Interferon-Gamma Secretion Is Significantly Decreased in Stage III Breast Cancer Patients.

Even though some studies have shown possible clinical relationship between molecular subtypes and tumor infiltrating natural killer (NK) cells around tumors, there are few studies showing the clinical relevance of peripheral NK cell activity at diagnosis in female patients with invasive breast cancer. A total of 396 female invasive breast cancer patients who received curative surgical treatment from March 2017 to July 2021 were retrospectively analyzed. NK cell activation-induced interferon-gamma (IFN-γ) secretion measured by enzyme-linked immunosorbent assay was used to measure the activity of peripheral NK cells. Statistical analyses were performed to determine clinical relationships with major clinicopathologic parameters. Quadripartite NK cell activity measured by induced interferon-gamma showed significant relevance with staging and body mass index, and some of the inflammatory serological markers, namely N/L (neutrophil/lymphocyte), P/N (platelet/neutrophil), and P/L (platelet/lymphocyte), showed significantly different NK activity in each interval by univariate analysis. A binary subgroup analysis, setting the IFN-γ secretion cut-off at 100 pg/mL, showed that stage III was significantly increased and axillary lymph node metastasis positivity was increased in the group of IFN-γ < 100 pg/mL, and IFN-γ secretion decreased with an increasing N stage, increased BMI (body mass index), and decreased production of IFN-γ. Following this, the same binary analysis, but with the IFN-γ secretion cut-off at 250 pg/mL, also showed that secretion in stage III was increased in those concentrations with <250 pg/mL, axillary lymph node positivity appeared to be correlated, and BMI ≥ 30 increased in prevalence. Additional ANOVA post hoc tests (Bonferroni) were performed on some serological markers that tended to be somewhat inconsistent. By subgroup analysis with Bonferroni adjustment between the IFN-γ secretion and TNM stage, no significant difference in IFN-γ secretion could be identified at stages I, II, and IV, but at stage III, the IFN-γ secretion < 100 pg/mL was significantly higher than 250 ≤ IFN-γ secretion < 500 pg/mL or IFN-γ secretion ≥ 500 pg/mL. According to this study, stage III was significantly associated with the lowest IFN-γ secretion. Compared to a higher level of IFN-γ secretion, a lower level of IFN-γ secretion seemed to be associated with increased body mass index. Unlike when IFN-γ secretion was analyzed in quartiles, as the IFN-γ secretion fell below 100 pg/mL, the correlation between axillary lymph node positivity and increased N stage, increased BMI, and increased N/L and P/L, which are suggested poor prognostic factors, became more pronounced. We think a peripheral IFN-γ secretion test might be convenient and useful tool for pretreatment risk assessment and selecting probable candidates for further treatment such as immunotherapy in some curable but high-risk invasive breast cancer patients, compared to other costly assaying of tissue NK cell activity at diagnosis.

Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis.

BACKGROUND: Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. METHODS: We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. RESULTS: From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001). CONCLUSIONS: This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

Effects of Ruxolitinib and Calcitriol Combination Treatment on Various Molecular Subtypes of Breast Cancer.

The anticancer effects of ruxolitinib and calcitriol against breast cancer were reported previously. However, the effect of ruxolitinib and calcitriol combination treatment on various molecular subtypes of breast cancer remains unexplored. In this study, we used MCF-7, SKBR3, and MDA-MB-468 cells to investigate the effect of ruxolitinib and calcitriol combination treatment on cell proliferation, apoptosis, cell cycle, and cell signaling markers, in vitro and in vivo. Our results revealed the synergistic anticancer effect of ruxolitinib and calcitriol combination treatment in SKBR3 and MDA-MB-468 cells, but not in MCF-7 cells in vitro, via cell proliferation inhibition, apoptosis induction, cell cycle arrest, and the alteration of cell signaling protein expression, including cell cycle-related (cyclin D1, CDK1, CDK4, p21, and p27), apoptosis-related (c-caspase and c-PARP), and cell proliferation-related (c-Myc, p-p53, and p-JAK2) proteins. Furthermore, in the MDA-MB-468 xenograft mouse model, we demonstrated the synergistic antitumor effect of ruxolitinib and calcitriol combination treatment, including the alteration of c-PARP, cyclin D1, and c-Myc expression, without significant drug toxicity. The combination exhibited a synergistic effect in HER2-enriched and triple-negative breast cancer subtypes. In conclusion, our results suggest different effects of the combination treatment of ruxolitinib and calcitriol depending on the molecular subtype of breast cancer.

