Second Primary Cancer

A second primary cancer is a second, unrelated cancer in a person who has previously experienced another cancer at any time. A second primary cancer may occur in the same tissue or organ as the first cancer or in another region of the body. These second cancers may be related to a genetic predisposition, common risk factors, treatments for the original cancer, or simply occur sporadically as cancer often does.

Nearly one in five cancers diagnosed today occurs in individuals with a previously diagnosed cancer. The incidence of second primary cancers is highest in childhood cancer survivors, but relatively common in adults as well.

Learn about common sites of second primary cancers, why they may occur, and the prognosis.

Is It Common to Have Two Primary Cancers?

The chance of developing a second primary cancer depends on many factors including:

• The age at diagnosis of the first primary cancer
• The type of primary cancer
• The stage of primary cancer (for obvious reasons, people who have an advanced stage first cancer are less likely to develop a second primary cancer)
• Treatments received for the first primary cancer
• Genetics
• Other risk factors (such as smoking and other lifestyle choices)

Statistics

The incidence of second primary cancers has been rising steadily, largely due to improving survival rates from cancer. From 1975 to 1979, 9% of all cancers represented a second primary cancer. That number has increased such that 19% of cancers diagnosed between 2005 and 2009 were a second primary cancer.

The incidence of second primary cancers is highest in childhood cancer survivors. This is not surprising as these people often live for many years after their original cancer diagnosis, and survival rates for childhood cancer have been improving. For example, of women who were treated with radiation for Hodgkin lymphoma as a child, the cumulative risk of developing breast cancer is 35% by the age of 50.

Types of Second Primary Cancers

Overall, the most common type of second primary cancer is lung cancer, and it's important for people who have survived cancer to understand this occurrence.

Second Primary Cancers at Different Sites

A surprising finding was noted in women who developed lung tumors after breast cancer. While nodules in the lungs in a person who has had breast cancer may strongly be suspected to be metastases, this is not always the case. In fact, in a 2018 study, only 47% of such nodules were metastases, and 40% were primary lung cancers (a second primary cancer).

Likewise, a person who has been successfully treated for lung cancer may later develop an unrelated prostate cancer.

Second Primary Cancer in the Same Tissue or Organ

An example of second primary cancer occurring in the same organ might include right-sided breast cancer in someone who previously had a mastectomy for left-sided breast cancer. The second primary cancer in this case is unrelated to the first cancer and may differ significantly in subtype and molecular profile. Another example would be a new and unrelated cancer occurring in another lobe of the lungs after successful surgery to remove a cancer in a different lobe.

Cancers Most Associated With Secondary Cancers

As noted earlier, childhood cancer survivors have the highest risk of developing a second primary cancer. In the 2016 study above, people who had non-Hodgkin's lymphoma or bladder cancer had the greatest risk of developing a secondary malignancy.

While the risk of a second primary cancer may be lower, among people with head and neck cancer, second primary cancers are the second leading cause of death.

Even primary non-melanoma skin cancers (such as basal cell carcinomas or squamous cell carcinomas of the skin) may be associated with secondary cancers. In a 2018 study looking at Asian men, the men were 43% more likely to develop a second primary cancer than men who did not have a non-melanoma skin cancer. This included a 2.99-fold increased risk of cancers of the lip, oral cavity, and pharynx, and a 3.51-fold increased risk of genitourinary cancers (such as cancers of the bladder and prostate).

An earlier large study in the U.S. also found an increased risk of second primary cancers associated with non-melanoma skin cancer, with breast cancer and lung cancer being most common in women, and melanoma common in both men and women.

Causes of Second Primary Cancers

There are a number of reasons why someone who has had cancer would have an increased risk of developing a second cancer.

Chance

Sometimes there's no clear explanation for a second primary cancer, and anyone is at risk of developing cancer. It's now thought that one in two men and one in three women will develop cancer (not including non-melanoma skin cancers) during their lifetime.

Secondary Cancers

Sometimes the treatments for cancer can predispose a person to second primary cancers as well. Both radiation and chemotherapy drugs are carcinogens. (Keep in mind that the risk is usually much lower than the benefits of treating the original cancer.)

Radiation therapy for childhood cancers significantly increases the risk of later second cancers. In some cases, the risk related to radiation therapy is very low, such as the risk of angiosarcoma of the breast in women who have had radiation therapy for breast cancer. Some chemotherapy drugs are more likely than others to be associated with second cancers.

Common Exposures

Risk factors for one cancer may predispose a person to developing other cancers. For example, smoking is linked to lung cancer but is also associated with cancers of the bladder, esophagus, liver, colon, and more. While not always thought of as smoking-related, it's thought that roughly 25% of cases of acute myelogenous leukemia are due to smoking.

Other lifestyle practices can predispose people to cancer as well, and obesity is racing head to head with smoking as the leading lifestyle-related risk factor for cancer.

Genetics and Second Primary Cancers

In some cases, a person may have a genetic predisposition to developing cancer that plays a role in both a primary and secondary cancer.

There are several genetic syndromes and gene mutations that raise the risk of a number of cancers. For example, BRCA gene mutations are associated with not only an increased risk of breast cancer, but also cancers of the ovary, prostate, pancreas, and lung.

Currently, available genetic tests are unable to define all familial cancers, and genetic counseling is important for anyone who has a strong family history of cancer.

In some cases, it's likely that a combination of common gene variants may be associated with cancer risk, and genome-wide association studies promise to improve our understanding of genetic risk in the future.

Summary

Second primary cancers are fairly common among cancer survivors and may be more of a threat to life than the original cancer. Risk factors for developing second primary cancer include age at first cancer diagnosis, the treatment originally received, and genetics. Rates of second primary cancers have been rising steadily, and the prognosis is less positive than for those with a first-time cancer diagnosis. Non-Hodgkin's lymphoma and bladder cancer have the greatest incidences of secondary cancer diagnosis.