Highlight HEALTH

Welcome to the 7th edition of the Cancer Research Carnival, a blog carnival devoted to cancer research. This edition includes some great articles on cancer research ethics, cancer therapeutics, cancer stem cells, cancer genetics and cancer biology.

I believe it’s important to maintain perspective on the significance of cancer research and the impact it has on patients. As such, this months edition of the Cancer Research Carnival includes narratives from some people affected by the disease. I think their stories will inspire us all with their determination and courage, and serve as motivation to continue searching for therapies to combat cancer.

How is research progressing on the battle against cancer?

The latest American Cancer Society (ACS) annual cancer statistics report finds that cancer deaths have decreased by 18.4% in men and 10.5% in women since mortality rates began to decline in the early 1990s [1]. However, despite a declining death rate, there was an increase in the number of cancer deaths in 2005 compared to 2004. The ACS says that it’s [2]:

… important to understand that for the number of cancer deaths to decrease, the decline in the overall cancer mortality rate must be large enough to offset the increasing numbers due to growth and aging of the population.

Over the last 15 years, researchers have been making progress. Although the rate of decline in cancer deaths in 2005 wasn’t enough to exceed population factors, cancer mortality rates continue to decrease. Indeed, between 1990/1991 and 2004, over a half million deaths from cancer were averted [2].

With these statistics in mind, let’s get to the research highlighted in this months edition of the Cancer Research Carnival.

Cancer Research Carnival #7

Adventures in Ethics and Science

A recent New York Times essay by Andrew Vickers ponders why cancer researchers are so reluctant to share their data [3]. Dr. Janet Stemwedel discusses the essay, asking Should Researchers Share Data?.

Bayblab

Autophagy, the self-removal of cellular components, is frequently observed in tumor cells following radiotherapy. Researchers have found that inhibition of genes associated with autophagy results in enhanced cytotoxicity of radiotherapy to otherwise resistant carcinoma cells [4]. Kamel talks about Autophagy and Radiation Resistance.

Mark’s Daily Apple

Increased body-mass index (BMI) is associated with the risk of some types of cancer. A systematic review and meta-analysis published in the Lancet journal last month assess the strength of associations between BMI and different sites of cancer [5]. Mark’s Daily Apple reports there’s a Higher Cancer Risk if You’re Fat and questions whether public education on the risks of obesity is truly enough.

The Pink Tee Shirt

Beep Beep - Emmy describes what it’s like to be living with breast cancer.

Stage 4 cancer is like a hungry coyote out there, watching, setting traps.
I wonder when he will catch me.

Cancer and Your Genes

Two papers in the February 28th issue of Nature provide understanding into a subset of breast and ovarian cancers, the action of drugs used to treat them and a novel mechanism of drug resistance to chemotherapy [6-7]. Dr. Matt Mealiffe reviews the articles and their significance, describing the Mechanism of Cisplatin-Resistance in BRCA2-Related Ovarian Cancers.

Cancer Genetics

SNPs (pronounced “snips”) are DNA sequence variations that occur when a single nucleotide in the genome is altered, producing different alleles (meaning sequences that code for the same gene). Two papers in the March issue of Nature Genetics identify multiple new SNPs associated with prostate cancer [8-9]. Ramunas breaks it down, describing Prostate Cancer — Old & New SNPs and deCODEPrCa.

Eye on DNA

As research identifies more disease-associated SNPs, new genetic tests allow consumers to test themselves for disease susceptibility. Dr. Hsien-Hsien Lei discusses this competitive market, reporting that deCODE Launches PrCa Prostate Cancer DNA Test.

Mystery Rays from Outer Space

Although it’s widely accepted that metastasis is a late event in cancer progress, a recent study demonstrated that tumor cells can spread systemically from early alterations in breast cancer [10]. Dr. Ian York deliberates Early Metastasis.

Z-Mail 101

David’s daughter Beth presents her thoughts on the situation her Aunt Wendy is in as she battles colon cancer.

You have to live life day by day and for each moment. Enjoy what you have in front of you and not take for granted the little things. We’re all going to die at some point; cancer patients just have more information.

