U.S. President Barack Obama Proclaims September 2014 As National Ovarian Cancer Awareness Month — What Should You Know?

Today, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. “This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.”

WhiteHouse-LogoToday, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will continue to honor the women who have lost their lives to the disease (including our own Elizabeth “Libby” Remick), support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

didyouknow

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2014, the American Cancer Society (ACS) estimates that there will be approximately 21,980 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,270 U.S. women will die from the disease, or about 39 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — each and every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

  • BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.
  • Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.
  • Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.
  • Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA-125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

  • Treatment includes surgery and usually chemotherapy.
  • Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.
  • In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.
  • Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.
  • For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.
  • For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.
  • Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).
  • New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.
  • Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.
  • The 10-year relative survival rate for all disease stages combined is only 38%.
  • Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word to “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

beatlogo_308x196B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 29, 2014

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

obama_signing

Ovarian cancer is the most deadly of all female reproductive system cancers. This year nearly 22,000 Americans will be diagnosed with this cancer, and more than 14,000 will die from it. The lives of mothers and daughters will be taken too soon, and the pain of this disease will touch too many families. During National Ovarian Cancer Awareness Month, we honor the loved ones we have lost to this disease and all those who battle it today, and we continue our work to improve care and raise awareness about ovarian cancer.

When ovarian cancer is found in its early stages, treatment is most effective and the chances for recovery are greatest. But ovarian cancer is difficult to detect early — there is no simple and reliable way to screen for this disease, symptoms are often not clear until later stages, and most women are diagnosed without being at high risk. That is why it is important for all women to pay attention to their bodies and know what is normal for them. Women who experience unexplained changes — including abdominal pain, pressure, and swelling — should talk with their health care provider. To learn more about the risk factors and symptoms of ovarian cancer, Americans can visit www.Cancer.gov.

Regular health checkups increase the chance of early detection, and the Affordable Care Act expands this critical care to millions of women. Insurance companies are now required to cover well-woman visits, which provide women an opportunity to talk with their health care provider, and insurers are prohibited from charging a copayment for this service.

For the thousands of women affected by ovarian cancer, the Affordable Care Act also prohibits insurance companies from denying coverage due to a pre-existing condition, such as cancer or a family history of cancer; prevents insurers from denying participation in an approved clinical trial for any life-threatening disease; and eliminates annual and lifetime dollar limits on coverage. And as we work to ease the burden of ovarian cancer for today’s patients, my Administration continues to invest in the critical research that will lead to earlier detection, improved care, and the medical breakthroughs of tomorrow.

Ovarian cancer and the hardship it brings have affected too many lives. This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2014 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

IN WITNESS WHEREOF, I have hereunto set my hand this twenty-ninth day of August, in the year of our Lord two thousand fourteen, and of the Independence of the United States of America the two hundred and thirty-ninth.

BARACK OBAMA

__________________________________________________________

Sources:

  • Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014 [PDF file].
  • Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 29, 2014.

U.S. President Barack Obama Proclaims September 2013 As National Ovarian Cancer Awareness Month — What Should You Know?

Yesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. “… During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer…. This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease. …”

WhiteHouse-LogoYesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will honor the women who have lost their lives to the disease, support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

didyouknow

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2013, the American Cancer Society (ACS) estimates that there will be approximately 22,240 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,030 U.S. women will die from the disease, or about 38 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

  • BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.
  • Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.
  • Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.
  • Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA-125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

  • Treatment includes surgery and usually chemotherapy.
  • Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.
  • In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.
  • Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.
  • For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.
  • For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.
  • Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).
  • New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.
  • Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.
  • The 10-year relative survival rate for all disease stages combined is only 38%.
  • Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word To “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

beatlogo_308x196B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 30, 2013

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

obama_signingEach September, America calls attention to a deadly disease that affects thousands of women across our country. This year, over 22,000 women will develop ovarian cancer, and more than half that number of women will die of this disease. During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer.

Because ovarian cancer often goes undetected until advanced stages, increasing awareness of risk factors is critical to fighting this disease. Chances of developing ovarian cancer are greater in women who are middle-aged or older, women with a family history of breast or ovarian cancer, and those who have had certain types of cancer in the past. I encourage all women, especially those at increased risk, to talk to their doctors. For more information, visit www.Cancer.gov.

