Cancer antigen tested as potential vaccine for hormone- negative breast cancer

Scientists have found that one specific cancer antigen—CT-X—is more frequently found in hormone receptor-negative breast cancer than in other types of breast tumors, according to research published online in advance of publication in Proceedings of the National Academy of Sciences.

And this means?

Ultimately, researchers say, vaccines based on CT-X might provide treatment for ER-negative patients. 

Whooheee.  Keep the research coming.  And let's turn it into treatment options.

SOURCE: Anita Grigoriadis, Otavia L. Caballero, Keith S. Hoek, Leonard da Silva, Yao-Tseng Chen, Sandra J. Shin, Achim A. Jungbluth, Lance D. Miller, David Clouston, Jonathan Cebon, Lloyd J. Old, Sunil R. Lakhani, Andrew J. G. Simpson, and A. Munro Neville. "CT-X antigen expression in human breast cancer," Proceedings of the National Academy of Sciences, 2009. www.pnas.org/cgi/doi/10.1073/pnas.0906840106 

New Vaccine Might Treat Hormone Negative Breast Cancers Such as TNBC

From the Ludwig Institute for Cancer Research:  Vaccine in Clinical Trials Shows Promise in Treating ER-Negative Breast Cancers, Including Triple Negative Breast Cancer: 

A comprehensive analysis of nearly 1,600 tumor samples has found that CT-X genes are expressed in nearly half the breast cancers that lack the estrogen receptor (ER). CT-X gene products are the targets of therapeutic cancer vaccines already in phase III clinical trials for lung cancer and melanoma. The study—to be published in the Early Edition of the Proceedings of the National Academy of Sciences this week—was led by the international Ludwig Institute for Cancer Research (LICR). ER negative breast cancers, which account for a third of all breast cancer cases, are a group of tumors that has a generally poor prognosis and few therapy options. A subgroup of the ER negative group is triple-negative breast cancer (TNBC), which lacks the estrogen, progesterone and HER2 receptors. TNBC is responsible for most of the breast cancers that strike down African American and young women.

In the current study, gene and protein expression studies showed that nearly half of primary ER negative and triple-negative breast cancers express members of either or both the MAGEA and NY-ESO-1/CTAG1B families of CT-X genes. Approximately half of the primary tumor samples from patients with the basal-like form of breast cancer, which is usually ER negative, also expressed either or both of these gene families, and nearly two-thirds of metastases from basal-like tumors also expressed these genes.

These findings suggest that a therapeutic vaccine combining members of the two CT-X families could be a new therapy approach to filling a critical unmet need.

Dr. Andrew Simpson, LICR scientific director and an author of the study, said that clinical trials based on the findings of the PNAS study could theoretically be initiated in the near future. "Vaccines targeting MAGEA3 are already in phase III trials, and the Cancer Vaccine Collaborative, a partnership between the Ludwig Institute and the Cancer Research Institute, has demonstrated the safety of different forms of the NY-ESO-1 antigen in phase I and II trials in a variety of tumor types."

According to LICR's Dr. A. Munro Neville, the senior author of the study, obtaining clinic-grade material for more members of the CT-X families and funding for a clinical trial will be the next steps in determining if therapeutic cancer vaccines can meet a critical need in breast cancer therapy.

CT genes—the X denotes chromosome localization—encode CT antigens, proteins that are recognized by the immune system. Spontaneous immune responses against CT antigens are thought to be a natural form of cancer control and might be the mechanism behind spontaneous remission.

Therapeutic cancer vaccines are being developed to induce, strengthen and/or sustain immune responses against cancer. GlaxoSmithKline (GSK), which licensed MAGEA3 and NY-ESO-1 from LICR, is currently conducting phase III clinical trials of a MAGEA3-based cancer vaccine, or "antigen-specific cancer immunotherapy" (ASCI) in non-small cell lung cancer and melanoma.

Source: Ludwig Institute for Cancer Research

Dr. Heads to Ghana to Study Triple Negative

A great story here:

For Dr. Lisa Newman, a 16-hour trip over two days from Michigan to Ghana in Africa is just part of the journey in uncovering clues about a rare form of breast cancer.

Dr. Lisa Newman hopes to uncover clues in Ghana about an aggressive and rare form of breast cancer.

1 of 3

Newman, a surgical oncologist specializing in breast cancer at the University of Michigan, collaborates with doctors in Kumasi, Ghana, in hopes of discovering the origins of an aggressive and difficult to treat form of breast cancer that disproportionately affects black women. It is called triple negative breast cancer or TNBC.