Terra Sigillata

The internet is increasing used as a source of health information. A current study of quality criteria for online content, specifically for breast cancer information, finds that most resources are accurate [11]. However, websites that contain information on complementary and alternative medicine (CAM) were likely to contain inaccurate statements. Abel Pharmboy suggests we Beware of Alternative Medicine Sites Offering Breast Cancer Advice.

Doctor David’s Blog

An investigation examining the role of BRCA1 in human mammary stem cell fate found that BRCA1 plays a critical role in the differentiation of ER-negative stem/progenitor cells to ER-positive luminal cells [12]. Dr. David Loeb reviews study and discusses Cancer Stem Cells and Familial Cancer Risk for Breast Cancer.

Gene Sherpas: Personalized Medicine and You

Men with a family history of prostate cancer have a much greater risk of developing the disease than men with no family history. A systematic review and meta-analysis demonstrated that the risks are greatest for relatives of those diagnosed when they were young and those with more than one affected relative
[13]. The Dr. Steve Murphy evaluates the study and its shortcomings, discussing the New England Journal, Prostate Cancer and Babel.

Britannica Blog

The World Health Organization’s International Agency for Research on Cancer (IARC) has been conducting research on the increased risk of cancer in night-shift workers as well as the increased cancer risk in painters and firefighters [14]. Kara Rogers reviews the biology of melatonin secretion and disruption of circadian rhythm, writing about Cancer on the Night Shift: Why Night Workers Are at Risk.

Chrysalis Angel

Chrysalis Angel worries when she hears the word “cured” and reminds us all to Remain Vigilant.

Stay on top of your check ups, follow the recommendations of your doctors, do your own breast self exams. Take back your life and your health. You can only do that by remaining vigilant. Then, get out, enjoy your life and loved ones. Make your life as much of what you want it to be as you can, and maybe someday soon – there will be an absolute cure for cancer.

Conclusion

Thanks to everyone that contributed articles — it’s been a pleasure to host this months edition of the Cancer Research Carnival. Be sure to take a moment and let your fellow bloggers know this issue is available so that everyone’s hard work can be appreciated and enjoyed by all. You can find more information about the carnival as well as the hosting schedule and past editions at the Cancer Research Blog Carnival.

References

1. Cancer Facts & Figures 2008. American Cancer Society. Atlanta, Ga. 2008.
2. Report Says Half a Million Cancer Deaths Have Been Averted Since Death Rate Drop. American Cancer Society Press Release. 2008 Feb 20.
3. Vickers A. Cancer Data? Sorry, Can’t Have It. The New York Times. 2008 Jan 22.
4. Apel et al. Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res. 2008 Mar 1;68(5):1485-94.
   View abstract
5. Renehan et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008 Feb 16;371(9612):569-78.
   View abstract
6. Edwards et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008 Feb 28;451(7182):1111-5. Epub 2008 Feb 10.
   View abstract
7. Sakai et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008 Feb 28;451(7182):1116-20. Epub 2008 Feb 10.
   View abstract
8. Eeles et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008 Mar;40(3):316-21. Epub 2008 Feb 10.
   View abstract
9. Thomas et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008 Mar;40(3):310-5. Epub 2008 Feb 10.
   View abstract
10. Hüsemann et al. Systemic spread is an early step in breast cancer. Cancer Cell. 2008 Jan;13(1):58-68.
    View abstract
11. Bernstam et al. Commonly cited website quality criteria are not effective at identifying inaccurate online information about breast cancer. Cancer. 2008 Feb 11;112(6):1206-1213 [Epub ahead of print].
    View abstract
12. Liu et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1680-5. Epub 2008 Jan 29.
    View abstract
13. Johns and Houlston. A systematic review and meta-analysis of familial prostate cancer risk. BJU Int. 2003 Jun;91(9):789-94.
    View abstract
14. Straif et al. Carcinogenicity of shift-work, painting, and fire-fighting. Policy Watch, The Lancet Oncology. 2007 Dec;8(12):1065-1066.