My Administration is investing in research to improve our understanding of ovarian cancer and develop better methods for diagnosis and treatment. As we continue to implement the Affordable Care Act, women with ovarian cancer will receive increased access to health care options, protections, and benefits. Thanks to this law, insurance companies can no longer set lifetime dollar limits on coverage or cancel coverage because of errors on paperwork. By 2014, the health care law will ban insurers from setting restrictive annual caps on benefits and from charging women higher rates simply because of their gender. Additionally, insurance companies will be prohibited from denying coverage or charging higher premiums to patients with pre-existing conditions, including ovarian cancer.

This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2013 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

IN WITNESS WHEREOF, I have hereunto set my hand this thirtieth day of August, in the year of our Lord two thousand thirteen, and of the Independence of the United States of America the two hundred and thirty-eighth.

BARACK OBAMA

__________________________________________________________

Sources:

  • Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013 [PDF file].
  • Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 30, 2013.

Ovarian Cancer Tumors Can Grow For Ten Years Or More Before Being Detected By Today’s Blood Tests

A new mathematical model developed by Stanford University School of Medicine scientists finds that ovarian cancer tumors can grow for 10 years or longer before currently available blood tests will detect them.

A new mathematical model developed by Stanford University School of Medicine scientists indicates that tumors can grow for 10 years or longer before currently available blood tests will detect them. The analysis, which was restricted to ovarian cancer tumors but is broadly applicable across all solid tumor types, was published online November 16 in Science Translational Medicine.

“The study’s results can be viewed as both bad and good news,” said Sanjiv “Sam” Gambhir, M.D., Ph.D., professor and chair of radiology and the study’s senior author. Sharon Hori, Ph.D., a postdoctoral scholar in Dr. Gambhir’s laboratory, is the lead study author.

The mathematical model developed by Dr. Sam Gambhir’s lab shows that it would be possible to detect tumors years before they grow big enough to metastasize if researchers can develop the right biomarkers.

The bad news, as explained by Dr. Gambhir, is that by time a tumor reaches a detectable size using today’s available blood tests, it is likely to have metastasized to other areas of the body, making it much more deadly than if it had been caught earlier. “The good news is that we have, potentially, 10 or even 20 years to find the tumor before it reaches this size, if only we can improve our blood-based methods of detecting tumors,” said Dr. Gambhir. “We think our mathematical model will help guide attempts to do that.”

The study advances previous research about the limits of current detection methods. For instance, it is strikingly consistent with a finding reported two years ago by Stanford biochemistry professor Patrick Brown, M.D., Ph.D., that current ovarian cancer tests could not detect tumors early enough to make a significant dent in the mortality rate. There is a push to develop more-sensitive diagnostic tests and find better biomarkers, and Dr. Gambhir’s new model could be an essential tool in this effort. For the first time, the new model connects the size of a tumor with blood biomarker levels being shed by that tumor.

To create their model, Drs. Gambhir and Hori used mathematical models originally developed to predict the concentration of drugs injected into the blood. The investigators linked these to additional models of tumor cell growth.

Tumors do not secrete drugs, but they can shed telltale molecules into surrounding tissue, from which those substances, known as “biomarkers,” diffuse into the blood. Some biomarkers may be made predominantly by tumor cells.  These substances can be measured in the blood as proxies for a tumor.

Some biomarkers are in wide use today. One is the well-known PSA (prostate specific antigen) for prostate cancer. Another example of a biomarker is CA-125 (cancer antigen 125) for ovarian cancer. But these and other currently used blood tests for cancer biomarkers were not specifically developed for early detection, and are generally more effective for relatively noninvasive monitoring of the progress of a late-stage tumor or tumor response to treatment. That is, rising blood levels of the substance may indicate that the tumor is growing, while declining levels may indicate possible tumor shrinkage.

Both CA-125 and PSA are also produced, albeit in smaller amounts, by healthy tissue, complicating efforts to detect cancer at an early stage when the tumor’s output of the biomarker is relatively low.

The new mathematical model employs separate equations, each governing the movement of a biomarker from one compartment into the next. Into these equations, one can plug known values — such as how fast a particular type of tumor grows, how much of the biomarker a tumor cell of this type sheds per hour, and the minimum levels of the biomarker that must be present in the blood for a currently available assay to detect it.

As a test case, Drs. Gambhir and Hori chose CA-125, a well-studied biomarker which is shed into the blood by ovarian cancer tumors. Ovarian cancer is a notorious example of a condition for which early detection would make a significant difference in survival outcomes.

