths due to breast cancer have been declining: from 1990 — 2006, death rates decreased by 3.2% per year among women younger than 50, and by 2.0% per year among women 50 and older [2]. This decline in breast cancer mortality has been attributed to improvements in breast cancer treatment and early detection [3].

Animal research has contributed significantly to advances in breast cancer treatment. Animal studies were essential for the development of two front-line drugs that shrink breast cancer tumors, Herceptin and Tamoxifen. Since their mechanisms of action are different, they are used to treat different types of tumors. The drug Tamoxifen blocks tumor growth by blocking the action of estrogen, a hormone involved in the growth of most breast cancers. Tamoxifen binds to the estrogen receptor and blocks estrogen from docking to it. The drug Herceptin binds to another growth-regulating receptor protein called HER2, blocking it’s action and shrinking the tumor. Indeed, there is great value in animal research for the development of treatments to fight breast cancer.

Let’s find out what’s happening this month with breast cancer research.

Cancer Research Blog Carnival #38

Medical Lessons

A recent study on the effect of mammography screening suggested that although screening availability was associated with a reduction in the death rate, the screening itself accounted for only about one third of the total reduction [4]. Dr. Elaine Schattner clues us in on what’s missing in the recent mammography value study.

Healthcare Hacks

Fred Lee reports on a study that finds that the phenolic compounds that may give peaches their distinctive flavor, appearance, and smell can also destroy breast cancer cells [5]. Indeed, it offers a peachy way to fight breast cancer.

Pharma Strategy Blog

Epigenetics is the study of changes in gene expression that don’t involve alterations in the genetic code but still get passed from on generation to the next. Dr. Sally Church reviews a study that found that diet and alcohol alter epigenetics of breast cancer and might predict severity of disease [6].

Cancer Research UK – Science Update Blog

Inheriting a mutated copy of the BRCA1 or BRCA2 gene greatly increases a woman’s risk of breast cancer. This is however a rare event and even when it happens, not all women go on to develop cancer. For women with a faulty BRCA1 gene, it turns out that other subtle genetic variations can affect how likely it is to go on to develop the disease [7]. Dr. Kat Arney reports that researchers discover genetic ‘volume control’ for inherited breast cancers.

The Scientist

Breast cancer tumors are thought to originate from the breast’s basal stem cells. Then again, maybe not. Jennifer Welsh describes the recent discovery of a surprise breast cancer source that suggests that different types of breast cancers derive from different cells of origin [8].

Science-Based Medicine

There are no good curative therapies for patients with stage IV cancer. Since science-based medicine can’t “cure” the disease, the decision on which drugs to approve for use is particularly challenging. Dr. David Gorski discusses Avastin and metastatic breast cancer: when science-based medicine collides with FDA regulation.

Connect with Kids

The symbol of breast cancer awareness — the pink ribbon — is well known. Starting in elementary school, children learn to recognize the symbol. With increased awareness, more and more women are being proactive and getting exams earlier. Today, even teenage girls are learning about the importance of female health and what they can do — from exercise to eating right — to prevent or reduce their risk of developing breast cancer. Connect with Kids focuses on kids and breast cancer awareness.

Biomarker Commons

Although disease biomarkers are used widely in medicine, very few biomarkers are useful for cancer diagnosis and monitoring. A recent commentary in the Journal of the National Cancer Institute suggests that the excess of parameters before, during and after sample analysis complicates biomarker discovery and validation, leading to false discoveries [9]. Biomarker Commons reposts The Cancer Biomarker Conundrum: Too Many False Discoveries.

Kevin M.D.

Dr. Karen Lu suggests that even young and healthy women should be aware of gynecologic cancers and reviews 10 cancer signs women shouldn’t ignore.

Healthcare Hacks

Watercress, one of the oldest known leaf vegetables consumed by people, is an aquatic or semi-aquatic plant native to Europe to central Asia. It’s been claimed to be a source of phytochemicals and antioxidants, a diuretic and an expectorant. An now perhaps a way to block blood blood vessel formation or angiogenesis. Fred Lee reports on a study that finds that a compound in watercress may help combat breast cancer [10].

