More than 1.5 million cancer deaths averted during 2 decades of dropping mortality

Each year, the American Cancer Society compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute and the Centers for Disease Control and Prevention, and mortality data from the National Center for Health Statistics. The data are disseminated in two reports: Cancer Statistics 2015, published in CA: A Cancer Journal for Clinicians, and its companion, consumer-friendly publication, Cancer Facts & Figures 2015. The reports also estimate the number of new cancer cases and deaths expected in the United States in the current year.

Largely driven by rapid increases in lung cancer deaths among men as a consequence of the tobacco epidemic, the overall cancer death rate rose during most of the 20th century, peaking in 1991. The subsequent, steady decline in the cancer death rate is the result of fewer Americans smoking, as well as advances in cancer prevention, early detection, and treatment.

Mortality

  • During the most recent five years for which data are available (2007-2011), the average annual decline in cancer death rates was slightly larger among men (1.8%) than women (1.4%). These declines are driven by continued decreases in death rates for the four major cancer sites: lung, breast, prostate, and colon.
  • Lung cancer death rates declined 36% between 1990 and 2011 among males and 11% between 2002 and 2011 among females due to reduced tobacco use.
  • Death rates for breast cancer (among women) are down more than one-third (35%) from peak rates, while prostate and colorectal cancer death rates are each down by nearly half (47%).
  • The magnitude of the decline in overall cancer mortality between 1991 and 2011 varied by state. The smallest declines were generally in the South, where drops were about 15%. They were largest in the Northeast. For example, there were declines of 25% to 30% in Maryland, New Jersey, Massachusetts, New York, and Delaware. As a result, a total of 29,000 cancer deaths were averted in 2011 in these states.

Estimates for the current year

  • The report estimates there will be 1,658,370 new cancer cases and 589,430 cancer deaths in the United States in 2015.
  • Prostate, lung, and colorectal cancers will account for about one-half of all cases in men, with prostate cancer alone accounting for about one-quarter of new diagnoses.
  • The three most commonly diagnosed types of cancer among women in 2015 will be breast, lung, and colorectal cancer, accounting for one-half of all cases in women. Breast cancer alone is expected to account for 29% of all new cancers among women in the U.S.
  • The report estimates that 589,430 Americans will die from cancer this year, corresponding to about 1,600 deaths per day.
  • The most common causes of cancer death are lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women. These four cancers account for almost one-half of all cancer deaths, with more than one-quarter (27%) of all cancer deaths due to lung cancer.

Additional findings

  • During the past five years for which there are data (2007-2011), the overall cancer incidence rate remained stable in women and declined by 1.8% per year in men.
  • The decrease in incidence in men is driven by the rapid declines in colorectal (3.6% per year), lung (3.0% per year), and prostate (2.1% per year) cancers.
  • While women in the U.S. have seen similar drops in colorectal and lung cancers, breast cancer incidence rates have flattened, and there’s been a dramatic rise in thyroid cancer incidence rates (an average of 4.5% per year from 2007 to 2011).

“The continuing drops we’re seeing in cancer mortality are reason to celebrate, but not to stop,” said John R. Seffrin, PhD, chief executive officer of the American Cancer Society. “Cancer was responsible for nearly one in four deaths in the United States in 2011, making it the second leading cause of death overall. It is already the leading cause of death among adults aged 40 to 79, and is expected to overtake heart disease as the leading cause of death among all Americans within the next several years. The change may be inevitable, but we can still lessen cancer’s deadly impact by making sure as many Americans as possible have access to the best tools to prevent, detect, and treat cancer.”

Each year, Cancer Facts & Figures includes a Special Section that focuses on a specific, timely cancer topic. This year, the report highlights breast carcinoma in situ. An estimated 60,290 new cases of breast carcinoma in situ are expected to be diagnosed in 2015, accounting for about one in five breast tumors diagnosed in women. Although in situ breast cancer is a relatively common diagnosis, it is not as widely known or understood as invasive breast cancer.

