If it is recognized and treated early, it is almost always curable. But if not, the cancer can advance and spread to other parts of the body. While it is not the most common of skin cancers, it causes the most deaths. About 120,000 new cases of melanoma are diagnosed in the US yearly, and of these, over 60,000 are invasive. Even though melanoma accounts for only 4% of all skin cancers, it accounts for 80% of all deaths from skin cancer.
The data is even scarier for young women. We don’t specifically understand this trend, but it could be the result of women spending more time outdoors and engaging in indoor tanning.
So we know that we are diagnosing melanoma more and more often. Some researchers have questioned whether that is because we are getting better at screening for it and catching lots of early melanomas. It would be nice if we dermatologists could look at these statistics and pat ourselves on the back and say bravo! We are catching more and more melanomas early because of careful skin examinations! If that were true, we would expect to see the mortality rates, or death rates, from melanoma decreasing. Unfortunately, that is not true. The mortality rates from melanoma continues to rise, faster than for any other cancer. In the past decade, the risk of dying from most cancers has dropped. But for several cancers, the mortality risk has risen. The most dramatic increase in mortality from 2000-2010 was for melanoma in both genders. In women, you can see a startling almost 50% increase of mortality rates.
Figure 2. Biologic Events and Molecular Changes in the Progression of Melanoma. At the stage of the benign nevus, BRAF mutation and activation of the mitogen-activated protein kinase (MAPK) pathway occur. The cytologic atypia in dysplastic nevi reflect lesions within the cyclin-dependent kinase inhibitor 2A (CDKN2A) and phosphatase and tensin homologue (PTEN) pathways. Further progression of melanoma is associated with decreased differentiation and the decreased expression of melanoma markers regulated by microphthalmia-associated transcription factor (MITF). The vertical-growth phase and metastatic melanoma are notable for striking changes in the control of cell adhesion. Changes in the expression of the melanocyte-specific gene melastatin 1 ( TRPM1 ) correlate with metastatic propensity, but the function of this gene remains unknown. Other changes include the loss of E-cadherin and increased expression of N-cadherin, αVβ3 integrin, and matrix metalloproteinase 2 (MMP-2).
Everyone is at some risk for melanoma, but increased risk depends on several factors. Both UVA and UVB rays are dangerous to the skin and can induce skin cancer, including melanoma. Blistering sunburns in childhood increase risk, but cumulative sun exposure can also be a factor. Tanning booths and tanning bed use has also been implicated in causing melanoma. I wanted to touch on this idea of a single episode of sun exposure being damaging on the next slide. The more moles you have on your body, the greater your risk for melanoma, even if the moles look entirely normal. People with fair skin, light hair and blue eyes are at elevated risk of melanoma. Family history plays a major role in melanoma. About 1 in 10 patients diagnosed with melanoma has a close family member with melanoma. Each person with a first degree relative with melanoma has a 50% greater chance of developing the disease than people who do not have a family history. There are a number of gene mutations that might be playing a role here. The BRAF switch gene, the tumor suppressor gene p53, and a gene called CDKN2A have all been implicated. Once you have had melanoma, you run an increased chance of recurrence. People who have had basal cell or squamous cell carcinoma are also at increased risk of developing melanoma. Compromised immune systems as the result of chemotherapy, organ transplantation, excessive sun exposure, immunosuppressive medications, and diseases such as HIV disease or lymphoma can increase your risk of melanoma.
This is my friend Bob, who attends a pre-Boston Marathon party that I hold every year for Masters runners. TIP #2: WEAR YOUR SUNSCREEN!
If you are in any of these risk groups, you can protect yourself and your children by practicing safe sun habits, remembering to examine yourself from head to toe, watching for the warning signs, and getting a yearly exam from a dermatologist. You can see in this diagram that many melanomas arise in locations that might be difficult to observe on your own! Your scalp, your back, and even the soles of your feet are not easy places to monitor, although I daresay that, as runners, most of us pay closer attention to our feet than many folks out there.
TIP #4: The best photo ops are not at the finish line. In fact, the finish line photos as Boston are dismal. If you want a good memory of the race, smile and look strong and peppy as you make the right onto Hereford Street. The MarathonFoto cameras are set up there…it is only ¼ mile to the finish, and the Magnolia trees and brownstones of Comm Ave look positively lovely behind you. The fellow behind me didn’t get the memo.
