Breast cancer risk high from family history, without mutations: study

Women with a strong family history of breast cancer may still have an increased risk of developing the disease even if they test negative for two genetic mutations, Canadian researchers have found.

The BRCA1 and BRCA2 mutations are linked to aggressive hereditary breast cancers, but only account for about 15 per cent of all cases.

'A negative test result doesn't provide reassurance.' Genetic counselor Beth Peshkin

In clinical practice, it's often difficult to counsel families with a significant history of breast cancer who test negative for the mutations, said Dr. Steven Narod, who holds the Canada Research Chair in breast cancer at the University of Toronto and Women's College Research Institute

The researchers followed 1,492 Canadian women with an average age of 48 who did not have either mutation but showed a strong family history.

After five years, the subjects showed a 4.3-fold increase in breast cancer rates compared with the average rate based on breast cancer registries.

"I think we were surprised that it was that high," said Narod, who led the study and presented the findings on Monday at a meeting of the American Association of Cancer Research in Washington. "But certainly at that level of risk, one would think about preventive measures."

MRI screening, preventive drugs recommended

For these women, Narod suggested magnetic resonance imaging or MRI exams of the breast, which are considered a more sensitive screening test for tumours than mammograms. The drugs tamoxifen or raloxifene could also be taken as a preventive measure, he added.

Tamoxifen suppresses estrogen and is used to prevent breast cancer tumours. Raloxifene reduces the risk of hormone-positive breast cancer.

The researchers hope to be able to prevent or pick up on breast cancers early, and they will follow the women in the study to evaluate the best prevention methods.

'Contrary to common perception'

The findings are crucial information for women considering gene testing, said Beth Peshkin, a genetics counsellor at Georgetown University in Washington who wasn't involved in the study.

"This is contrary to what I think the common perception is," Peshkin said. "Unless a mutation is identified in the family, a negative test result doesn't provide reassurance."

The BRCA tests cost about $3,700 and tests for other genes linked to breast cancer are being developed.

For women in the study, the absolute risk was highest among those aged 50 to 70 at one per cent per year, compared with 0.4 per cent per year for 30- to 40-year-olds.

The findings translate into about 30 to 40 per cent risk over their lifetime, compared with the roughly 80 per cent lifetime risk for women with the BRCA1 or BRCA2 mutations,

Carrying the BRCA1 and BRCA2 mutations is also associated with an increased risk of ovarian cancer, but the women in this study did not show a greater likelihood for that disease, the researchers found.