The term “carcinoma in situ” describes abnormal cells that have not invaded nearby tissues, but that look very similar to cells of invasive carcinoma when viewed under a microscope. For many years, it was assumed that these cells were potentially able to become invasive, and that in the absence of treatment, they would eventually progress to cancer. More recent research indicates that the transition from normal tissue to carcinoma in situ to invasive carcinoma involves a series of molecular changes that are more complex and subtle than the older view based on microscopic appearances. Long-term follow-up studies of patients with carcinoma in situ also find that even without treatment, not all patients develop invasive cancer.

The vast majority (83%) of in situ breast cancers will be ductal carcinoma in situ (DCIS). DCIS refers to abnormal cells lining the breast duct that appear similar to those of invasive breast cancers, but are still within the tissue layer of origin. It is most often detected by a mammogram. While DCIS cannot spread to other organs and cause serious illness or death, it has the potential if left untreated to evolve into invasive cancer and is considered a true cancer precursor. Studies of women with DCIS that was untreated because it was originally misclassified as benign found that 20 to 53% were eventually diagnosed with an invasive breast cancer.

Lobular carcinoma in situ (LCIS) refers to cells that look like cancer cells growing within the walls of the lobules of the milk-producing glands of the breast. LCIS is not generally thought to be a precursor of invasive cancer, but is considered a marker for increased risk of developing invasive breast cancer.

The authors say they hope that the information in the Special Section will help patients facing the disease, as well as friends, family, and others who can provide support and perspective for women who are newly diagnosed and those living after a diagnosis of DCIS or LCIS.

source : http://www.sciencedaily.com/releases/2014/12/141231095649.htm

Stereotactic Body Radiation Therapy Plus Chemotherapy Improves Survival Among Stage 4 Lung Cancer Patients

The combination of the chemotherapy regimen, erlotinib, with stereotactic body radiation therapy, known as SBRT, improved overall survival time to 20 months compared to historic 6- to 9- month survival times among erlotinib-only treated patients. The combination improved progression free survival – the time without the reappearance of cancer − from the historical two to four months to 14.7 months for similarly selected lung cancer patients.

“Our approach dramatically changed the pattern of relapse. We saw a shift in failure from existing, local sites to new, distant sites,” said senior author Dr. Robert Timmerman, Director of the Annette Simmons Stereotactic Treatment Center, and Vice Chairman of Radiation Oncology at UT Southwestern. “This shift resulted in a surprisingly long remission from the reappearance of cancer in treated patients.”

According to the National Cancer Institute, lung cancer will be diagnosed in an estimated 224,210 men and women during 2014. Five year relative survival rates remain low at just 16.8 percent from 2004-10. Of these cancer cases, about 85 percent fall into the category of non-small cell lung cancer.

Dr. Timmerman, holder of the Effie Marie Cain Distinguished Chair in Cancer Therapy Research, is a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, the only National Cancer Institute-designated cancer center in North Texas and a National Clinical Trials Network Lead Academic Site.

This Phase 2 clinical trial involved 24 patients with stage 4 non-small cell lung cancer (NSCLC) whose cancer has continued to spread during their initial therapy. Such patients typically have poor survival rates, and SBRT is not typically used in these patients, said first author Dr. Puneeth Iyengar, Assistant Professor and Director of Clinical Research of Radiation Oncology, and co-leader of the Simmons Cancer Center Thoracic Oncology Group.

The revolutionary SBRT technique is a type of radiation therapy in which a few very high doses of radiation are delivered from multiple angles to small, well-defined tumors. The goal is to deliver a radiation dose high enough to kill the cancer, while minimizing exposure to surrounding healthy tissue and organs, explained Dr. Timmerman, who directs Clinical Research and the Image-Guided Stereotactic Radiation Therapy in the Department of Radiation Oncology.

SBRT has been shown to offer better cure rates in certain instances, particularly for cancers that have metastasized, said Dr. Timmerman, Professor of Radiation Oncology and Neurological Surgery, who was one of the first researchers in the world to use the SBRT techniques initially developed for brain tumors to treat cancer in the body.

“Technologies have developed in the last few years that have yielded game-changing, paradigm-shifting approaches, allowing us to reconsider how radiation is delivered in combination with surgery, chemotherapy, and other systemic therapies,” said Dr. Timmerman, who served as the lead investigator in several national trials designed to evaluate the efficacy and safety of SBRT to treat cancer in the lung, liver, spine, and prostate. “I am motivated by the need I see every day in the clinic to provide better treatments for our patients.”

