Hope For Cancer

A large study strongly supports the value of regular mammogram screenings starting at age 40. From 1990 to 2008, while more women age 40 to 49 were getting screening mammograms:

• more breast cancers were diagnosed
• breast cancers tended to be diagnosed at an earlier and more treatable stage
• more women were eligible for lumpectomy instead of mastectomy
• treatment outcomes improved

The research was published in the March 2012 issue of Radiology.

In November 2009, the U.S. Preventive Services Task Force (USPSTF) recommended that routine screening mammograms for women with an average risk of breast cancer should start at age 50, instead of age 40. These recommended changes were very controversial and were not adopted. U.S. guidelines call for all women age 40 and older to have screening mammograms every year. While not ideal, some women may choose to have a screening mammogram every other year.

The study in Radiology looked at diagnosis, treatment, and outcome information from 2,000 women age 40 to 49 who were diagnosed with breast cancer between 1990 and 2008. All the women got their cancer care at the same medical center in Seattle, Wash.

During the same time period when the women were diagnosed, there were public campaigns to make women aware of the value of starting screening mammograms at age 40. So the number of women between age 40 and 50 getting screened went up, and more breast cancers were diagnosed by mammography. Mammogram-detected breast cancer was 28% of all diagnoses in 1990 and went up to 58% of all diagnoses in 2008.

The benefits of mammogram screening for younger women can be measured by a number of factors:

1. Breast cancers were less likely to be advanced-stage at diagnosis: Advanced-stage breast cancers at diagnosis decreased from 24% in 1990 to 8% in 2008
2. Compared to women with breast cancer detected by self-exam or doctor’s exam, women with breast cancer detected by screening mammography were:
   • more than 40% more likely to have lumpectomy instead of mastectomy to remove the cancer
   • nearly 50% less likely to need chemotherapy
   • 33% less likely to have the cancer come back (recur) 5 years after diagnosis and 42% less likely to have a recurrence 10 years after diagnosis
   • more likely to survive breast cancer

Taken together, the results strongly suggest that breast cancer screening starting at age 40 leads to diagnoses of breast cancer at earlier, more treatable stages. Other studies have shown that regular screening starting at age 40 means better prognoses for women diagnosed — and lives saved. Despite that evidence and the current guidelines, many women age 40 to 49 don’t get regular screening mammograms.

If you’re 40 or older and have an average risk of breast cancer, yearly screening mammograms should be part of your healthcare. If your breast cancer risk is higher than average, you may want to talk to your doctor about a more aggressive breast cancer screening plan that makes the most sense for your particular situation.

There’s only one of you and you deserve the best care possible. Don’t let any obstacles get in the way of regular screening mammograms.

• If you’re worried about cost, talk to your doctor, a local hospital social worker, or staff members at a mammogram center. Ask about free programs in your area.
• If you’re having problems scheduling a mammogram, call the National Cancer Institute (800-4-CANCER) or the American College of Radiology (800-227-5463) to find certified mammogram providers near you.
• If you find mammograms painful, ask the mammography center staff members how the experience can be as easy and as comfortable as possible for you.

For more information on mammograms and other tests to detect breast cancer, visit the Breastcancer.org Breast Cancer Tests: Screening, Diagnosis, and Monitoring pages. …source …more about breast cancer

Cancer is tough to kill and has many ways of evading the drugs used by oncologists to try and eliminate it. Now, researchers at UCLA’s Jonsson Comprehensive Cancer Center have uncovered how an advanced form of melanoma gets around an inhibitor, Zelboraf, which targets the mutated BRAF gene.

By examining the part of the melanoma genome that encodes proteins, called the exome, Jonsson Cancer Center scientists discovered that in some patients with BRAF-mutated metastatic melanoma, the mutated BRAF gene driving the cancer becomes amplified as the cancer develops resistance to a BRAF inhibitor. Quite simply, by increasing the copies of the mutated BRAF gene, the melanoma is trying to over produce the drug target protein and outnumber the inhibitor. The findings may lead to alternative ways of preventing or treating resistant melanomas.

“Understanding and solving the problem of how cancer gets around targeted drugs is arguably one of the highest priorities in modern day cancer medicine. In this study, we found that in some patients, the cancer simply makes more of the target—the mutated BRAF gene—so that the drug dose becomes too weak to fight the cancer,” said study senior author Dr. Roger Lo, an assistant professor of dermatology and molecular and medical pharmacology and a Jonsson Cancer Center scientist. “If you think of the mutation as a right hand and the BRAF inhibitor as a left hand and the two clasp to be effective, there’s clearly an optimal ratio to ensure the mutated gene is fully inhibited. Here, we get more of the drug target, which has the same effect as dropping the drug level.”

The one-year study is published March 6, 2012, in the peer-reviewed journal Nature Communications.

About 50 percent of patients with metastatic melanoma, or 4,000 people a year, have the BRAF mutation and can be treated with Zelboraf, taken at a dose of two pills taken twice a day. Zelboraf was approved by the U.S. Food and Drug Administration for use in metastatic melanoma in August of 2011. Many other common human cancers, including colon, thyroid and lung, also harbor BRAF-mutated subsets, Lo said.

Oncologists cannot give more Zelboraf to these patients to combat the increased number of mutated BRAF genes because the dose approved by the FDA is the maximum tolerated dose, Lo said. However, Zelboraf could perhaps be given with inhibitors of other cell signaling pathways in metastatic melanoma to try and stop patients from becoming resistant.

Lo and his team examined samples of 20 patients for this study, taking their normal tissue, their tumor tissue before treatment with Zelboraf, and a sample when the cancer had responded earlier but subsequently became resistant. Using high-throughput DNA sequencing technology, the scientists examined the entire cancer exome to see what changes were occurring that may point to resistant mechanisms. Lo found that five of the 20 patients showed increased copies of the mutated BRAF gene. Cell lines developed from melanoma patients also showed pathways downstream of the amplified gene that could be blocked with inhibitors to fight resistance.

“For the first time, we were able to see in actual patient tissue samples how the cancer gets around this drug by altering the target,” Lo said. “It appears that the drug target is not only mutated and hyper-activated, but it’s also massively over-produced in some cases of clinical relapse.”

Lo said there’s an experimental drug that also inhibits mutated BRAF which may be effective against this form of melanoma at a dose that does not result in substantial side effects. In that case, an oncologist might have room to increase the drug dose once a relapse driven by BRAF amplification is encountered in the clinic.

Scientists so far have discovered five mechanisms of BRAF inhibitor resistance in melanoma patients, accounting for about 60 to 70 percent of patients. However, 30 to 40 percent of patients are relapsing by as yet uncovered mechanisms.

Going forward, Lo and his team will seek to find out what is happening molecularly in every patient that relapses after therapy, so novel combination drug strategies can be developed to help them.

“If we know what happens in every relapse, we can have a plan in place that will help us avoid or overcome resistance,” he said. …source …more about melanoma