Clinical characteristics and prognosis of postpartum breast cancer.

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.

Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type.

BACKGROUND: Breast cancer is a heterogeneous disease with various histopathologic subtypes. Except for invasive carcinoma of no special type (NST), other subtypes are rare with limited data. The purpose of this study was to analyze the characteristics and prognosis of special histopathologic subtypes of breast cancer compared to NST. METHODS: A total of 136,140 patients were analyzed using the Korean Breast Cancer Society Registry database between January 1996 and March 2019. The clinicopathologic features and survival outcomes of special type breast carcinoma were compared with those of NST. RESULTS: The prevalence of special subtypes other than NST was 13.7% (n = 18,633). Compared to NST, patients with lobular, medullary, metaplastic, and micropapillary carcinoma had larger tumors (p < 0.001). Patients with mucinous, tubular, medullary, metaplastic, and cribriform carcinoma presented with less node metastasis (p < 0.001), contrary to patients with micropapillary carcinoma. Patients with lobular, mucinous, tubular, papillary, and cribriform carcinoma presented as luminal A subtype much more often (p < 0.001). Micropapillary carcinoma included more luminal B subtype (p < 0.001). Typically, medullary and metaplastic carcinoma included more triple-negative subtypes (p < 0.001). In survival analysis, only medullary (Hazard Ratio (HzR) 0.542, 95% CI 0.345 to 0.852, p = 0.008) and metaplastic carcinoma (HzR 1.655, 95% CI 1.317 to 2.080, p < 0.001) showed significantly different overall survival from NST by multivariate analysis. CONCLUSION: Breast cancer had distinct clinicopathologic features according to histopathologic subtype. However, special types of breast cancer had similar survival outcomes compared to NST when adjusting for other prognostic factors, except for metaplastic carcinoma and medullary carcinoma.

EGFR is a Therapeutic Target in Hormone Receptor-Positive Breast Cancer.

BACKGROUND/AIMS: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. METHODS: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. RESULTS: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. CONCLUSION: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.

The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry.

PURPOSE: Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial. METHODS: We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015. RESULTS: The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01-4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23-7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS. CONCLUSION: Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

Clinical subtypes and prognosis in breast cancer according to parity: a nationwide study in Korean Breast Cancer Society.

PURPOSE: We explored the association between parity and the risk of developing a specific subtype of breast cancer. We also assessed the association between parity and prognosis according to subtypes. METHODS: A total of 158,189 patients were enrolled in the Korean Breast Cancer Society Registry database between 1996 and 2015 in Korea. The database provided information on sex, age, number of parity, surgical method, stage, histological findings, presence of biologic markers, adjuvant therapy, and date and cause of death. RESULTS: The patients with higher parity showed a higher ratio of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) subtypes. In univariate analysis, women with TNBC who had more than three children had a worse prognosis compared to other groups (HR 1.83; 95% CI 1.34-2.49; P < 0.001). This association was also observed in women younger than 50 years (HR 1.63; 95% CI 1.07-2.48; P = 0.021). In multivariate analysis stratified by subtypes, women who had more than three children were associated with a worse prognosis in TNBC in the total population (HR 1.53; 95% CI 1.11-2.12; P = 0.011). This association was also observed in patients younger than 50 years of age (HR 1.53; 95% CI 1.09-2.61; P = 0.017). CONCLUSION: Women who had more than three children were more likely to develop hormone receptor-negative (HR-) subtypes. Women who had more than three children were associated with worse prognosis in patients younger than 50 years of age and in patients with TNBC.

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database.

PURPOSE: We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC. METHODS: A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. 'PABC' is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as 'non-PABC' patients. RESULTS: In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1-2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7-29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1-3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6-12.3). CONCLUSION: PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer.

PURPOSE: TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC. METHODS: A total of 11,393 TNBC patients who had between stage I and stage III enrolled in the Korean Breast Cancer Society Registry database from January 1, 2000 to December 31, 2015. There were 6,331 'p53-positive (+) TNBC' patients and 5062 'p53-negative (-) TNBC' patients. RESULTS: In univariate analysis, p53(+) TNBC had a worse prognosis than p53(-) TNBC in patients not receiving chemotherapy (P = 0.003). However, there was no difference in prognosis between p53(+) TNBC and p53(-) TNBC for patients receiving chemotherapy. In multivariate analysis adjusted for age and stage, the risk of p53(+) TNBC was 1.84 times higher than that of p53(-) TNBC in the non-chemotherapy group. However, there was no difference between p53(+) TNBC and p53(-) TNBC in patients receiving chemotherapy. In p53(+) TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. However, in p53(-) TNBC, there was no risk reduction effect by chemotherapy. CONCLUSION: The prognosis of p53(+) TNBC has worse than p53(-) TNBC, but the risk for survival was significantly reduced with chemotherapy. It suggests that p53(+) TNBC would be more sensitive to chemotherapy than p53(-) TNBC.

