Neutrophil-to-Lymphocyte Ratio Is Associated With the Proportion of Poorly Differentiated Components in Papillary Thyroid Carcinoma.

INTRODUCTION: Diagnosis of poorly differentiated thyroid cancer (PDTC) requires ≥ 50% of poorly differentiated components (PDC) in Japan. However, the optimal cutoff percentage of PDC for PDTC diagnosis remains controversial. Although high neutrophil-to-lymphocyte ratio (NLR) correlates with the aggressiveness of papillary thyroid cancer (PTC), whether NLR is associated with the proportion of PDC in PTC remains unstudied. MATERIALS AND METHODS: Patients with the pure PTC (n = 664), PTC with < 50% PDC (n = 19), or PTC with ≥ 50% PDC (n = 26) who underwent surgery were retrospectively analyzed. Twelve-year disease-specific survival and preoperative NLR were compared among these groups. RESULTS: Twenty seven patients died from thyroid cancer. The PTC with ≥ 50% PDC group (80.7%) showed significantly worse 12-year disease-specific survival than the pure PTC group (97.2%) (P < 0.001); however, the < 50% PDC group (94.7%) did not (P = 0.91). The PTC with ≥ 50% PDC group had a significantly higher NLR than the pure PTC (P < 0.001) and the PTC with < 50% PDC groups (P < 0.001), whereas there was no significant difference in the NLR between the pure PTC and the PTC with < 50% PDC groups (P = 0.48). CONCLUSIONS: PTC with ≥ 50% PDC is more aggressive than either pure PTC or PTC with < 50% PDC, and NLR potentially reflects the PDC proportion. These results support the validity of 50% PDC as a cut-off for PDTC diagnosis and indicate the utility of NLR as a biomarker for PDC proportion.

Skeletal muscle loss during neoadjuvant chemotherapy predicts poor prognosis in patients with breast cancer.

BACKGROUND: The skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level divided by height squared, has been considered a prognostic factor in patients with breast cancer. However, the prognostic impact of changes in SMI during treatment remains unclear. This study aimed to evaluate the influence of SMI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). METHODS: We reviewed patients with breast cancer who underwent NAC and subsequent surgery for breast cancer between 2010 and 2017. The rate of SMI change during NAC was calculated, and the association between SMI changes and prognosis was retrospectively analyzed. RESULTS: In total, 141 patients were evaluated. 48 (34.0%), 53 (37.6%), and 40 (28.4%) patients exhibited increased (≥ 3%), maintained (- 3% <, < 3%), and decreased (- 3% ≥) SMI during NAC, respectively. The decreased SMI group showed significantly poorer disease-free survival than the maintained and increased SMI groups (hazard ratio [HR] 8.29, p <  0.001 for the decreased vs. increased SMI groups; HR 3.49, p <  0.001 for the decreased vs. maintained SMI groups). Moreover, decreased SMI was an independent risk factor for disease-free survival in multivariate analysis (HR 3.68, p <  0.01). CONCLUSIONS: Skeletal muscle loss during NAC predicts poor prognosis. Our results underscore the importance of monitoring and maintaining skeletal muscle mass during NAC.

Surgical resection of the primary tumor prevents an undesirable locoregional condition and improves the quality of life in patients with anaplastic thyroid cancer.

PURPOSE: Anaplastic thyroid cancer (ATC) is a highly aggressive tumor that invades surrounding tissues and rapidly metastasizes throughout the body. Growth of the primary tumor in the neck often causes serious conditions that decrease the quality of life (QOL) of patients. The objective of this study was to investigate the role of surgical resection in improving the QOL of patients with ATC. METHODS: This was a retrospective review of 62 patients with ATC treated at Shinshu University Hospital between January 2001 and June 2019. RESULTS: Fourteen patients underwent R0/R1 resection. Thirteen of the 14 patients received postoperative radiation, and 4 received chemotherapy. The mean survival period was 15.4 ± 18.2 (range, 2-75) months. Distant metastases appeared within 3.2 ± 2.3 months postoperatively in 12 patients. A permanent tracheostomy was required in six patients; however, eight patients did not show airway obstruction until death. Daily treatment for exudate or bleeding from tumors that eroded in the neck, which deteriorated the QOL, was unnecessary in 12 patients. CONCLUSIONS: As surgical resection can improve the QOL in patients with ATC, thyroid surgeons should promptly and carefully evaluate the resectability of the tumor and favor resection as much as possible.

Prognostic significance of neutrophil-to-lymphocyte ratio for long-term outcomes in patients with poorly differentiated thyroid cancer.

