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.

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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.”