The results are reported in the Journal of Clinical Oncology of the American Society of Clinical Oncology.

source : http://www.sciencedaily.com/releases/2014/12/141231154014.htm

Women with atypical hyperplasia are at higher risk of breast cancer

Atypical hyperplasia of the breast is a precancerous condition found in about one-tenth of the over 1 million breast biopsies with benign findings performed annually in the United States. Viewed under a microscope, atypia contains breast cells that are beginning to grow out of control (hyperplasia) and cluster into abnormal patterns (atypical). Atypia lesions are considered benign, but by its risk and appearance and genetic changes, they exhibit some of the early features of cancer.

Data from hundreds of women with these benign lesions indicate that their absolute risk of developing breast cancer grows by over 1 percent a year. The study found that after five years, 7 percent of these women had developed the disease; after 10 years, that number had increased to 13 percent; and after 25 years, 30 percent had breast cancer.

The finding places the more than 100,000 women diagnosed each year with atypical hyperplasia — also known as atypia — into a high-risk category, where they are more likely to benefit from intense screening and use of medications to reduce risk.

“By providing better risk prediction for this group, we can tailor a woman’s clinical care to her individual level of risk,” says Lynn Hartmann, M.D., an oncologist at Mayo Clinic and lead author of the study. “We need to do more for this population of women who are at higher risk, such as providing the option of MRI screenings in addition to mammograms and encouraging consideration of anti-estrogen therapies that could reduce their risk of developing cancer.”

Previous research has shown that women with atypia have a fourfold to fivefold increased “relative risk” — meaning that they are four to five times more likely to develop breast cancer than women who don’t have these lesions. But few studies have had the patient numbers and follow-up time to report the patients’ “absolute risk” — the chance that she will develop breast cancer over a certain period of time.

To clearly define this risk, the Mayo Clinic team followed 698 women with atypia who had been biopsied at Mayo Clinic between 1967 and 2001. They reviewed pathology and medical records, and used patient follow-up questionnaires to determine which women developed breast cancer and when. The researchers found that after an average follow-up of 12.5 years, 143 women had developed the disease.

Importantly, the Mayo findings were validated by researchers at Vanderbilt University using biopsies from a separate cohort of women with atypia. Both data sets revealed that at 25 years following biopsy, 25 to 30 percent of these women had developed breast cancer.

The Mayo team had previously showed that two common statistical risk prediction models (the BCRAT and the IBIS models) performed poorly in women with atypical hyperplasia, underscoring the need to provide alternative approaches for predicting risk in this population.

“Instead of relying on a statistical model, our study provides actual data of breast cancer cases that occurred in a population of women with atypia. These absolute risk data are preferable to a hypothetical model,” says Amy Degnim, M.D., co-lead author and a breast surgeon at Mayo Clinic.

The researchers were able to give an even more accurate estimate of risk by incorporating information from a patient’s pathology specimen. They found that as the extent of atypia in a biopsy increased, as measured by the number of separate atypia lesions or foci, so did the woman’s risk of developing breast cancer. For example, at 25 years post-biopsy, 47 percent women with three or more foci of atypia in the biopsy had developed breast cancer, compared to only 24 percent of women with one focus.

Based on these results, the research team recommends that women with atypical hyperplasia be recognized as having significantly increased lifetime risk of breast cancer and thus be candidates for screening MRI. Moreover, anti-estrogen medications like tamoxifen have already been tested in clinical trials in women with atypia and shown to lower their risk of breast cancer by 50 percent or more. Yet, Dr. Degnim says, many women with atypia are not taking the medications, in part because they and their physicians have not had solid estimates of their breast cancer risk to guide them.

source : http://www.sciencedaily.com/releases/2014/12/141231190106.htm

Researchers target the cell’s ‘biological clock’ in promising new therapy to kill cancer cells

Dr. Jerry W. Shay, Professor and Vice Chairman of Cell Biology at UT Southwestern, and colleague, Dr. Woodring E. Wright, Professor of Cell Biology and Internal Medicine, found that 6-thio-2′-deoxyguanosine could stop the growth of cancer cells in culture and decrease the growth of tumors in mice.

