Second cancers may develop in women with early invasive breast cancer

Women treated for early invasive breast cancer have a slightly higher risk of a second primary cancer than those in the general population, reveals a study. Such risk is greater among younger women.

“For patients with a diagnosis of early breast cancer, the long-term risks of developing a second cancer depend chiefly on age at diagnosis of breast cancer,” the researchers said. “The excess risk of nonbreast cancer, over that experienced by the general population, is small compared with the risk of mortality from breast cancer for most women.”

This population-based observational cohort study used data from the National Cancer Registration and Analysis Service for England. A total of 476,373 women with breast cancer as their first invasive (index) cancer registered from January 1993 to December 2016, with follow-up until October 2021, were included in the analysis.

Of the women, 64,747 developed a second primary cancer, but the absolute excess risks compared with those in the general population were small. [BMJ 2025;390:e083975]

By 20 years, 13.6 percent (95 percent confidence interval [CI], 13.5–13.7) of women had developed a nonbreast cancer (2.1-percent greater than expected vs the general population), and 5.6 percent (95 percent CI, 5.5–5.6) had developed a contralateral breast cancer (3.1 percent more than expected).

Notably, younger women had a higher absolute excess risk of contralateral breast cancer than their older counterparts.

The largest 20-year absolute excess risks among specific nonbreast cancer types were noted for uterine and lung cancer. Moreover, the standardized incidence ratios for cancers of the uterus, soft tissue, bones and joints, and salivary glands, as well as acute leukaemias, exceeded those of the general population, but absolute excess risks at 20 years were <1 percent for each nonbreast cancer type.

Adjuvant treatment

The researchers also categorized patients according to adjuvant therapy and found that radiotherapy correlated with increased contralateral breast and lung cancers. In addition, they observed that endocrine therapy was associated with increased uterine cancer (but reduced contralateral breast cancer) and chemotherapy with increased acute leukaemia.

“These were consistent with effects reported in randomized trials, but positive associations for soft tissue, head and neck, ovarian, and stomach cancers were also identified, and these have not previously been observed in trials,” the researchers said. 

“This suggested that approximately 2 percent of all the 64,747 second cancers and 7 percent of the 15,813 excess second cancers in the cohort may be attributable to adjuvant therapies,” they added.

Small risks

Breast cancer survivors are at greater risks of developing invasive cancers than other women in the general population. However, these risks are small compared with those of recurrence and death from breast cancer in most women diagnosed with early invasive breast cancer despite the significant reductions in breast cancer mortality recently reported. [BMJ 2023;381:e074684]

“This is an important consideration in efforts to reduce morbidity by de-escalating treatments, as it may compromise breast cancer cure,” the researchers said. 

“Lifestyle factors including smoking and obesity have a greater impact on second cancer risk than does a previous breast cancer diagnosis,” they added. [Br J Cancer 2018;118:1130-1141]