"The women that are most likely to be afflicted with the triple negative breast cancers are younger aged women, women in the pre-menopausal age range, and women with African ancestry," says Newman.

Read the entire story here.

New clinical trial scheduled for BSI-201 for triple negative

Sanofi-aventis and its  subsidiary, BiPar Sciences, today announce  Phase 3 trial for BSI-201 in combination with chemotherapy in patients with metastatic triple-negative breast cancer.   BSI-201 is a targeted therapy that inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair.

Results of the  Phase 2 study were presented at  the American Society of Clinical Oncology (ASCO) annual conference on May 31, 2009. The l trial involved 116 women with metastatic TNBC who were randomly assigned to receive GC in combination with the  BSI-201 or GC alone.

• 62 percent of patients receiving BSI-201 in combination with GC showed clinical benefit,

•  21 percent in the group receiving chemotherapy alone  benefitted.

•  48 percent of patients who received BSI-201 combined with chemotherapy had some level of tumor reduction.

* 16 percent of  those receiving chemotherapy alone had tumor reductions.

•  Women who received BSI-201 had a median progression-free survival of 6.9 months and overall survival of 9.2 months compared with 3.3 and 5.7 months for women who received chemotherapy alone. T

In the  Phase 3 trials, 60-75 sites will be distributed throughout the United States. All patients will  have the opportunity to receive BSI-201.

Read the news release here.

African Americans Get Different Form of Cancer, Study Says

A study on racial disparities in breast cancer published in the Journal of the National Cancer Institute challenges the assumption that receptor status is the primary reason African-Americans have more agressive forms of breast cancer.

Researchers discovered that black patients with breast cancer had worse survival than white patients, despite identical treatment and follow-up and irrespective of hormone receptor status.  They say this shows that African-American women may get a different type of cancer altogether--something that cannot be entirely explained as hormone-receptor negative or triple-negative. And this cancer is highly aggressive.  The research also casts doubt on the theory that lower survival rates among African-Americans for certain cancers are due solely to factors such as poverty and poor access to quality health care.

The study used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)  program on 244,786 women diagnosed  from January 1990 through December 2003 and followed through December 2004.

According to an article from the National Institutes of Health, researchers found that:

...regardless of ER status, black women with breast cancer were still more likely to die of the disease than white women. This disparity remained even when the researchers adjusted for age at diagnosis, stage and grade of the tumor, year of diagnosis, and socioeconomic status. When the researchers examined the hazard rate trends in black and white women, they noticed that the largest differences occurred in the first three years after diagnosis in both ER- and ER+ tumors.

Why do blacks have more aggresive tumors, even allowing for receptor status? Researchers suggest the environment and genetics may both be an issue.  The NIH added:

This analysis confirmed that, despite the higher incidence of ER- tumors (which are associated with a less favorable prognosis) among black women, the differences in survival outcomes between the two populations were driven largely by differences in the hazard rate as opposed to differences in estrogen-receptor status.

EZH2 Protein Being Studied for Effect on Triple Negative

The protein EZH2 is expressed in a great majority (74 percent) of hormone-receptor-negative tumors, mostly triple negative tumors. It is linked to larger tumor size—more than 2 cm—and increased likelihood of spread to the lymph nodes, according to research presented at the 2009 annual meeting of the American Society of Clinical Oncology.  “EZH2 could be an important therapeutic target in this patient population,” the researchers note. The study is ongoing with the goal to determine EZH2's role in survival.

Rochester NY: Discussion on Triple-Negative

The Breast Cancer Coalition of Rochester will host a discussion on triple negative breast cancer and inflammatory breast cancer from 7 to 9 p.m. July 22 at 840 University Ave.

Dr. Zachary Kramer of the Lipson Cancer Center will speak.

Admission is free. Call (585) 473-8177 for more information.

Women with Hormone-Negative Breast Cancer Face Triple the Risk of Cancer in the Second Breast

Women with hormone-receptor-negative breast cancer, including triple negative, face another triple threat, as though they needed it:  three-times the risk of developing breast cancer in the second breast.  And the chances of that cancer also being HR- are ten times that of the general population.

The research is published in the July 9 issue of the Journal of the National Cancer Institute.  Researchers say this could impact follow-up care, which now often includes mammograms of the affected breast every six months, but only yearly mammos on the second breast.   Because some HR- tumors grow so rapidly but are not detected on mammograms until they are so large they are deadly, the researchers suggest that women with HR- be given a yearly MRI.

