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Highlights of Progress

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Every year thousands of NCI-funded research projects move us closer to at time when cancer can be controlled or eliminated. The recent doubling of NCI's budget has been instrumental in funding numerous studies across the cancer continuum and from foundational laboratory research to patient care. These highlights of recent progress provide a snapshot of the breadth of our research advances.



Trends in Research and Care

NCI Releases the Cancer Progress Report. To build on areas of greatest success and pinpoint areas of greatest need, NCI is working with many partners to stay abreast of progress in cancer research and care in the United States. NCI's Cancer Progress Report, first published in December 2001, describes the Nation's progress in reducing the cancer burden, encompassing the continuum from prevention to deaths from specific cancers. Also reflected are declines in certain behaviors that cause cancer, especially cigarette smoking by adults. More people are getting screened for breast, cervical, and colorectal cancers, and more practitioners are adopting state-of-the-art cancer treatments. At the same time, work needs to be done to reduce rates of some cancers that are on the rise. These include non-Hodgkin's lymphoma, melanoma, cancers of the liver and esophagus, as well as breast and lung cancer in women. Greater efforts also are needed to reduce tobacco use, weight gain, and sun exposure and to increase physical activity. We must also redouble our efforts to eliminate persistent cancer-related health disparities among population groups.

Changing Age Structure of the United States Will Help Guide the Future of Cancer Research and Care. The Annual Report to the Nation on the Status of Cancer, 1973-1999, featuring Implications of Age and Aging on the U.S. Cancer Burden, was released in May of 2002. The report is encouraging. Overall cancer death rates decreased from 1993 to 1999, while rates of cancer incidence stabilized over a similar timeframe. However, trends in various populations groups differed substantially - e.g. by cancer site, sex, and race. Most notably, because of the increasing population and the growing proportion of older persons, researchers expect the cancer burden in the United States to increase substantially over the next several decades. Our changing age structure will require aggressive strategies for cancer prevention and early detection, social support, treatment and medical care, clinical trial design and enrollment, research, and surveillance. In addition, access to supportive, palliative, and general medical services must be optimized.

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Prevention and Control

Smoking Cessation Drug May Help Address Smoking-Related Health Disparities. In a recent landmark study, investigators found that bupropion, a promising smoking cessation drug previously studied in mostly White populations, is effective in helping African Americans quit smoking. Bupropion also seemed to curb both weight gain and feelings of depression among study participants, key indicators of whether a person will return to smoking. The success of this treatment is especially significant given that smoking rates are higher for African Americans than for the overall population of the United States. For example, close to half of African Americans who live in inner cities smoke compared to about one quarter of the general population. Smoking is the leading cause of lung cancer and a major risk factor for other cancers as well as heart disease, respiratory disorders, and other diseases prevalent in African American groups. Researchers hope that a successful smoking cessation program, aided by bupropion, may help reduce smoking-related health disparities experienced by African Americans as well as the overall cancer burden caused by tobacco use.

Potential of Dietary Aids for Cancer Prevention Is Complex. Over the years, many studies have examined how what we eat or drink affects our risk of developing cancer. The sometimes conflicting results point to the need for large, careful studies to clarify some of these findings. In one recent study, with tens of thousands of participants, investigators discovered that both men and women could reduce their risk of developing cancer of the distal colon by consuming high levels of calcium daily. A similar study showed that high levels of calcium and dairy products substantially increase the risk for prostate cancer, while lycopene, a component of tomatoes, provided some protection against prostate cancer. The finding that calcium can reduce the risk of one cancer while increasing the risk of another illustrates the complexity of the interaction between diet and cancer. Further study is needed before clear advice can be communicated to the public about the usefulness of calcium for cancer prevention.

