Breast & Ovarian Cancer

^^ increasing age^^ OCP use (though not long term)^^ Affected relatives (shared variants and environment)^^ Early menarche and late menopause^^ HRT usevv Early first pregnancy

Claus & Gail model: Take into account breast risk factors (gail) and family history (claus) Significantly underestimate risk in families w cancer syndromes Tyrer-Cuzick Incorporates personal risk factors Can estimate the likelihood an individual carriers a BRCA1/2 gene BOADICEA Incorporates family history into the model Takes into BRCA and non-BRCA genetic risk factors Manchester scoring system - likelihood indv has BRCA1/2

Single greatest ovarian risk factor is FHReproductive, demographic and lifestyle factors also affect risk^^ Age^^ Nulliparity - never giving birth (for BRCA1/2 carriers)^^ Use of fertility drugs w/o getting pregnantvv tubal ligation & hysterectomy vv long-term OCP use

Screening offered to those whose risk is >1/6 (moderate risk) - annual mammographic screening from 401/3 is considered high risk - annual mammographic screening from 30low risk - TP53 carriers - screening from age 20Screening: MRI mammography Chemoprevention Tamoxifen Raloxifen Predictive genetic testingRisk reducing surgery: Bilateral mastectomy  Bilateral salpingo-oophorectomy 

BRCA1Lifetime risk: breast cancer 80% Risk diminution with age (if unaffected at 60 risk of being carrier goes from 50% to 25%) ovarian cancer up to 60% typically triple negative cancer and high grade (poorly differentiated) BRCA2Lifetime risk:  breast cancer 60-80% No risk diminution ovarian cancer 20-30% Male breast cancer 10% Prostate cancer 14%  Biallelic form can present as fanconi anaemia (congenital abnormalities, bone marrow failure, high risk of cancer) Both BRCA1/2 carried by approx 1% of the Ashkenazi jewish pop - BUT lower cancer risks associated with these mutationsTP53 - Li Fraumeni Syndrome Bone and soft tissue sarcomas Adrenocortical carcinoma breast cancer brain tumour multiple malignancies 100% lifetime penetrance in women, 73% in men

Breast risk factors

risk models

Ovarian risk factors

BRCA1/brca2/tp53

screening/surgery