Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.

To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer-Lemeshow goodness of fit test. The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.

Vacuum-assisted breast biopsy (VABB) has been replacing excisional biopsy in the treatment of benign breast lesions. Complete surgical excision is still needed for the lesions occasionally diagnosed with breast cancer after VABB. We aimed to characterize residual tumors after VABB and define a subset of patients who do not need surgical excision after VABB. From a retrospective database, we identified patients diagnosed with breast cancer after VABB guided with ultrasonography. Patients who underwent stereotactic biopsies were excluded. We reviewed clinicopathologic data and radiologic findings of the sample. We identified 48 patients with 49 lesions. After surgical excision, the residual tumors were identified in 40 (81.6%) lesions, and there was no residual tumor in nine (18.3%) patients. Imaging studies could not accurately locate residual tumors after VABB. A small tumor size on a VABB specimen was associated with no residual tumor on final pathology. However, residual tumors were identified in four (40%) of 10 lesions with a pathologic tumor size less than 0.5 cm. In conclusion, complete surgical excision remains the primary option for most of the patients diagnosed with breast cancer after VABB. Imaging surveillance without surgery should be carefully applied for selected low-risk patients.

The relationship between cancer and venous thromboembolism (VTE) has long been described. The risk of VTE in Asian patients with breast cancer remains largely unknown. This study described the incidence and risk factors of VTE in Korean patients with breast cancer. Data were collected from a retrospective database of patients who underwent breast cancer surgery between 2011 and 2020 at a single institution. The Cox proportional-hazards model was used to identify factors associated with VTE occurrences. Among the 2246 patients with breast cancer, 48 (2.1%) developed VTE during a median follow-up period of 53 months. The average incidence of VTE was 459 per 100,000 person-years. Age ≥ 60 years, male sex, chronic kidney disease, reconstructive procedures, and stage II or higher were independent predictive factors for VTE. VTE was associated with poor disease-free survival (hazard ratio (HR), 6.140; 95% confidence interval (CI), 3.480–10.835), and overall survival (HR, 8.842; 95% CI 4.386–17.824). Most VTE events were manageable with anticoagulation; three (6.3%) patients died of VTE, despite intensive care. The incidence of VTE was significantly elevated in Korean patients with breast cancer. Since VTE has a negative effect on oncologic outcomes of breast cancer, clinicians should manage its risk throughout their lifetime.

Obesity is a risk factor for breast cancer and associated with increased estrogen levels that stimulate the progesterone receptor (PgR). Understanding interplay between obesity, PgR, and prognosis in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER+/HER2-) is crucial. This study aimed to investigate the association between body mass index (BMI) and the prognostic value of PgR. Study included 10,125 postmenopausal patients with ER+/HER2-breast cancer between January 1991 to December 2019. Patients were categorized according to BMI (cutoff: 25 kg/m²) and PgR (positive/negative). The primary outcomes were the 6-year overall survival (OS) in the Korean Breast Cancer Registry (KBCR) cohort and 6-year recurrence-free survival (RFS) in the multi-institutional cohort. In both cohorts, a greater proportion of patients with high BMI were PgR-positive, and the mean BMI was higher in the PgR-positive group. PgR-negativity was associated with worse 6-year OS in the KBCR cohort among patients with BMI ≥25 kg/m² (hazard ratio [HR], 1.45; 95 % confidence intervals [CI], 1.06-1.97; P = .02), but not in those with BMI <25 kg/m². Similarly, in the multi-institutional cohort, PgR-negativity was associated with worse 6-year RFS only in patients with BMI ≥25 kg/m² (HR, 2.93; 95 % CI, 1.29-6.69; P = .01). The mean 21-gene recurrence score was higher in the PgR-negative group, regardless of the BMI. In postmenopausal patients with ER+/HER2-breast cancer, the prognostic impact of PgR is modified by BMI. PgR-negativity is a strong predictor of poor outcomes in obese patients but not in non-obese patients.

Kim S, et al. J Korean Med Sci. 2023 Jun;38(30):e224. https://doi.org/10.3346/jkms.2023.38.e224