How Much Does Cancer Risk Increase in Families of Patients with Early-Onset Breast Cancer?

Early-onset breast cancer is generally defined as breast cancer diagnosed before age 40 . It is important because genetic and familial predisposition may play a greater role in this age group, and the disease may follow a more aggressive course. These patients are therefore particularly relevant to research on familial cancer risk and genetic factors.

Early-onset disease accounts for approximately 5% to 10%of all breast cancers, although rates vary between countries and populations. Breast cancer diagnoses have generally increased in recent decades as screening and awareness have improved. However, there are no clear data showing whether early-onset incidence has increased substantially.

Genetic and familial factors are thought to play a greater role in women diagnosed at a young age. These cases may also be more aggressive and have a poorer prognosis. Monitoring and studying early-onset breast cancer is therefore important.

Cancer Risk in Families of People with Early-Onset Disease

Early-onset breast cancer risk rises with the number of affected first-degree female relatives. First-degree relatives of patients with breast cancer are also at increased risk of other cancers, particularly ovarian and prostate cancer.

Less is known about the degree to which first-degree relatives of early-onset (EO) breast cancer patients are at risk of particular other early-onset cancers. Various associations between breast and other cancers have been established among first-degree relatives at all ages.

Cancer clustering in certain families may reflect genetic predisposition or acquired mutations arising from shared environmental exposures.

The study discussed here used a prospective, population-based Finnish family cohort to estimate relative risks of early-onset cancers other than breast cancer among relatives of EO breast cancer patients.

Study Details

A Finnish study indicating that certain relatives of women with early-onset breast cancer face increased risks of other early-onset cancers was published on April 19, 2023 in International Journal of Cancer .

The study examined breast cancers diagnosed in women aged 40 or younger between 1970 and 2012, together with their families. Using the Finnish Cancer Registry and Population Information System, researchers assessed 54,753 relatives of 5,562 women diagnosed with early-onset breast cancer. A cancer was considered familial if it occurred in a family with a previously diagnosed patient, and early-onset if diagnosed before age 41.

• The study found that only 5.5% of relatives had early-onset cancers other than breast cancer.
• Children of the patients had a 27% higher risk of other early-onset cancers, and patients' siblings had a 7.6-fold higher risk of early-onset pancreatic cancer.
• The children of patients' siblings also had significantly increased testicular and ovarian cancer risks.

The researchers noted that familial risk extended to different early-onset cancers, especially ovarian, testicular and pancreatic cancer, and beyond first-degree relatives. They also emphasized the need to investigate unresolved genetic and environmental mechanisms.

A potential limitation was the inability to identify individuals with hereditary cancer syndromes or concerning gene mutations, such as BRCA carriers. However, the authors considered the number of BRCA carriers likely to be low because few ovarian cancers occurred among first-degree relatives of diagnosed patients.

Overall, the findings suggest that familial risk is "mathematically and statistically a much more complex problem" than a single genetic factor. Shared environmental exposures that increase cancer risk among family members are one possibility.

What Did This Study Add?

Using a large prospective, population-based cohort, researchers estimated familial risks of other early-onset cancers among relatives of women with early-onset breast cancer. The findings show that risk extends beyond first-degree relatives and includes different early-onset cancers, such as ovarian, testicular and pancreatic cancer.

Conclusion

The study found increased risks of early-onset testicular, ovarian and pancreatic cancer among relatives of patients with early-onset breast cancer. Interactions between genetic and environmental factors may explain this increase. Children of affected women showed higher risks of other early-onset cancers. However, shared genetic and environmental influences may be responsible, and the study could not clearly separate their contributions.

Strengths included population-based registry data and the ability to link the cancer registry with the Population Information System, enabling reliable assessment of affected relatives. A cohort involving people diagnosed with cancer at a young age is particularly useful for evaluating familial clustering and its underlying causes.

A potential limitation, however, was the inability to identify accurately individuals with inherited cancer syndromes or predisposition mutations in these families. Comprehensive information about such mutations was unavailable. This may contribute to the higher risks of other cancers observed among children of women with early-onset breast cancer. Future research could clarify these factors and potentially support more effective screening and prevention strategies for patients and their families.