“We observed broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodG, as well as tumor burden shrinkage in mice,” said Dr. Shay, Associate Director of the Harold C. Simmons Comprehensive Cancer Center.

Dr. Shay and Dr. Wright, who hold The Southland Financial Corporation Distinguished Chair in Geriatrics, are co-senior authors of the paper appearing in the journal Cancer Discovery.

6-thiodG acts by targeting a unique mechanism that is thought to regulate how long cells can stay alive, a type of aging clock. This biological clock is defined by DNA structures known as telomeres, which cap the ends of the cell’s chromosomes to protect them from damage, and which become shorter every time the cell divides. Once telomeres have shortened to a critical length, the cell can no longer divide and dies though a process known as apoptosis.

Cancer cells are protected from this death by an RNA protein complex called telomerase, which ensures that telomeres do not shorten with every division. Telomerase has therefore been the subject of intense research as a target for cancer therapy. Drugs that successfully block its action have been developed, but these drugs have to be administered for long periods of time to successfully trigger cell death and shrink tumors, leading to considerable toxicities. This outcome is partially because cells in any one tumor have chromosomes with different telomere lengths and any one cell’s telomeres must be critically shortened to induce death.

6-thiodG is preferentially used as a substrate by telomerase and disrupts the normal way cells maintain telomere length. Because 6-thiodG is not normally used in telomeres, the presence of the compound acts as an ‘alarm’ signal that is recognized by the cell as damage. As a result, the cell stops dividing and dies.

Telomerase is an almost universal oncology target, yet there are few telomerase-directed therapies in human clinical trials, researchers noted.

“Using telomerase to incorporate toxic products into telomeres is remarkably encouraging at this point,” said Dr. Wright.

Importantly, unlike many other telomerase-inhibiting compounds, the researchers did not observe serious side effects in the blood, liver and kidneys of the mice that were treated with 6-thiodG.

“Since telomerase is expressed in almost all human cancers, this work represents a potentially innovative approach to targeting telomerase-expressing cancer cells with minimal side effects on normal cells,” said Dr. Shay. “We believe this small molecule will address an unmet cancer need in an underexplored area that will be rapidly applicable to the clinic.”

source : http://www.sciencedaily.com/releases/2015/01/150101142230.htm

‘Bad luck’ of random mutations plays predominant role in cancer, study shows

“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,’ but the truth is that most of them simply had good luck,” adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.

The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say. “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” says biomathematician Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. “We should focus more resources on finding ways to detect such cancers at early, curable stages,” he adds.

In a report on the statistical findings, published Jan. 2 in Science, Tomasetti and Vogelstein say they came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual’s lifetime. Stem cells “self-renew,” thus repopulating cells that die off in a specific organ.

It was well-known, Vogelstein notes, that cancer arises when tissue-specific stem cells make random mistakes, or mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer. The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known, says Vogelstein.

To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, Tomasetti and Vogelstein determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.

“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Vogelstein. One example, he says, is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.

“You could argue that the colon is exposed to more environmental factors than the small intestine, which increases the potential rate of acquired mutations,” says Tomasetti. However, the scientists saw the opposite finding in mouse colons, which had a lower number of stem cell divisions than in their small intestines, and, in mice, cancer incidence is lower in the colon than in the small intestine. They say this supports the key role of the total number of stem cell divisions in the development of cancer. Using statistical theory, the pair calculated how much of the variation in cancer risk can be explained by the number of stem cell divisions, which is 0.804 squared, or, in percentage form, approximately 65 percent.

Finally, the research duo classified the types of cancers they studied into two groups. They statistically calculated which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence. They found that 22 cancer types could be largely explained by the “bad luck” factor of random DNA mutations during cell division. The other nine cancer types had incidents higher than predicted by “bad luck” and were presumably due to a combination of bad luck plus environmental or inherited factors.

“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking, skin cancer, linked to sun exposure, and forms of cancers associated with hereditary syndromes,” says Vogelstein.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery,” adds Vogelstein.