Scepticon

Clinical thermography is a non-invasive, infrared imaging procedure used to screen for breast cancer or other breast diseases, based on the measurement of skin surface temperature as a reflection of normal or abnormal human physiology. The principle behind the technique is the angiogenic characteristic of tumors in the breast. The Cancer Society of New Zealand recently published a position statement to raise public awareness that there is a lack of large scale data available to judge the technique’s sensitivity and specificity [11]. Darcy Cowan questions breast cancer thermography — good, bad or in-between?

Stem Cell Network Blog

Mild stress can activate the protein NF-kB and downstream cellular pathways that can lead to future stress resistance. While this is good for normal cells, it’s bad when it’s pancreatic cancer cells being targeted with chemotherapy. Although the drug Sorafenib has anti-tumor activity in pancreatic cancer, following an initial response period cancer cells become insensitive, possibly because Sorafenib activates NF-kB. Chris Kamel discusses a recent study focused on enhancing cancer stem cell drugs by interfering with NF-kB [12].

Science-Based Medicine

Science-based medicine is challenging because, as new evidence and data become available, adjustments have to be made. Most recently, mammography screening has come under scrutiny and has been found to be less effective in preventing death from breast cancer that previously thought. Another recent study in the New England Journal of Medicine supports this conclusion [13]. As the mammography wars heat up again, Dr. David Gorski chooses a middle ground and describes a recent NEJM editorial, suggesting that screening for breast cancer is not a black-and-white decision for every woman [14].

Kevin M.D.

Pseudoscience is everywhere today, especially in medical therapies. In this day and age, Jackie Fox asks, how can anyone deny scientifically sound treatment for breast cancer?

Communicate Science

Dr. James Watson, one of co-discoverers of the structure of DNA in 1953, presented the inaugural Cancer Lecture of the Cork Cancer Research Centre at University College Cork in Ireland last month. Watson is Chancellor Emeritus at the Cold Spring Harbor Laboratory in New York and his ongoing research is focused on finding a cure for cancer. Eoin Lettice reports on a geneticist’s view of cancer.

Conclusion

That concludes the 38th edition of the Cancer Research Blog Carnival. If you’d like to make a difference in the fight against breast cancer during the month, visit the American Cancer Society and make a donation. Be sure to ‘designate’ your gift for breast cancer.

If you’d like to follow the latest in cancer research every month, the Cancer Research Blog Carnival has subscription options; you can follow by email or RSS feed. An aggregated feed of credible, rotating health and medicine blog carnivals is also available.

The Cancer Research Blog Carnival is looking for future hosts. You can find both the hosting schedule and past editions at the Cancer Research Blog Carnival website.

References

1. Breast Cancer Overview. The American Cancer Society. Accessed 2010 Sep 27.
2. Breast Cancer Facts & Figures 2009-2010. The American Cancer Society. Accessed 2010 Sep 27.
3. Berry et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005 Oct 27;353(17):1784-92.
   View abstract
4. Kalager et al. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010 Sep 23;363(13):1203-10.
   View abstract
5. Noratto et al. Identifying peach and plum polyphenols with chemopreventive potential against estrogen-independent breast cancer cells. J Agric Food Chem. 2009 Jun 24;57(12):5219-26.
   View abstract
6. Christensen et al. Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. PLoS Genet. 2010 Jul 29;6(7):e1001043.
   View abstract
7. Antoniou et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet. 2010 Sep 19. [Epub ahead of print]
   View abstract
8. Molyneux et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell. 2010 Sep 3;7(3):403-17.
   View abstract
9. Diamandis EP. Cancer Biomarkers: Can We Turn Recent Failures into Success? J Natl Cancer Inst. 2010 Aug 12. [Epub ahead of print]
   View abstract
10. Syed Alwi et al. In vivo modulation of 4E binding protein 1 (4E-BP1) phosphorylation by watercress: a pilot study. Br J Nutr. 2010 Jun 15:1-9. [Epub ahead of print]
    View abstract
11. Position Statement: The use of thermography as a breast cancer screening or diagnostic tool. The Cancer Society of New Zealand. 2010 June.
12. Rausch et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 2010 Jun 15;70(12):5004-13. Epub 2010 Jun 8.
    View abstract
13. Kalager et al. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010 Sep 23;363(13):1203-10.
    View abstract
14. Quanstrum and Hayward. Lessons from the mammography wars. N Engl J Med. 2010 Sep 9;363(11):1076-9.
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Experts agree that diet and nutrition can reduce risk of many diseases, including different types of cancer and chronic disease. A recent update to a 2007 report by the American Institute for Cancer Research/World Cancer Research Fund (AICR/WCRF) concludes that breast cancer deaths can be prevented by physical activity, breast feeding, a healthy diet and other preventative measures. The study is an update to the breast cancer chapter of Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective [1]. Earlier conclusions were based on data from 873 studies evaluating the relationship between diet, physical activity, obesity and cancer [2]. The 2009 update includes evidence from an additional 81 studies.

