Recently, Xiao Wang, a breast cancer patient, was diagnosed with acute leukemia in a tertiary care hospital, a news that both surprised and saddened the medical and nursing staff on our ward! Speaking of Xiao Wang, the medical and nursing staff in our ward all know that she was diagnosed with breast cancer (triple negative breast cancer) seven years ago when she was ready to be a bride at the age of 29! Having this disease at such an age makes people both bitter and sympathetic. But fortunately, she was post-operative stage II, and after about half a year of radiotherapy, she was doing well until now, and later became a bride as she wished. In the years of recovery, she also came to review on time, and every time she came to review was normal, but last month when she came to review, she said her gums often bleeding for several months, and often weakness, blood count found anemia, thrombocytopenia, leukocytosis, the doctor suggested her to go to the hematology department for consultation, and then confirmed the diagnosis of acute leukemia after the external bone marrow biopsy. Faced with such an unfortunate encounter of Xiao Wang, what do doctors think about this phenomenon of having one kind of tumor first and then having another kind of tumor (also called second primary tumor) after a few years? As we all know now, cancer treatment is a comprehensive treatment. For breast cancer like Xiao Wang’s, there are many effective treatments available, such as surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy, but because Xiao Wang has triple negative breast cancer, the latter two treatments are not so suitable. Although radiotherapy has some side effects such as gastrointestinal reactions and bone marrow suppression, it is still a hard work and if used properly, the benefits to patients far outweigh its side effects. The side effects (side effects) or complications of radiotherapy are not only the above mentioned gastrointestinal reactions (such as nausea, vomiting and constipation) and bone marrow suppression (decreased white blood cells, reduced platelets and anemia), but also impaired heart, liver and kidney function, neurological damage, hair loss and hand-foot syndrome. Most of these side effects are transient, or acute, and most of them disappear or diminish significantly after a period of time, and even if a few complications remain, they do not have much impact on the quality of life of patients, especially on their survival. However, very few long-term complications after radiotherapy, such as second primary tumor (cancer), are little known! Second primary cancer is the most serious complication of radiotherapy-related long-term side effects. Since the 1970s, many studies have evaluated the relevance of radiotherapy to second primary tumors. One study concluded that the risk of developing a second cancer after radiotherapy in pediatric oncology patients is nearly six times higher than in the general population. Among cancers caused after radiotherapy, leukemia is the most frequently reported, while second solid tumors are more often associated with whether patients are treated with radiotherapy or not. Among chemotherapeutic agents, alkylating agents, onychotoxins, anthracyclines, and platinum drugs are considered to be carcinogenic, and the risk increases with their cumulative dose. Alkylating agents that may cause leukemia include nitrogen mustard, cyclophosphamide, simustine, and marineland, etc. Studies have concluded that leukemia caused by these drugs begins to increase 1 to 2 years after chemotherapy, reaches a peak in 5 to 10 years, and the risk slowly begins to decrease after 10 years. Some studies have concluded that the risk of leukemia from cyclophosphamide, a drug commonly used in clinical practice, is small relative to other alkylating agents (but the risk of developing bladder cancer is elevated). Studies have found that platinum-containing combination chemotherapy regimens can significantly increase the risk of leukemia, probably because their mechanism of action is very similar to that of alkylating agents. An expert study analyzed the occurrence of second tumors in more than 4,000 patients with ovarian cancer who used platinum-containing combination chemotherapy regimens and survived 10 years, and found that the risk of leukemia was more than four times higher than in the general population. The risk of leukemia was also significantly increased after etoposide (VP16) and teniposide (VM26) chemotherapy, which are commonly used regimens for small cell lung cancer. Since the end of the last century, high-dose chemotherapy plus autologous peripheral blood stem cell transplantation (ASCT) has become one of the treatments for hematologic tumors and some chemotherapy-sensitive solid tumors. This treatment also puts patients at a significantly increased risk of later leukemia (mainly acute granulocytic leukemia and myelodysplastic syndromes). In fact, in animal studies, scientists have found that many of the chemotherapeutic agents commonly used in clinical practice are mutagenic and carcinogenic, which corroborates the above clinical findings. Regarding radiotherapy (radiation) causing cancer, you may know more from some news reports (e.g., “the incidence of leukemia in survivors of the atomic bombings increased significantly”). In fact, soon after Roentgen discovered X-rays, it was discovered that radiation may cause cancer. Existing studies concluded that whether radiotherapy causes leukemia may be related to the dose of irradiation received by the bone marrow. Surprisingly, the bone marrow seems to be more likely to cause leukemia when it receives low doses of irradiation, while the risk of leukemia decreases at doses of 4 Gy (irradiation units: grays) and above. In addition to leukemia, radiotherapy is also significantly associated with a second type of solid tumor, and studies have concluded that the risk of causing thyroid cancer in pediatric patients is highest at radiation doses of 20-29 Gy after five years, with a decreasing trend once the risk is greater than 30 Gy. However, for the second type of solid tumor that resulted there was a positive relationship with radiation dose. Patients with malignant lymphoma who received doses greater than 40 Gy had eight times the risk of developing breast cancer than those who received less than 40 Gy. Among the second primary tumors caused by radiotherapy, the peak incidence of leukemia is 5-9 years after radiotherapy, while solid tumors tend to occur at least 5-10 years after radiotherapy, where the risk of breast cancer seems to increase until more than 15 years after radiotherapy. In fact, in clinical practice, besides radiotherapy, some other anti-tumor drugs may also lead to the elevation of the second primary tumor: for example, tamoxifen, an endocrine drug commonly used in breast cancer, may lead to an increased risk of endometrial cancer in women, etc. Now let’s go back to the unfortunate encounter of Xiao Wang, who initially used the chemotherapy drugs cyclophosphamide (alkylating agent) and adriamycin (anthracycline), plus local radiotherapy. Scientifically speaking, the risk of leukemia is much higher than the average person. Of course, it should be noted that the occurrence of second primary tumors is not always related to radiotherapy, but the patient’s lifestyle, genetic factors and low immune function are all factors that contribute to the occurrence of second primary tumors. So, how should we avoid or detect the occurrence of Xiao Wang’s second primary tumor at an early stage? First of all, radiotherapy for cancer patients must be standardized. This involves two factors: firstly, doctors must strictly follow the indications of radiotherapy to avoid excessive radiotherapy; secondly, patients or family members should not force doctors to do radiotherapy, and resolutely not to do it if it can be done or not. Secondly, after radiotherapy, besides paying attention to the acute toxicity, we should also closely observe whether there is a possibility of second primary tumor after radiotherapy in the long and slow recovery process, such as paying attention to the changes of blood routine, paying attention to some abnormal or uncomfortable symptoms, etc. Of course, it is especially important to remind that the recurrence and metastasis of the first primary tumor is our top priority for monitoring after treatment, especially in the first 3-5 years after treatment. Once again, we should build up confidence and try to prevent the disease before it happens. Cancer recovery is a long-term process, which needs our full attention in terms of psychological state, lifestyle and abnormal physical condition, only then we can be invincible in front of cancer.