The scientists note that some cancers, such as breast and prostate cancer, were not included in the report because of their inability to find reliable stem cell division rates in the scientific literature. They hope that other scientists will help refine their statistical model by finding more precise stem cell division rates.

source : http://www.sciencedaily.com/releases/2015/01/150101142318.htm

3-D culture system for pancreatic cancer has potential to change therapeutic approaches

In work published in Cell, the research team describes a three-dimensional “organoid” culture system for pancreatic cancer. Co-led by David Tuveson, CSHL Professor and Director of Research for The Lustgarten Foundation, and Hans Clevers, Professor and Director of the Hubrecht Institute and President of the Royal Netherlands Academy of Arts and Sciences, the team developed a method to grow pancreatic tissue not only from laboratory mouse models, but also from human patient tissue, offering a path to personalized treatment approaches in the future.

All cancer research relies on a steady supply of cells — both normal and cancerous — that can be grown in the laboratory. By comparing normal cells to cancer cells, scientists can then identify the changes that lead to disease. However, both types of pancreatic cells have been extremely difficult to culture in the laboratory.

Furthermore, the normal ductal cells that are able to develop into pancreatic cancer represent about 10 percent of the cells in the pancreas, complicating efforts to pinpoint the changes that occur as the tumor develops. Until now, scientists have been entirely unable to culture human normal ductal pancreatic cells under standard laboratory conditions. Because of these limitations, most pancreatic cancer research relies on genetically engineered mouse models of the disease, which can take up to one year to generate. “With this development, we are now able to culture both mouse and human organoids, providing a very powerful tool in our fight against pancreatic cancer,” explains Tuveson.

The organoids are entirely made up of ductal cells, eliminating the surrounding cell types that often contaminate samples from the pancreas. They grow as hollow spheres within a complex gel-like substance filled with growth-inducing factors and connecting fibers. Once they have grown to a sufficient size, the organoids can be transplanted back into mice, where they fully recapitulate pancreatic cancer. “We now have a model for each stage in the progression of the disease,” says Chang-Il Hwang, Ph.D., one of the lead authors working in The Lustgarten Foundation’s Pancreatic Cancer Research Lab at CSHL directed by Dr. Tuveson.

Traditionally, cancer cells are isolated during surgery or autopsies. Unfortunately, approximately 85 percent of cancer patients are ineligible for surgery at the time of diagnosis, either because the tumor is entwined in critical vasculature or the disease has progressed too far. Researchers therefore have had limited access to patient samples. The new research provides a way for scientists to grow organoids from biopsy material, which is comparatively easy to obtain. “Biopsies are the standard for diagnosis,” says Dannielle Engle, Ph.D., also a lead author on the paper. “We can now rapidly generate organoids from any patient, which offers us the potential to study the disease in a much wider population.”

The team is now working to create a repository of pancreatic tumor samples, coordinating with the National Cancer Institute. “We hope to make this available to the entire pancreatic cancer research community,” says Tuveson. Additionally, Lindsey Baker, Ph.D., another lead author of the paper, has started holding an “organoid school” for other researchers, and has already taught six laboratories from around the world this technique.

source : http://www.sciencedaily.com/releases/2014/12/141231140427.htm

More than 1.5 million cancer deaths averted during 2 decades of dropping mortality — ScienceDaily

Each year, the American Cancer Society compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute and the Centers for Disease Control and Prevention, and mortality data from the National Center for Health Statistics. The data are disseminated in two reports: Cancer Statistics 2015, published in CA: A Cancer Journal for Clinicians, and its companion, consumer-friendly publication, Cancer Facts & Figures 2015. The reports also estimate the number of new cancer cases and deaths expected in the United States in the current year.

Largely driven by rapid increases in lung cancer deaths among men as a consequence of the tobacco epidemic, the overall cancer death rate rose during most of the 20th century, peaking in 1991. The subsequent, steady decline in the cancer death rate is the result of fewer Americans smoking, as well as advances in cancer prevention, early detection, and treatment.

