title: Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy.
abstract: Risk-reducing salpingo-oophorectomy (RRSO) is associated with 50% reduction of BRCA1/2-associated breast cancer (BC) risk, possibly through decreased growth activity. In this pilot study, tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO were compared with those of PBCs originating without RRSO. From a cohort of 271 women with BRCA1/2-associated screen detected BC, we selected 20 patients with PBC detected ≥12 months after RRSO (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at diagnosis (± 2.5 y) and for BRCA1 or BRCA2 mutation. Pathology samples were revised for histological subtype, tumor differentiation grade, mitotic activity index (MAI), estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated from revised magnetic resonance and mammographic images. Median age at PBC diagnosis was 52 y (range 35-67). PBCs after RRSO had lower MAIs (12 vs. 22 mitotic counts/2 mm, P = 0.02), were smaller (11 vs. 17 mm, P = 0.01), and tend to be PR-positive more often than PBCs without RRSO (38% vs. 13%, P = 0.07). Differentiation grade, ER, and HER2 status were not different. Median DT was 124 d (range 89-193) in the RRSO group and 93 days (range 54-253) in the non-RRSO group (P = 0.47). BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological phenotype. When confirmed in larger series, this may have consequences for BC screening protocols after RRSO.
authors.affiliation: Department of Surgical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Victorien Mt
authors.initials: VM
authors.lastname: van Verschuer
authors.affiliation: Department of Medical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Bernadette Am
authors.initials: BA
authors.lastname: Heemskerk-Gerritsen
authors.affiliation: Department of Pathology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Carolien Hm
authors.initials: CH
authors.lastname: van Deurzen
authors.affiliation: Department of Radiology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Inge-Marie
authors.initials: IM
authors.lastname: Obdeijn
authors.affiliation: Department of Surgical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Madeleine Ma
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.affiliation: Department of Surgical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Epidemiology; Antoni van Leeuwenhoek Hospital; Netherlands Cancer Institute; Amsterdam, the Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.affiliation: Department of Surgical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Linetta B
authors.initials: LB
authors.lastname: Koppert
authors.affiliation: Department of Medical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.affiliation: Department of Medical Oncology; Erasmus MC Cancer Institute; Rotterdam, the Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery; D002277:Carcinoma / Q000235:genetics* / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D008938:Mitosis; D010052:Ovariectomy; D010865:Pilot Projects
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1/2; breast cancer; estrogen; mitotic activity; risk-reducing salpingo-oophorectomy; tumor characteristics; tumor growth