Second Primary Cancer Overview

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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. 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.

Incidence and Statistics

The exact incidence of second primary cancers is uncertain, though studies have given some insight. The chance of a second primary cancer developing depends on many factors such as:

  • The age at diagnosis of the first primary cancer
  • The type of the primary cancer
  • The stage of the 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 lifestyle factors)

Metastases vs. Second Primary Cancer

It's important to distinguish a second primary cancer from metastases due to the first cancer. For example, metastases to the lungs from breast cancer are not a second primary cancer but rather the spread of the first cancer. In this case, the cells in the lungs would be cancerous breast cells under the microscope and not cancerous lung cells.

Often times it's possible to distinguish a second primary cancer from metastases, yet this is not always possible. Some tumors are very undifferentiated, meaning that the cells appear very abnormal. When this occurs it is sometimes difficult to tell the tissue or organ from which the cells originated.

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 was 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.

A 2016 study looked more closely at the risk of second primary cancer related to specific cancer types. In this study, researchers evaluated over 2 million people who developed the 10 most common types of cancer from 1992 to 2008. Over 10% developed a second primary cancer. Among the people who developed a second primary cancer, 13% died from their original cancer and 55% died from their second primary cancer.

Risk

The chance of developing a second primary cancer depends on many factors, such as your age, the type of cancer you had initially, your risk factors, family history, lifestyle habits, and much more.

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 concept.

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 a right-sided breast cancer in someone who previously had a mastectomy for a left-sided breast cancer. The second primary cancer is 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. 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 in 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 both men and women.

Causes

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

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 1 in 2 men and 1 in 3 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 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

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.

A Word From Verywell

Second primary cancers are common among cancer survivors, and in some cases, may be more of a threat to life than the original cancer. It's important to be your own advocate in your cancer, and talk to your doctor about your potential risk factors for a second primary cancer and any special screening or genetic counseling/tests that would be recommended.

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Article Sources

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