Poorly differentiated thyroid cancer (PDTC) is a distinct but rare type of thyroid cancer with intermediate biological behavior between differentiated and anaplastic thyroid cancers. PDTC was first defined in 2005 in Japan, but the diagnostic criteria changed in 2015, requiring the tumor to have more than 50% of poorly differentiated components for diagnosis. Because only six years have passed since the PDTC definition change, prognostic factors for long-term survival who meet the latest criteria have not been determined. Neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in various solid malignancies. However, its impact on PDTC remains unclear. This study aimed to evaluate the significance of NLR as a prognostic factor for patients with PDTC diagnosed based on the latest criteria. In total, 28 PDTC cases (4.4%) of 637 thyroid cancer patients who underwent surgery between 2002 and 2012 were retrospectively analyzed. The median follow-up period was 120 months (range, 7-216 months). Of the 13 deaths (46.4%), 9 patients (32.1%) died from PDTC. The median preoperative NLR was 2.7 (0.67-8.62), and the NLR cut-off value determined by the receiver operating characteristic curve was 2.88. Patients with a high NLR (>2.88) showed significantly worse disease-specific survival (hazard ratio [HR] 4.67, p = 0.036) and overall survival (HR 4.94, p = 0.007) than those with a low NLR (≤2.88). Multivariate analysis revealed that a high NLR independently predicted a worse prognosis (HR 6.06, p = 0.0087). In conclusion, NLR is a useful prognostic marker for patients with PDTC.

Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer.

BACKGROUND: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). METHODS: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. RESULTS: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). CONCLUSIONS: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis.

The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57-81 and 19 months, 95% CI: 9-29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25-56 and 31 months, 95% CI: 19-43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.

Correlation of Clinicopathological Features and LGR5 Expression in Triple-Negative Breast Cancer.

LGR5 is the most robust known stem cell marker for gastrointestinal tumors, but there are few reports in breast cancer. Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer, and thus identification of new cancer stem cell populations in TNBC may help to identify targeted therapies. LGR5 expression was evaluated by RNAscope, a newly developed RNA in situ hybridization technique, using a tissue microarray consisting of 43 patient samples of TNBC selected from the medical archives at our hospital. Patients were stratified into negative and positive LGR5 expression groups. Tumor necrosis was greater in the LGR5-positive group compared with the LGR5-negative group (P = .026). Mitosis tended to show a high value in the LGR5-positive group compared with the LGR5-negative group (P = .0831), while stage tended to show a high stage in the LGR5-positive group compared with the LGR5-negative group (P = .0617). Cox proportional hazards models revealed that the LGR5-positive group (overall survival (OS) = 2.12; 95% CI: 2.12-2.12; P = 0.1575) had no relationship with OS. LGR5 expression is associated with tumor necrosis of TNBC and suggested higher malignant potential.

[A Case of Arteritis That Developed after Pegfilgrastim Administration during Chemotherapy for Breast Cancer].

A 61-year-old woman presented with metastatic breast cancer in her right lung 4 years and 11 months after the operation for her right breast cancer(HER2 enriched type). Chemotherapy(pertuzumab plus trastuzumab plus docetaxel)were ad- ministered. On day 2 of cycle 2, pegfilgrastim was administered because her neutrophils decreased to 54 cells/mL on day 8 of cycle 1. On day 9 of cycle 2, she developed left neck and chest pain. Moreover, she developed a fever of 39°C on day 14 and visited our hospital. Her WBC and CRP increased to 18,300 cells/mL and 25.48mg/dL, respectively. Computed tomography revealed an increased CT value of the panniculus, around the aorta and left pleural effusion. Ultrasonography of the neck showed a marginal hypoechoic area around the left carotid artery, which corresponded with the pain. Arteritis induced by PFG was suspected. The neck pain and fever almost completely improved 19 days later, and cycle 3 was performed 28 days after cycle 2. To our knowledge, the present case is the second report of arteritis that was suspected to be associated with PFG.

A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of 18 F-Fluorodeoxyglucose on a Positron Emission Tomography.

An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73-year-old woman presented to our hospital with a 3.5-cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5-cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG-PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.

Initial clinical presentation of single soft tissue metastasis of medullary thyroid carcinoma without primary tumor in the thyroid gland.