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The American Society of Clinical Oncology (ASCO) recently published its third annual Clinical Cancer Advances report, Clinical Cancer Advances 2007: Major Research Advances in Cancer Treatment, Prevention and Screening [1]. It was developed under the guidance of a 21-person editorial board consisting of leading oncologists and cancer specialists, including specialty editors for each of the disease-specific and issue-specific sections. The report highlights 6 major advances in cancer research in 2007 and describes an additional 18 other findings of significant importance, demonstrating the pace of progress being made in cancer prevention, screening, treatment, epidemiology and survivorship.

The top 6 most important cancer advances of 2007

1. Magnetic resonance imaging (MRI) for breast cancer screening.

   Several recent studies have led to new guidelines regarding the use of MRI for breast imaging. The first study evaluated whether MRI could improve on clinical breast examination and mammography in the detection of breast cancer in the other breast soon after the initial diagnosis of cancer in one breast. Researchers found that patients recently diagnosed with unilateral breast cancer may benefit from MRI of the other breast to increase the chance of detecting additional cancers that may have been missed by mammography or clinical examination [2]. A second study found that MRI is significantly more sensitive for the detection of the most common type of noninvasive breast cancer in women, ductal carcinoma in situ (meaning the development of cancer within the milk ducts of the breast that has not moved out of the duct into surrounding tissue) [3]. Despite these findings, there are a number of limitations to MRI screening. MRI is expensive and there is a high rate of false positives (meaning the positive detection of cancer that really isn’t there). MRI screening has not yet been shown to improve the overall survival rate of patients with breast cancer.

2. Decreasing hormone replacement therapy (HRT) use linked to declines in breast cancer incidence.

   In 2007, two studies reported a link between the recent decrease in breast cancer incidence and the decline in the use of HRT in menopausal women [4-5]. Both studies examined large databases of patients, finding declines in breast cancer only in women aged 50 years and older. The declines were more significant in breast cancers that were estrogen receptor positive, the specific type of cancer whose growth could be fueled by the use of HRT. Other factors that could have played a role in the decreased incidence were analyzed, and while those factors could not be completely ruled out, the association with HRT was strong and warrants further study.

3. Sorafenib improves survival in liver cancer.

   Primary liver cancer is the third leading cause of cancer death, often progressing rapidly from initial diagnosis. A 2007 phase III study found that patients taking sorafenib (Nexavar) for hepatocellular carcinoma (the most common type of liver tumor) lived 44% longer than patients receiving placebo [6]. Sorafenib is currently approved by the U.S. Food and Drug Administration for the treatment of a form of advanced kidney cancer and is being evaluated in patients with other types of cancer.

4. Bevacizumab and interferon-alpha 2a for renal carcinoma.

   A recent large, multicenter study found that adding bevacizumab to an older kidney cancer drug called interferon-alpha 2a almost doubled progression-free survival (meaning the time during and after treatment when the cancer does not grow) [7]. In patients with metastatic kidney cancer, the combination therapy increased progression-free survival from 5.4 months to 10.2 months. One-third of tumors responded to the therapy compared to just 13% for the placebo. Bevacizumab is currently approved by the U.S. Food and Drug Administration for the treatment of metastatic colorectal cancer and non-small cell lung cancer.

5. The role of human papilloma virus (HPV) in head and neck cancers.

   In 2007, two studies increased our understanding of HPV infection and cancer. The first study evaluated the associations between HPV infection and oropharyngeal cancer in 100 newly-diagnosed patients and 200 control patients without cancer. The oropharynx is the middle part of the pharynx (throat) behind the mouth and includes the back one-third of the tongue, the soft palate, the side and back walls of the throat, and the tonsils. The study found that DNA from HPV-16, one of the strains of HPV most commonly associated with cervical cancer, was detected in 72% of tumors. Further, 64% of patients with cancer had antibodies for cancer-related proteins commonly found in HPV-16. The study thus demonstrates a strong association between oral HPV infection and oropharyngeal cancer [8]. Another study, a phase II clinical trial evaluating HPV infection and treatment response and survival outcome for patients with head and neck squamous cell carcinoma, found that cancers that are HPV-positive may have a better prognosis than patients that are HPV-negative [9]. Case in point: newly diagnosed patients with head and neck squamous cell carcinoma were treated with a combination of chemotherapy and radiation therapy. After a median follow-up of approximately 39 months, patients infected with HPV had a 72% lower risk progression and a 79% lower risk of death than those who were uninfected. Researchers suggest that HPV infection causes cancers that are biologically different than other cancers.