The study included 4,927 women with breast cancer; 3,701 of those had HR+ and 1,226 had HR-.  There was no information on Her2 status.

Some stats from the research:

• Nearly 1 in 25 breast cancer survivors will develop a second breast cancer in the same breast within 6 months of the original diagnosis.

• Women with HR+ breast cancer had twice the risk of cancer in the second breast than the general population.

• Women with HR- had more than three times the risk compared to women with HR+. NOTE:  THis is compared the HR+ women who had twice the risk of the general population.

• Women under 30 with HR- had a significantly increased risk of getting HR- in the second breast.

• Blacks, Hispanics, and Asians or Pacific Islanders were at a higher risk than non-Hispanic whites.

Read more here. 

P53 Mutation Most Common in Women with Hormone-Negative Breast Cancer

Researchers say that nearly 26 percent of women with breast cancer have a mutation in the p53 gene, which repairs damage to the DNA.  And it’s most prevalent among premenopausal women with ER-/PR- breast cancer and in postmenopausal hormone-negative women with a high body mass index (BMI).  The latter group had higher-grade tumors and a poorer outcome.  High BMI is already considered a risk factor for breast cancer.

The study included 1,170 women diagnosed with breast cancer between 1996 and 2001 and 2,116 women without cancer, and was designed to look at how lifestyle and environmental factors affect breast cancer.

 "The p53 gene is the guardian of the genome because it signals the cell to repair DNA damage when that occurs. If we can find genetic or environmental risk factors that lead to damage of p53 or stress on the gene, we may be able to help prevent development of breast cancer as well as other cancers," says the study's lead investigator, Catalin Marian, MD, PhD, a research instructor of cancer genetics and epidemiology at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC)

The research was presented at the 2009 annual meeting of the American Association for Cancer Research.  Read more here. 

New Gene May Provide Key to Basal Breast Cancer

Many triple-negative breast cancer tumors are basal, and these are the most aggressive.  Researchers have isolated a gene—the Met gene—that is in the majority of breast cancers.  More aggressive forms of cancer—basal types—have more of the gene.  There are existing inhibitors for this gene, so  scientists say this study may lead to new treatment for triple negative and other hormone negative forms.  Researchers were associated with the Van Andel Research Institute in Grand Rapids, Michigan, headed by George Vande Woude, Ph.D., who has been studying the Met gene since the 1980s.

"This very exciting work by the Van Andel Research Institute gives us a new target for treatment of patients with one of the worst types of breast cancer — basal breast cancer," said Dr. Daniel D.  Von Hoff, Physician-in Chief of the Translational Genomic Research Institute (TGen) in Phoenix, Arizona, which initiated an alliance with Van Andel Institute in February. "Since there are many new inhibitors of Met available for clinical trials, we now have a direct route for immediate application of these important findings in the care of patients with this very aggressive form of breast cancer."

Read more here.

 

 

 

Vitamin A May Lead to Drug for Triple Negative

Retinoic acid, a component of Vitamin A, has the potential to treat breast cancer, including triple negative, according to research in the June 24, 2009 issue of the journal Cell.

The main story being reported is on retinoic acid’s influence on hormone-positive breast cancer, helping the body balance the effect of hormones.  Here’s how it goes: estrogen makes cells grow rapidly; retinoic acid slows that process down.  And that's an important story.

But researchers say retinoic acid can even help cancers that are not fueled by estrogen—that is, hormone-negative cancers such as triple negative.  And that's a bigger story, because at this point triple negative breast cancer has no drug therapy, as the primary breast cancer drugs, tamoxifen and Arimidex, are designed to combat estrogen, which is not a factor in estrogen-negative cancer.

From a news release from the University of Chicago, whose scientists conducted the research: 

"Understanding all the components of this process could be used against breast cancer care in three ways," said study leader, Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and System Biology at the University of Chicago. "It suggests new ways to think about preventing the disease in those at high risk. It offers molecular tools that could provide a more precise diagnosis and predict outcomes. It could also be used to enhance current therapies, making existing drugs, such as tamoxifen, that selectively block estrogen's effects even more powerful, or even to develop new anti-cancer drugs."

White's team studies the effects of nuclear receptors, a class of proteins found within cells that control the response to various hormones. When a hormone enters a cell and connects with its receptor, that receptor alters the pattern of expression of specific genes--often hundreds or more.

