“What women should bear in mind is that they should seek out specific recommendations from their physicians that are based on the molecular pathology of their individual breast cancer. That’s not how we’ve treated this disease for the past 40 years.”

Dr. Lawrence Shulman, Chief Medical Officer and Senior Vice President of Medical Affairs at Dana-Farber Cancer Institute, a PinnacleCare Center of Excellence.

July 2006-- As scientists have learned more about the molecular structure of the tumors involved in breast cancer, they’ve made an important discovery—not all breast cancers are alike.

“Breast cancer is not one disease,” explains Dr. Lawrence Shulman, Chief Medical Officer and Senior Vice President of Medical Affairs at Dana-Farber Cancer Institute, a PinnacleCare Center of Excellence. “It is in fact a series of different diseases that require different treatments. Genetic studies have helped us to understand there are a variety of types of breast cancers and these diseases do not respond to the same types of treatment. Basal-type breast cancer, for example, a particularly aggressive form of the disease that accounts for 20% of breast cancers in the U.S., is not responsive to hormone therapy, HerceptinR, or standard chemotherapy. That’s why we are seeking newer, innovative ways to treat the different types of breast cancer.”

Targeted treatment improves outcomes
Dr. Laura J. Esserman, a member of PinnacleCare’s Medical Advisory Board and Associate Professor of Surgery and Radiology, University of California, San Francisco (UCSF) and Director of the Carol Franc Buck Breast Care Center at the UCSF Comprehensive Cancer Center, foresees the dawning of what she terms, “a new era of targeted treatment.”

Her colleague, Medical Oncologist Dr. John W. Park, notes in a recent article in the Winter 2006 issue of the center’s newsletter, “Targeted therapies have been made possible by recent advances in our understanding of the biology of cancer cells. These new insights have paved the way for drugs specifically designed to defeat the mechanisms that underlie the cancer process. Once considered experimental, targeted therapies such as monoclonal antibodies, signal transduction inhibitors, and immunotherapy are becoming part of the standard treatment for many cancers, including breast cancer.”

One of the best known targeted therapies for breast cancer is Trastuzumab (HerceptinR). This monoclonal antibody attacks the HER2 protein which is present in approximately 25 to 30% of breast cancers. Explains Dr. Shulman, “The development of targeted therapies like HerceptinR is the most important finding in the last 10 years. It has an extraordinary effect on HER2-positive cancers in the early stages, reducing recurrence 50%. It has literally changed how we treat this type of cancer.”

New drugs and new approaches bring new hope
While HerceptinR does help many women with HER2-positive cancer, there are many for whom the drug eventually stops holding their cancer in check. A recent clinical trial of a new drug called lapatinib or Tykerb, gives new hope to women with advanced breast cancer whose disease has continued to progress while taking HerceptinR. At the June 2006 annual meeting of the American Society of Clinical Oncology in Atlanta, Georgia, researchers announced promising results.

Tykerb taken in pill form in combination with the chemotherapy drug capecitabine was twice as effective at preventing tumor growth. Women who took Tykerb and capecitbine had a median time of 8.5 months before their tumors recurred compared to a median of 4.5 months for those who received chemotherapy alone. Because of these dramatic results, the trial was stopped early because it was deemed unethical to withhold Tykerb from the control group.

“Those results are quite impressive and clearly more impressive than any of us would have expected,” says Dr. Eric Winer, one of the researchers and a breast cancer specialist at Dana-Farber. He also notes another potential advantage of Tykerb—it may help prevent the spread of tumors from the breast to the brain, a problem that confronts between 25 and 45 percent of women who take HerceptinR. Tykerb also blocks the growth of another protein that is involved in lung and colon cancer, so the drug may be a step forward in the treatment of those diseases as well.

At the UCSF Comprehensive Cancer Center, researchers are exploring strategies to prevent breast cancer cells from becoming resistant to this new drug. Previous studies at the center found that this class of drugs, which disrupt the cancer cells ability to defend themselves and make them more sensitive to chemotherapy, only seem effective for a few days. Then the cells adapt, making the drug less effective.

The researchers are trying a new way to use the drug that they hope will preserve its power against cancer. They deliver the drug in a short 2-day pulse to diminish the cancer’s defense mechanisms, then hit it with powerful chemotherapy while it’s weak. The Phase I trial is ongoing.

Doctors at Dana-Farber are also involved in efforts to develop new strategies to make older treatments more effective. Chemotherapy is delivered in low, frequent doses, called “metronomic” delivery, in combination with the drug bevacizumab (AvastinR). In the pilot study which included 55 patients, this regimen delayed the progression of breast cancer an average of 5.5 months versus 2 months with low-dose chemotherapy alone.

