Second Cancers Related to Treatment

Second Cancers Related to Treatment

It's not possible to predict who might get a second cancer, but sometimes having cancer treatment can put a person at higher risk for second cancers. As more new treatments emerge and standard treatments continue to be used, studies continue to look at how genetics and different cancer treatments interact, as well as links between the treatments, lifestyle habits, and known cancer-causing agents.

Risk of developing second cancers after radiation therapy Radiation therapy was recognized as a possible cause of cancer many years ago. In fact, much of what we know about the health effects of radiation has come from studying survivors of atomic bomb blasts in Japan. We also have learned from workers in certain jobs that included radiation exposure, and patients treated with radiation therapy for cancer and other diseases.

Leukemia and myelodysplastic syndrome

Past radiation exposure is one risk factor for most kinds of leukemia, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and acute lymphoblastic leukemia (ALL). Myelodysplastic syndrome (MDS), a bone marrow cancer that can turn into acute leukemia, has also been linked to past radiation exposure. The risk of these diseases after radiation treatment for cancer depends on a number of factors, such as:

• How much of the bone marrow was exposed to radiation
• The amount of radiation that reached the bone marrow
• The radiation dose rate (how much was given in each dose, how long it took to give the dose, and how often it was given)

Most often, these cancers develop within several years of a person's radiation treatment. Then the chance of developing a new cancer slowly declines over the following years.

Solid tumors

There is also a risk for other cancers, which are mostly solid tumors, after having radiation therapy. Most of these cancers develop 10 years or more after radiation therapy. The effect of radiation on the risk of developing a solid tumor cancer depends on factors such as:

• The age of the patient when they were treated with radiation. For example, the risk of developing breast cancer after radiation is higher in those who were treated when they were young compared with those given radiation as adults. The chance of developing breast cancer after radiation seems to be highest in those exposed as children. Risk decreases as the age at the time of radiation increases; women who had radiation after the age of 40 have a lower risk of breast cancer. Your age when you get radiation treatment has a similar effect on the development of other solid tumors, including lung cancer, thyroid cancer, bone sarcoma, and gastrointestinal or related cancers (stomach, liver, colorectal, and pancreatic).
• The dose of radiation. In general, the risk of developing a solid tumor after radiation treatment goes up as the dose of radiation increases. Some cancers require larger doses of radiation than others, and certain treatment techniques use more radiation.
• The area treated. The area treated is also important, since these cancers tend to develop in or near the area that was treated with radiation. Certain organs, such as the breast and thyroid, seem to have a higher risk for developing cancers after exposed to radiation than other organs.

Risk of developing second cancers after chemotherapy and targeted therapy

Chemotherapy

Some types of chemotherapy (chemo) drugs have been linked with different kinds of second cancers. The cancers most often linked to chemo are myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Sometimes, MDS occurs first, then turns into AML. Acute lymphocytic leukemia (ALL) has also been linked to chemo. Chemo is known to be a greater risk factor than radiation therapy in causing leukemia.

The risk gets higher with higher drug doses, longer treatment time, and higher dose-intensity (more drug given over a short period of time). Chemotherapy agents that have an increased risk for second cancers include:

• Alkylating agents (mechlorethamine, chlorambucil, cyclophosphamide, melphalan, lomustine, carmustine, busulfan)
• Platinum-based drugs (cisplatin, carboplatin)
• Anthracycline topoisomerase II inhibitors (etoposide or VP-16, teniposide, mitoxantrone)

Targeted therapy drugs

Some drugs used to treat cancer are called targeted therapy drugs because they were designed to find and attack certain genes or proteins that are in specific types of cancer. Targeted therapies are newer, so not a lot is known about the risk for second cancer yet. More will be known as more patients get these types of drugs and become survivors who are monitored for future health problems and second cancers.

Vemurafenib (Zelboraf®) and dabrafenib (Tafinlar®) are drugs that target the BRAF protein. They are used to treat melanoma and are being studied for use in other cancers. People taking these drugs have a higher risk of squamous cell carcinomas of the skin.

Written by: The American Cancer Society medical and editorial content team. Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

References:

American Cancer Society (ACS). Cancer Facts & Figures 2020. Atlanta, GA: American Cancer Society; 2020.

https://www.cancer.org/cancer/survivorship/long-term-health-concerns/second-cancers-in-adults/treatment-risks.html

American Cancer Society (ACS). Cancer Prevention and Early Detection Facts & Figures, 2019-2020. Atlanta, GA: American Cancer Society; 2019.

American Cancer Society (ACS). Cancer Treatment and Survivorship Facts & Figures 2019-2021. Atlanta, GA: American Cancer Society; 2019.

Division of Cancer Epidemiology and Genetics (NIH). Second primary cancers. Accessed at https://dceg.cancer.gov/research/what-we-study/second-cancers September 19, 2019.

Fung C, Bhatia S, Allan JM, et al. Second cancers. In DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2019:2155-2173.

Rowland, JH, Mollica, M, Kent EE. Survivorship. In Niederhuber JE, Armitage JO, Kastan MB, Doroshow JH, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia