Bone Scan Index predicts skeletal-related events in patients with metastatic breast cancer.

BACKGROUND: Bone Scan Index (BSI) expresses tumor burden in bone as a percentage of total skeletal mass, but its significance for metastatic breast cancer patients is unknown. We investigated whether baseline BSI is associated with skeletal-related events (SREs) or survival and identified the cut-off BSI score for predicting SREs in metastatic breast cancer patients. METHODS: We retrospectively reviewed 144 patients with bone metastatic breast cancer. Bone scan examinations were performed and BSI was calculated using the Bonenavi(®) automated method. All patients received standard medical treatment for metastatic breast cancer. For bone metastasis prophylaxis, bisphosphonates were infused initially with analgesics as needed. We defined SRE as either bony, requiring intervention (surgery and/or radiotherapy) for pain or prevention of fracture, or spinal cord compression. The rates of SRE and overall survival (OS) were evaluated according to baseline BSI, and the cut-off score of BSI for predicting SRE in metastatic breast cancer patients was identified. RESULTS: Thirty-three patients (25.6 %) had SREs. The median BSI was 1.08 % (inter-quartile range 0.50-3.23 %). To identify the cut-off BSI score for predicting SRE, we performed sensitivity analysis to check P-value at every 0.1 BSI interval (0.4-2.4) by multiple-variable proportional hazard analysis. A BSI cut-off point of 1.4 % showed the lowest P value. Patients with BSI scores ≥1.4 had a significantly higher rate of SRE than those with lower BSI (P = 0.022). However there was no significant difference in OS. CONCLUSION: BSI may predict SRE in patients with metastatic breast cancer. A high BSI value (≥1.4) at diagnosis of bone metastasis may be a predictor of SREs in bone metastatic breast cancer patients.

Impact of intrinsic subtype on predicting axillary lymph node metastasis in breast cancer.

Axillary lymph node (LN) metastasis is one of the most important prognostic factors for the survival of breast cancer. The correlation between LN metastasis and the tumor (T) category has previously been investigated in certain case series. At present, the initial treatment approach is to define the intrinsic subtype, as it is significant in determining medical treatments, as well as being a prognostic factor. However, the intrinsic subtype is not known to predict the frequency of LN metastasis. The aim of the present study was to evaluate the frequency of LN metastasis with regard to tumor size according to the intrinsic subtype. In total, 654 patients with primary breast cancer were evaluated who underwent surgical resection between 2010 and 2011 at the Aichi Cancer Center Hospital (Nagoya, Aichi). The clinical and pathological data were analyzed for patients who underwent an axillary LN dissection or a sentinel LN biopsy for primary breast cancer. The intrinsic subtype of the primary tumors was classified using immunohistochemical staining of thin, paraffin-embedded sections. In total, 157 (24.0%) of the 654 patients exhibited LN metastasis, and according to the primary tumor category, a larger tumor size was found to correlate with a higher proportion of LN positivity, as well as with the luminal A subtypes (n=364). In luminal B subtypes (n=110), T1a (n=2), T1b (n=12), T1c (n=55), T2 (n=34), and T3 (n=2) exhibited 50, 8.3, 38.2, 55.9 and 50% LN positivity, respectively. In luminal-human epidermal growth factor receptor 2 (HER2) subtypes (n=46), T1c (n=17), T2 (n=10), and T3 (n=1) exhibited 40.1, 60 and 100% LN positivity, respectively. In HER2 subtypes (n=53), T1a (n=6), T1b (n=4), T1c (n=15), and T2 (n=10) exhibited 16.7, 25, 46.7 and 60% LN positivity, respectively. In triple-negative subtypes (n=81), T1b (n=15), T1c (n=29), T2 (n=20), and T3 (n=2) exhibited 26.7, 24.1, 50 and 50% LN positivity, respectively. In conclusion, the intrinsic subtype is significant in predicting the frequency of LN metastasis with regard to tumor size.

[Assessment of the clinical efficacy and safety of fulvestrant in heavily pretreated patients with hormone-receptor positive metastatic breast cancer-a single-institution experience].

