Winning the war on Breast Cancer ...a progress report
Over the past 30 years, “the pink ribbon” has become synonymous with breast cancer and the fight to “find a cure”. Finding a cure means prevention, early detection and treatment of breast cancer and more survivors.
In spite of approximately 39,520 breast cancer deaths in 2012, second only to lung cancer, there is great progress being made, especially in the later and more deadly stages of the disease.
Awareness efforts have certainly led to an earlier diagnosis for many, but we haven’t been able to reach the ultimate goal—a cure. For patients in the advanced stages of breast cancer such as Stage IV or metastatic, they too often feel abandoned or left out of the fight. But according to physicians like Dr. Mariana Chavez-MacGregor, Assistant Professor at the Breast Medical Oncology Department at The University of Texas MD Anderson Cancer Center, the fight for advanced stage cancer patients is becoming more aggressive than ever – with more wins seemingly every day.
In the United States, approximately 40,000 women and 500 men die every year from Metastatic Breast Cancer (MBC). Metastatic, or Stage IV is when breast cancer has spread to other parts of the body, including organs like the liver, lung, bones and others. The challenge is to stop the spread and extend the life expectancy of the patient. That means finding a drug that targets the cancer. Easier said than done.
According to the National Foundation for Cancer Research (NFCR), “breast cancer is most likely to become fatal when cancerous cells metastasize, or spread, to other parts of the body. In fact, more than 90% of cancer mortalities are due to cancer that has metastasized. Even after successful removal of a primary tumor, cancer patients still live under the constant fear that a few cancer cells have escaped the surgery, and these cells may eventually become secondary tumors in other locations of the body.
“We are looking at new drugs that act differently than standard chemotherapy – we know them as ‘targeted therapies’ and they usually act in a specific pathway. We are trying to understand and identify those targets. We are trying to identify the highway inside the cell that has been identified as a problem so we can treat that cancer cell with a specific targeted therapy directed to revert the course in that highway.”
The key to survival or even extended life expectancy for advanced cancer is to find effective drugs that can target the pathways and stop the spread. It’s surprising – and refreshing – to realize how much effort is going into research. At MD Anderson Cancer Center alone, Dr. Chavez-MacGregor said, more than 100 drugs (or compounds) are under research as part of clinical trials for different tumor types at any given time. Happily, the research some times (I wish it more often) turns out a little more hope.
Metastatic cancer patients can be on medications for the rest of their life. Once the cancer has spread to other parts of the body, treatments can slow down or stop the spread. But as a general rule, it can’t be totally cured. It can only be controlled.
“A typical treatment plan for a metastatic cancer patient involves finding the right drug. We may find one to work for a while and it may stop working. That means we have to go back to our arsenal of options and find something else that works,” said Dr. Chavez-MacGregor. “I often tell my patients, I’m like a plumber and I have a belt with a number of tools – those are my therapeutic options. I keep using them until I find the right tool for the situation. As physicians, we don’t ever want to run out of options. We know there has been a lot of progress in the development of tools, but we want more”.
The FDA recently approved three new drugs that Dr. Chavez-MacGregor says are a welcomed addition to the fight against advanced stages of breast
® cancer. The three include: Afinitor (Everolimus), Perjeta™ (Pertuzumab) and Kadcyla™ (TDM1).
The greatest breakthrough in these new drugs is their ability to “hitchhike” or “latch onto” the cancer cells and slow down or even stop their progression.
® According to Novartis, makers of Afinitor (everolimus), the FDA approval for the drug marks a significant milestone for women battling advanced
® breast cancer. The approval of Afinitor : * Represents the first major advance for US patients with advanced HR+ breast cancer since aromatase inhibitors were introduced more than 15 years ago · In a Phase III trial, Afinitor plus exemestane more than doubled the time women lived before the cancer worsened compared to exemestane alone
® Afinitor (everolimus) is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2negative breast cancer (advanced HR+ breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole .
While endocrine therapy remains the cornerstone of treatment for these women, most will eventually develop treatment resistance. Therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR
® pathway. Afinitor targets the mTOR pathway, which is hyperactivated in many types of cancer cells. mTOR is a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism.
