Family History of Breast Cancer Matters — Even When Genetic Test Results Are Negative

By Eleanor Griffith, MS, CGC · Apr 2018

A study published in the American Journal of Clinical Oncology underscored the significance of family history of breast cancer for guiding surgical management — even when genetic test results are negative.

Positive genetic testing results indicating a pathogenic variant should prompt a different conversation about chances of a second primary breast cancer or other cancers. But what about when results are negative? Even with a striking family history and even when a large gene panel is ordered, genetic testing results are negative more often than not. Then what?

What the WECARE Study Found

The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study examined women diagnosed with invasive breast cancer under age 55. Women who had both a breast cancer diagnosis and a first-degree relative with breast cancer had an 8% risk of developing cancer in the opposite breast. If the relative was diagnosed under age 40, that risk rose to 13.5%. Crucially, for a subset tested for mutations in BRCA1/2, PALB2, CHEK2, and ATM, risk estimates were unchanged even for those with negative genetic test results.

The authors concluded: family history of breast cancer confers meaningful contralateral cancer risk even after excluding women with known mutations. Clinicians should use detailed family histories to guide treatment and screening decisions — not just to qualify patients for genetic testing.