Introduction

Epidemiological studies show that women with breast cancer have a slightly increased risk of primary ovarian cancer, which is highest among women below 50 at the time of their original diagnosis of breast cancer. The risk is much greater in breast-cancer patients with mutations in their BRCA1 or BRCA2 genes - reaching 50% cumulative risk by age 70.

Screening for genetic mutations is impracticable and expensive. An easier approach in a clinical setting would be using information from the patient's family history, if this were a reliable predictor. Scientists from the Karolinska Institute, Sweden, have now reported the results of a study they did to test this.

Methods

The Swedish Cancer Register and the Swedish Generation Register are comprehensive databases that have an extremely high level of completeness. Data from these two registries were linked in order to generate a cohort of 30,552 breast-cancer patients born after 1931 for whom there were data on breast and ovarian cancer, as well as family histories, in first-degree female relatives. A total of 146,162 first-degree relatives with this information were identified.

Standardized Incidence Ratios (SIRs) for ovarian cancers were calculated for three different age groups and various family histories (observed numbers divided by expected numbers obtained from the Cancer Register).

Results

The mean age at diagnosis of breast cancer was 48 years. There were 122 cases of ovarian cancer during the follow-up period in these 30,552 women. Among the first-degree relatives, 3,689 cases of breast or ovarian cancer occurred. These figure yielded a SIR of 2.0 (95% CI, 1.6-2.4).

The SIRs for ovarian cancer for different groups are given in the table below:

	< 40 years	40 - 49 years	> 49 years	All ages
Overall	3.8	1.9	1.4*	2.0
No family history	3.3	1.6	1.1*	1.6
Any family history	7.3	3.6	3.9	4.3
History of breast cancer	5.6	2.7	3.2	3.3
History of ovarian cancer	17.0	8.7	6.1*	9.4
Relative <50 at diagnosis	14.7	3.6*	7.6	7.1

* all SIRs statistically significant except for those with *

Breast cancer patients without a family history of either tumor had a 60% increased risk of developing ovarian cancer, and if they were below 40 the risk was three-fold (3.3).

For patients diagnosed with breast cancer before 40, a family history of breast cancer yielded a SIR of ovarian cancer of 5.6, and with a family history of ovarian cancer, an SIR of 17.0. In breast-cancer patients over 40 at diagnosis the risks of ovarian cancer were smaller, but still raised.

A further analysis was done to estimate the absolute risk of developing ovarian cancer within 30 years of breast-cancer diagnosis. This analysis showed no obvious effect of age at diagnosis, or for the length of follow-up. The risk of developing ovarian cancer within 30 years was about 10% in women with a family history of ovarian cancer, and about 3% if they had a family history of breast cancer.

Conclusions

The findings of this study confirm that women with breast cancer, in particular those diagnosed at a young age and with a history of breast or ovarian cancer in first-degree relatives, are at an increased risk of ovarian cancer.

A significant value of the study lies in its demonstration of a practical alternative approach to gene mutation testing; the latter is not readily available in all areas, and can be an expensive procedure.

Mutations in BRCA1 or BRCA2 genes are only present in <5% of breast-cancer patients, whereas hereditary associations (as shown in this study) suggest that there may be other, as yet unknown, genes responsible for cancer susceptibility. It can therefore be argued that the tumor history of first-degree relatives gives a better picture of breast and ovarian cancer risk than genetic testing. At all events, a careful family history can provide the necessary information to justify appropriate screening, counseling, and perhaps even prophylactic oophorectomy in women at increased risk.