Fulvestrant, a pure estrogen receptor antagonist with no known agonist effects, was approved in September 2011 for the treatment of hormone-receptor positive metastatic breast cancer(MBC)in postmenopausal women in Japan. Here, we present a retrospective review of data from 73 heavily pretreated patients who received a high-dose regimen of fulvestrant in our hospital. Patients received a median of 3 endocrine therapies(range: 1-7)prior to the fulvestrant regimen. Partial response was observed in 4 patients, and 10 patients experienced stable disease for more than 6 months(objective response rate: 5.5%; clinical benefit rate: 19.2%). The median time to progression was 2.8 months. Fulvestrant was well tolerated; however, Grade 3 neuropathy at the injection site was observed in 2 patients. Of 12 patients, 3 responded to endocrine therapy following fulvestrant treatment. Our clinical experience indicates that fulvestrant can be administered to patients pretreated with several lines of endocrine therapy, although its efficacy as first- or second-line endocrine therapy has been demonstrated in clinical trial settings.

[Clinical efficacy and safety assessment of eribulin monotherapy in patients with metastatic breast cancer - a single- institute experience].

Eribulin mesylate, a novel microtubule inhibitor with a unique mechanism of action, was approved in Japan in April 2011 for the treatment of metastatic breast cancer patients who had been administered at least two prior chemotherapeutic agents. Here, we present a retrospective review of data from 27 patients who received eribulin monotherapy in our hospital. The overall response rate and clinical benefit rate were 25. 9% and 29. 6%, respectively, and the median progression-free survival was 9. 9 weeks(95% CI: 3. 5-16. 2 weeks). The toxicities of treatment were tolerable and manageable; responses were lower in patients who were triple negative subtype, and higher in patients who had responded to prior taxane treatment. The relative dose intensity of our data indicates that appropriate modification of dose and schedule may be an important part of eribulin monotherapy.

Long-term results of surgery for papillary thyroid carcinoma with local recurrence.

PURPOSE: Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. METHODS: A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. RESULTS: The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. CONCLUSIONS: Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.

Phase I/II study of intraoperative radiotherapy for early breast cancer in Japan.

BACKGROUND: Intraoperative radiotherapy (IORT) is under evaluation in breast-conserving surgery. We have begun our study with the first step being a phase I-II study. This study was designed to identify the recommended dose and to test the feasibility of and tolerance to IORT in Japanese patients (UMIN000000918). METHODS: A phase I study was designed using a scheme of dose escalation from 19 to 20 to 21 Gy. We designed the phase II study to use the recommended dose. The primary endpoint was early toxicity. Secondary endpoints were efficacy for a long period and late toxicity. Inclusion criteria included the following: (1) T < 2.5 cm, (2) age >50 years, (3) surgical margin >1 cm, (4) intraoperative pathologically free margins, and (5) sentinel node negative. Partial resection was performed with at least a 1 cm margin around the tumor. Radiation was delivered directly to the mammary gland with the use of a Mobetron(®). The toxicity was evaluated with the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. RESULTS: Nine patients were enrolled for the phase I study. All patients tolerated and we therefore recommend 21 Gy. The following 23 patients were enrolled in a phase II study and received 21 Gy. After a median follow-up of 26.0 months, their toxicities within 3 months included deep connective tissue fibrosis (G1 23/26, G2 2/26), hematoma (G1 9/26), infection in the musculoskeletal soft tissue (G1 4/26), and soft tissue necrosis (G2 3/26). There have been no local recurrences. CONCLUSIONS: The first group of Japanese female patients treated with IORT showed very good tolerability in the phase I/II study.

The effect of toremifene on lipid metabolism compared with that of tamoxifen in vitro.

BACKGROUND: Tamoxifen (TAM) and toremifene (TOR) prevent estrogen from stimulating breast cancer growth and also have agonistic effects in a number of physiological systems. TAM is known to increase intracellular triglyceride, but the action of TOR on lipid metabolism in vitro has not yet been determined. AIM: To compare the effect of TOR on lipid metabolism with that of TAM in vitro, using HepG2 cell lines. METHODS: Intracellular concentrations of total cholesterol and triglyceride in HepG2 cells were measured by an enzymatic method after TAM or TOR treatment. RESULTS: Intracellular concentrations of total cholesterol were decreased by both TAM and TOR, but not significantly different from the control level. TOR produced no changes in the intracellular concentrations of triglyceride, whereas TAM increased the intracellular concentrations of triglyceride at concentrations ranging from 10(-7) to 10(-5) mol/l of TAM (p < 0.05). Moreover, significant differences were noted between the two treated groups at concentrations ranging from 10(-9) to 10(-5) mol/l (p < 0.05). CONCLUSION: TOR treatment did not increase intracellular concentrations of triglyceride, although TAM treatment did so.