CA-125 is a protein made almost exclusively by ovarian tumor cells. The well-known pharmacokinetics, metabolic fates (typical amounts secreted by an ovarian cell), typical ovarian tumor growth rates, and other properties of CA-125 make the biomarker an excellent candidate for “road testing” with Gambhir and Hori’s model. CA-125 is by no means the ideal biomarker, said Dr. Gambhir, while noting that it can still be used to better understand the ideal properties of biomarkers for early ovarian cancer detection.

Applying their equations to CA-125, Drs. Gambhir and Hori determined that an ovarian cancer tumor would need to reach a size of approximately 1.7 billion cells, or the volume of a cube with a 2-centimeter edge, before the currently available CA-125 blood test could reliably detect it. At typical tumor-growth rates, it would take a single cancer cell approximately 10.1 to 12.6 years of development to become a tumor containing 1.7 billion cells.

The model further calculated that a biomarker otherwise equivalent to CA125 — but shed only by ovarian tumor cells — would allow reliable detection within 7.7 years, while the tumor’s size would be that of a tiny cube about one-sixth of an inch high.

In the last decade, many potential new biomarkers for different forms of cancers have been identified. There’s no shortage of promising candidates — six for lung cancer alone, for example. But validating a biomarker in large clinical trials is a long, expensive process. So it is imperative to determine as efficiently as possible which, among many potential tumor biomarkers, is the best prospective candidate.

“This [mathematical] model could take some of the guesswork out of it,” Gambhir said. He also stated:

“It [the mathematical model] can be applied to all kinds of solid cancers and prospective biomarkers as long as we have enough data on, for instance, how much of it a tumor cell secretes per hour, how long the biomarker can circulate before it’s degraded and how quickly tumor cells divide. We can tweak one or another variable — for instance, whether a biomarker is also made in healthy tissues or just the tumor, or assume we could manage to boost the sensitivity of our blood tests by 10-fold or 100-fold — and see how much it advances our ability to detect the tumor earlier on.”

There are new detection technologies capable of detecting biomarkers at concentrations as low as a few hundred molecules per milliliter (1-cubic centimeter) of blood. In 2009, Dr. Gambhir and his colleagues reported on one such developing technology: “magneto-nanosensors” that can detect biomarkers with a 100-fold greater sensitivity than current methods.

Better biomarker detection alone might allow ovarian cancer tumor detection at the 9-year point, said Gambhir.

A second priority is to come up with new and better biomarkers. “It’s really important for us to find biomarkers that are made exclusively by tumor cells,” Dr. Gambhir said.

Under the right conditions (a highly sensitive assay measuring levels of a biomarker that is shed only by cancer cells), Gambhir stated, the model predicts that a tiny tumor with a volume equivalent to a cube less than one-fifteenth of an inch (or 1.7 millimeters) on a side could be detected.

Dr. Gambhir is also the Virginia and D.K. Ludwig Professor in Cancer Research and director of the Molecular Imaging Program at Stanford, the director of the Canary Center at Stanford for Cancer Early Detection, and a member of the Stanford Cancer Institute.

The study was funded by the Canary Foundation and the National Cancer Institute.

Sources:

Mesothelin Antibodies Occur In Some Women With An Epidemiologic Risk For Ovarian Cancer.

Researchers at Rush University Medical Center discover mesothelin antibodies in the bloodstream of infertile women, who possess a higher risk of ovarian cancer.

Using a new approach to developing biomarkers for the very early detection of ovarian cancer, researchers at Rush University Medical Center have identified a molecule in the bloodstream of infertile women, who possess a higher risk of ovarian cancer. This finding may be relevant in the future for screening women at high risk for the disease — or even those with early-stage ovarian cancer.

The molecule — an antibody that the human body manufactures — is an autoimmune response to mesothelin. Mesothelin a well-characterized ovarian cancer antigen and protein which is found in abundance on the surface of ovarian cancer cells, but present only in limited amounts in normal human tissue.

The study is published in the August 16 online version issue of Cancer Epidemiology, Biomarkers & Prevention, published by the American Association for Cancer Research (AACR).

Judith Luborsky, Ph.D., Lead Study Author; Professor, Pharmacology, Obstetrics & Gynecology and Preventive Medicine, Rush Medical College

“The finding is extremely important because at present medical tests are unable to detect ovarian cancer in its early stages, which is why death rates from this disease are so high,” said Judith Luborsky, Ph.D., professor of pharmacology, obstetrics and gynecology and preventive medicine at Rush and the lead author of the study.

