Dataset Information

Association of molecular subtype concordance and survival outcome in synchronous and metachronous bilateral breast cancer.

ABSTRACT:

Background

The aim of this study was to analyze the association of molecular subtype concordance and disease outcome in patients with synchronous bilateral breast cancer (SBBC) and metachronous breast cancer (MBBC).

Patients and methods

Patients diagnosed with SBBC or MBBC in the Surveillance, Epidemiology, and End Results (SEER) database or Comprehensive Breast Health Center (CBHC) Ruijin Hospital, Shanghai were retrospectively reviewed and included. Clinicopathologic features, molecular subtype status concordance, and prognosis were compared in patients with SBBC and MBBC. Other prognostic factors for breast cancer-specific survival (BCSS) and overall survival (OS) were also identified for bilateral breast cancer patients.

Results

Totally, 3395 and 115 patients were included from the SEER and Ruijin CBHC cohorts. Molecular subtype concordance rate was higher in the SBBC group compared to MBBC in both SEER cohort (75.8% vs 57.7%, p < 0.001) and Ruijin CBHC cohort (76.2% vs 45.2%, p = 0.002). Survival analyses indicated that SBBC was related to worse BCSS than MBBC (p = 0.015). Molecular subtype discordance was related to worse BCSS (hazard ratio (HR), 1.64, 95% confidential interval (CI), 1.18-2.27, p = 0.003) and OS (HR, 1.59, 95% CI, 1.24-2.04, p < 0.001) in the SBBC group, but not for the MBBC group (p = 0.650 for BCSS, p = 0.669 for OS).

Conclusions

Molecular subtype concordance rate was higher in the SBBC group than MBBC group. Patients with discordant molecular subtype was associated with worse disease outcome in the SBBC patients, but not in MBBC, which deserves further clinical evaluation.

SUBMITTER: Ding S

PROVIDER: S-EPMC8027898 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC. Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses. Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126-0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses. Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC.

Project description:BackgroundAt the molecular level breast cancer comprises a heterogeneous set of subtypes associated with clear differences in gene expression and clinical outcomes. Single sample predictors (SSPs) are built via a two-stage approach consisting of clustering and subtype predictor construction based on the cluster labels of individual cases. SSPs have been criticized because their subtype assignments for the same samples were only moderately concordant (Cohen's κ<0.6).MethodsWe propose a semi-supervised approach where for five datasets, consensus sets were constructed consisting of those samples that were concordantly subtyped by a number of different predictors. Next, nine subtype predictors - three SSPs, three subtype classification models (SCMs) and three novel rule-based predictors based on the St. Gallen surrogate intrinsic subtype definitions (STGs) - were constructed on the five consensus sets and their associated consensus subtype labels. The predictors were validated on a compendium of over 4,000 uniformly preprocessed Affymetrix microarrays. Concordance between subtype predictors was assessed using Cohen's kappa statistic.ResultsIn this standardized setup, subtype predictors of the same type (either SCM, SSP, or STG) but with a different gene list and/or consensus training set were associated with almost perfect levels of agreement (median κ>0.8). Interestingly, for a given predictor type a change in consensus set led to higher concordance than a change to another gene list. The more challenging scenario where the predictor type, gene list and training set were all different resulted in predictors with only substantial levels of concordance (median κ=0.74) on independent validation data.ConclusionsOur results demonstrate that for a given subtype predictor type stringent standardization of the preprocessing stage, combined with carefully devised consensus training sets, leads to predictors that show almost perfect levels of concordance. However, predictors of a different type are only substantially concordant, despite reaching almost perfect levels of concordance on training data.