In August, Zelboraf was approved by the FDA for the treatment of inoperable or advanced metastatic melanoma. This is the first targeted genetic therapy for melanoma approved to date, and it is approved for patients whose tumors harbor a mutation in the BRAF gene, which is present in about 40-60% of melanomas. By inhibiting the defective BRAF gene, Zelboraf slows or halts the uncontrolled cell growth associated with gene mutation. In March, the FDA approved a treatment for advanced stage melanoma patients called Yervoy, or ipilimumab. This monoclonal antibody is injected and binds to a molecule called CTLA-4 and prevents it from functioning, thus kicking the immune system into higher gear so that it can identify, attack and eliminate melanoma cells. MoleMate is a unique skin imaging system that was approved by the FDA to allow physicians to better view suspicious moles. In most cases, a full skin examination by a dermatologist is sufficient, but in individuals at high risk for melanoma or with numerous moles, this may be a big help in homing in on the troublesome lesions. The rate of skin cancer screening by primary care physicians has increased. This is good news, but unfortunately, the accuracy of skin cancer screening by general physicians turns out not to be quite as high as with dermatologists. Recently, there has been a decrease in death rates from melanoma in Australia. This is important, because Australians adopted aggressive public health campaigns much earlier than in the US, with regard to sun protection and skin self examination education. So this declining death rate may finally reflect these changes that were implemented years ago.
There has been some debate in past years about the efficacy of sunscreens in preventing skin cancers. But earlier this year, an Australian group published the first ever randomized controlled human trial (the most convincing form of human research) showing that regular use of sunscreen can prevent melanoma. Other ways that you can minimize your sun exposure are to seek shade, avoid the midday sun, wear sun protective clothing and sunglasses. Make sure to take a look at your own skin monthly, and see your doctor for a full head to toe skin examination yearly. Educate those around you about the risks. Give out sunscreen samples. Sport a stylish hat! Finally, you can do what you are doing right now, and support the Melanoma Foundation. You’ll hear more about how your fundraising can help in the next talk.
Robin L. Travers, MD SkinCare Physicians Boston Marathon Qualifier 2005-2011
<ul><li>The most serious form of skin cancer </li></ul><ul><li>Curable if recognized and treated early </li></ul><ul><li>In advanced state, serious illness and death </li></ul><ul><li>120,000 cases diagnosed every year </li></ul><ul><li>2010: 68,130 invasive melanomas diagnosed </li></ul><ul><li>4% of all skin cancers </li></ul><ul><li>80% of all deaths from skin cancers </li></ul>
<ul><li>Number of melanoma cases worldwide is increasing faster than any other cancer! </li></ul><ul><li>Doubling of melanoma incidence every 10-20 years </li></ul><ul><li>Even greater incidence rates among young women. </li></ul>
<ul><li>In the past decade, the risk of dying from cancer has dropped. But for several cancers, the mortality risk has risen. The most dramatic increase in mortality from 2000-2010 was found for lung cancer (in women) and for melanoma (for both genders) </li></ul>
<ul><li>Melanomas arise from melanocytes </li></ul><ul><li>Melanocytes produce pigment: MELANIN </li></ul><ul><li>Colors our skin, hair and eyes </li></ul><ul><li>Most melanomas arise in the skin </li></ul>
How Melanocytes Evolve Into Melanoma Miller AJ, Mihm MC Jr. N Engl J Med 2006;355:51-65.
<ul><li>Sun exposure </li></ul><ul><li>Moles </li></ul><ul><li>Skin Type </li></ul><ul><li>Family History </li></ul><ul><li>Personal History </li></ul><ul><li>Weakened Immune System </li></ul>
<ul><li>Breakthrough drugs for advanced and metastatic melanoma </li></ul><ul><li>New technologies for early detection </li></ul><ul><li>Primary care physicians becoming more skilled and performing more skin examinations </li></ul><ul><li>Mortality decrease in Australia </li></ul>
<ul><li>Wear sunscreen and seek shade </li></ul><ul><li>Wear sun protective clothing and sunglasses </li></ul><ul><li>Take your Vitamin D </li></ul><ul><li>Monitor your skin monthly, see your doctor yearly </li></ul><ul><li>Educate </li></ul><ul><li>Run 26.2 miles to support the Melanoma Foundation of New England! </li></ul>