But, they note, cancers that do not respond to hormones can also be affected.

This competition between the two signals also provides a new tool to predict outcomes. The researchers compared the effects of retinoic acid on tissues from 295 breast cancer patients against the results from their initial study using a typical breast cancer cell line. They found that the more responsive a tumor was to retinoic acid, the better the odds of long-term relapse-free survival.

Some of the genes that respond to retinoic acid were expressed even in difficult-to-treat tumors, such as those that do not have estrogen receptors or the molecule targeted by the drug Herceptin, the so-called double- or triple-negative breast cancers. "Some of these genes may provide new drug targets," White said.

Although retinoic acid is approved for treatment of leukemia, it can be quite toxic and patients can develop resistance to the drug. This study suggests a long series of downstream targets that are activated by the RA receptor.

"The goal would be to develop drugs that could activate these cancer-inhibiting targets," said White. “Retinoic acid itself is probably not the solution because of its side effects and metabolic byproducts," He cautioned, "but our results provide a molecular justification for finding ways to overcome its limitations in the clinic.”

 

 

 

 

PARP Inhibitors May Help More Than Triple Negative

I’ve written about PARP inhibitors recently, but they’re back in the news. 

Patients with cancer genes—BRCA1 and BRCA2—have been shown to react positively to a type of PARP inhibitor, a drug called olaparib.  In a small but significant study, olaparib was successful in shrinking breast and prostate cancer tumors, with some disappearing entirely.  The study was reported in the New England Journal of Medicine.

Read more about it here.

PARP is short for poly (ADP-ribose) polymerase, an enzyme used by cancer cells to repair DNA damage.

 

 

Herceptin May Be Effective Drug for Hormone Negative Breast Cancer

The drug commonly used for Her2-positive breast cancers may actually turn ER-negative status into positive. It’s a two-step process, though, and the research was done on ER-negative, Her2-positive laboratory cells, not on human subjects.  Still, it offers amazing potential and could ultimately provide much-needed therapy for hormone-negative breast cancer, including triple negative.

After being treated with trastuzumab (Herceptin), ER-negative cells actually turned into ER-positive cells, making them then react to anti-estrogen drugs like tamoxifen and aromatase inhibitors, according to research presented at the Endocrine Society meeting this month.

The research was done in vitro—in a lab, on existing cells, rather than in human subjects. Cells were ER-negative, Her2-postive and  were treated with  trastuzumab; after 72 hours they were treated with the hormones estradiol  and androstenedione.  After that they were given aromatase inhibitors and antiestrogens.

The tumors then reacted in much the way ER-positive tumors do to aromatase inhibitors and antiestrogens.

Read more about the study here.

SOURCE: Sabnis G, Brodie A "Trastuzumab sensitizes ER negative, HER-2 positive breast cancer cells (SKBr-3) to endocrine therapy" ENDO 2009; Abstract OR38-02.

Oral Contraceptives Increase the Risk of Triple Negative Breast Cancer

Women under the age of 40 who used oral contraceptives increase their risk of triple-negative breast cancer by more than 2.5 times, according to research in Cancer Epidemiology Biomarkers and Prevention (April, 2009).   There was no increase in the risk for hormone-positive breast cancer.

 

 

Scientists study protein linked to triple negative

The protein EZH2 is found in a great majority (74 percent) of hormone-receptor-negative tumors, mostly in triple negative. It is linked to larger tumor size—over 2 cm—and affected lymph nodes, according to research presented at the 2009 annual meeting of the American Society of Clinical Oncology.

Researchers speculate that EZH2 could ultimately be much-needed therapy for women with hormone-negative breast cancer. The study is continuing with the goal of determining EZH2's role in survival of hormone-negative cancer.

More perspective on PARP inhibitors for triple negative

An expansion on my previous post on PARP inhibitors:

A Curetoday.com blog gives a bit more explanation on the recent research (presented at the American Society of Clinical Oncology annual meeting)  showing how PARP inhibitors can help advanced triple negative breast cancers:

What happens when a preliminary study that was not designed for drug approval ends up showing dramatic results?

A study in patients with advanced "triple negative" breast cancer (defined as being negative for estrogen, progesterone, and HER2 receptors) compared chemotherapy (Gemzar and carboplatin) with or without BSI-201, a poly ADP-ribose polymerase (PARP) inhibitor.