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. METHODS: A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). RESULTS: PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2-12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1-11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2-87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. CONCLUSION: In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC.

Genetic Diagnosis before Surgery has an Impact on Surgical Decision in BRCA Mutation Carriers with Breast Cancer.

BACKGROUND: The first aim of our study was to evaluate surgical decision-making by BRCA mutation carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. The second aim was to evaluate breast cancer outcome following surgical treatment. METHODS: This was a retrospective study of 164 patients diagnosed with invasive breast cancer, tested for BRCA mutation, and treated with primary surgery between 2004 and 2015 at Samsung Medical Center in Seoul, Korea. We reviewed types of surgery and timing of the BRCA test result. We compared surgical decision- making of BRCA carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. RESULTS: Only 15 (9.1%) patients knew their BRCA test results before their surgery, and 149 (90.9%) knew the results after surgery. In patients with unilateral cancer, there was a significant difference between groups whose BRCA mutation status known before surgery and groups whose BRCA status unknown before surgery regarding the choice of surgery (p = 0.017). No significant difference was observed across surgery types of risk of ipsilateral breast tumor recurrence (p = 0.765) and contralateral breast cancer (p = 0.69). CONCLUSION: Genetic diagnosis before surgery has an impact on surgical decision choosing unilateral mastectomy or bilateral mastectomy in BRCA mutation carriers with breast cancer. Knowledge about BRCA mutation status after initial surgery led to additional surgeries for patients with BCS. Thus, providing genetic counseling and genetic testing before surgical choice and developing treatment strategies for patients with a high risk of breast cancer are important.

Breast cancer-specific mortality in small-sized tumor with node-positive breast cancer: a nation-wide study in Korean breast cancer society.

Tumor size and number of lymph node (LN) metastases are well known as the most important prognostic factors of breast cancer. We hypothesized that very small breast cancers with LN metastasis represent a progressive biologic behavior and evaluated tumor size stratified by LN metastasis. Data between 1990 and 2010 were obtained retrospectively from the Korean Breast Cancer Society Registry with inclusion criteria of female, non-metastatic, unilateral, and T1/2 breast cancer. We collected the following variables: age at surgery, tumor size, number of LN metastases, nuclear grade (NG), lymphovascular invasion (LVI), estrogen receptor status, progesterone receptor status, and epidermal growth factor receptor-2 status. Patient characteristics were compared by means of independent t-tests for continuous variables and the Chi-square or Fisher's exact test for categorical variables. Kaplan-Meier curves, with corresponding results of log-rank tests, were constructed for breast cancer-specific survival (BCSS). Five- and eight-year breast cancer-specific mortality (BCSM) was obtained in groups of 300 patients, followed by smoothing according to the confidence interval using the lowess method. We identified 39,826 breast cancer patients who met the inclusion criteria. Among them, 1433 (3.6 %) patients died due to breast cancer. The median follow-up duration was 63.4 (3-255) months. In the multivariate analysis, age at surgery, NG, LVI, subtype, and tumor size-nodal interactions were independently associated with BCSM. The N1 group had lower BCSS for T1a than T1b. The N2+ group also had lower BCSS for T1b than T1c or T2. In the N1 group of tumors smaller than 10 mm, 5- and 8-year BCSM decreased with larger tumor size. Patients with very small tumors with LN metastasis have decreased BCSM according to increase tumor size. Small tumors with LN metastasis could have aggressive biological behavior.

Feasibility of Nipple-Sparing Mastectomy with Immediate Breast Reconstruction in Breast Cancer Patients with Tumor-Nipple Distance Less Than 2.0 cm.