BACKGROUND: Single soft tissue metastasis of medullary thyroid carcinoma is extremely rare. In addition, several occult medullary thyroid carcinomas with distant metastasis were reported, but undetectable primary lesion at diagnosis was also extremely rare. CASE PRESENTATION: A 74-year-old man was admitted to our hospital because of a painful nodule in his left buttock for over 1 year. Needle biopsy was performed, and the histological findings revealed adenocarcinoma positive for thyroid transcription factor-1. No evidence of a primary tumor, including the lung and thyroid gland, could be found elsewhere despite detailed examinations, including thyroid echography, chest computed tomography, and fluorodeoxyglucose-positron emission tomography. The soft tissue tumor was resected with a wide margin. Immunohistochemical analysis showed the tumor cells to be positive for cytokeratin-AE1/3, cytokeratin 7, synaptophysin, chromogranin A, calcitonin, and carcinoembryonic antigen, but negative for cytokeratin 20, Napsin A, Pax8, and p40, resulting in a diagnosis of metastasis of medullary thyroid carcinoma. CONCLUSION: Initial presentation with a single metastasis to soft tissue and undetectable primary tumor in the thyroid gland is an extremely rare clinical manifestation in patients with medullary thyroid carcinoma.

[A Case of Retroperitoneal Abscess Due to Acute Appendicitis during Neo-Adjuvant Chemotherapy for Breast Cancer].

When acute appendicitis occurs in patients treated with chemotherapy, neutropenia and abdominal complaints caused by chemotherapy can contribute to the diagnostic difficulty, masking the increase in white blood cell(WBC)counts and physical findings of acute appendicitis. A 43-year-old premenopausal woman who was diagnosed with stage IIIA left breast cancer was scheduled for neoadjuvant chemotherapy includingfluorouracil plus epirubicin plus cyclophosphamide(FEC), followed by docetaxel and trastuzumab(DOC plus HER). The patient developed fever and lower abdominal pain on day 17 of DOC plus HER cycle 1, and was diagnosed with acute gastroenteritis in the emergency room. These symptoms were almost improved 4 days later, and then cycle 2 was performed as scheduled. WBC counts decreased to 1,530 cells/mL due to DOCinduced myelosuppression on day 8 of cycle 2 when the patient developed lower abdominal pain again. However, WBC counts increased to 21,680 cells/mL on day 13 of cycle 2. Computed tomography scans revealed an intraperitoneal abscess due to acute appendicitis, and consequently urgent operation was performed. It is necessary to understand that patients with acute appendicitis duringchemotherapy can present less clinical findings.

Changes in the pathophysiology of primary hyperparathyroidism and analysis of postoperative recurrence cases at a regional core hospital in Japan: experience of 35 years in Shinshu University Hospital.

BACKGROUND: Since reoperation for recurrent primary hyperparathyroidism (PHPT) increases the risk of complications, such as recurrent laryngeal nerve palsy, it is vital to prevent recurrence as much as possible when performing the initial surgery. Therefore, we retrospectively analyzed the PHPT cases at Shinshu University Hospital from 1986 to 2020 for changes in the characteristics of PHPT over time and features of the recurrent cases to establish treatment strategies to prevent a postoperative recurrence. METHODS: Hereditary PHPT was diagnosed through endocrinological tests, systemic imaging, and/or genetic testing. Localization of swollen parathyroid glands was identified through neck ultrasonography (US), contrast-enhanced computed tomography, magnetic resonance imaging (MRI), and 99mTc-sestamibi scintigraphy. RESULTS: Among the 536 patients with PHPT (374 women and 162 men) with a mean age of 56.9±13.6 years, 90 (16.8%) had hereditary PHPT, while the other 446 (83.2%) had sporadic PHPT. Overall, 314 (58.6%) patients were asymptomatic, whereas 132 (24.6%) had symptoms related to PHPT. Asymptomatic PHPT was significantly more prevalent after 2001 (81.8%) than before 2001 (51.2%) (P<0.01), although the number of PHPT cases increased during the last decade. Resection of an enlarged parathyroid gland alone was performed for sporadic PHPT, while focused parathyroidectomy was performed after 2001. Total parathyroidectomy (TPTx) with autotransplantation was performed in patients with hereditary PHPT. In addition, the intraoperative rapid pathological diagnosis of the resected gland throughout the period and intraoperative serum intact parathyroid hormone (PTH) measurement from 2014 were used. Overall, 11 patients with hereditary PHPT (2.1%) developed recurrence. A recurrent parathyroid gland was identified in 10 of 11 cases through 99mTc-sestamibi scintigraphy. CONCLUSIONS: Although the incidence of asymptomatic PHPT has been increasing recently, focused parathyroidectomy is considered an appropriate procedure for sporadic PHPT that has been carefully examined preoperatively. Therefore, in the future, it will be necessary to conduct genetic testing for sporadic PHPT cases as much as possible to accurately diagnose the disease type and decide on a treatment strategy.