Oophorectomy after Childbearing Years Lowers Cancer Risk in Women with BRCA Mutations. Women who were born with certain mutations to the genes BRCA1 and BRCA2, are more likely to develop breast and/or ovarian cancer, and at a younger age than the general population. Based on the findings of a number of small studies, physicians have been recommending that women with these mutations undergo prophylactic oophorectomy (removal of the ovaries), once they have finished having children. Recently completed large studies have validated this practice to reduce cancer risk. In an NCI-supported study, ovarian cancer risk was reduced by a striking 96 percent and breast cancer risk was reduced by about 50 percent. Side effects brought on by premature menopause are manageable by medication. The researchers found no evidence to suggest that the ovaries should be removed before the childbearing years.

Other cancer prevention and control highlights in this document:

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Detection, Diagnosis, and Prognosis

New Blood Test for Early Detection of Prostate Cancer Looks Promising. To screen for prostate cancer, doctors currently use a blood test to measure the levels of a protein called prostate-specific antigen (PSA), which is consistently elevated in men with prostate cancer. However, since PSA is sometimes elevated even in the absence of cancer, a follow-up biopsy must be performed if the PSA test is positive. The PSA test is quite helpful to many men by detecting their cancer in its earliest stages. The down side is that a number of men without the disease are subjected to biopsy, and associated anxiety, to rule out cancer. To address this concern, researchers used the emerging technology of protein profiling to fashion a new blood test. The new test uses computer-based artificial intelligence to study the dynamic patterns of nine separate proteins in the blood. In preliminary study, this test correctly identified most men with prostate cancer and misclassified far fewer men without the disease than could be hoped for with the PSA test. With further development, this new test may lead to a more accurate means to detect and diagnose prostate cancer at a very early stage, with fewer false positives and unnecessary biopsies.

SPORE Study Suggests New Molecular Test Useful for Prognosis of Colorectal Cancer. To estimate the chance that colorectal cancer might recur after surgery, health professionals must examine small amounts of tumor tissue under the microscope. This is called histopathological staging. Many scientists are looking for molecular markers, such as suspicious abnormalities in tumor DNA, to develop a more reliable prognostic tool. Previously, scientists discovered that patients with allelic imbalance in certain chromosomes of the tumor tend to have a poorer prognosis. Until recently, however, it has been very difficult to accurately measure allelic imbalance in tumor tissue.

Now, investigators have developed a highly sensitive test using a technique called "digital SNP analysis." This new test measures the allelic imbalance in two colon cancer-associated chromosomes, 8 and 18. They found that, after 5 years of follow up, cancer recurred in 42 percent of patients with allelic imbalance in both chromosomes and in 26 percent of those with one chromosome affected. In contrast, all patients with no detectable allelic imbalance in chromosomes 8 or 18 remained disease free after 5 years. Since routine histopathological staging would have mistakenly predicted recurrence in at least some of these disease-free patients, this new test appears to provide an improved prognostic indicator of colorectal cancer. Further research must be done to show whether this technique will work as well for other cancer sites.

Ovarian Cancer patients with BRCA Mutation have Better Survival than Non-Carriers. Women who inherit mutations to the BRCA1 or BRCA2 gene, have a greater risk of developing ovarian cancer. However, until recently, researchers could not predict whether women with these mutations would fare better, the same, or worse than other women with ovarian cancer. To examine this issue, researchers studied the medical records of almost 900 newly diagnosed ovarian cancer patients with inherited BRCA mutations and followed their progress for five years. Investigators compared the progress of these women to that of patients who had no BRCA mutation. On average, the patients with BRCA mutations survived for about 53.4 months, almost 20 months longer than women without the mutations. This survival advantage was not due to earlier detection, but seems to reflect a difference in the pattern of the disease in women with and without BRCA mutations. The mechanism of this phenomenon is not known. Further follow up in this continuing study should reveal whether the better survival of BRCA mutation carriers is long-term or limited to the first few years of the disease.

Other detection, diagnosis, and prognosis highlights in this document:

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Treatment

New Approach to Immunotherapy for Advanced Melanoma Results in Dramatic Tumor Regression. In a recent study of melanoma patients, researchers discovered a way to enhance the immune system's natural, but weak, ability to attack cancer cells. Investigators began by collecting a small number of white blood cells from the tumors of each of 13 patients. From these, they isolated the cells that were most adept at attacking melanoma - those that could best recognize an antigen abundantly expressed on melanoma cells and to a lesser extent on normal melanocytes. They grew large quantities of these white blood cells and injected them back into each patient along with an immune-boosting protein. To prevent the patient's naturally occurring white blood cells from crowding out the melanoma-attacking cells, investigators temporarily depleted the patient's immune system with chemotherapy prior to injection.