Mortality

  • During the most recent five years for which data are available (2007-2011), the average annual decline in cancer death rates was slightly larger among men (1.8%) than women (1.4%). These declines are driven by continued decreases in death rates for the four major cancer sites: lung, breast, prostate, and colon.
  • Lung cancer death rates declined 36% between 1990 and 2011 among males and 11% between 2002 and 2011 among females due to reduced tobacco use.
  • Death rates for breast cancer (among women) are down more than one-third (35%) from peak rates, while prostate and colorectal cancer death rates are each down by nearly half (47%).
  • The magnitude of the decline in overall cancer mortality between 1991 and 2011 varied by state. The smallest declines were generally in the South, where drops were about 15%. They were largest in the Northeast. For example, there were declines of 25% to 30% in Maryland, New Jersey, Massachusetts, New York, and Delaware. As a result, a total of 29,000 cancer deaths were averted in 2011 in these states.

Estimates for the current year

  • The report estimates there will be 1,658,370 new cancer cases and 589,430 cancer deaths in the United States in 2015.
  • Prostate, lung, and colorectal cancers will account for about one-half of all cases in men, with prostate cancer alone accounting for about one-quarter of new diagnoses.
  • The three most commonly diagnosed types of cancer among women in 2015 will be breast, lung, and colorectal cancer, accounting for one-half of all cases in women. Breast cancer alone is expected to account for 29% of all new cancers among women in the U.S.
  • The report estimates that 589,430 Americans will die from cancer this year, corresponding to about 1,600 deaths per day.
  • The most common causes of cancer death are lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women. These four cancers account for almost one-half of all cancer deaths, with more than one-quarter (27%) of all cancer deaths due to lung cancer.

Additional findings

  • During the past five years for which there are data (2007-2011), the overall cancer incidence rate remained stable in women and declined by 1.8% per year in men.
  • The decrease in incidence in men is driven by the rapid declines in colorectal (3.6% per year), lung (3.0% per year), and prostate (2.1% per year) cancers.
  • While women in the U.S. have seen similar drops in colorectal and lung cancers, breast cancer incidence rates have flattened, and there’s been a dramatic rise in thyroid cancer incidence rates (an average of 4.5% per year from 2007 to 2011).

“The continuing drops we’re seeing in cancer mortality are reason to celebrate, but not to stop,” said John R. Seffrin, PhD, chief executive officer of the American Cancer Society. “Cancer was responsible for nearly one in four deaths in the United States in 2011, making it the second leading cause of death overall. It is already the leading cause of death among adults aged 40 to 79, and is expected to overtake heart disease as the leading cause of death among all Americans within the next several years. The change may be inevitable, but we can still lessen cancer’s deadly impact by making sure as many Americans as possible have access to the best tools to prevent, detect, and treat cancer.”

Each year, Cancer Facts & Figures includes a Special Section that focuses on a specific, timely cancer topic. This year, the report highlights breast carcinoma in situ. An estimated 60,290 new cases of breast carcinoma in situ are expected to be diagnosed in 2015, accounting for about one in five breast tumors diagnosed in women. Although in situ breast cancer is a relatively common diagnosis, it is not as widely known or understood as invasive breast cancer.

The term “carcinoma in situ” describes abnormal cells that have not invaded nearby tissues, but that look very similar to cells of invasive carcinoma when viewed under a microscope. For many years, it was assumed that these cells were potentially able to become invasive, and that in the absence of treatment, they would eventually progress to cancer. More recent research indicates that the transition from normal tissue to carcinoma in situ to invasive carcinoma involves a series of molecular changes that are more complex and subtle than the older view based on microscopic appearances. Long-term follow-up studies of patients with carcinoma in situ also find that even without treatment, not all patients develop invasive cancer.

The vast majority (83%) of in situ breast cancers will be ductal carcinoma in situ (DCIS). DCIS refers to abnormal cells lining the breast duct that appear similar to those of invasive breast cancers, but are still within the tissue layer of origin. It is most often detected by a mammogram. While DCIS cannot spread to other organs and cause serious illness or death, it has the potential if left untreated to evolve into invasive cancer and is considered a true cancer precursor. Studies of women with DCIS that was untreated because it was originally misclassified as benign found that 20 to 53% were eventually diagnosed with an invasive breast cancer.

Lobular carcinoma in situ (LCIS) refers to cells that look like cancer cells growing within the walls of the lobules of the milk-producing glands of the breast. LCIS is not generally thought to be a precursor of invasive cancer, but is considered a marker for increased risk of developing invasive breast cancer.

