[Successful Treatment of Estrogen Receptor Positive, HER2 Negative Breast Cancer with Life-Threatening Multiple Bone Metastases Using the Combination of Fulvestrant and Palbociclib-A Case Report].

Palbociclib, a CDK4/6 inhibitor, is found to be an effective therapeutic drug in the treatment of estrogen receptor positive (ER+)metastatic breast cancer. In this report, we describe a case of rapid progression of life-threatening multiple bone metastases of breast cancer treated with a combination of fulvestrant and palbociclib. The patient, a 58-year-old postmenopausal woman, was diagnosed with left breast cancer at the age of 43 years and underwent breast-conserving surgery. After the completion of postoperative adjuvant endocrine therapy and radiotherapy, the patient was placed on regular follow-up. Eleven years after the surgery, multiple bone metastases and multiple lymph node metastases occurred, and the patient was treated with letrozole as first-line therapy for recurrent breast cancer. Although she continued to receive this treatment for 2 years and 10 months, her general condition worsened due to the occurrence of new liver metastases and the rapid progression of existing metastatic lesions. Thus, she was sent to an emergency room. Marked hypercalcemia and a severe decrease in erythrocyte and platelet counts were observed, which could be the cause of her worsening general condition. Her performance status(PS)was 4, and palliative treatment was also considered. However, she received treatment for hypercalcemia and red blood cell transfusion; as a result, she recovered to the PS 2 where she could begin chemotherapy. Then, she began a treatment consisting of a combination of fulvestrant and palbociclib as a second-line treatment for the recurrence. The patient responded well to the treatment, and her general condition improved to PS 1. She has since maintained a good quality of life for 2 years and 11 months without serious adverse events. In conclusion, the combination of fulvestrant and palbociclib has a low risk of serious adverse events and is a worthwhile treatment for rapidly progressing, life-threatening multiple bone metastases of breast cancer.

[A Case of Breast Mucinous Carcinoma with Bladder Metastasis Effectively Treated with Endocrine Therapy and Chemotherapy].

A 57-year-old Japanese woman underwent partial mastectomy of the right breast and sentinel lymph node biopsy in July 2005. The diagnosis was mucinous carcinoma with negative margins and no lymph node metastases(pT1cN0M0, pStage Ⅰ A). Postoperative adjuvant therapy included radiation therapy and oral administration of anastrozole for 5 years. In December 2015, we observed enlargement of left supraclavicular lymph nodes; a needle biopsy revealed lymph node metastases from breast cancer. We administered toremifene and the swelling disappeared. The patient was subsequently referred to the hospital for urinary frequency in November 2016. Imaging demonstrated a bladder tumor. Transurethral biopsy of bladder revealed adenocarcinoma with mucin production consistent with breast primary. After systemic chemotherapy(UFT, eribulin), endocrine therapy(fulvestrant), and molecular targeted therapy(palbociclib), her urologic symptoms were relieved. However, 2 years and 8 months after diagnosis of bladder metastasis, the patient showed disease progression and decided to discontinue all chemotherapy and pursue palliative care. We also present a review and discussion of the relevant literature.

Atypical femoral fracture in patients with bone metastasis receiving denosumab therapy: a retrospective study and systematic review.

BACKGROUND: While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy. METHODS: To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions. RESULTS: The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF. CONCLUSIONS: We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.

Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety.

BACKGROUND: This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer. METHODS: Patients with HER2-positive, stage I-III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m2, day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks. The primary endpoint was pathological complete response (pCR) of both breast and axillary lymph node disease. RESULTS: Fifty patients were enrolled in this study. Median age was 58 (range 32-75) years. All patients underwent definitive surgery. Thirty-three (66%) patients completed the chemotherapy course, while the treatment was delayed or discontinued in the other 17 (34%) patients because of adverse events (AEs). The pCR rate was 52%; the overall response rate was 66%. Grade 3/4 AEs due to nonhematological toxicity were anorexia (4%), diarrhea (2%), and rash (2%), and those due to hematological toxicity were neutropenia (36%), anemia (12%), and thrombocytopenia (2%). CONCLUSION: Although the triweekly six-course regimen of TCbH achieved a high pCR rate, hematological AEs frequently occurred during the latter part of the chemotherapy course. One-third of patients experienced delayed or discontinued chemotherapy. Clinical registration number: http://www.umin.org.au UMIN000013513.

Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.).

In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: a comparison to bevacizumab.

BACKGROUND: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents. METHODS: Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO2) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies. RESULTS: Baseline DOSI measurement of all 29 patients (eribulin, n=14 and bevacizumab, n=15) revealed significantly higher tumour concentrations of O2Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O2Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF-ß1. CONCLUSIONS: Eribulin, but not bevacizumab, treatment increased tumour SO2. Suppression of TGF-ß1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.

Phase I study of weekly nab-paclitaxel combined with S-1 in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer.