Significance of skeletal muscle index-to-body mass index ratio as a predictor of post-surgical bleeding after mastectomy in patients with breast cancer.

BACKGROUND: Post-surgical bleeding is a major complication of mastectomy in patients with breast cancer. However, the risk factors for post-surgical bleeding have not been well studied. Although obesity or reduced skeletal muscle mass is an indicator of cancer surgery complications, its impact on post-surgical bleeding after mastectomy remains unknown. METHODS: In total, 563 patients with breast cancer who underwent mastectomy were included in this study. We evaluated the preoperative body mass index (BMI), skeletal muscle index (SMI), and SMI-to-BMI ratio and analyzed the association between these values and the incidence of post-surgical bleeding. RESULTS: Post-surgical bleeding occurred in 33 (5.6%) patients. Mean BMI was significantly higher in the bleeding group (26.3 ± 4.7) than in the no-bleeding group (23.0 ± 4.1) (p < 0.001), whereas mean SMI was lower in the former group (45.0 ± 8.5) than in the latter group (48.0 ± 8.5) (p = 0.08). The bleeding group had significantly lower SMI-to-BMI ratio (1.71 ± 0.16) than the no-bleeding group (2.10 ± 0.23) (p < 0.001). Among these three parameters, SMI-to-BMI ratio had the highest area under the curve value in their receiver operating characteristic curves (0.73 for BMI, 0.59 for SMI, 0.92 for SMI-to-BMI ratio). Furthermore, on multivariate analysis, SMI-to-BMI ratio was an independent risk factor for post-surgical bleeding (hazard ratio, 38.4; 95% confidence interval, 13.9-136.2; p < 0.001). CONCLUSIONS: SMI-to-BMI ratio is a superior predictive factor of post-surgical bleeding after mastectomy to either BMI or SMI alone.

Development of a predictive score for post-hemithyroidectomy hypothyroidism using skeletal muscle index, remnant thyroid index, and thyroid-stimulating hormone levels: a retrospective cohort study.

Background: Hypothyroidism is a major complication of hemithyroidectomy. Low remnant thyroid volume and high serum thyroid-stimulating hormone (TSH) levels are suggested as risk factors for post-hemithyroidectomy hypothyroidism. Reduced skeletal muscle mass is associated with a variety of postoperative complications. However, its impact on post-hemithyroidectomy hypothyroidism has not yet been studied. This study aimed to evaluate the association between skeletal muscle mass and the onset of post-hemithyroidectomy hypothyroidism and develop a predictive score using skeletal muscle mass in combination with previously reported risk factors. Methods: This study retrospectively analyzed 226 consecutive patients who underwent hemithyroidectomy at Shinshu University Hospital between January 2011 and December 2020. The skeletal muscle area at the fourth thoracic vertebral level and maximal remnant thyroid area were quantified using preoperative computed tomography and standardized by dividing them by the square of the patient's height, designated as the skeletal muscle index (SMI) and remnant thyroid volume index (RTI). Subclinical hypothyroidism was defined as a postoperative elevated serum TSH level (>5 µU/mL) with a normal free thyroxine (FT4) level (≥0.9 ng/dL), overt hypothyroidism as a postoperative increase in serum TSH level (>5 µU/mL) and a decrease in serum FT4 level (<0.9 ng/dL), and symptomatic hypothyroidism as an elevated serum TSH level (>5 µU/mL) with hypothyroidism-related symptoms. Logistic regression analysis was used to determine the factors associated with the onset of hypothyroidism. Results: Patients with euthyroid status had significantly higher SMI and RTI than those who developed post-hemithyroidectomy hypothyroidism (SMI, euthyroid: 12.0±2.4 vs. subclinical hypothyroid: 10.2±1.7, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 10.1±1.7, P<0.001, RTI, euthyroid: 1.19±0.41 vs. subclinical hypothyroid: 0.92±0.35, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 0.84±0.30, P<0.001). Multivariable analysis demonstrated that low SMI, low RTI [hazard ratio (HR): 3.35, P<0.001], and preoperative high serum TSH levels (HR: 2.54, P=0.003) were independent predictive factors for hypothyroidism. Patients who had low SMI, low RTI, and preoperative high serum TSH levels were more likely to develop hypothyroidism (68.8%) than those with either one (25.3%), two (47.8%), or none (15.2%) of these three factors. Conclusions: Preoperative evaluation of the SMI, RTI, and serum TSH levels may be useful in predicting the development of post-hemithyroidectomy hypothyroidism.

