Which cancer treatments can cause other cancers later in life?

A secondary malignancy is a new malignant cancer that occurs after a patient has been treated for an initial (primary) cancer. These may occur months to years after the patient receives treatment for their initial malignancy. Secondary malignancies may be attributed to previous anticancer therapy, the presence of a genetic syndrome, etiologic factors (such as tobacco or alcohol use), or a combination of the above.

Secondary malignancies account for approximately 1 in 6 cancers in the United States.1 Overall, the risk of a secondary malignancy is low, although a patient’s specific risk depends on their treatment, lifestyle factors, and the presence of other risk factors. Most of the data on secondary malignancies is in survivors of childhood cancers, although this is changing as the number of adult cancer survivors increases.

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Treatment-related secondary malignancies can be caused by radiation and certain types of chemotherapy. There are multiple theories behind why these treatments can cause secondary malignancies, including noncancerous cells being damaged by the chemotherapy/radiation and effects on the immune system. Some chemotherapy drugs have a higher risk of secondary malignancies than others. These include the anthracyclines (eg, doxorubicin [Doxil, generics]), certain alkylating agents (eg, cyclophosphamide [Cytoxan, generics], carmustine [BiCNU]), and the epipodophyllotoxins (eg, etoposide [Etopophos, generics]). Chemotherapy drugs are most strongly associated with causing secondary leukemias and some solid tumors including lung, gastric, and bladder cancers.

The risk for secondary cancers after radiotherapy depends on the dose of radiation administered, the site to which it was given, and the age of the patient at the time of treatment. Secondary malignancies caused by radiation typically occur within or near the edges of the previous radiation field, and vary depending on the location and nature of the radiation. For example, a female patient who received radiation to the chest may have a higher risk of developing breast cancer later in life.

Some of the newer, targeted chemotherapy drugs can also cause malignancies. For example, the BRAF inhibitor vemurafenib (Zelboraf), used to treat melanoma, was found to cause secondary squamous cell carcinomas in up to 24% of patients.2