Hormone Receptor Subtype in Ductal Carcinoma in Situ: Prognostic and Predictive Roles of the Progesterone Receptor.

BACKGROUND: We investigated the prognostic and predictive roles of the hormone receptor (HRc) subtype in patients with ductal carcinoma in situ (DCIS). We focused on identifying the roles of the progesterone receptor (PR) independent of estrogen receptor (ER) status. METHODS: Nationwide data of 12,508 female patients diagnosed with DCIS with a mean follow-up period of 60.7 months were analyzed. HRc subtypes were classified as ER-/PR-, ER-/PR+, ER+/PR-, and ER+/PR+ based on ER and PR statuses. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The ER+/PR+ group showed better prognoses than the ER+/PR- and ER-/PR- groups in the patients who received tamoxifen therapy (p = .001 and p = .031, respectively). HRc subtype was an independent prognostic factor (p = .028). The tamoxifen therapy group showed better survival than the patients who did not receive tamoxifen, but only in the ER+/PR+ subgroup (p = .002). Tamoxifen therapy was an independent prognostic factor (HR, 0.619; 95% CI, 0.423 - 0.907; p = .014). PR status was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy (p < .001), and it remained a prognostic factor independent of ER status (HR, 0.576; 95% CI, 0.349 - 0.951; p = .031). CONCLUSION: The HRc subtype can be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Tamoxifen therapy can improve overall survival in the ER+/PR+ subtype. PR status has significant prognostic and predictive roles independent of ER status. Testing for the PR status in addition to the ER status is routinely recommended in patients with DCIS to determine the HRc subtype in clinical settings. IMPLICATIONS FOR PRACTICE: The hormone receptor (HRc) subtype was an independent prognostic factor, and the estrogen receptor (ER)+/progesterone receptor (PR) + subtype showed a better survival in patients with ductal carcinoma in situ (DCIS) who received tamoxifen therapy. PR was an independent prognostic factor independent of ER, and PR was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy. The HRc subtype could be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Testing of PR status in addition to ER status is routinely recommended for patients with DCIS to determine the HRc subtype in clinical settings.

Intermuscular fat density as a novel prognostic factor in breast cancer patients treated with adjuvant chemotherapy.

BACKGROUND: Body composition, including sarcopenia and fat parameters, has received much attention as a prognostic factor in breast cancer. METHODS: A total of 479 breast cancer patients who underwent surgery and received adjuvant chemotherapy were enrolled in this study. Body composition, including the index and density of skeletal muscle, visceral fat, subcutaneous fat, and intermuscular fat calculated by CT scan, was used as a prognostic factor. The endpoints were breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: The number of patients with stages I, II, and III was 146 (30.5%), 237 (49.5%), and 96 (20%), respectively. Sarcopenia and muscle density were not significant prognostic factors for BCSS and OS. A high visceral fat index (VFI) was an independent prognostic factor for BCSS (HR, 2.55; 95% CI 1.10-5.95, p = 0.03) and OS (HR 2.55, 95% CI 1.26-5.16, p = 0.01). In addition, high intermuscular fat density (IMFD) was also a significant prognostic factor for BCSS (HR, 2.95; 95% CI 1.34-6.46, p = 0.007) and OS (HR 2.28, 95% CI 1.22-4.26, p = 0.01) in multivariate analysis. CONCLUSION: VFI and IMFD were significant prognostic factors for BCSS and OS in breast cancer patients treated with adjuvant chemotherapy.

Imaging surveillance for the detection of ipsilateral local tumor recurrence in patients who underwent oncoplastic breast-conserving surgery with acellular dermal matrix: abbreviated MRI versus conventional mammography and ultrasonography.