“Our approach to discovering cancer biomarkers was unique in this study. Instead of investigating molecules specific to ovarian cancer alone, we asked what molecules women with a risk of ovarian cancer and those with ovarian cancer had in common,” Luborsky said.

The study may have enabled the researchers to explain, in part, the link between infertility and ovarian cancer that has been established in numerous epidemiological surveys.

“More important, with the discovery of the mesothelin antibody, we now have what appears to be a biomarker that can potentially be used in screening tests to help us conquer ovarian cancer,” Luborsky said.

According to the American Cancer Society’s most recent estimates, it is anticipated that 21,900 new cases of ovarian cancer will be diagnosed in the U.S. in 2011, and approximately 15,460 deaths will occur in connection with the disease. Ovarian cancer is the ninth most common cancer in women (not counting skin cancer) and ranks as the fifth highest cause of cancer death in women. It is the most lethal gynecologic cancer. The poor prognosis for women with ovarian cancer is due to the lack of both clinical symptoms when the cancer first develops and the absence of laboratory tests specific to the disease.

In the study at Rush, researchers tested for mesothelin antibodies in the bloodstream of 109 women who were infertile; 28 women diagnosed with ovarian cancer, 24 women with benign ovarian tumors or cysts, and 152 healthy women. Causes of infertility included endometriosis, ovulatory dysfunction, and premature ovarian failure. Some causes of infertility were unexplained.

Significant levels of mesothelin antibodies were found in women with premature ovarian failure, ovulatory dysfunction and unexplained infertility, as well as in women with ovarian cancer. The same results were not found in women with endometriosis, good health, or benign disease. Endometriosis is generally associated with the clear cell and endometrioid subtypes of epithelial ovarian cancer, as compared to other forms of the disease associated with infertility, which may explain why mesothelin antibodies were not found in the endometriosis cases.

It is important to emphasize that the explanation as to why the presence of mesothelin antibodies in the bloodstream should be linked with ovarian cancer is not clear.

“It has been hypothesized that an autoimmune response precedes or somehow contributes to the development and progression of malignant tumors,” Luborsky said. “We think that antibodies may arise in response to very early abnormal changes in ovarian tissue that may or may not progress to malignancy, depending on additional triggering events. Or, alternatively, antibodies may bind to normal cells in the ovary, causing dysfunction and leading to infertility — and, in a subpopulation of women, to the development of ovarian cancer.”

Other researchers involved in the study were Yi Yu, MS, and Seby Edassery, MS, both from Rush, as well as a group led by Ingegerd Hellstrom, M.D., Ph.D., and Karl Eric Hellstrom, M.D., Ph.D., which included Yuan Yee Yip, BS, Jade Jaffar, BS, and Pu Liu, Ph.D. from Harborview Medical Center at the University of Washington.

The study was supported by funding from the National Institutes of Health and Fujirebio Diagnostics, Inc.

About Rush

Rush is a not-for-profit academic medical center comprising Rush University Medical Center, Rush University, Rush Oak Park Hospital and Rush Health.

Rush’s mission is to provide the best possible care for its patients. Educating tomorrow’s health care professional, researching new and more advanced treatment options, transforming its facilities and investing in new technologies—all are undertaken with the drive to improve patient care now, and for the future.

Sources:

  • Luborsky JL, et al. Autoantibodies to Mesothelin in Infertility. Cancer Epidemiol Biomarkers Prev. 2011 Aug 16. PubMed PMID: 21846819 [Epub ahead of print]
  • Researchers at Rush University Medical Center Discover Antibody That May Help Detect Ovarian Cancer in its Earliest Stages, News Release, Rush University Medical Center, August 16, 2010.

2011 ASCO: Screening With CA-125 & Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

Findings from a large, long-term study – the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial – showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related follow-up procedures.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Ill. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a large clinical trial involving ovarian cancer screening were highlighted in today’s press briefing as summarized below.

Screening with CA-125 and Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

A randomized, multicenter screening study of nearly 80,000 women in the general population showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related biopsies and follow-up procedures. The results indicate that while these tests are widely and appropriately used to evaluate symptoms, and to gauge disease status and effectiveness of treatment in women already diagnosed with ovarian cancer, they are not useful in screening the general population.

