Women with high mammographic breast density have at least four times the risk of breast cancer compared to those with less dense breasts (which have a higher percentage of fat). In fact, high breast density is one of the most powerful risk factors for breast cancer. Women with a family history of breast cancer tend to have dense breasts, suggesting that breast density is a heritable risk factor. One 2011 study reported that breast density was higher in women with at least one first-degree relative (parent, sibling or child) with breast cancer, but only among the breast cancer patients and not among the healthy women. However, a new study has reported that family history outweighs breast density as a risk factor. In fact, in women with a first-degree female relative with breast cancer, the existence of one or more second-degree relatives (grandmother, granddaughter, aunt, niece, or half-sister) with breast cancer heightens risk further.

Breast cancer risk has heritable and family components

As noted above, evidence of a genetic contribution to breast cancer risk incudes the fact that women with a family history of breast cancer are more likely to have dense breasts than the general population. They are also more likely to be diagnosed with triple negative (ER-/PR-/HER2-) disease and other aggressive breast cancer types. Levels of circulating sex hormones, which can contribute to breast cancer risk, are partially heritable. In addition, the likelihood of breast cancer-specific survival runs in families, even after accounting for other prognostic factors.

One 2015 Scandinavian study was designed to investigate the contribution of genetic factors compared to shared lifestyle and environmental factors to familial breast cancer risk in twins. The study included 21,054 identical and 30,939 fraternal female twin pairs. The BRCA mutation status of study participants was unknown. However, based on previous research, a minority of Scandinavian breast cancer patients are BRCA mutation carriers.

The cumulative lifetime risk of breast cancer was 8.1% for both identical and fraternal twins. However, the cumulative risk for women whose co-twins had breast cancer was 28% for identical and 20% for fraternal twins. The authors estimated that the (heritable) genetic factors accounted for 31% of breast cancer risk, whereas shared lifestyle/environmental factors accounted for 16%. According to this study, family-specific factors explain almost half of the variation in breast cancer risk.

Latest research finds 2nd-degree relatives linked to increased risk

The study referenced at the beginning of this news story was designed to investigate the associations between family history and breast cancer risk while also assessing the contribution of breast density. The usefulness of taking detailed family history into account when forecasting breast cancer risk depends on whether it contributes independently to this risk. To conduct the study, the authors used data from 222,019 participants (ages 35 to 74) in the Breast Cancer Surveillance Consortium. A total of 2,456 of these women developed invasive breast cancer. Breast cancer risk was estimated taking account both family history (in female first-degree and second-degree relatives) and breast density.

Women with a first-degree relative with breast cancer were found to have 1.5 times the breast cancer risk as those with no first-degree history at age 40 and also at age 50, 1.4 times at age 60, and 1.3 times at age 70. When breast cancer in second-degree relatives was also taken into account, women having both first- and second-degree relatives with breast cancer were found to have 1.9 times the risk as those without a family history. The association was weaker in older women (1.2 times by age 70). These associations did not change substantially when adjusted for breast density. In other words, while breast density tends to be higher among women with familial breast cancer, it does not meaningfully explain the link between family history and breast cancer risk. The authors conclude that a history of breast cancer in both first- and second-degree relatives is more strongly associated with risk of breast cancer than a simple first-degree family history even after adjusting for breast density. Breast cancer risk prediction models should take detailed family history into account.

Please see our article on family history for more information.