The authors say they hope that the information in the Special Section will help patients facing the disease, as well as friends, family, and others who can provide support and perspective for women who are newly diagnosed and those living after a diagnosis of DCIS or LCIS.

source : http://www.sciencedaily.com/releases/2014/12/141231095649.htm

Women with atypical hyperplasia are at higher risk of breast cancer — ScienceDaily

Atypical hyperplasia of the breast is a precancerous condition found in about one-tenth of the over 1 million breast biopsies with benign findings performed annually in the United States. Viewed under a microscope, atypia contains breast cells that are beginning to grow out of control (hyperplasia) and cluster into abnormal patterns (atypical). Atypia lesions are considered benign, but by its risk and appearance and genetic changes, they exhibit some of the early features of cancer.

Data from hundreds of women with these benign lesions indicate that their absolute risk of developing breast cancer grows by over 1 percent a year. The study found that after five years, 7 percent of these women had developed the disease; after 10 years, that number had increased to 13 percent; and after 25 years, 30 percent had breast cancer.

The finding places the more than 100,000 women diagnosed each year with atypical hyperplasia — also known as atypia — into a high-risk category, where they are more likely to benefit from intense screening and use of medications to reduce risk.

“By providing better risk prediction for this group, we can tailor a woman’s clinical care to her individual level of risk,” says Lynn Hartmann, M.D., an oncologist at Mayo Clinic and lead author of the study. “We need to do more for this population of women who are at higher risk, such as providing the option of MRI screenings in addition to mammograms and encouraging consideration of anti-estrogen therapies that could reduce their risk of developing cancer.”

Previous research has shown that women with atypia have a fourfold to fivefold increased “relative risk” — meaning that they are four to five times more likely to develop breast cancer than women who don’t have these lesions. But few studies have had the patient numbers and follow-up time to report the patients’ “absolute risk” — the chance that she will develop breast cancer over a certain period of time.

To clearly define this risk, the Mayo Clinic team followed 698 women with atypia who had been biopsied at Mayo Clinic between 1967 and 2001. They reviewed pathology and medical records, and used patient follow-up questionnaires to determine which women developed breast cancer and when. The researchers found that after an average follow-up of 12.5 years, 143 women had developed the disease.

Importantly, the Mayo findings were validated by researchers at Vanderbilt University using biopsies from a separate cohort of women with atypia. Both data sets revealed that at 25 years following biopsy, 25 to 30 percent of these women had developed breast cancer.

The Mayo team had previously showed that two common statistical risk prediction models (the BCRAT and the IBIS models) performed poorly in women with atypical hyperplasia, underscoring the need to provide alternative approaches for predicting risk in this population.

“Instead of relying on a statistical model, our study provides actual data of breast cancer cases that occurred in a population of women with atypia. These absolute risk data are preferable to a hypothetical model,” says Amy Degnim, M.D., co-lead author and a breast surgeon at Mayo Clinic.

The researchers were able to give an even more accurate estimate of risk by incorporating information from a patient’s pathology specimen. They found that as the extent of atypia in a biopsy increased, as measured by the number of separate atypia lesions or foci, so did the woman’s risk of developing breast cancer. For example, at 25 years post-biopsy, 47 percent women with three or more foci of atypia in the biopsy had developed breast cancer, compared to only 24 percent of women with one focus.

Based on these results, the research team recommends that women with atypical hyperplasia be recognized as having significantly increased lifetime risk of breast cancer and thus be candidates for screening MRI. Moreover, anti-estrogen medications like tamoxifen have already been tested in clinical trials in women with atypia and shown to lower their risk of breast cancer by 50 percent or more. Yet, Dr. Degnim says, many women with atypia are not taking the medications, in part because they and their physicians have not had solid estimates of their breast cancer risk to guide them.

source : http://www.sciencedaily.com/releases/2014/12/141231190106.htm

Neonatal HBV vaccine reduces liver cancer risk

The researchers report long-term outcomes from the Qidong Hepatitis B intervention Study (QHBIS), a randomized controlled trial of neonatal HBV vaccination that was conducted between 1983 and 1990 in Qidong County, a rural area in China with a high incidence of HBV-related primary liver cancer (PLC) and other liver diseases. In this study, 41 rural towns (including a total of 77,658 newborns over the study period) were randomized to the intervention (HBV vaccination for all newborns) or control (no vaccination) groups, with two-thirds of the control group participants receiving a catch-up vaccination at age 10-14 years.