An experimental therapy called 17-AAG has recently been developed at Memorial Sloan-Kettering Cancer Center, one of PinnacleCare’s Centers of Excellence. 17-AAG, a derivative of the naturally occurring antibiotic geldanamycin, has demonstrated anti-tumor activity when given with HerceptinR to patients with HER-2 positive metastatic breast cancer. The therapy inhibits a protein that protects certain proteins, including the HER-2 receptor protein on the surface of breast cancer cells. In addition, the side-effects of this therapy appear milder than many other chemotherapy drugs. A Phase II study of the trial is planned to further examine the effectiveness of 17-AAG.

Will your cancer recur? Your genes hold the answer.
In the fight against breast cancer, a new front has been opened by a test called MammaPrint from the Molecular Profiling Institute that looks at genes to determine the risk of a recurrence of breast cancer. “The test requires fresh tissue removed from the tumor in the breast. DNA from that tissue is placed on a microchip and examined at the molecular level, measuring the level of 70 genes found in the tissue,” says Todd Maney, Director of New Product Development, Molecular Profiling Institute, a PinnacleCare resource. “The information gathered is used to determine the risk of recurrence. That information is particularly valuable if a physician is on the fence about whether or not chemotherapy is necessary. The information this test provides can swing the decision one way or the other.”

The next generation of early detection
At the Duke Comprehensive Cancer Center, one of PinnacleCare’s Centers of Excellence, researchers are pioneering another new breast cancer test that will help detect the disease at the earliest stage. Dr. Victoria Seewalt, breast oncologist, is developing a cellular test that is much more sensitive than a mammogram for early detection.

“This is potentially the ‘breast pap smear’ that we never had before,” she says. “Just as we do with a cervical pap smear, we can now survey cells from the whole breast, examine them under the microscope and test for early changes that often precede breast cancer. Then we can give women a preventive agent to see if we can eradicate her abnormal cells and thus prevent cancer from developing.”

The test involves using a slender needle to sample cells from several segments in each breast. The cells will be studied for the presence or absence of a gene called RAR beta, which regulates the proper use of vitamin A to control the growth, division, and death of epithelial cells in the breast.

“RAR beta gives us a potential marker to monitor if the preventive agents we’re giving have an impact on preventing breast cancer. We’ll test women before, during, and after treatment to see if any of the various agents are able to reduce the number of abnormal cells,” explains Dr. Seewalt.

Dr. Esserman at UCSF is also involved in research that will help track women’s reponse to breast cancer treatment and correlate the response to molecular markers on breast cancer tumors. The trial uses MRI and tissue biopsy to study the response of women who undergo chemotherapy before surgery.

Let an Advocate bring it all together for you
While the wealth of breakthroughs and new frontiers in the fight against breast cancer are great news, determining which treatments are most appropriate for you can be difficult if not impossible. That’s where a PinnacleCare Advocate plays a vital role—helping you learn what’s available in terms of treatment options and trials, providing you with expedited access to top specialists in the field, and offering support and guidance throughout your diagnosis and treatment.

An Advocate recently received a midnight call from a new overwhelmed and worried Member whose wife was battling breast cancer. That same evening, the Advocate spoke to the Members, assuring them PinnacleCare would immediately begin managing the wife’s care. After carefully reviewing the current treatment, the Advocate began researching other medical options. Within a week, their Advocate had secured an immediate appointment with a Clinical Professor of Medicine and Co-Director of the Breast Oncology Clinical Trials Program at a top-rated Center of Excellence. The physician discovered diagnostic discrepancies that had limited the treatment options during earlier care, potentially allowing the cancer to metastasize to other parts of her body. The physician immediately implemented a new treatment plan for our Member and embraced our Member's wishes to integrate traditional and alternative medical techniques.

“What women should bear in mind is that they should seek out specific recommendations from their physicians that are based on the molecular pathology of their individual breast cancer,” encourages Dr. Shulman. “That’s not how we’ve treated this disease for the past 40 years, but our better molecular understanding of breast cancer now allows us to tailor therapies for each individual woman.”

PinnacleCare delivers the benefits of leading edge research
Rapid advances are being made in the tools used to diagnose and treat a wide range of diseases, including breast and cervical cancer. A PinnacleCare Advocate and our research team can help you stay current with the latest research and news.

Our Advocates stay abreast of the latest FDA approvals and recalls, as well as clinical trials and newly approved diagnostics and treatments. Recently, for example, several Members have inquired about the new FDA-approved cervical cancer vaccine, Gardasil. The vaccine protects against two strains of the HPV virus which are most often the cause of cervical cancer, HPV-16 and HPV-18, and the two strains responsible for 90% of genital warts, HPV-6 and HPV-11.

To date, studies have shown the vaccine to be 100% effective against HPV-16 and 18, though this does not mean a woman cannot develop cervical cancer caused by another form of the virus. The FDA has approved the vaccine, which costs $120 per dose and has a three-dose regimen given over a period of six months, for females ages 9 to 26. The vaccine is not a live virus, which boosts its safety.

PinnacleCare Advocates give our Members unparalleled access to the latest information that helps them fight disease and live a healthier life.