We conducted a phase I study of a weekly nab-paclitaxel and S-1 combination therapy in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. The primary objective was to estimate the maximum tolerated and recommended doses. Each treatment was repeated every 21 days. Levels 1, 2a, 2b, and 3 were set depending on the S-1 dose (65 or 80 mg/m(2) ) and nab-paclitaxel infusion schedule (days 1 and 8 or days 1, 8, and 15). Fifteen patients were enrolled. Dose-limiting toxicity was observed in one patient at Level 3 (100 mg/m(2) nab-paclitaxel on days 1, 8, and 15 with 80 mg/m(2) S-1 daily for 14 days, followed by 7 days of rest). Although the maximum tolerated dose was not reached, the recommended dose was determined to be Level 3. Neutropenia was the most frequent grade 3-4 treatment-related adverse event. For patients with measurable lesions, the response rate was 50.0% and the median time to treatment failure and median progression-free survival was 13.2 and 21.0 months, respectively. The present results show the feasibility and potential for long-term administration of this combination therapy.

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety.

OBJECTIVE: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. METHODS: Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. RESULTS: Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. CONCLUSION: Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management.

[Progress in second-line therapies for metastatic breast cancer].

It may be difficult to achieve complete cure for most metastatic breast cancer patients;thus, prolongation of overall survival and maintenance of the quality of life are often the main focus of treatment. In the treatment of metastatic breast cancer patients, it is important to choose the most appropriate therapeutic strategy based on substantial evidence that considers the biology of the tumor, including estrogen receptor(ER), progesterone receptor(PgR), and human epidermal growth factor receptor 2(HER2)status;the site and extent of the metastatic focus;the time to recurrence;prior treatment regimens;age; menopausal status;performance status;and the preference of the patient. A clinical subtype classification that is based on the tumor biology is typically utilized for devising a treatment strategy specific to each subtype. Expressly, first-line treatment options may include hormone therapy for hormone-positive breast cancers, antiHER2 therapy for HER2-positive breast cancers, and chemotherapy for hormone-negative and HER2-negative(triple negative)breast cancers. In recent years, with the development of regimens that are effective for every subtype, the treatments for breast cancer have undergone significant changes. In this section, we introduce the progress in the treatment for metastatic breast cancer, focusing specifically on second-line therapies according to each subtype.

Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy.

Near-infrared diffuse optical spectroscopy (DOS) imaging can non-invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time-resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2 ) of the tumors was compared with clinicopathological variables and 10-year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis . Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10-year relapse-free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.

Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast.

BACKGROUND: Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer. METHODS: Fifty-five consecutive TNM stage I/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as "hotspots," while others were considered "uniform." The findings in either tumor type were compared with clinicopathological factors. RESULTS: "Hotspot" tumors were significantly larger (P= 0.002) and exhibited significantly more advanced TNM stage (P=0.01), higher mitotic counts (P=0.01) and higher levels of FDG uptake (P=0.0004) compared with "uniform" tumors; however, other pathological variables were not significantly different between the two groups. CONCLUSIONS: Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment.

[Successful treatment of trastuzumab-resistant HER2-positive breast cancer with extensive liver metastases using the combination of trastuzumab and capecitabine - a case report].

We report a case of a trastuzumab-resistant human epidermal growth factor receptor-2(HER2)-positive breast cancer patient with extensive liver metastases and associated impaired liver function, who showed an excellent response to the combination of trastuzumab and capecitabine. The patient was a 59-year-old postmenopausal woman with multiple liver metastases at first examination. She first received anthracycline-based chemotherapy, and after progression was followed up with a combination of trastuzumab and paclitaxel. Despite an initial response to this treatment, liver metastases rapidly progressed. Although palliative treatment was considered because of her impaired liver function, she received capecitabine while continuing trastuzumab. This combination therapy showed an excellent response, and a good quality of life(QOL)was maintained for a long time without any severe adverse events. The continuation of trastuzumab is considered effective after having progressed by trastuzumab including pretreatment, and we consider it worth while to give a combination of trastuzumab and capecitabine to patients with extensive liver metastases and associated impaired liver function, because of the treatment's synergistic effect and low risk of causing severe adverse events.

Immunohistochemical detection of breast cancer stem cells in hormone receptor-positive breast cancer and their role in response to endocrine therapy and clinical outcome.