6. Preventive radiation therapy decreases brain metastases and prolongs survival for patients with advanced lung cancer.

   A 2007 clinical trial found that radiation therapy to the head for patients who responded to chemotherapy for advanced small cell lung cancer decreased the incidence of brain metastases and prolonged disease-free and overall survival [10]. The cumulative risk of brain metastases within 1 year was 14.6% in patients receiving head irradiation compared to 40.4% in the control group, thus extending patients’ lives.

Nancy E. Davidson, M.D., president of the American Society of Clinical Oncology (ASCO), said [11]:

This report demonstrates what many of us in the cancer research and practice community have known for some time. The long-term federal investment in cancer research is paying off. But this impressive pace of progress will slow if we don’t recommit to funding cancer research. Adjusted for inflation, cancer research funding has actually declined 12 percent since 2004 –this has never happened in our nation’s history. Without additional funding, the chance to build on the extraordinary new scientific knowledge, and provide new treatments for 1.4 million Americans diagnosed with cancer every year, will be delayed or lost.

Editors of the report reviewed studies published in peer-reviewed scientific journals and early research results presented at major scientific meetings from November 2006 to October 2007. Only studies that significantly altered the way a cancer is understood or had an important impact on patient care were included.

References

1. Gralow et al. Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening–a report from the american society of clinical oncology. J Clin Oncol. 2008 Jan 10;26(2):313-25. Epub 2007 Dec 17.
   View abstract
2. Lehman et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.
   View abstract
3. Kuhl et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet. 2007 Aug 11;370(9586):485-92.
   View abstract
4. Glass et al. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007 Aug 1;99(15):1152-61. Epub 2007 Jul 24.
   View abstract
5. Ravdin et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.
   View abstract
6. llovet et al. Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC). Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL. 2007 June.
7. Escudier et al. A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-alpha 2a vs placebo/interferon-alpha 2a as first-line therapy in metastatic renal cell carcinoma. Presented at the 43rd Annual Meeting of the American Society of Clinical
   Oncology, Chicago, IL. 2007 June.
8. D’Souza et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.
   View abstract
9. Fakhry et al. Prognostic significance of human papillomavirus (HPV) tumor status for patients with
   head and neck squamous cell carcinoma (HNSCC) in a prospective, multi-center phase ii clinical trial.
   Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL. 2007 June.
10. Slotman et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72.
    View abstract
11. ASCO announces top cancer advances of 2007 in annual progress report. Hematology & Oncology News & Issues (HONI) online. 2007 Dec. 18.

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With all the recent discussion and debate by the presidential candidates regarding healthcare issues, I thought a study published last month in CA: A Cancer Journal for Clinicians was quite timely. The study, titled Association of Insurance with Cancer Care Utilization and Outcomes, presents evidence that lack of adequate health insurance coverage is associated with reduced access to care and poorer outcomes for cancer patients [1]. The article further presents data on the association between health insurance status and screening, stage at diagnosis and survival for breast and colorectal cancer.

American Cancer Society (ACS) researchers analyzed over half-a-million patient cases using data from the National Cancer Data Base as well as data from the 2005 and 2006 National Health Interview Survey conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention (CDC). Perhaps not surprisingly, the results show that uninsured individuals are (1) less likely to receive cancer screening, (2) more likely to be diagnosed at an advanced disease stage and (3) less likely to survive than privately insured individuals.

National health survey and healthcare

People who are uninsured or insured by government programs may face significant obstacles obtaining healthcare. Indeed, some physicians do not accept new patients without private insurance or uninsured individuals who are not able to pay the full cost at the time of visit. A recent national survey found that while 96% of office-based physicians were currently accepting new patients, 40.3% indicated they would not accept new charity cases, 25.5% did not accept new Medicaid cases and 13.9% did not accept new Medicare cases [2]. This lack of access to healthcare can have adverse affects on preventive care and management for chronic conditions.