The report estimates that over 70,000 breast cancer cases in the U.S. — 40% of cases every year– could be avoided every year by simple lifestyle changes. The update reinforces the following AICR recommendations:

• Due to the link between excess body fat and cancer, people should aim to be as lean as possible without being underweight.
• Be physically active for at least 30 minutes daily.
• If you drink, limit alchohol consumption to two drinks a day for a man and one for a woman.
• Mothers should breastfeed exclusively for up to six months after birth.

The report did not examine other protective factors that may overlap and contribute to breast cancer, such as the effect of taking postmenopausal hormone therapy and oral contraceptives, or risk factors, some of which cannot be avoided, such as genetic background or certain environmental factors.

The AICR recommends a mostly plant-based diet with limited consumption of salt, red meats and alcoholic drinks. The report does not provide a decisive picture of particular food groups that can reduce the incidence of cancer. As of 2006, the largest ever clinical trial of low-fat diet showed that longer term follow-up was needed to determine whether reducing total fat intake had a signficant impact on the incidence of breast cancer [2].

Even so, following the AICR’s recommendations can lead to better prevention practices: a study from Johns Hopkins University School of Medicine found that obese women are less likely to undergo regular mammography, which is key to screening breast cancer and lowering mortality rates [3]. The National Cancer Institute provides risk profiles and other tools that examine multiple factors that impact your risk to develop breast cancer.

The AICR/WCRF report — Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective — is the most comprehensive report on diet and cancer ever compiled. Over 7,000 studies were independently reviewed, compiled and presented to an expert panel of 21 world-renowed scientists, who evaluated the data and developed recommendations for cancer prevention.

The report on breast cancer is part of the Continuous Update Project, which continuously updates the findings of the AICR/WCRF 2007 report [1]. This allows for cancer prevention information that is always based on the latest research. Breast cancer is the first type of cancer researchers have reviewed evidence on as part of the update project. They have started reviewing data on colorectal cancer and prostate cancer, and the results are expected early next year. The long-term goal of the Continuous Update Project is to continually update evidence on all types of cancer.

About the author: Allison Bland is a communications fellow at Research!America and a graduate of McGill University with degrees in English and History of Science. She is interested in science and health communication on the web.

References

1. Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective. World Cancer Research Fund/American Institute for Cancer Research. 2007 Nov 1.
2. Prentice et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):629-42.
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3. Maruthur et al. Obesity and mammography: a systematic review and meta-analysis. J Gen Intern Med. 2009 May;24(5):665-77. Epub 2009 Mar 11.
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The authors of the report had previously evaluated the association between coffee consumption and the risk of breast cancer among women who had detrimental mutations in either BRCA1 or BRCA2. They observed a statistically significant reduction in the risk of breast cancer among women who consumed six or more cups of coffee per day compared to those who never drank coffee [5]. The association was only observed for BRCA1 and for caffeinated coffee.