Saundra S. Buys, M.D., Medical Director, Huntsman Cancer Institute’s High Risk Breast Cancer Clinic; Professor, Depart. of Internal Medicine, Univ. of Utah School of Medicine

“There hasn’t been a good method for the early detection of ovarian cancer, and our hypothesis was that CA-125 and transvaginal ultrasound, which are useful in measuring disease, would also identify ovarian cancer early, at a stage in which it is more likely to be cured,” said lead author Saundra Buys, M.D., professor of medicine at the University of Utah and Huntsman Cancer Institute in Salt Lake City. “The results were disappointing, but not necessarily surprising. The study shows that the available tests are not effective and may actually cause harm because of the high number of false positives. These results point to the continued need for more precise and effective screening tools for this disease.”

In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 78,216 women ages 55 to 74 were assigned to either annual screening (39,105 women) or usual care (39,111 women) between 1993 and 2001. Women in the screening arm were offered annual CA-125 testing for six years and transvaginal ultrasound for four, and followed for up to 13 years. Those in the usual care arm were not offered the screening tests.

The results showed no statistically significant difference in ovarian cancer cases or mortality between the two arms. Ovarian cancer was diagnosed in 212 women in the screening group arm compared to 176 in the usual care arm; 118 women in the screening arm died from ovarian cancer, while 100 died from ovarian cancer in the usual care group.

Among women in the screening arm, there were a high number of false positives – 3,285 false positives, compared to just 212 true positives. Of women who had a false positive test, 1,080 underwent surgery for biopsy – the procedure generally required to evaluate positive test results; 163 of them had serious complications.

The authors emphasized that the study results don’t apply to screening women with symptoms or abnormal findings on physical examination. [emphasis added] Physical examination based on symptoms and appropriate follow-up testing remains the best available approach for ovarian cancer detection.

[Note: This summary contains updated data and a correction from the original abstract. Correction:  Of the 3,285 women who received a false positive exam, 1,080 underwent surgery. Of those surgical patients, 163 encountered at least one serious complication.]

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The Cancer Biomarker Conundrum: Too Many False Discoveries

The boom in cancer [including ovarian] biomarker investments over the past 25 years has not translated into major clinical success. The reasons for biomarker failures include problems with study design and interpretation, as well as statistical deficiencies, according to an article published online August 12 in The Journal of the National Cancer Institute.

The boom in cancer [including ovarian] biomarker investments over the past 25 years has not translated into major clinical success. The reasons for biomarker failures include problems with study design and interpretation, as well as statistical deficiencies, according to an article published online August 12 in The Journal of the National Cancer Institute.

The National Institutes of Health defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” In the past decade, there have been numerous biomarker discoveries, but most initially promising biomarkers have not been validated for clinical use.

Eleftherios P. Diamandis, M.D., Ph.D., Head, Section of Clinical Biochemistry, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

To understand why so-called biomarker “breakthroughs” have not made it to the clinic, Eleftherios P. Diamandis, M.D., Ph.D., professor of pathology and laboratory medicine at Mount Sinai Hospital in Toronto and associate scientist at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, reviewed some biomarkers initially hailed as breakthroughs and their subsequent failings.

Diamandis first describes the requirements for biomarkers to be approved for clinical use: A biomarker must be released into circulation in easily detectable amounts by a small asymptomatic tumor or its micro-environment; and it should preferably be specific for the tissue of origin. Also, if the biomarker is affected by a non-cancer disease, its utility for cancer detection may be compromised. For example, the prostate-specific antigen (PSA) biomarker, which is used to detect prostate cancer, is also elevated in benign prostatic hyperplasia.

Diamandis looks at seven biomarkers that have emerged in the past 25 years, all of which were considered promising when they were first described. These include nuclear magnetic resonance of serum for cancer diagnosis; lysophosphatidic acid for ovarian cancer; four– and six-parameter diagnostic panels for ovarian cancer; osteopontin for ovarian cancer; early prostate cancer antigen-2 (EPCA-2) for prostate cancer detection; proteomic profiling of serum by mass spectrometry for ovarian cancer diagnosis; and peptidomic patterns for cancer diagnosis. Problems ranged from inappropriate statistical analysis to biases in case patient and control subject selection. For example, the problems with EPCA-2 included reporting values that were beyond the detection limit of the assay and using inappropriate reagents to test EPCA-2, such as solid surfaces coated with undiluted serum.

