Understanding the Risk of Second Primary Cancers After Early Breast Cancer

Breast cancer survivors often are forced to ask themselves if their diagnosis means that they will be more likely to develop a second, unrelated cancer later in life. While the risk is real, new research suggests that it is relatively small, and depends on the patient’s age at diagnosis, therapy type, and lifestyle factors. A large study published in The BMJ provides particularly important insights, showing that the risk of a second cancer is only slightly higher than in the general population but still significant enough to warrant close follow-up and tailored survivorship care.¹

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The BMJ study tracked 476,373 women in England who were diagnosed with early invasive breast cancer from 1993 to 2016, all of whom had surgery.¹ After 20 years of follow-up, 64,747 women were diagnosed with a second primary cancer. Twenty years after diagnosis, the absolute risk of a second non-breast cancer was 13.6%, which was about 2.1% higher than expected compared with women in the general population. In the case of contralateral breast cancer, or cancer in the opposite breast, the risk was 5.6%, indicating an excess of 3.1% over population estimates. Younger women had higher relative risks than older women, with those diagnosed at age 40 having about a 6% chance of developing a second cancer by age 60.¹ It was found that adjuvant therapies like chemotherapy and radiotherapy only marginally fueled the increased risk.

Other recent studies support these findings while adding important context. A large South Korean cohort study using propensity score matching compared patients with breast cancer who underwent radiotherapy with those who were not treated with radiotherapy and found no significant difference in the overall risk of secondary malignant neoplasms, even when the groups were divided by age, latency period, and number of radiation treatments.² This result indicates that, although radiation has been historically associated with the occurrence of certain second cancers, it may not be as major a source of risk as previously assumed, particularly with the use of modern treatment methods.

On the other hand, a study conducted in a US integrated health care delivery system involving more than 16,000 breast cancer survivors reported that treatment type was a determinant of second cancer risk. The investigators found that the risk of soft tissue sarcoma was elevated after radiotherapy, while that of myelodysplastic syndrome was also increased following chemotherapy. However, the risk of new breast cancer was lower in the group with endocrine therapy.³ This points to the intricate connection between cancer treatments and long-term effects, as well as the vital role of personalized risk counseling.

Lifestyle and modifiable factors can also influence the risk of secondary cancers. A systematic review and meta-analysis concluded that excess body weight is the main cause of the second primary cancers of breast cancer survivors, making obesity and overweight important risk factors.⁴ This gives pharmacists, along with other healthcare professionals, the chance to provide counseling on weight management as part of the care of the survivors.

Furthermore, the occurrence of second primary cancers has a long-term effect on mortality. Recent research revealed that breast cancer survivors who developed a second malignancy had a 27% greater risk of cancer-related death and an 18% increased risk of all-cause death in comparison to those who did not develop another cancer.⁵

For pharmacists, these findings carry several practical implications. Cancer survivors should be advised that their total chance of a second cancer is only slightly higher than average but still a matter of concern. Endocrine therapy must be strictly adhered to if prescribed, not only for the purpose of recurrence reduction but also for lowering the risk of a second breast cancer. Pharmacists should actively support adherence, monitor for adverse effects, and provide education on the importance of long-term therapy. Lifestyle counseling is equally important, particularly for weight control, smoking cessation, and alcohol consumption, all of which are factors both for recurrence and secondary cancer risk.

In conclusion, women who survive early invasive breast cancer do carry a small but real increased risk of developing second primary cancers, both in the opposite breast and elsewhere in the body. The absolute excess risk over 20 years is limited; it is usually only 2% to 3% higher than the baseline for non-breast cancers and slightly higher for contralateral breast cancers. Young survivors and those who have been exposed to certain treatments have different risk profiles, and lifestyle factors that can be changed also have an impact on the results. The scientific research in the areas of genetics, treatment exposures, and preventive measures will continue to present risk stratification and enhance the quality of survivorship care.

REFERENCES

1. McGale P, Dodwell D, Challenger A, Cutter D, Williams A, Broggio J et al. Second cancers in 475 000 women with early invasive breast cancer diagnosed in England during 1993-2016: population based observational cohort study BMJ 2025; 390 :e083975 doi:10.1136/bmj-2024-083975

2. Kim S, Boo D, Yoo S, et al. Secondary Cancer Risk in Breast Cancer with and without Radiotherapy: The Observational Health Data Sciences and Informatics (OHDSI) Cohort Study. Cancer Res Treat. Published online June 5, 2025. doi:10.4143/crt.2024.968

3. Ramin, C., Veiga, L.H.S., Vo, J.B. et al. Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort. Breast Cancer Res 25, 50 (2023). https://doi.org/10.1186/s13058-023-01647-y

4. Allen I, Hassan H, Walburga Yvonne Joko-Fru, et al. Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study. The Lancet regional health Europe. Published online April 1, 2024:100903-100903. doi:https://doi.org/10.1016/j.lanepe.2024.100903

5. Deng, Z., Jones, M.R., Wang, MC. et al. Mortality after second malignancy in breast cancer survivors compared to a first primary cancer: a nationwide longitudinal cohort study. npj Breast Cancer 8, 82 (2022). https://doi.org/10.1038/s41523-022-00447-5