Patrick (MSII) presents on the Management of BRCA positive patients.
Case: 30 yo AAF with a mass in the UIQ of the R breast. Maternal aunt with Breast CA at 44, also paternal grandmother with breast cancer and ovarian cancer at 86.
Biopsy: Poorly differentiated 1.3cm cancer. Triple negative. Lumpectomy and SLNB negative. (T1N0M0 triple negative). BRCA1 positive.
BRCA1: 17q21 activated by DNA damage. Interacts with CHK1 and CHK2
BRCA2: 13q12 regulates cell cycle, promotes S/G2 arrest
BRCA mutations in 1%
Enriched in the Ashkenazi Jewish population (Icelandic, Swedish, Hungarian populations as well).
Criteria for testing: Early breast cancer <=50. Two primaries in a single individual or close relative. Breast and ovarian primaries. Family member with male breast cancer.
Testing costs 300-3000$ depending on the extent of the test.
Breast Cancer 65-85% 45-85%
Ovarian Cancer 37-62% 11-23%
high grade low grade
triple negative er/pr + her2-
Early Screening. Self Breast exams at 18, clinical exams at 25. Mammograms and MRI testing at 25 or 10 years before the youngest age a relative was diagnosed with breast cancer.
Breast MRI Kriege NEJM 351:427. 1909 high risk patients (358 BRCA carriers), MRI sensitivity 80%, spec 90%, Mammo sens 33%, spec 95%.
Warner JAMA. 236 carriers. MRI sens 77%, spec 95.4%. Also looked at mammo, U/S, and CBE.
Meijers NEJM 2001;345:159. 139 carriers, 76 underwent prophylactic mastectomy, the rest choosing surveillance. With f/u of 3 years. 0/76 cancers in the mastectomy group. 8/63 in the the surveillance group, p=0.003. 5yr incidence in the surveillance group was 17%.
PROSE JCO 2004 22:1055. 90% reduction in breast cancer in carriers. In patients who also had a BSO, there was a 95% reduction.
Kauff: Prospective prophylactic bilateral salpingo-oophorectomy (BSO), HR of 0.25 for the development of ovarian or breast cancers.
Eisen: JCO 23:7491 - BSO conferred a 46-56% reduction in breast cancers. Benefit was greater if performed before 40 years of age.
Domcheck Lancet Onc 7:233. 426 with some getting BSO, some observation (prospective cohort). Overall Survival HR was 0.24 (SS) with BSO.
Pierce 160 BRCA carriers undergoing BCT. Incidence of contralateral cancers was in carriers 39%, vs 7% controls, p<0.001 at 15years. Pierce also reports in the JCO 2000, that there was no clear survival detriment to breast consevation (BCT) in carriers (though follow up was only 5 years).
Case resolution: Pt consuled about prophylactic mastectomy, BCT, prophylactic BSO, and TC chemotherapy. Pt elected to pursue BCT with close followup, with BSO after child bearing in complete (preferably before age 40).