Diamandis concludes that “problems with pre-analytical, analytical, and post-analytical study design could lead to the generation of data that could be highly misleading.”

Sources:

The Cancer Biomarker Conundrum: Too Many False Discoveries, Journal of the National Cancer Institute Advance Access,  published on August 12, 2010, DOI 10.1093/jnci/djq335.

Eleftherios P. Diamandis. Cancer Biomarkers: Can We Turn Recent Failures into Success? Commentary, Journal of the National Cancer Institute Advance Access published on August 12, 2010, DOI 10.1093/jnci/djq306.

On the Path to Early Detection: Fox Chase & Sloan-Kettering Researchers Identify Early Ovarian Cancers

Researchers at the Fox Chase Cancer Center and the Memorial Sloan-Kettering Cancer Center discover early tumors and precancerous lesions in cysts that fold into the ovary from its surface, called inclusion cysts. “This is the first study giving very strong evidence that a substantial number of ovarian cancers arise in inclusion cysts and that there is indeed a precursor lesion that you can see, put your hands on, and give a name to,” says Jeff Boyd, PhD, Chief Scientific Officer at Fox Chase and lead author on the study …

Ovarian cancer kills nearly 15,000 women in the United States each year, and fewer than half of the women diagnosed with the disease survive five years. A screening test that detects ovarian cancer early, when it is still treatable, would likely reduce the high mortality, yet scientists have not known where the tumors originate or what they look like. Now, researchers at Fox Chase Cancer Center think they have answered both questions. The study, published on April 26th in PLoS ONE, reports that they have uncovered early tumors and precancerous lesions in cysts that fold into the ovary from its surface, called inclusion cysts.

Jeff Boyd, Ph.D., Professor, Chief Scientific Officer & Senior Vice President, The Robert C. Young, MD, Chair in Cancer Research, Fox Chase Cancer Center

“This is the first study giving very strong evidence that a substantial number of ovarian cancers arise in inclusion cysts and that there is indeed a precursor lesion that you can see, put your hands on, and give a name to,” says Jeff Boyd, PhD, Chief Scientific Officer at Fox Chase and lead author on the study, which also involved colleagues at the Memorial Sloan-Kettering Cancer Center. “Ovarian cancer most of the time seems to arise in simple inclusion cysts of the ovary, as opposed to the surface epithelium.”

Clinicians and researchers have been looking for early ovarian tumors and the precancerous lesions from which they develop for years without success. In this study, Boyd and colleagues used a combination of traditional microscopy and molecular approaches to reveal the early cancers.

“Previous studies only looked at this at the morphologic level, looking at a piece of tissue under a microscope,” Boyd says. “We did that but we also dissected away cells from normal ovaries and early stage cancers, and did genetic analyses. We showed that you could follow progression from normal cells to the precursor lesion, which we call dysplasia, to the actual cancer, and see them adjacent to one another within an inclusion cyst.”

To learn where and how the tumors arise, the team examined ovaries removed from women with BRCA mutations, who have a 40% lifetime risk of developing ovarian cancer, and from women without known genetic risk factors. In both groups, they found that gene expression patterns were dramatically different in cells in the inclusion cysts compared to the normal surface epithelium cells, including increased expression of genes that control cell division and chromosome movement.

Moreover, when they used a technique called FISH (fluorescence in situ hybridization), which can be used to identify individual chromosomes in cells, they saw that cells from very early tumors and precursor lesions frequently carried extra chromosomes. In fact, the team found that 9% of the normal cells isolated from the cysts had extra chromosomes, even though the tissue appeared completely benign under the microscope. By contrast, virtually none of the cells isolated from the surface of the ovary, which was previously thought to be the site of early ovarian cancers, carried extra chromosomes.

With these new data on the origin of ovarian cancer in hand, Boyd and others can now start to develop screening tests, perhaps based on molecular imaging, that could be used to detect early ovarian cancers in asymptomatic women.

Co-authors on the study include Bhavana Pothuri, Mario M. Leitao, Douglas A. Levine, Agnès Viale, Adam B. Olshen, Crispinita Arroyo, Faina Bogomolniy, Narciso Olvera, Oscar Lin, Robert A. Soslow, Mark E. Robson, Kenneth Offit, and Richard R. Barakat of Memorial Sloan-Kettering Cancer Center.

About the Fox Chase Cancer Center

Fox Chase Cancer Center is one of the leading cancer research and treatments centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE or 1-888-369-2427.

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