BACKGROUND: To evaluate the usefulness of surveillance-abbreviated magnetic resonance imaging (AB-MRI) for the detection of ipsilateral local tumor recurrence (LTR) in patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) by comparing its diagnostic performance with that of mammography (MG) and ultrasonography (US). METHODS: The postoperative MG, US, and AB-MRI findings of the ipsilateral breast and pathological results of 324 patients who underwent oncoplastic BCS using ADM were reviewed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV) for biopsy, accuracy, and area under the curve (AUC) for each imaging modality were calculated. RESULTS: A total of 8 ipsilateral LTRs were diagnosed, and most cancers (87.5%) were stage 0 or 1 (median size of invasive cancer, 1.44 cm; range, 0.7-2 cm). The CDRs of MG, US, MG + US, and AB-MRI were 0.009, 0.012, 0.015, and 0.025 per woman, respectively. Three cancers were detectable on only AB-MRI, and the additional CDR of AB-MRI was 0.010. The sensitivity and specificity of MG, US, MG + US, and AB-MRI were 37.5%, 50%, 62.5%, and 100% and 99.7%, 98.4%, 98.1%, and 97.8%, respectively. The PPVs for biopsy were 75%, 44.4%, 45.5%, and 53.3%, respectively. The AUC was significantly higher for AB-MRI (0.989) than for MG alone (0.686, P = 0.0009), US alone (0.742, P = 0.009), and MG + US (0.803, P = 0.04). A total of 66.7% of cancers visible on only AB-MRI were located at the deep posterior portion of the excision cavity, which might have been missed with MG or MG + US due to masking by the ADM filler. CONCLUSION: AB-MRI can improve the detection of ipsilateral LTR despite postoperative changes caused by ADM fillers compared to conventional MG and US. Patients who undergo BCS with ADM can be candidates for AB-MRI surveillance considering improved cancer detection and high sensitivity.

The long-term effect of age on cardiovascular disease in patients with breast cancer who received chemotherapy.

PURPOSE: As breast cancer survival has significantly improved and patient life expectancy has increased, greater numbers of elderly breast cancer survivors are at risk for cardiovascular disease (CVD). Therefore, this study investigated the impact of age on the incidence, mortality, and predictors of CVD following adjuvant chemotherapy in the late period of survivorship. METHODS: 761 Patients who underwent chemotherapy were enrolled and divided into patients aged < 50 years (n = 413, 54.3%) and patients aged ≥ 50 years (n = 348, 45.7%). Among the entire cohort, 445 patients underwent transthoracic echocardiography. RESULTS: During long-term follow-up (median 122 months, range 12-340 months), CVD events developed in 50 (6.57%) patients, including 17 (4.1%) aged < 50 years and 33 (9.5%) aged ≥ 50 years (p = 0.003). 8 (1.1%) of 50 patients with CVD died, including 1 patient aged < 50 years and 7 patients aged ≥ 50 years. CVD-free survival was significantly lower in patients aged ≥ 50 years compared with patients aged < 50 years (p < 0.001). In multivariate analyses, age ≥ 50 years [p < 0.001, hazard ratio (HR) = 3.802, 95% confidence interval (CI) 1.986-7.278], the radio of the peak early and mitral tissue Doppler velocities (p = 0.014, HR = 1.102, 95% CI 1.020-1.190), and global longitudinal strain (p < 0.001, HR = 1.208, 95% CI 1.096-1.332) are significant predictors of CVD. CONCLUSIONS: Age, diastolic function, and strain value in patients with breast cancer who underwent chemotherapy has a long-term effect on CVD. Therefore, it is important to consider ethnic and age-specific risks for CVD in breast cancer survivors.

Incidence, Risk Factors, and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma.

OBJECTIVE: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma. METHODS: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2. RESULTS: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism. CONCLUSION: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2. ABBREVIATIONS: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic.

Volume replacement with diced acellular dermal matrix in oncoplastic breast-conserving surgery: a prospective single-center experience.

BACKGROUND: Several studies have reported the use of acellular dermal matrix in breast reconstruction. However, the primary role of acellular dermal matrix in these studies was to support the implant; there are no reports on the use of acellular dermal matrix exclusively as volume replacement. Thus, we aimed to evaluate the safety and effectiveness of filling of the defect with acellular dermal matrix in oncoplastic breast-conserving surgery. METHODS: We prospectively recruited 120 adult breast cancer patients who were scheduled to undergo oncoplastic breast-conserving surgery with acellular dermal matrix filling from 2017 to 2018. Intraoperatively, diced human acellular dermal matrix measuring 3-5 mm was used on each side to fill in the excisional defect immediately. After 6 months, satisfaction of the patients and surgeons with overall and cosmetic outcomes was evaluated with a survey using a 10-point scale. Postoperative complications were assessed at 2 weeks and 6 months postoperatively. RESULTS: Of the 117 patients who were evaluated for their satisfaction, 94.0% were strongly satisfied with the cosmetic outcomes and 90.4% were strongly satisfied overall. Patient overall satisfaction scores were higher than surgeon satisfaction scores (p < 0.001). Of the 117 patients who underwent evaluation of complications 6 months postoperatively, six (5.1%) had hematoma and seven (6.0%) had seroma. The overall reoperation rate due to complications was 8.5%. Only two patients needed acellular dermal matrix removal due to hematoma and inflammation. CONCLUSION: Oncoplastic breast-conserving surgery with acellular dermal matrix filling of defects can be performed safely with high cosmetic satisfaction. TRIAL REGISTRATION: ICTRP, KCT0003886; retrospectively registered May 3, 2019, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0003886.