® “Afinitor is the first and only treatment that boosts the effectiveness of endocrine therapy, significantly extending the time women with advanced breast cancer live without tumor progression,” said Gabriel Hortobagyi, MD, former Chair of Breast Medical Oncology, University of Texas MD Anderson Cancer Center. “This approval redefines the treatment and management of advanced hormone receptorpositive breast cancer, offering a critical new option for physicians and patients.” The second new drug approved recently by the FDA is Kadcyla™ (ado-trastuzumab) from Genentech. The U.S. Food and Drug Administration (FDA) approved Kadcyla™ (ado-trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer. Kadcyla™ is the first FDAapproved Antibody Drug Conjugate for treating HER2-positive, an aggressive form of the disease.
In a recent study, people who received Kadcyla™ lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months). Also, those receiving Kadcyla™ experienced a 32 percent reduction in the risk of dying compared to people who received other medications.
The U. S. Food and Drug Administration approved Perjeta™ (pertuzumab), also from Genentech, injection for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior antiHER2 therapy or chemotherapy for metastatic disease. Pertuzumab targets the cellular domain of HER2.
Pertuzumab is being studied in early and advanced stages of HER2-positive breast cancer and advanced HER2-positive gastric cancer. Pertuzumab is unique in that it is designed specifically to prevent the HER2
receptor from pairing with other HER receptors, a process believed to play a critical role in the growth and formation of several different cancer types. By preventing receptor pairing, pertuzumab is thought to block cell signaling, which may inhibit cancer cell growth or lead to the death of the cancer cell. Binding of pertuzumab to HER2 may also signal the body's immune system to destroy the cancer cells.
The mechanisms of action of pertuzumab and Herceptin are believed to complement each other, as both bind to the HER2 receptor but on different regions. The goal of combining pertuzumab with Herceptin and chemotherapy is to determine if the combination may provide a more comprehensive blockade of HER signaling pathways.
A Massive Challenge
“We have done a lot better, especially with these new advanced therapies. We categorize advanced breast cancer into three groups: Horomone receptor positive, HER2 positive and Triple Negative,” Dr. ChavezMacGregor noted. “Of the three, we have made the least progress with Triple Negative subtype because it is the most complex. For these tumors we don’t have targeted therapies, chemotherapy is our only option and many times the tumors become resistant to chemotherapy. We are desperately trying to find answers. Triple negative breast cancer is our greatest challenge”.
The drugs above represent only three approvals for virtually hundreds of other drugs under study for the fight against cancer. The first question for many, particularly those fighting for their lives, is why aren’t we seeing more medications becoming available, particularly when time is not on the side of an advanced cancer patient? Why, with so many in clinical trials, are so few drugs being approved by the FDA?
Dr. Chavez-MacGregor explains that while everyone involved in the process – from the patient to the doctors to the pharmaceutical companies to the government – want nothing more than more and better medications, and while the process seems to be painfully drawn out, it can only be accelerated so much.
“We have to be careful,” she pointed out. “We have to be certain the drug is effective and that it has been thoroughly tested. It could be disastrous to introduce a drug that hasn’t been properly and thoroughly tested. If a drug has gone through the proper processes, and clinical trials, as physicians, we can be confident in prescribing a medication as part of a treatment plan.”
In addition to time and money, testing a drug requires clinic trials and patients for these trials. According to Dr. Chavez-MacGregor, clinical trials include thousands of patients to obtain the necessary results to safely add a new tool to the battle against breast cancer.
Medical research is expensive with never a promise of a positive outcome. There is a fear from the medical community that recent government spending cuts may affect research. However, a great deal of drug research comes from pharmaceutical companies looking for effective products to bring to market. Other funding comes from non-profit organizations such as the Susan G, Komen Foundation, the Breast Cancer Research Foundation and the Avon Breast Cancer Foundation. The process will still require federal government funding through such organizations as the National Cancer Institute. Time will tell if the budget cuts will slow down the government’s most important role – approving the drugs.
Perhaps the greatest question on the mind of any advanced stage breast cancer patient and their doctor is: Are we winning the war? -Mariana Chavez-MacGregor, MD, MSC
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