Ninety-five percent of caffeine is metabolized in the human body by a member of the cytochrome P450 family of enzymes, CYP1A2, which stands for cytochrome P450, family 1, subfamily A, polypeptide 2. The cytochrome P450 proteins catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. CYP1A2 also metabolizes acetaminophen (Tylenol) and caffeine. Decreased enzyme activation and impaired caffeine metabolism is associated with a common A to C polymorphism in the CYP1A2 gene (meaning a genetic variation in an individual’s DNA sequence, in this case a specific A to C basepair substitution that alters the function of CYP1A2) [6].

In the present study, the authors examined whether the CYP1A2 genotype (meaning a person’s genetic makeup, in this case the difference in the CYP1A2 DNA sequence between individuals) modifies the association between a history of coffee consumption and the risk of breast cancer. A total of 411 BRCA1 mutation carriers (170 cases and 241 controls) and their coffee consumption habits were evaluated. The CYP1A2 genotype did not affect breast cancer risk. However, among women with at least one variant C allele (meaning an alternative DNA coding sequence) in CYP1A2, specifically the CYP1A2*1F allele (an A to C basebair substitution at a specific location in one or both copies of the DNA coding sequence for CYP1A2), those who drank coffee had nearly a 3-fold decrease in the risk of breast cancer compared with women who never drank coffee.

The authors suggest that mechanisms other than induction of CYP1A2 may account for the influence of caffeine on breast cancer risk. Coffee contains a number of biochemically active compounds including caffeine, phytoestrogens (including flavonoids) and other phytonutrients (including tocopherols). However, caffeine is the only major compound in coffee known to be metabolized by CYP1A2. Thus the authors attribute the decrease in breast cancer risk to prolonged caffeine exposure among individuals that are “slow metabolizers”.

Coffee is a major contributor to the total in vitro antioxidant capacity of the diet. An investigation of the quality of vitamin and polyphenolic antioxidants in beverages found that black tea contained the highest concentration of high-quality antioxidants, followed by coffee [7]. Here’s the breakdown:

This may be particularly relevant for women who carry the BRCA1 mutation as a decrease in the expression of genes involved in the antioxidant response has been shown for BRCA1-deficient cells [8].

A separate hospital-based, case-control study done last year evaluating the role of coffee in breast cancer etiology found among premenopausal women that consumption of caffeinated coffee was associated with a decrease in breast cancer risk [9]. The study included 1,932 women with primary, incident breast cancer and 1,895 controls. Women who consumed four or more cups of coffee per day experienced a 40% reduction in breast cancer risk. Although this study didn’t examine individual genetics, it is one of many demonstrating coffee’s protective effects against breast cancer.

It’s fascinating that impairment of caffeine metabolism coupled with high coffee consumption can result in a reduction in breast cancer risk for women who have an otherwise increased risk due to a BRCA1 gene mutation. The BRCA1 variant C allele isn’t common; in their previous study, the authors indicate that >95% of the mutations identified weren’t pathogenic [5]. Nevertheless, these results underscore the importance of addressing individual genetic variability in the metabolism when evaluating diet-disease associations.

References

1. Kotsopoulos et al. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):912-6. DOI: 10.1158/1055-9965.EPI-06-1074
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2. Ferla et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007 Jun;18 Suppl 6:vi93-8.
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3. Antoniou et al. Risk models for familial ovarian and breast cancer. Genet Epidemiol. 2000 Feb;18(2):173-90.
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4. Ford et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 Mar 19;343(8899):692-5.
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5. Nkondjock et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2006 Jan 1;118(1):103-7.
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6. Sachse et al. Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999 Apr;47(4):445-9.
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7. Vinson et al. Vitamins and especially flavonoids in common beverages are powerful in vitro antioxidants which enrich lower density lipoproteins and increase their oxidative resistance after ex vivo spiking in human plasma. J Agric Food Chem. 1999 Jul;47(7):2502-4.
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8. Bae et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004 Nov 1;64(21):7893-909.
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9. Baker et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer. 2005;52(1):15-21.
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