Second Cancers Caused by Cancer Treatment

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Breast cancer

Women with breast cancer are at a 3-to 4-fold increased risk of developing a new primary cancer in the opposite breast. Increased risk is also seen for cancers of the ovary, uterus, lung, colon, rectum, and connective tissue, as well as melanoma and leukemia. But for some of these cancers, such as cancer of the opposite breast, ovary, and uterus, the second cancer may be linked to the same thing that caused the first cancer, like genetics or a hormonal risk factor.

The most common second cancer seen in survivors of breast cancer is another breast cancer. Women who were treated with breast-conserving surgery (such as a lumpectomy) can develop a cancer in the same breast, but anyone can get a new cancer in the other breast. The risk of a second breast cancer is high no matter what treatment is used for the first cancer. Even women who receive no radiation or chemotherapy have an increased risk of cancer in the opposite breast. This increase in risk also shows up in close relatives of women with breast cancer, so there may be a shared pre-existing factor causing the first and second breast cancers in many of these women. Still, depending on the patient's age when they were treated, radiation therapy can increase the risk even more. Radiation therapy does not seem to increase the risk of cancer in the opposite breast if the patient is past the age of 45 at the time of treatment. But in women who had radiation therapy before the age of 45, an increased risk is seen 10 years after treatment.

The risk of lung cancer is also increased in women who had radiation therapy for breast cancer. The higher lung cancer risk is first seen 10 years after radiation, and gets higher over time. The risk of lung cancer after radiation is even higher in women who smoke.

Radiation therapy to the breast also increases the risk of sarcomas of blood vessels (angiosarcomas), bone (osteosarcomas), and other connective tissues. These cancers are most often seen in the remaining breast area, chest wall, or in the arm that had been treated with the radiation therapy. This risk remains high even 30 years after treatment.

Taking tamoxifen for 5 years not only makes it less likely that the breast cancer will come back, it also helps to lower the risk of breast cancer in the opposite breast by half. This appears to be true for women who have been followed for 10 years after their first treatment. But tamoxifen increases the risk for endometrial cancer in 5-year and 10-year survivors. Still, the benefits of treatment for breast cancer are greater than the risk of a second cancer.

There is a small risk of developing leukemia after treatment for breast cancer. The risk is highest when both chemotherapy and radiation therapy are given, especially if the chemotherapy includes an alkylating agent (see the list of alkylating agents above). Cyclophosphamide (Cytoxan®), an alkylating agent, has been used for over 30 years to treat breast cancer. It is a part of the regimen known as CMF (cyclophosphamide, methotrexate, and 5-FU), and is also included in the regimens AC (Adriamycin® [doxorubicin] and cyclophosphamide) and FAC (adds 5-FU to the drugs in AC). Studies have shown that higher doses of cyclophosphamide increase the risk of developing AML. The dose of cyclophosphamide that is now used in standard CMF and AC is linked with a low risk of leukemia. The risk also goes up with dose intensity (when a higher amount of drug is given over a shorter amount of time). Still, even with a risk of leukemia that is several times higher than what is usually seen, the leukemia risk even with high doses is only about 1%.

Follow-up care

Even women who were not treated with radiation have an increased risk of a second breast cancer in the opposite breast. Follow-up care should include annual screening for breast cancer (if there is any remaining breast tissue). Good gynecologic care is also important to watch for endometrial cancer.

All patients should be encouraged to avoid tobacco smoke.


Last Medical Review: 01/30/2012
Last Revised: 01/30/2012