By collecting data on new cases of liver diseases over 30 years from a population-based tumor registry, the researchers estimated that the protective efficacy of vaccination was 84% for primary liver cancer (vaccination reduced the incidence of liver cancer by 84%), 70% for death from liver diseases, and 69% for the incidence of infant fulminant hepatitis. Based on survey data collected in 1996-2000 and 2008-2012 on HBsAg seroprevalence, an indicator of current hepatitis B virus (HBV) infection, they conclude that the efficacy of the catch-up vaccination on HBsAg seroprevalence in early adulthood was weak compared to neonatal vaccination (21% versus 72%). While these findings support the importance of neonatal HBV vaccination, the small number of cases of primary liver cancer and other liver diseases observed during the 30-year follow up, the length of follow-up, and the availability of incomplete data on seroprevalence all limit the accuracy of these findings.

The authors say: “Neonatal HBV vaccination significantly decreased HBsAg seroprevalence in childhood through young adulthood and subsequently reduced the risk of PLC and other liver diseases in young adults.” They continue: “Our results also suggest that an adolescence booster should be considered in people who were born to HBsAg-positive mothers and completed HBV neonatal vaccination series.”

source : http://www.sciencedaily.com/releases/2014/12/141230145158.htm

Cancer treatment potential discovered in gene repair mechanism

If the laboratory findings are supported by tests in animal models, the breakthrough could hold the promise of increasing the effectiveness of radiation and chemotherapy in shrinking or even eliminating tumors. The key is to build up a “good” protein — p53-binding protein 1 (53BP1) — so that it weakens the cancer cells, leaving them more susceptible to existing cancer-fighting measures.

The breakthrough detailed appeared in the Nov. 24 online edition of the journal PNAS (Proceedings of the National Academy of Sciences).

“Our discovery one day could lead to a gene therapy where extra amounts of 53BP1 will be generated to make cancer cells more vulnerable to cancer treatment,” said senior author Youwei Zhang, PhD, assistant professor of pharmacology, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. “Alternatively, we could design molecules to increase levels of 53BP1 in cancers with the same cancer-killing end result.”

The cornerstone of the research involves DNA repair — more specifically, double-stand DNA repair. DNA damage is the consequence of an irregular change in the chemical structure of DNA, which in turn damages and even kills cells. The most lethal irregularity to DNA is the DNA double-strand break in the chromosome. DNA double-strand breaks are caused by everything from reactive oxygen components occurring with everyday bodily metabolism to more damaging assaults such as radiation or chemical agents.

The body operates two repair shops, or pathways, to fix these double strand breaks. One provides rapid, but incomplete repair — namely, gluing the DNA strand ends back together. The problem with the glue method is that it leaves the DNA strands unable to transmit enough information for the cell to function properly — leading to a high cell fatality rate.

The second shop, or pathway, uses information from intact, undamaged DNA to instruct damaged cells on how to mend broken double strands. During his study, Zhang and fellow investigators discovered a previously unidentified function of a known gene, UbcH7, in regulating DNA double-strand break repair. Specifically, they found that depleting UbcH7 led to a dramatic increase in the level of the 53BP1 protein.

“What we propose is increasing the level of 53BP1 to force cancer cells into the error-prone pathway where they will die,” Zhang said. “The idea is to suppress deliberately the second accurate repair pathway where cancer cells would prefer to go. It is a strategy that would lead to enhanced effectiveness of cancer therapy drugs.”

The next research step for Zhang and his team will be to test their theory in animal models with cancer. Investigators would study the effects of introducing the protein 53BP1 in lab mice with cancer and then applying chemotherapy and radiotherapy as treatment.

“Each cell in our bodies already contains these UbcH7 proteins that regulate 53BP1,” Zhang said. “In patients with cancer, we want to induce more of 53BP1 proteins within their bodies to make their cancer cells vulnerable to radiation therapy and chemotherapy drugs.”

source : http://www.sciencedaily.com/releases/2014/12/141230145202.htm