Metastasis Risk Assessment Using BAG2 Expression by Cancer-Associated Fibroblast and Tumor Cells in Patients with Breast Cancer.

Few studies have examined the role of BAG2 in malignancies. We investigated the prognostic value of BAG2-expression in cancer-associated fibroblasts (CAFs) and tumor cells in predicting metastasis-free survival in patients with breast cancer. Tissue-microarray was constructed using human breast cancer tissues obtained by surgical resection between 1992 and 2015. BAG2 expression was evaluated by immunohistochemistry in CAFs or the tumor cells. BAG2 expression in the CAFs and cytoplasm of tumor cells was classified as positive and negative, and low and high, respectively. BAG2-CAF was evaluated in 310 patients and was positive in 67 (21.6%) patients. Kaplan-Meier plots showed that distant metastasis-free survival (DMFS) was lesser in patients with BAG2(+) CAF than in patients with BAG2(-) CAF (p = 0.039). Additionally, we classified the 310 patients into two groups: 109 in either BAG2-high or BAG2(+) CAF and 201 in BAG2-low and BAG2(-) CAF. DMFS was significantly reduced in patients with either BAG2-high or BAG2(+) CAF than in the patients of the other group (p = 0.005). Multivariable analysis demonstrated that DMFS was prolonged in patients with BAG2(-) CAF or BAG2-low. Evaluation of BAG2 expression on both CAFs and tumor cells could help in determining the risk of metastasis in breast cancer.

Local Treatment in Addition to Endocrine Therapy in Hormone Receptor-Positive and HER2-Negative Oligometastatic Breast Cancer Patients: A Retrospective Multicenter Analysis.

BACKGROUND: Recent trials have provided robust evidence demonstrating that endocrine therapy with/without targeted therapy, such as cyclin-dependent kinase 4/6 inhibitors or mTOR (mammalian target of rapamycin) inhibitors, effectively halts disease progression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We investigated the survival impact of local treatment of metastases as a first-line treatment after metastasis in HR-positive and HER2-negative breast cancer patients with a very low metastatic volume. MATERIALS AND METHODS: From a retrospectively constructed database for three institutes, we identified HR-positive and HER2-negative breast cancer patients with recurrent distant oligometastatic disease after initially curative treatment. De novo stage 4 patients were excluded, and only those with recurrent metastatic disease were included. Oligometastatic disease was defined as follows: (1) ≤2 metastatic lesions in a single organ, (2) a maximal diameter ≤3 cm, and (3) organ involvement, including the lung, liver, adrenal gland, bone, or distant lymph nodes. Local treatment comprised surgery or radiotherapy. Progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-nine patients were included; 33 underwent local treatment. Of these 33 patients, 5 underwent surgical resection and 27 received radiotherapy. One patient underwent both surgical resection and radiotherapy. Median PFS was significantly longer among the patients with local treatment than among the patients without local treatment (30.0 vs. 18.0 months, p = 0.049). In multivariate analysis, local treatment was shown to prolong PFS. However, median OS after metastasis did not differ with regard to local treatment (72.3 vs. 91.0 months, p = 0.272). CONCLUSION: We showed that local treatment could positively affect disease progression in HR-positive and HER2-negative oligometastatic breast cancer.

Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy.

We aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398-0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691-3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167-3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.

Comparison of complications according to incision types in nipple-sparing mastectomy and immediate reconstruction.