Hard X-ray self-seeding commissioning at PAL-XFEL.

A wake monochromator based on a large-area diamond single crystal for hard X-ray self-seeding has been successfully installed and commissioned in the hard X-ray free-electron laser (FEL) at the Pohang Accelerator Laboratory with international collaboration. For this commissioning, the self-seeding was demonstrated with a low bunch charge (40 pC) and the nominal bunch charge (180 pC) of self-amplified spontaneous emission (SASE) operation. The FEL pulse lengths were estimated as 7 fs and 29.5 fs, respectively. In both cases, the average spectral brightness increased by more than three times compared with the SASE mode. The self-seeding experiment was demonstrated for the first time using a crystal with a thickness of 30 µm, and a narrow bandwidth of 0.22 eV (full width at half-maximum) was obtained at 8.3 keV, which confirmed the functionality of a crystal with such a small thickness. In the nominal bunch-charge self-seeding experiment, the histogram of the intensity integrated over a 1 eV bandwidth showed a well defined Gaussian profile, which is evidence of the saturated FEL and a minimal electron-energy jitter (∼1.2 × 10-4) effect. The corresponding low photon-energy jitter (∼2.4 × 10-4) of the SASE FEL pulse, which is two times lower than the Pierce parameter, enabled the seeding power to be maximized by maintaining the spectral overlap between SASE FEL gain and the monochromator.

FEL performance achieved at PAL-XFEL using a three-chicane bunch compression scheme.

PAL-XFEL utilizes a three-chicane bunch compression (3-BC) scheme (the very first of its kind in operation) for free-electron laser (FEL) operation. The addition of a third bunch compressor allows for more effective mitigation of coherent synchrotron radiation during bunch compression and an increased flexibility of system configuration. Start-to-end simulations of the effects of radiofrequency jitter on the electron beam performance show that using the 3-BC scheme leads to better performance compared with the two-chicane bunch compression scheme. Together with the high performance of the linac radiofrequency system, it enables reliable operation of PAL-XFEL with unprecedented stability in terms of arrival timing, pointing and intensity; an arrival timing jitter of better than 15 fs, a transverse position jitter of smaller than 10% of the photon beam size, and an FEL intensity jitter of smaller than 5% are consistently achieved.

Long-Term Prognosis of Unilateral and Multifocal Papillary Thyroid Microcarcinoma After Unilateral Lobectomy Versus Total Thyroidectomy.

BACKGROUND: Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with poor outcomes; however, we often encounter pathologically confirmed unilateral multifocal PTMC after surgery. To date, no consensus on the proper surgical extent for patients with this form of PTMC has been reported. OBJECTIVE: The aim of this study was to analyze the effect of the type of surgical treatment on disease recurrence in patients with unilateral multifocal PTMC. METHODS: We retrospectively analyzed data from 255 patients with unilateral, multifocal, node-negative PTMC between March 1999 and December 2012. We evaluated two groups of patients: those who underwent unilateral lobectomy (Group I, n = 127) and those who underwent total thyroidectomy (Group II, n = 128). During the follow-up period, which lasted a median of 94.8 months, we assessed locoregional recurrence (LRR). RESULTS: There was no statistically significant difference between the two groups with regard to LRR at follow-up (3.15% for Group I vs. 0.78% for Group II; p = 0.244). The association between the type of surgical treatment and LRR remained nonsignificant after adjusting for potential confounders such as age, tumor size, microscopic extrathyroidal extension, and lymphovascular invasion (p = 0.115). During follow-up, the incidence of transient hypocalcemia (0% vs. 8.6%; p = 0.001) and vocal fold paralysis (1.6% vs. 9.4%; p = 0.011) was higher in Group II than in Group I. CONCLUSIONS: Even though randomized controlled trials are the only option to obtain a definitive answer to this question, unilateral lobectomy may be a safe operative option for selected patients with unilateral, multifocal, node-negative PTMC.

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.

Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population.

