title: Tumor-associated inflammation as a potential prognostic tool in BRCA1/2-associated breast cancer.
abstract: The prognosis of BRCA1/2-associated breast cancer partly depends on histologic characteristics. Most of these breast cancers, however, are poorly differentiated. BRCA1-associated cancers are mainly negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Consequently, the use of these histologic features for risk stratification in BRCA1/2 breast cancer is limited. We assessed the prognostic value of additional histologic features, including tumor-associated inflammation and tumor-associated stroma in BRCA1/2 breast cancer patients. From the Rotterdam Family Cancer Clinic database, we collected demographics, tumor characteristics, and follow-up data from female BRCA1/2 breast cancer patients. Tumor samples were centrally reviewed including histologic subtype, differentiation grade, tumor-associated inflammation density, amount of tumor-associated stroma, and intratumor necrosis. The impact of these factors on recurrence-free survival (RFS) was evaluated using univariate and multivariate Cox regression, adjusted for established prognostic features and year of diagnosis. We included 138 BRCA1 and 37 BRCA2 breast cancer patients. Median follow-up after diagnosis was 9.7 years. Independent prognostic factors for RFS were tumor size (hazard ratio [HR], 2.47 for >2 versus ≤2 cm; 95% confidence interval [95% CI], 1.10-5.57), tumor-associated inflammation (HR, 0.18 for moderate/marked versus absent/mild; 95% CI, 0.05-0.61), and intratumor necrosis (HR, 2.60 for presence versus absence; 95% CI, 1.12-6.05). Established prognostic factors as nodal status and differentiation grade were not significantly related to RFS. Subgroup analyses of 138 BRCA1 and 118 triple-negative breast cancer cases showed similar results. Tumor-associated inflammation density was the strongest predictor for RFS in this series of BRCA1/2 breast cancer patients. This provides a potential risk stratification tool that can easily be implemented in routine histologic examination.
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands. Electronic address: v.vanverschuer@erasmusmc.nl.
authors.forename: Victorien M T
authors.initials: VM
authors.lastname: van Verschuer
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands; Netherlands Forensic Institute, 2497 The Hague, GB, the Netherlands.
authors.forename: Radka D
authors.initials: RD
authors.lastname: van Baare-Georgieva
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Timmermans
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Linetta B
authors.initials: LB
authors.lastname: Koppert
authors.affiliation: PATHAN Pathology Laboratory, 3045 Rotterdam, PM, the Netherlands.
authors.forename: Leon C
authors.initials: LC
authors.lastname: Verhoog
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands; Cancer Genomics Center, 3584 Utrecht, CG, the Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, 3075 Rotterdam, EA, the Netherlands.
authors.forename: Carolien H M
authors.initials: CH
authors.lastname: van Deurzen
mesh_terms: D024682:BRCA2 Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012306:Risk; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases
keywords: BRCA1/2; Breast cancer; Prognostic features; Tumor-associated inflammation; Tumor-associated stroma