Comprehensive Analysis of Breast Cancer in Very Young Women (<35 years), a Single Institution Experience.

BRCA1

Pathogenic germline variants twice as frequent before 36 years as at 36-40 years, with BRCA1 predominating

This single-centre retrospective study covers the 2,742 primary breast carcinomas diagnosed between 2014 and 2020 at an academic institution, including 271 (9.8%) in women aged 40 or younger and 128 (4.6%) in women aged 35 or younger. Compared with patients aged 36-40, very young patients had higher-grade tumours (53.4% vs 39.1%), lower oestrogen receptor positivity and more triple-negative (27.3% vs 16.0%) and Luminal B (38.8% vs 31.1%) subtypes, with an enrichment in metaplastic carcinomas (7.0% vs <1%). A pathogenic germline variant was found in 22.7% of very young patients versus 11.3% of those aged 36-40, with BRCA1 predominating. On multivariable analysis, age 35 or younger was an independent predictor of recurrence (HR 2.02; 95% CI 1.095-3.744; p=0.024), but not of disease-specific survival.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The 22.7% rate of germline variants in women aged 35 or younger supports systematic germline testing in this age group, but the abstract does not state how many patients were tested, making the denominator uncertain. The metaplastic carcinoma signal rests on a few cases, and the abstract does not link it to germline status. The age-related excess recurrence risk is more an oncological than a genetic finding, and this single-centre series provides no penetrance data.

Analysis by Dr Thibaut Benquey