When people think of inherited breast cancer risk, they think of BRCA. Yet a large part of a high-risk clinic’s caseload has nothing to do with BRCA1 or BRCA2.

The main routes

• High-risk genes: BRCA1, BRCA2, PALB2 and TP53 (Li-Fraumeni syndrome).

• Moderate-risk genes: CHEK2 and ATM, where family history weighs heavily on the plan.

• Family history without a variant: risk estimated with models such as CanRisk.

• Chest radiotherapy before 30, often for Hodgkin lymphoma.

• Biopsy findings such as atypical hyperplasia or LCIS.

Each route changes when screening starts, which tests are used, whether risk-reducing medicine or surgery is discussed, and whether relatives should be told. For TP53, for example, mammograms are usually avoided; for CHEK2, surgery is rarely advised.

That is why a single fixed BRCA pathway is not enough. A coordination tool has to carry one protocol per route, set by the centre’s clinicians, and apply the right one to each woman.

Figures and starting ages vary between guidelines and countries. The protocols in HYPHAE are always the centre’s own.