In the present ACS study, analyses of the 2006 National Health Interview Survey showed that 53.6% of uninsured people aged 18 to 64 years had no usual source of healthcare compared to just 9.9% of privately insured and 10.8% of individuals with Medicaid insurance. People who are uninsured were much more likely to report no healthcare visits in the past year than people who are privately- or Medicaid-insured. Compared to insured individuals, people who were uninsured were more likely to report that they did not get care due to cost, delayed care due to cost, did not get prescription drugs due to cost and had no healthcare visits in the past 12 months due to cost.

National health survey and cancer prevention

Up to two-thirds of cancers may be prevented through healthy lifestyle changes. Healthcare visits provide an opportunity for health providers to counsel people on smoking cessation and weight loss. However, uninsured individuals are much more likely to report no healthcare visits in the past 12 months than people who are Medicaid- or privately-insured and are thus much less likely to be advised to quit smoking or to lose weight. Further, analyses of the 2006 National Health Interview Survey showed that the likelihood of receiving recommended cancer screening tests varied by insurance status. Privately-insured women were most likely to have had a mammogram or Pap test, followed by Medicaid-insured women. Similarly, privately-insured men were most likely to have had a test for prostate cancer, followed by Medicaid-insured men. Further, both men and women who were privately insured were most likely to have had a colorectal cancer screening test. In all cases, uninsured individuals were least likely to have had any type of cancer screening.

Health insurance status is associated with other sociodemographic characteristics (e.g. race, level of education). However, when the data was analyzed by race, at every level of education, individuals with health insurance were about twice as likely as those without to have had mammography or colorectal cancer screening. Thus, having health insurance is an important predictor of cancer screening.

Insurance status, cancer stage at diagnosis and survival

ACS researchers also analyzed data from the National Cancer Data Base to investigate the relationship between insurance status, cancer stage at diagnosis and survival. In analyses of cancer survival for all cancers, uninsured individuals and Medicaid-insured individuals were 1.6 times more likely to die in 5 years than those with private insurance. Specifically, 35% of uninsured patients died in five years compared with 23% of privately insured patients. Since cancer screening tests are key to diagnosing and treating cancer in its early stages, not surprisingly people with health insurance were more likely to be diagnosed with early stage disease than individuals without insurance.

These results are consistent with previous studies showing that people who are uninsured or have Medicaid insurance are more likely to be diagnosed with late-stage cancer (breast and cancer of the mouth or throat, respectively) than people who are privately insured [3-4].

According to Dr. Otis Brawley, chief medical officer of the American Cancer Society [5]:

This report clearly suggests that insurance and cost-related barriers to care are critical to address if we want to ensure that all Americans are able to share in the progress we have achieved by having access to high-quality cancer prevention, early detection, and treatment services.

Research has shown that healthy lifestyle changes can prevent cancer. Additionally, advances in cancer detection and treatment have resulted in a decline in US cancer deaths in 2003 and 2004, the first decrease seen since 1930.

The American Cancer Society launched the Access to Care campaign in 2007. Access to Care is a national initiative dedicated to raising awareness about the predicament of uninsured and underinsured people in the United States. The campaign encourages Americans to find ways to fix the problem and make access to healthcare a national priority.

What are your thoughts? How can we reasonably and responsibly make healthcare accessible to everyone?

References

1. Ward et al. Association of insurance with cancer care utilization and outcomes. CA Cancer J Clin. 2008 Jan-Feb;58(1):9-31. Epub 2007 Dec 20.
   View abstract
2. Hing and Burt. Characteristics of office-based physicians and their practices: United States, 2003–04. Series 13, No. 164. Hyattsville, MD: National Center for Health Statistics. 2007.
3. Halpern et al. Insurance status and stage of cancer at diagnosis among women with breast cancer. Cancer. 2007 Jul 15;110(2):403-11.
   View abstract
4. Chen et al. The impact of health insurance status on stage at diagnosis of oropharyngeal cancer. Cancer. 2007 Jul 15;110(2):395-402.
   View abstract
5. Report Links Health Insurance Status With Cancer Care. American Cancer Society News Center. 2007 Dec 20.

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