BACKGROUND: Nipple-sparing mastectomy (NSM), followed by immediate reconstruction (IR) of the breast, has become a preferred surgical procedure with good cosmesis results and patient satisfaction. However, nipple-areolar complex (NAC) ischemia and necrosis remain major problems after NSM and IR. METHODS: We retrospectively analyzed patients who underwent NSM and IR at Gangnam Severance Hospital from January 2009 to June 2018. We compared the patient characteristics and complication rate among three different incisions (inframammary fold [IMF], radial, periareolar). Additionally, we identified the risk factors of NAC necrosis. RESULTS: Data from 290 eligible breasts in 275 patients were analyzed. Patients with IMF incision had relatively lower breast weights. The overall complication rate was the highest with periareolar incision and the lowest with IMF incision (42.6% vs. 18.8%, p < 0.001). The rate of NAC ischemia or necrosis was significantly different among the three incisions (9.7%, 17.0%, and 31.1% in IMF, radial, and periareolar, respectively; p < 0.001). Moreover, surgical treatments were more frequently needed in patients with periareolar incision. Periareolar incision, short distance from the tumor to the nipple base, and large breast weight were independent risk factors of NAC ischemia or necrosis in multivariable analysis. CONCLUSIONS: Compared with IMF incision, periareolar incision was associated with higher incidences of surgical complications and NAC necrosis. Careful consideration is needed when planning NSM in patients with a large breast volume or a tumor close to the nipple.

Comparison of patients with small (≤2 cm) breast cancer according to adherence to breast screening program.

BACKGROUND: We investigated whether adherence to breast screening would yield a clinical benefit even among patients with small breast cancer (≤2 cm) by comparing differences between those who did and did not adhere to breast screening. METHODS: Patients who were diagnosed with invasive T1 breast cancer and treated at Gangnam Severance Hospital from January 2006 to June 2014 were included. Of the 632 study patients, 450 and 182 were classified as screen-adherent and non-adherent. Adherence to the breast screening program was defined as the completion of breast screening examinations within 3 years before cancer diagnosis. Recurrence-free survival (RFS) and metastasis-free survival (MFS) were compared between the groups. Propensity score matching were applied to compare survival outcome. RESULTS: Adherent patients were more likely to have a lower histologic grade (P < 0.001), high estrogen receptor expression (P = 0.040), and lower HER2-positivity (P = 0.026). The adherent group had more favorable subtypes compared to the non-adherent group, with a greater percentage of Luminal/HER2-negative subtype (66.7% vs. 56.5%) and a lower percentage of HER2 subtype (8.3% vs. 16.7%). The RFS and MFS were significantly better in the adherent group (P = 0.003, 0.010, respectively). In the case-matched cohort, superior survival of the adherent group was maintained. CONCLUSIONS: Adherence to breast screening in patients with small breast tumors was associated with more favorable tumor biology and better prognosis. Our findings suggest that adherence to breast screening might offer clinical benefits in terms of tumor biology as well as early detection.

Chemosensitivity to doxorubicin of ER-positive/HER2-negative breast cancers with high 21-gene recurrence score: A study based on in vitro chemoresponse assay.

AIM: The 21-gene recurrence score (RS) predicts a clinical benefit of chemotherapy for individuals with ER-positive/HER2-negative breast cancer. Using in vitro chemoresponse assay, we compared the chemosensitivity according to RS in these patients. METHOD: Among the patients with Oncotype Dx assay, we identified 63 patients who had chemotherapy response assays to doxorubicin based on adenosine triphosphate. The degree of chemosensitivity to doxorubicin was translated into the cell death rate (CDR). The RS was also dichotomized with a cutoff of 26. RESULTS: Of 63 patients, 34 (54%), 17 (27%), and 12 patients (19%) had a low, intermediate, and high RS, respectively. The mean CDR differed significantly according to categorized RS, with 17.3±10.8 in the low RS group vs. 23.6±16.3 in the intermediate RS group vs. 28.8±12.6 in the high RS group (P = 0.024, One-way ANOVA test). The mean CDR was significantly higher in the higher RS (26≥) group compared with the lower RS (<26) group (P = 0.025, the Student's t-test), as well as in the high RS (>30) group compared with the low RS (<18) group (P = 0.012, the Student's t-test). Also, continuous RS and CDR correlated positively (Pearson's R = 0.337; P = 0.007). High RS demonstrated the odds ratio (OR = 26.33; 95% CI = 1.69-410.0) for predicting tumors with chemosensitivity on the multivariate analysis. CONCLUSIONS: The chemosensitivity measured by in vitro chemoresponse assay was different according to the RS. Our findings support that tumors with high RS has the chemosensitivity even though they are luminal/HER2-negative tumors.