BACKGROUND AND OBJECTIVE: Debate continues concerning the oncological risk of nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) if the tumor-nipple distance (TND) is less than 2.0 cm. In this retrospective study, we analyzed oncological outcomes after NSM with IBR for the treatment of breast cancer to determine the risk posed by NSM in cases in which magnetic resonance imaging (MRI) showed a TND <2.0 cm but intraoperative frozen biopsy results were negative for tumor cells at the nipple base. MATERIALS AND METHODS: We conducted a retrospective review of patients with breast cancer who underwent NSM with IBR at Samsung Medical Center between 2008 and 2014. Preoperative MRI was done in all cases to define the TND, and frozen biopsy specimens were obtained intraoperatively. RESULTS: Among the 266 NSMs performed, TND was <2.0 cm in 145 cases (54.5 %) and ≥2.0 cm in 121 cases (45.5 %). Median follow-up was 25.6 months. There were no significant differences between the two patient groups with respect to disease-free survival or local recurrence-free survival. CONCLUSION: Our results suggest that NSM can be a feasible treatment option when the intraoperative frozen biopsy is negative for tumor cells even with a TND <2.0 cm in MRI.

Immediate postoperative inflammation is an important prognostic factor in breast cancer.

OBJECTIVE: Inflammation is associated with worse outcomes in cancer. Operations induce an acute inflammatory response and could impact the clinical outcomes in breast cancer. The neutrophil-lymphocyte ratio (NLR) is a well-known indicator of inflammation. We investigated the prognostic significance of perioperative inflammation with the NLR in breast cancer. METHODS: We reviewed the clinical and pathological records of women diagnosed with invasive breast carcinoma at the Samsung Medical Center between 2000 and 2010. The NLR levels in the immediate preoperative period and the postoperative periods (1 week and 1 month) were assessed. RESULTS: The NLRs of a total of 3,116 breast cancer patients were examined. In the univariate analysis, the NLR in postoperative week 1, total mastectomy, the presence of lymphovascular invasion, a higher nuclear grade and pathologic TNM stage, and negative hormone receptor and subtypes were factors associated with poor disease-specific survival. The NLR in postoperative week 1 remained a significant prognostic factor in the multivariate analysis. A cutoff level of 5.2, determined by the minimum p value approach, was found to be a significant level for discriminating the impact on breast cancer-specific mortality (p = 0.0116 adjusted by the Bonferroni correction). CONCLUSIONS: Immediate postoperative inflammation is an important prognostic marker in breast cancer patients.

Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer.

BACKGROUND: Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. Generally, hormone receptor-positive (HR+) breast cancers have favorable prognosis. In order to understand the exact clinical characteristics and prognosis of single HR-positive breast cancer (ER + PR- tumors and ER-PR+ tumors), we compared these tumors to double HR+ tumors as well as HR- negative tumors (ER-PR-). METHODS: We examined the clinical and biological features of 6,980 women with invasive ductal carcinoma, and these patients were stratified according to ER and PR expression as double HR+ (ER + PR+), single HR+ (ER + PR- and ER-PR+) and double HR-negative (HR-, ER-PR-) tumors. RESULTS: In this study, 571 (8.2%) cases were single HR+ tumors, of which 90 (1.3%) were ER-PR+ tumors and 481 (6.9%) were ER + PR- tumors. Our multivariate analysis showed that in patients without HER2 overexpression ER + PR- tumors were associated with an increased risk of recurrence and death compared with ER + PR+ tumors, with a hazard ratio of 2.12 for disease-free survival (DFS) and 4.79 for overall survival (OS). In patients without HER2 overexpression ER-PR+ tumors had increased risk of recurrence and death compared with ER + PR+ tumor, with a hazard ratio of 4.19 for DFS and 7.22 for OS. In contrast, in patients with HER2 overexpression, the difference in survival between single HR+ tumors and double HR+ HR- tumors was not statistically significant. In patients without HER2 overexpression the DFS and OS of ER + PR- and ER-PR+ tumors were not significantly different from those of ER-PR- tumors. CONCLUSION: We have identified clinically and biologically distinct features of single HR+ tumors (ER-PR+ and ER + PR-) through comparison with both ER + PR+ and ER-PR- tumors. These differences were only significant in HER2- tumors, not in HER2+ tumors. Single HR+ tumors without HER2 overexpression (ER + PR-HER2- or ER-PR + HER2-) were associated with poorer survival than ER + PR + HER2- tumors, and had comparable poor survival to ER-PR-HER2- tumors (triple-negative breast cancer).

Zerumbone suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1ß is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1ß-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1ß-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1ß treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1ß-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1ß-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

Berberine suppresses TPA-induced fibronectin expression through the inhibition of VEGF secretion in breast cancer cells.

BACKGROUND/AIMS: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. METHODS: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. RESULTS: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. CONCLUSION: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer.

HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients.

Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.

Round block technique without cerclage in breast-conserving surgery.

BACKGROUND: Round block technique is a unique breast resection through periareolar doughnut incision. However, it is more technically challenging and time consuming. We simplified the procedure by exclusion of round block cerclage. The purpose of this study was to introduce our round block technique without cerclage and to evaluate the results of oncological and cosmetic outcomes. METHODS: A total of 92 patients with centrally located breast cancer were treated with breast-conserving surgery using round block technique at Samsung Medical Center from July 2009 to May 2012. All patients had a small breast defect with excised breast volume less than 20 % compared to the total breast volume. We minimized the extent of skin removal and used simple interrupted inverted intradermal sutures without cerclage in doughnut closure. Patient's cosmetic satisfaction was assessed by subjective questionnaires at least 6 months after the operation. RESULTS: The median size of tumors was 1.7 cm (range 0.5-5.0 cm). The average distance of the tumors from the nipple was 2.0 cm (range 0.0-4.0 cm) on sonogram and most of the tumors were located upper breast (82.6 %). The median operative time was 101.5 min (range 55-180), including axillary surgeries. Median follow-up was 12.0 months (range 2-36), and none of patients have developed local recurrence. Up to the longest 3 years of follow-up, favorable cosmetic results have been found in patients treated with round block technique. CONCLUSIONS: Round block without cerclage is technically easy and feasible for centrally located breast tumors with favorable cosmetic results.

A new subfascial approach in open thyroidectomy: efficacy for postoperative voice, sensory, and swallowing symptoms. A randomized controlled study.

BACKGROUND: After open thyroidectomy, patients usually complain of voice, sensory, and swallowing symptoms. We approached the thyroid via the subfascial method to reduce these symptoms and compared postthyroidectomy symptoms with the conventional subplatysmal method. METHODS: Eighty-six patients undergoing thyroidectomy were recruited and randomized into either a conventional subplatysmal approach group (subplatysmal, 42 patients) group or a subanterior fascia of strap muscle approach group (subfascial, 44 patients). Voice symptoms were assessed using the Voice Handicap Index questionnaire and acoustic voice analysis. Sensory alterations were evaluated by the light touch and pain touch methods. Swallowing symptoms were assessed using the Swallowing Impairment Score (SIS) questionnaire, barium swallowing time, and hyoid bone movement range. Each variable was measured preoperatively, and at 2 weeks and 3 months after thyroidectomy. RESULTS: In both groups, the subjective symptoms of voice, sensation, and swallowing were significantly worsened at 2 weeks after operation, but improved 3 months after operation. Patients in the subplatysmal group had worse SIS scores than patients in the subfascial group (p = 0.016) and delayed barium swallowing time 2 weeks after operation (p = 0.008 compared to preoperative level). In the cohort over 50 years of age, SIS score did not recover to preoperative levels in the subplatysmal group 3 months after operation (p = 0.005 compared to preoperative level). CONCLUSIONS: The subfascial approach may be an effective method for reducing postthyroidectomy swallowing symptoms based on swallowing impairment score, especially in patients over 50 years of age.

Prognosis according to the timing of recurrence in breast cancer.

Purpose: Clinically, breast cancer can be divided into 4 subtypes based on the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67. Because the pattern and time of recurrence vary according to the subtype, we evaluated whether there was a difference in overall survival (OS) among the subtypes according to the time and type of recurrence. Methods: A total of 2,730 patients who underwent breast cancer surgery were analyzed. Early and late recurrence were defined as recurrence within and after 5 years of diagnosis, respectively. Recurrence type was categorized as locoregional recurrence or systemic recurrence. Results: Hormone receptor-positive tumors were significantly more frequent in the late recurrence group than in the early recurrence group (estrogen receptor positive, 47.8% [early] vs. 78.7% [late]). However, there was no difference in the rate of HER2 overexpression (HER2+, 38.1% [early] vs.39.0% [late]). In subgroup analysis, early recurrence was a significant prognostic factor for OS in all subtypes. However, late recurrence was a significant prognostic factor for OS only in the luminal B subtype (hazard ratio of 4.30). In addition, the luminal B type had the highest proportion in late recurrence patients (63.2%). Conclusion: The luminal B subtype had a high rate of late recurrence, and late recurrence was a poor prognostic factor for OS only in this subgroup. Therefore, further targeted treatments for luminal B breast cancer are needed and patients with this subtype require close long-term surveillance.