PARP inhibitors have been shown to work exceptionally well in the laboratory against cancers that have defects in DNA repair – this is an abnormality that is prominent in cancers that derive from patients who have inherited mutations in the breast and ovarian cancer predisposing genes BRCA1 and 2. It turns out that BRCA1-associated tumors tend to be triple negative (although not all triple negative tumors have abnormalities of the BRCA pathways).

This was a preliminary phase II study, so even though it was randomized, it did not have enough patients to qualify as an FDA-approval trial. But it nevertheless showed unprecedented effects on inducing tumor responses, delaying time to progression, and improving survival – even greater than hormonal therapy and Herceptin have.

Read the entire article here.

Two stories of women coping with triple negative

From the Grand Island (NE) Independent:

“We’re a package deal.”

That’s how Heather Gideon describes her relationship with Angie Huxtable.

So when Huxtable agreed to be in today’s style show for the annual Cattlemen’s Ball of Nebraska, Gideon said, there was absolutely no question she would appear on the runway as well.

The style show is just one of the many activities that will help raise money for cancer research as part of the 2009 

Cattlemen’s Ball, which has a goal of collecting $1 million.

Whatever amount is raised will go to the UNMC Eppley Cancer Center and local health care organizations.

That money for research is important to both Wood River women, who were each diagnosed with breast cancer in May 2007.

While Huxtable remains cancer free, Gideon’s cancer re-emerged just months after her initial round of treatment was finished. Gideon is now diagnosed with Stage 4 breast cancer.

“I’ve been given one to four years to live,” said Gideon, who noted there is no current treatment that doctors say will cure her cancer.

Treatments now are designed to hold the cancer at bay.

Read the entire article here.

Another Triple Negative Survivor Story

From the Albany (NY) Herald online:

Hope and healing are often found in the unlikeliest of places. Breast cancer survivor Candy Reid found source of hope in a circle of tubing better known as the hula hoop.

Reid is the founder of Hoops for Healing, a online business that sell hula hoops custom made by Reid and her family.

She said that she cannot believe how the business has taken off and that the journey from battling cancer to operating a successful business was as circular as the hoops she now makes from her home in Albany.

"What came from this horrible experience is amazing to me," said Reid. "I've grown a lot, I've changed a lot. God has really been able to show his goodness through so many ways."

She said that before hearing the terrible news that she had breast cancer in December 2007, she was a busy housewife dedicated to home schooling her four children.

"I am really dedicated to my family and they have been so supportive through all this," Reid said.

She said that she was diagnosed with triple negative breast cancer, a specific subtype of cancer that is clinically characterized as more aggressive and less responsive to standard cancer treatments.

"I immediately began chemotherapy treatments which ended in May 2008 and then I had a bilateral mastectomy in June 2008," Reid explained. "This was followed by seven weeks of radiation."

Read the entire story here.

Your Nurse Can be Your Advocate

In the confusing days and weeks after a breast cancer diagnosis, a nurse navigator or patient advocate can help you make sense of your disease and its treatment and even guide you in getting a second option.  Nurse navigators follow cancer patients from diagnosis through follow-up care and help make sense of the doctors, treatments, jargon, and options while providing a supportive presence.  In most cases, navigators collaborate with all members of the medical team; educate and counsel patients and their families; and coordinate care with oncologists, surgeons, pharmacists, dieticians, and counselors. 

Check to see if your healthcare provider offers access to such a professional.  If not, lobby for them to start.  We all need more information than we have after a breast cancer diagnosis.  We should not be left to our own devices to figure it all out.

 

Cancer-Fighters in Your Kitchen

Stock your cupboards and fridge with tasty cancer fighters. A diet rich in fruits and vegetables and low in fat is the recipe for breast health, according to numerous studies:

• Whole grain breads and cereals fortified with B vitamins, especially folate. Folate is important in fighting hormone-negative breast cancer.

• Cruciferous vegetables: broccoli, cauliflower, cabbage, kale. These are high in Indole-3-Carbonale (I3C) that has been shown to have anti-cancer properties.

• Fruits and vegetables, especially brightly colored. Red and purple plants—red cherries, blueberries, acai—are high in anthocyanins, which are potent antioxidants.

•  Green tea, which contains plant chemicals called catechins, a plant chemical that may inhibit the invading capacity of breast cancer cells.

•  Flaxseeds, which contain cancer-fighting lignans.

• Organic foods when possible, especially dairy products. Organic food is grown or produced without the use of pesticides, fertilizers, antibiotics or growth hormones, all of which are implicated in breast cancer.