With this treatment regimen, six patients experienced dramatic regression of metastatic tumors. Surgeons removed remaining traces of tumors from two of these patients who have remained cancer-free, one for over two years. In some patients, the melanoma-killing cells also attacked normal melanocytes, resulting in patches of skin without pigmentation (a non-threatening condition known as vitiligo). Other side effects were treatable. This pioneering study establishes two landmark principles of cancer research. First, this unique approach to harnessing the immune system can be an effective treatment for patients with metastatic cancer. Secondly, naturally occurring antigens that are over-expressed on cancer cells may provide useful immunotherapy targets for cancers such as prostate, breast, ovarian, and thyroid, since the organ function is either not necessary for survival or can readily be replaced.

SPORE Scientists Find Ways to Overcome Resistance to Tamoxifen for Breast Cancer Treatment. A subclass of breast cancer known as "estrogen receptor positive" (ER-positive) grows more aggressively when exposed to estrogen. The drug tamoxifen works well against ER-positive breast cancer by lowering estrogen levels in the body. However, scientists have been faced with the puzzle of why some women never respond to this drug and, in those who are helped, it often works only for a limited time. Also, high levels of a certain protein, HER-2, seem to make tumors more resistant to tamoxifen, but only in some women. In studying these problems, researchers found that another drug, fluvestrant, works against tumors that don't respond to tamoxifen. Investigators also discovered that HER-2, by itself, does not interfere with tamoxifen. Only in women where HER-2 and a second protein, AIB1, are simultaneously elevated were tumors resistant to tamoxifen. This research on the mechanisms of tamoxifen resistance is yielding new, more effective treatment approaches. The United States Food and Drug Administration recently approved fluvestrant for treatment of tamoxifen-resistant, ER-positive breast cancers, and scientists anticipate that further research on HER-2 and AIB1 may open highly promising avenues for both diagnostic and therapeutic interventions.

Molecularly Targeted Drug Slows Tumor Growth in Patients with Kidney Cancer. Researchers have identified another promising molecularly targeted cancer treatment drug. In a recent clinical trial, the drug bevacizumab significantly slowed the growth of metastatic renal cancer in patients with advanced disease and no known treatment options. Patients given this drug showed no measurable tumor growth for about five months, as compared to two months in patients taking a placebo. Bevacizumab targets a protein, called VEGF, needed by the tumor to generate new blood vessels (angiogenesis) to bring oxygen and nutrients for growth. This study is an important first step toward showing that recent exciting laboratory advances in attacking cancer by thwarting angiogenesis will work in patients. More than 20 additional clinical trials are currently underway to evaluate bevacizumab as a cancer treatment, including Phase III trials for breast and colorectal cancers and Phase II trials for prostate, breast, colorectal, cervical, ovarian, pancreatic, and lung cancers, mesothelioma, and several types of leukemia.

Experimental Drug Improves Survival of Patients with Advanced Colorectal Cancer. Researchers conducting a large clinical trial have discovered a new chemotherapy drug that, in combination with current drugs, appears to improve the survival of colorectal cancer patients. Patients with advanced colorectal cancer who were treated with the "FOLFOX4 regimen" (which includes the experimental drug oxaliplatin) lived about four months longer than patients receiving standard therapy, the "Saltz regimen." Patients treated with FOLFOX4 responded better to their medication and tumors were slower to progress. Although many patients developed a neurotoxicity not seen with the Saltz regimen, severe side effects were significantly fewer overall. Furthermore, 71 percent of patients on FOLFOX were living after one year, compared to 58 percent of those on the Saltz regimen. These results are impressive for a disease that is the second leading cause of cancer death in the United States. As further tests are being conducted, the manufacturer of oxaliplatin is submitting data to the United States Food and Drug Administration for possible use of this drug as a second-line treatment for colorectal cancer.

