Secondary Cancer Types and Causes

The term secondary cancer may be used to refer to either a second primary cancer or to cancer that has spread from one part of the body to another (metastatic cancer). In this discussion, we will not talk about metastatic cancer, but only a second primary cancer.

Treatments for cancer such as chemotherapy and radiation can extend life, but these treatments are themselves carcinogenic (can cause cancer). While the benefits of these treatments usually greatly outweigh the risk, it's important for people to be aware of the possibility. Second primary cancers are seen most commonly in people who have chemotherapy or radiation at a young age, such as for Hodgkin lymphoma or breast cancer. Learn about other treatments that may also raise the risk.

Types

It's important to make yet another distinction with secondary cancers. If someone develops a second cancer, it could be for a few reasons. One, and the one we will discuss here is a second cancer that results because of the cancer-causing effects of treatments we use for cancer.

Another way in which the term secondary cancer or second primary cancer is sometimes used is when someone develops a second cancer — either in the location of the first cancer or elsewhere — that is not related to the treatments of the first cancer. These are fairly common as whatever predisposed someone to develop cancer in the first place may be responsible for the later development of a second cancer. This is referred to as the concept of "shared risk factors."​

Related to Previous Cancer Treatment

Second cancers related to treatments from a previous cancer are not common, but certainly, do occur. We know that many chemotherapy drugs, in addition to killing cancer cells, have the ability to cause cancer by damaging the DNA in normal cells. The same is true of radiation therapy.

To understand this, it can help to talk about how chemotherapy and radiation therapy work. These treatments often work by causing "oxidative damage" to the genetic material in cells. The reason they are used with cancer is that cancer cells, in general, divide more rapidly than healthy cells, and this damage is thus more likely to occur in cancer cells. The term oxidative simply means that a reaction occurs that requires the presence of oxygen.

A way to further understand this damage — and to understand how cancer may develop both initially and in response to cancer treatments, is to look at this reaction. We hear a lot about antioxidants. Antioxidants work by stopping this reaction. For this reason, people are often advised to avoid antioxidants during cancer treatment — you don't want to protect cancer cells from damage. 

The damage from chemotherapy and radiation therapy can, however, affect the DNA of normal cells. In time, this damage may result in these normal cells becoming cancer cells. When that happens, another cancer develops.

After Radiation Treatment

We first began to see evidence of secondary cancer in people who had been exposed to radiation treatment. The risk of a secondary cancer from radiation depends upon:

• The dose of radiation
• The area exposed to radiation
• The age of the patients
• How much time has passed since the radiation treatments

The risk of secondary cancers from radiation therapy is improving as there is less "scatter" with newer techniques than in older techniques, meaning that less tissue is exposed. Still, there is an increased risk of a secondary cancer from radiation therapy after a mastectomy.

After Chemotherapy

Secondary cancers may occur after chemotherapy, with the most common cancer being leukemia. Drugs which are more likely to cause leukemia include alkylating agents, the platinum drugs, and topoisomerase inhibitors.

Some targeted therapy drugs may increase the risk of developing a secondary cancer as well.

After Targeted Therapy

Some targeted therapy drugs may increase the risk of developing a secondary cancer as well, specifically those designed to attack the BRAF protein (BRAF inhibitors). BRAF inhibitors are often used to treat metastatic melanoma and may be used to treat some people with non-small cell lung cancer as well. In the setting of metastatic cancer, concern over a secondary cancer is small, though this risk may become of greater concern if BRAF inhibitors are used in earlier stages of cancer (as adjuvant therapy) in the future.

After Stem Cell Transplants

Stem cell transplant patients have a high risk of secondary cancers. This can be related both to radiation and high dose chemotherapy drugs before the transplant, and the immunosuppressive drugs that are needed to prevent rejection after the transplant.

Risk of Secondary Cancers

The risk of secondary cancers varies considerably between different cancer types. Those at greatest risk are people who develop cancer at a young age (partly due to many years after treatment in which these cancers may develop). An example is Hodgkin lymphoma, a cancer that often occurs in adolescents or young adults and has a high survival rate. People who were treated for Hodgkin lymphoma are thought to have a 20 percent to 30 percent risk of developing a secondary cancer. While treatment has improved greatly, such as better localization of radiation so that fewer normal cells are damaged, a high rate of secondary cancers persists.