by Dr. C.H. Weaver M.D. updated 5/2019
People with a history of certain types of cancer, prior melanoma and certain cancer treatments may be at increased risk of developing melanoma—an aggressive form of skin cancer. Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma.
Melanoma is a very aggressive cancer that often begins in the form of a mole. If melanoma is detected and removed prior to its spread, cure rates may be high. However, once the cancer has spread from its site of origin, cure rates fall dramatically. Therefore, it is imperative that patients who are considered to be at a high risk of developing melanoma be screened regularly by their dermatologist.
History of Melanoma Increases Risk of Second Melanoma
First and foremost, individuals who have been diagnosed with melanoma have an increased risk of developing sites of second or third melanomas. If you have a history of melanoma you should undergo frequent dermatologic monitoring.
Researchers from Memorial Sloan-Kettering Cancer Center in New York conducted a study to determine if patients who have been diagnosed with melanoma are at risk for the development of additional melanomas. This study included a maintained database of 4,484 patients who had been diagnosed with an initial melanoma.(1) Researchers made the following observations:
- 8.6% of patients developed two or more melanomas.
- 59% developed their second melanoma within one year of diagnosis of their first melanoma.
- Of those who developed a second melanoma, 31% developed a third melanoma within 5 years.
- At 5 years, 11.4% of patients are expected to develop a second melanoma.
- Family history of dysplastic nevi (atypical moles) increased risk of the development of second melanomas to 24% at 5 years.
The researchers concluded that patients diagnosed with melanoma are at an increased risk of developing a second or greater number of melanomas, particularly within 1 to 5 years of diagnosis from the initial melanoma. Furthermore, patients with a family history of dysplastic nevi have an even greater increased risk of developing a second or greater number of melanomas.
Does history of cancer increase risk of melanoma?
To explore whether people with a history of cancer are more likely to develop melanoma, researchers collected information from a large US cancer database (the Surveillance, Epidemiology, and End Results database).(2)
- Having an initial diagnosis of melanoma before the age of 45 increased the risk of a subsequent diagnosis of melanoma by almost 12 times. Certain other cancer diagnoses before the age of 45 were linked with a smaller increase in melanoma risk. These other cancers were nonepithelial skin cancer, Kaposi sarcoma, female breast cancer, and lymphoma.
- Having an initial diagnosis of melanoma after the age of 45 increased the risk of a subsequent diagnosis of melanoma by more than 8 times. Other cancers that were linked with a smaller increase in melanoma risk were nonepithelial skin cancer, ocular melanoma, female breast cancer, prostate cancer, thyroid cancer, lymphoma, and leukemia.
These results suggest that certain groups of cancer survivors may be at increased risk of melanoma. Risk of melanoma is particularly high for people who have already had a first diagnosis of melanoma, highlighting the importance of ongoing skin surveillance in this group.
Melanoma Drug Accelerates Secondary Skin Cancers In Some Patients
Zelboraf® (vemurafenib) improves outcomes among patients with advanced melanoma that harbors a BRAF gene mutation, but also accelerates the development of squamous cell carcinoma in some patients. A study that explores the reasons for these secondary cancers was published in the New England Journal of Medicine. These findings may lead to treatment that preserves Zelboraf’s effectiveness against melanoma while reducing the risk of secondary skin cancers.
In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Approximately half of all late-stage melanomas carry a specific BRAF mutation known as V600E. Zelboraf blocks the function of the protein produced by this mutated gene and inhibits cell growth.
Patients treated with BRAF inhibitors such as Zelboraf have been reported to have high rates of secondary squamous cell skin cancers. To understand the reasons for this, researchers evaluated tumor samples from melanoma patients who had developed squamous cell carcinoma during treatment with Zelboraf.
- Roughly 60 percent of the secondary squamous cell carcinomas had a mutation in the RAS gene. These RAS mutations are thought to be the result of prior skin damage from sun exposure. Zelboraf appears to accelerate the development of squamous cell carcinoma in skin cells with a preexisting RAS mutation.
Researchers are now exploring the use of a second type of drug in combination with Zelboraf; the goal is to preserve the effectiveness of Zelboraf against melanoma while also reducing the occurrence of secondary skin cancers.(3)
Since melanoma is curable if detected and removed early, frequent dermatologic screening is imperative for patients at a high risk of developing this disease. Patients diagnosed with melanoma should speak with their physician regarding individual screening schedules with a dermatologist.
Knowledge is power. Are you facing a new diagnosis, recurrence, living with metastatic disease, or supporting a loved one through their cancer journey?
- Ferrone C, Porat L, Panageas K, et al. Clinicopathological Features of and Risk Factors for Multiple Primary Melanomas. Journal of the American Medical Association. 2005;294: 1647-1654
- Yang GB, Barnholtz-Sloan JS, Chen Y, Bordeaux JS. Risk and survival of cutaneous melanoma diagnosed subsequent to a previous cancer. Archives of Dermatology. 2011;147:1395-1402.
- Su F, Viros A, Milagre C et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. New EnglandJournal of Medicine. 2012;366:207-15.