Younger Age at Breast Cancer Diagnosis Associated With Subsequent Primary Cancer

Are younger women with breast cancer more likely to develop another primary cancer later in life as compared to their older counterparts? According to some experts, younger women may have more unfavorable tumor characteristics. Others hypothesize this increase is observed because younger women can be observed for longer periods. To better understand this phenomenon, Dr Lene Mellemkjaer, senior researcher at the Institute of Cancer Epidemiology of the Danish Cancer Society in Copenhagen, Denmark, and colleagues conducted a study of 304,703 women who received a diagnosis of breast cancer between 1943 and 2006 according to registries in Denmark, Norway, and Finland.

The researchers used the registries to identify women with breast cancer who developed subsequent primary cancer of another kind. Women who reportedly had a different cancer diagnosis prior to the breast cancer diagnosis were excluded. Subsequent cancers were sorted into 1 of 6 groups: radiotherapy-related, chemotherapy-related, tamoxifen-related, BRCA-gene–related, alcohol-related, and overweight/obesity-related. If a cancer was associated with more than one category, the researchers chose the most appropriate/likely category. Women were followed up until death, emigration, or study cessation. On average, the women were observed for 8.8 years.

Overall, the researchers found 23,304 new malignancies in this cohort. Using standardized incidence ratios, the expected number of new cancers was 20,330. In looking at the countries independently as well as the cohort as a whole, the risk of developing a new primary cancer decreased as age increased. This phenomenon held true even after adjusting for calendar period of breast cancer diagnosis, length of follow-up, and country of residence; this association also was largely unchanged after adjusting for radiotherapy, chemotherapy, and hormonal therapy. Similar age and subsequent cancer risk associations were found when looking at excess absolute risks; as age increased, the risk decreased (Figure). When looking at relative risk, the researchers found that it decreased as age increased until age 50; at that point, the relative risk stabilized. Even after adjusting for treatment types, the associations remained largely unchanged. The exception was for endometrial cancer, where the researchers found that the risk increased by increments of ages older than 50 years at diagnosis.

Figure. Excess absolute risk of subsequent primary cancer diagnosis per 100,000 person-years.

“Age at breast cancer diagnosis remains a key determinant for the RR [relative risk] of developing a new primary non-breast cancer when calendar year of breast cancer diagnosis, length of follow-up, and breast cancer treatment have been taken into consideration,” Mellemkjaer and colleagues explained. They added, “The risk pattern by age was observed during the last 5 decades, despite major changes in treatment and in prevalence of risk factors within the populations.”

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References:

Reference
Mellemkjær L, Christensen J, Frederiksen K, et al. Risk of primary non-breast cancer after female breast cancer by age at diagnosis. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1784-92.