Previous studies have not considered the axillary lymph node status when investigating the prognostic role of tumor location according to each molecular subtype. The present study aimed to investigate the prognostic implication of tumor location according to each molecular subtype in Korean invasive ductal carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856 Korean IDC women with axillary lymph node metastasis were retrospectively analyzed. According to tumor location, patients were divided into the following groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower-inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated according to tumor location and molecular subtype. A subgroup analysis based on tumor size categorization was also performed. The patients' mean age was 47.97 ± 9.64 years, and the median follow-up time was 90 months. The LIQ group showed significantly worse prognosis in OS and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which was only significant in human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative (TN) subtypes. In the subgroup analysis according to tumor size, the LIQ group showed a significantly worse prognosis in OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in patients with more than T2 stage. In Korean IDC patients with axillary lymph node metastasis, LIQ tumor location was associated with poor prognosis among those with HER2 and TN molecular subtypes and especially in those with more than T2 stage.

Correlation Between Surgical Extent and Prognosis in Node-Negative, Early-Stage Papillary Thyroid Carcinoma Originating in the Isthmus.

BACKGROUND: The association between surgical extent and prognosis in papillary thyroid carcinoma originating in the isthmus is unclear. METHODS: We included 233 patients with early-stage, node-negative papillary thyroid cancer originating in the isthmus; 126 were treated by lobectomy plus isthmusectomy with ipsilateral central neck dissection and 97 were treated by total thyroidectomy with bilateral central neck dissection. Subgroup analysis was performed according to tumor size (≤ 1 vs. >1 cm) to evaluate whether tumor size had a significant impact on determining the optimal extent of surgery in our cohort. RESULTS: Total thyroidectomy patients had longer recurrence-free survival (RFS) than those treated by lobectomy plus isthmusectomy. Subgroup analysis showed that this was true only for tumors >1 cm. In multivariate analysis, total thyroidectomy was an independent risk factor for RFS only for tumors >1 cm. CONCLUSIONS: Lobectomy plus isthmusectomy may be optimal for early-stage, node-negative papillary thyroid carcinoma originating in the isthmus for tumors ≤ 1 cm; total thyroidectomy might be better for tumors >1 cm.

Synergistic effect between celecoxib and luteolin is dependent on estrogen receptor in human breast cancer cells.

The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.

Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival.

BACKGROUND: The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. METHODS: We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox's proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. RESULTS: A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. CONCLUSIONS: We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules.

A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population.

BACKGROUND: To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype. METHODS: We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n = 14,547) and ILC (n = 528). RESULTS: The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype. CONCLUSIONS: Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.

Survival analysis for patients with metachronous contralateral breast cancer: Insights from a retrospective study.

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors.

Prognostic Implications of Maintaining the Target Thyroid-Stimulating Hormone Status Based on the 2015 American Thyroid Association Guidelines in Patients with Low-Risk Papillary Thyroid Carcinoma after Lobectomy: A 5-Year Landmark Analysis.

Background: The 2015 American Thyroid Association guidelines recommend the maintenance of serum thyroid stimulating hormone (TSH) levels ≤2 mIU/L in patients with low-risk papillary thyroid carcinoma (PTC) who underwent lobectomy; however, the evidence is insufficient. We investigated the association between maintaining the TSH status at ≤2 mIU/L and tumor recurrence in patients with low-risk PTC who underwent lobectomy through a 5-year landmark analysis. Methods: Between 2010 and 2016, 662 patients with low-risk PTC were included. The postoperative TSH status was determined using the 'TSH > 2 ratio', which was calculated using the TSH test results during the 5-year follow-up. The optimal cutoff value of 'TSH > 2 ratio' for tumor recurrence was determined using a receiver operating characteristic curve analysis. Recurrence-free survival (RFS) was compared between the groups using Kaplan-Meier and Cox proportional hazard regression analyses. Results: Patients with 'TSH > 2 ratio' > 0.1833 (n = 498) had a worse RFS outcome compared to patients with 'TSH > 2 ratio' ≤ 0.1833 (n = 164; p < 0.001). 'TSH > 2 ratio' > 0.1833 was a significant risk factor for tumor recurrence after the 5-year landmark (hazard ratio: 4.795, 95% confidence interval: 2.102-10.937, p < 0.001). Conclusions: Maintaining TSH levels ≤ 2 mIU/L below a certain percentage among the total TSH tests during the 5-year follow-up period has a negative impact on tumor recurrence.