CSLEX (Sialyl Lewis X) is a useful tumor marker for monitoring of breast cancer patients.

BACKGROUND: CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. METHODS: The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. RESULTS: Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). CONCLUSIONS: These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

Full-thickness chest-wall resection followed by thorax reconstruction for recurrent malignant phyllodes tumor.

We present a case of a 39-year-old woman with a giant recurrent malignant phyllodes tumor accompanied with bleeding and infection. She underwent full-thickness chest-wall resection. Bony thorax reconstruction and stabilization was accomplished using a Composix mesh™, and soft tissue reconstruction was performed with a musculocutaneous flap of latissimus dorsi muscle. The patient had a good postoperative outcome, and the surgical treatment remarkably improved her quality of life. Because chemotherapy and radiation are not established for treating malignant phyllodes tumors, an aggressive surgical approach should be considered for patients with a locally advanced malignant phyllodes tumor.

[A retrospective study of high-dose toremifene treatment for patients with aromatase inhibitor refractory advanced or metastatic hormone receptor-positive breast cancer].

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.

Prognostic Nutritional Index Is Superior to Neutrophil-to-lymphocyte Ratio as a Prognostic Marker in Metastatic Breast Cancer Patients Treated With Eribulin.

BACKGROUND/AIM: The prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) are prognostic markers for operable breast cancer. However, their importance in patients with metastatic breast cancer (MBC) remains unclear. This study aimed to evaluate these parameters as prognostic markers in MBC patients treated with eribulin. PATIENTS AND METHODS: A total of 60 patients with MBC treated with eribulin were included. RESULTS: Although high PNI and low NLR were correlated with better progression-free survival (PFS) and overall survival (OS), PNI had stronger impact as prognostic marker than NLR (PNI: HR=0.35, p=0.0008 for PFS and HR=0.27, p=0.0068 for OS; NLR: HR=0.71, p=0.081 for PFS and HR=0.63, p=0.14 for OS). Multivariate analysis demonstrated that PNI was an independent predictor of PFS (HR=0.30, p=0.0009). CONCLUSION: PNI could be a more reliable prognostic marker for MBC patients treated with eribulin than NLR.

Concomitant use of 18F-FDG PET-CT SUVmax is useful in the assessment of Ki67 labeling index in core-needle biopsy specimens of breast cancer.

BACKGROUND: Ki67 is a recognized proliferative and predictive marker in invasive breast cancer. However, results of Ki67 evaluation are affected by the method employed for sample fixation or biopsy, as well as by intratumor heterogeneity. Here, we aimed to compare the Ki67 labeling index (Ki67LI) between core-needle biopsy specimens (CNBSs) and surgically resected specimens (SRSs) of invasive breast cancer, and verify whether the discordance in Ki67LI can be reduced by analyzing the maximum standardized uptake value (SUVmax) obtained from pretreatment whole-body positron emission tomography/computed tomography (PET/CT) in combination with Ki67LI. METHODS: Tumor tissues were obtained from 118 patients with invasive breast cancer. Ki67LI was evaluated in CNBSs and SRSs by immunohistochemistry. First, we directly compared Ki67LI between CNBS and SRS, "allowing a tolerance margin of 5%." We divided the Ki67LI values into three groups (Low: 0≤ Ki67LI ≤10, Intermediate: 10< Ki67LI <30, and High: 30≤ Ki67LI) and the SUVmax into three groups (SUVmax ≤4, 4< SUVmax <8, and 8≤ SUVmax). We then verified the concordance rate between CNBS and SRS in each group in combination with the SUVmax obtained by PET/CT. RESULTS: The median Ki67LI was 17.8% (0.5-75.9%) and 17.0% (1.0-75.7%) in CNBS and SRS, respectively. The overall Ki67LI concordance rate between CNBS and SRS was 37.3% (44/118). The concordance was improved in the Low and High Ki67LI groups by applying SUVmax thresholds of 4 [82.6% (19/23), P=0.033 and 8 (92.3% (12/13), P=0.009], respectively. CONCLUSIONS: Our results indicated that CNBS Ki67LI alone was not able to reflect SRS Ki67LI with sufficient accuracy. By dividing CNBS Ki67LI into three classes in combination with SUVmax, tumor proliferation could be predicted with higher accuracy in patients with invasive breast carcinoma.