We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2-, luminal B and HR+/HER2+, HR-/HER2+ and HER2-enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS. In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation-related discordant breast cancer including the VHL gene in the HR+/HER2- group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01). A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.

Min SK, et al. J Breast Cancer. 2020 Sep;24:e4. https://doi.org/10.4048/jbc.2021.24.e4

Ryu JM, et al. J Breast Cancer. 2023 Apr;26:e17. https://doi.org/10.4048/jbc.2023.26.e17

The association between serum lipid level and prognosis of breast cancer is controversial. The purpose of this study was to evaluate the impact of serum lipid level in breast cancer recurrence. We analyzed a total of 4190 patients with operable breast cancer who had baseline serum lipid profiles; total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A-1, and apolipoprotein B. Recurrence-free survival is defined as the elapsed time from the date of curative surgery to the detection of any recurrence, and recurrence includes locoregional recurrence, distant metastasis, or both local and distant metastasis. Cox-proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals (CI) for study outcomes comparing the three lowest quartiles of each lipid parameter to the highest quartile adjusting for age, body mass index (BMI), and pathologic stage, estrogen receptor (ER), progesterone receptor (PR), comorbidities (hypertension, diabetes, or vascular event) at time of breast cancer diagnosis. Patients with dyslipidemia (high bad cholesterol and low good cholesterol level) had worse prognostic factors (i.e., negative hormone receptor status, positive human epidermal growth factor receptor 2 (HER2) expression, higher nuclear grade). After adjusting for these poor prognostic factors, the patients with dyslipidemia showed good prognosis for breast cancer recurrence. Our study showed that baseline high lipid level could be a good prognostic factor of breast cancer. This study indicates that desirable changes in lipid profile for cardiovascular disease risk are not always beneficial for patients with breast cancer. However, as proper control of lipid level has advantages for cardiovascular disease, these findings require careful interpretation.

Background: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified. Methods: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis. Results: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476–3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147–3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882–2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875–2.718, p = 0.1340) after PSM. Conclusion: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.

Purpose Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant.Materials and Methods This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants (PVs/LPVs) were reviewed.ResultsA younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected.ConclusionWe suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.