Other treatment highlights in this document:

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Understanding the Causes of Cancer

SPORE Scientists Say Inherited BRCA2 Mutations May Increase Risk for Pancreatic Cancer. Scientists believe that 10 percent of all cases of pancreatic cancer are hereditary. However, although mutations have been found in the tumors of patients with non-hereditary pancreatic cancers, the major gene(s) responsible for inherited cases have yet to be discovered. Uncovering the causal mutations would provide a way to identify people who might benefit from special surveillance because of an increased genetic risk of developing this disease. In a recent study, investigators searched for suspicious mutations in the BRCA2 gene of pancreatic patients who had at least three relatives with this disease. They discovered mutations likely to be involved in tumor development in 5 out of 29 (or 17 percent) of patients in the study. Further research is needed to better define the risk of pancreatic, and other cancers, in patients with these mutations. There are probably additional genetic as well as environmental factors that influence this risk.

SPORE Study of Tumor Microenvironments Yields New Insights into Cancer. Unique molecular interactions occur between cancer cells and their surrounding tissues, the "tumor microenvironment." For example, when healthy tissues of the body are invaded with cancer cells, they become inflamed and form fibrous, scar-like tissue - known as "desmoplastic tissue." In certain tumors that penetrate into surrounding tissues as they grow (known as infiltrating tumors), this desmoplastic tissue comprises the bulk of the tumor, outpacing the actual cancer cells. Recently, a team of scientists characterized the patterns of genes expressed in the cancerous growth and the microenvironment of two types of infiltrating cancer - pancreatic and infiltrating breast cancer. They discovered a highly ordered, coordinated process of tumor invasion, involving four distinct kinds of tissue and structured molecular interactions between the cancer and its surrounding tissues. This kind of insight into how cancers interact with their microenvironment may lead to previously unimagined strategies for imaging, diagnosis by blood test, and drug development and delivery for pancreatic, infiltrative breast, and numerous other cancers.

Gene-Environment Interactions Are Identified for Non-Hodgkin's Lymphoma. Despite much research, the relationship between exposures experienced by farm workers and non-Hodgkin's lymphoma (NHL) is unclear. However, past studies did not consider gene-environment interactions that might occur in some genetic subtypes of this disease. Because of the way statistical analysis works, when the genetic subtypes of NHL are not studied individually, real associations between farming exposures and NHL might remain hidden. Investigators recently reviewed the exposure data and studied NHL biopsies from about 200 patients who had participated in a prior study. These researchers were able to identify a particular genetic subtype of NHL that appears to be susceptible to the effects of pesticides. Larger studies are needed to clarify the mechanisms behind this gene-environment interaction and to discover ways to intervene to prevent NHL.

Survivorship

African American Cancer Survivors Report Poorer Functional Health Than Whites. Older and minority patients have been under-represented in research of post-cancer treatment issues. Investigators interviewed 180 African American and White long-term breast, colorectal, and prostate cancer survivors to identify differences in reported health problems, illness symptoms, functional difficulties, health worries and concerns, and overall perceptions of health. Although African Americans did not report significantly more symptoms resulting from their cancer or its treatment, they did report a greater decrease in physical functioning, perhaps related to treatment. Older African Americans also reported less concern about development of second cancers, suggesting a need for targeted education about the importance of follow-up care and screening. Continued research is needed to understand post-cancer treatment issues among older and minority patients.

Adult Survivors of Childhood Cancer Lack Detailed Knowledge of Their Past Illness. Childhood cancer cure rates have risen dramatically over the past few decades, creating a growing body of adult survivors who face long-term health risks related to their cancer and treatment. Researchers interviewed 635 adult survivors of childhood cancer to find out how much they knew about their previous illness and treatment. None of the survivors were able to give a detailed summary of their disease, including the name of their cancer, whether they received certain chemotherapy drugs, and the site or sites of radiation treatment. Only 35 percent of those interviewed realized that past treatments could cause serious health problems in the future. Such missing information could prevent survivors from understanding their need for special follow-up care and surveillance. This study highlights a need for educating childhood cancer survivors about their past illness and how it was treated.