BACKGROUND: Breast cancer stem cells are rich in triple negative or human epidermal growth factor receptor-2-positive breast cancers. The role of these stem cells in hormone receptor-positive breast cancers is unknown. Therefore, we launched this retrospective biomarker analysis to clarify the role of stem cells in relation with endocrine therapy in hormone receptor-positive breast cancer. METHODS: Formalin-fixed paraffin-embedded tissue samples from primary stage IV, hormone receptor-positive breast cancers prior to endocrine therapy were obtained from 4 cancer centers in Japan between 1999 and 2008. We examined the expression of ALDH1 and CD44/CD24 in breast tissue and correlated the results with response to endocrine therapy and patient prognosis. RESULTS: ALDH1-positive and CD44+ CD24- cancer cells were found in 16% of 92 samples and 27% of 77 samples, respectively. Response to endocrine therapy was similar in the ALDH1-positive and ALDH1-negative tumor groups, and between CD44+ CD24- and other tumor groups. After a median follow-up period of 793 days, neither ALDH1 positivity nor CD44+ CD24- status of tumor cells was related to progression-free survival (ALDH1 positive vs. negative, 378 vs. 292 days, p = 0.53; CD44+ CD24- vs. others, 224 vs. 269 days, p = 0.52) or overall survival (ALDH1 positive vs. negative, 1,348 vs. 1,479 days, p = 0.17; CD44+ CD24- vs. others, 1,071 vs. 1,462 days, p = 0.54). CONCLUSIONS: There is no correlation between biomarker expression and outcome in hormone receptor-positive breast cancer.

18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response.

BACKGROUND: To assess the usefulness of positron emission tomography combined with computed tomography using (18)F-fluorodeoxyglucose (FDG PET/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. METHODS: One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. RESULTS: Tumors with pCR had significantly higher baseline SUV (9.3 ± 3.7 SD) compared to those with non-pCR (7.2 ± 3.8 SD) (p = 0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. CONCLUSION: The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR.

[A case of primary breast cancer responding to pre-operative chemotherapy with the combination of paclitaxel and carboplatin for ovarian cancer].

A 62-year-old woman was diagnosed with primary left breast cancer during a follow-up for an ovarian tumor. She had at first undergone surgical resection of an ovarian tumor, and a pathological examination had revealed ovarian cancer. Gynecologists decided to treat her ovarian cancer with chemotherapy, and we were initially planning to provide treatment for breast cancer after that was completed. Sentinel lymph node biopsy performed before chemotherapy revealed no axillary metastases. The patient received six courses of intravenous PTX (175 mg/m2 on day 1, every 3 weeks) and intravenous CBDCA (AUC6 on day 1, every 3 weeks) as combination therapy. Abdominal lymph node dissection was performed between chemotherapy courses 3 and 4. The lump in the left breast showed partial clinical response, and partial resection of the left breast was performed after completion of chemotherapy. In Japan, few cases of primary breast cancer treated preoperatively using carboplatin-containing regimens have been described.

BiClamp forceps significantly shorten the operation time for breast surgery.

PURPOSE: A novel approach was introduced for breast surgery using the BiClamp, a new bipolar thermal energy device, to avoid complications and to shorten the time required for the dissection of the axillary lymph nodes. METHODS: Thirty-six patients with early breast cancer were assessed. The surgical parameters were compared between the procedures performed using the BiClamp technique (n = 14) and conventional surgery with suture ligation (n = 22). The parameters included the operation time, blood loss, and discharge on the first postoperative day. In addition, each of those parameters was compared between the patients with a high body mass index (BMI) (>22) and a low BMI (< or =22). The sealed vessels were examined histologically and heat-associated morphological vessel wall alterations were evaluated. RESULTS: The operation time was significantly shorter in the BiClamp group than in the control group (P = 0.017, 90 +/- 18 vs 115 +/- 33 min). In addition, the blood loss in the BiClamp group tended to be smaller than in the control group, but the difference was not significant (P = 0.54, 61 +/- 47 vs 74 +/- 67 g). No other parameters showed any significant differences between the two groups. CONCLUSION: The BiClamp thermofusion technique was safe and useful in breast surgery involving axillary dissection.

Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer.

OBJECTIVE: Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer. METHODS: Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC). RESULTS: High SUV level was significantly correlated with tumor invasive size (< or = 2 cm) (P < 0.0001), higher score of nuclear grade (P < 0.0001), nuclear atypia (P < 0.0001) and mitosis counts (P < 0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P < 0.0001,< 0.0001, and < 0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P < 0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P < 0.0001). CONCLUSIONS: High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pre-therapeutically predict biological characteristics and baseline risk of breast cancer.

Squamous cell carcinoma of the breast in the form of an intracystic tumor.

Squamous cell carcinoma of the breast is thought to arise through metaplasia of ductal carcinoma cells. We report a case of pure squamous cell carcinoma of the breast with features of intracystic tumor, which was considered to have arisen from metaplastic squamous epithelial cells lining the cyst wall. A 71-year-old woman presented at our hospital with a 40 x 30-mm mass in the lower outer quadrant of the right breast. Mammography revealed a round, high-density mass, which had a mostly regular but partially irregular margin. Ultrasonography demonstrated a solid tumor with an irregular shape protruding into a cystic space, suspicious of intracystic carcinoma. Aspiration cytology confirmed squamous cell carcinoma. A modified radical mastectomy was performed. Histopathologically, the intracystic tumor was a pure squamous cell carcinoma. The epithelial cells lining the inner cyst wall showed mostly squamous metaplasia, and there was continuity between these cells and the squamous cell carcinoma. 13 months later, the patient is free of disease with no adjuvant therapy.