Smoking Rates Characterized among Childhood Cancer Survivors. Researchers are working to characterize smoking patterns among childhood cancer survivors, who are at high risk for tobacco-related health problems. A recent survey of almost 10,000 adult survivors of childhood cancer showed that, although these survivors were less likely to smoke than the general population, 17 percent were current smokers, and 11 percent former smokers. Survivors who had been diagnosed with cancer in later childhood were more likely to start smoking, as well as those with a lower household income and/or less education. African Americans and survivors having had either pulmonary related cancer treatment or brain radiation were less likely to smoke. Among survivors who did start smoking, some were more likely to continue smoking: those who were at least thirteen years old when beginning to smoke, those with less education, and those who had brain radiation. The information gained by this research will help craft needed interventions to prevent smoking and to promote quitting in this high-risk population.

Other survivorship highlights in this document:

  • Tool used for studies on the consequences of cancer treatment
  • Chemotherapy dosage and congestive heart failure
  • Lung cancer survivor quality of life
  • Growth hormone replacement for children following treatment for leukemia
  • Social interventions for breast cancer survivors

Quality of Cancer Care

Racial and Ethnic Minorities Receive Less Appropriate Cancer Treatment. Racial and ethnic minorities in the United States bear a disproportionate burden of invasive cancers and cancer deaths. African Americans, for example, are more likely to develop a number of cancers and are 33 percent more likely than Whites to die of cancer. Hispanics are more likely to develop cervical cancer, and Asian/Pacific Islanders are more likely to develop stomach cancer. A group of investigators extensively reviewed published scientific studies to find out whether any of these disparities stem from access to or use of specific cancer treatments. Their review confirmed that racial differences are evident in who receives the best available primary, conservative (such as breast conserving), and adjuvant therapies. Those receiving inferior therapy were also more likely to relapse and die. These disparities could be accounted for, at least in part, by non-clinical factors, such as socioeconomic status, patient concerns about body image, age at diagnosis, the size of the hospital where surgery is performed, the number of previous surgeries performed by the surgeon, geographic location, and insurance coverage. Patient preferences and decisions also played a part.

Rates of Complications from Prostate Surgery Decreases with the Number Performed. For many cancers requiring surgery, patient survival is better when the surgery is conducted at hospitals and/or by surgeons that perform the highest volume of this operation. Although this is not true for patients receiving prostate cancer surgery, where survival is high overall, researchers wondered whether the choice of hospitals or surgeons might affect postoperative morbidity (e.g. urinary complications, incontinence). Investigators discovered that men who underwent removal of the prostate at hospitals and by surgeons who performed a high volume of this surgery, experienced fewer postoperative and late urinary complications. The researchers point out a need for more careful scrutiny of adverse outcomes to reduce the burden of suffering among patients who undergo surgery for prostate cancer.

Other quality of care highlights in this document:

  • Social factors and survival among African American patients with advanced non-small cell lung cancer
  • Educational interventions and cervical screening within the Chinese-American population
  • African American men and risk for advanced prostate cancer

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Chromosomes come in pairs that are typically nearly identical in makeup. For example chromosome 8p and chromosome 8q together comprise what we call "chromosome 8." Sometimes errors occur that make one chromosome of a pair substantially different from the other. This is known as "allelic imbalance."back

Melanoma is cancer of the melanocytes, the pigment producing cells of the skin. It is almost always fatal once it spreads beyond the initial site.back

An antigen is a protein or protein fragment located on the outside of a cell.Back

Molecularly targeted drugs are designed to interact with and disrupt certain molecular features that are critical to the survival of the cancer cell, without harming healthy tissuesBack

FOLFOX4 regimen: 5-fluorouracil/leucovorin/oxaliplatin Saltz regimen: irinotecan/5-fluorouracil/leucovorin Back