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.

[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.

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.

[Automatic Quantification of Breast Density from Mammography Using Deep Learning].

BACKGROUND: In the field of breast screening using mammography, announcing to the examinees whether they are dense or not has not been deprecated in Japan. One of the reasons is a shortage of objectivity estimating their dense breast. Our aim is to build a system with deep learning algorithm to calculate and quantify objective breast density automatically. MATERIAL AND METHOD: Mammography images taken in our institute that were diagnosed as category 1 were collected. Each processed image was transformed into eight-bit grayscale, with the size of 2294 pixels by 1914 pixels. The "base pixel value" was calculated from the fatty area within the breast for each image. The "relative density" was calculated by dividing each pixel value by the base pixel value. Semantic segmentation algorithm was used to automatically segment the area of breast tissue within the mammography image, which was resized to 144 pixels by 120 pixels. By aggregating the relative density within the breast tissue area, the "breast density" was obtained automatically. RESULT: From each but one mammography image, the breast density was successfully calculated automatically. By defining a dense breast as the breast density being greater than or equal to 30%, the evaluation of the dense breast was consistent with that by a computer and human (76.6%). CONCLUSION: Deep learning provides an excellent estimation of quantification of breast density. This system could contribute to improve the efficiency of mammography screening system.

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.

Axillary ultrasound examination is useful for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy.

BACKGROUND: Controversy surrounds the reliability of sentinel lymph node biopsy after primary systemic chemotherapy. In this study, we assessed axillary ultrasound for selecting patients most likely to optimally benefit from biopsy. METHODS: The study included 87 patients who received primary systemic chemotherapy and underwent a sentinel lymph node biopsy followed by axillary lymph node dissection. Lymph nodes >10 mm in diameter, irregularly swollen, round, and homogeneously hypoechoic without an echo-rich center were considered axillary ultrasound positive. RESULTS: In axillary ultrasound-negative patients before and after primary systemic chemotherapy, identification, sensitivity, and false-negative rates were 81%, 100%, and 0%, respectively. However, in patients whose lymph nodes converted from positive to negative after primary systemic chemotherapy, these values were 83%, 70.8%, and 29.2%, respectively. CONCLUSIONS: Axillary ultrasound-negative patients before and after primary systemic chemotherapy were suitable for sentinel lymph node biopsy. Axillary ultrasound should be used during primary systemic chemotherapy and before surgery.

A false positive for metastatic lymph nodes in the axillary region of a breast cancer patient following mastectomy.

Recent advanced imaging modalities such as positron emission tomography (PET) detect malignancies using 2-[18F]-fluoro-2-deoxy-D: -glucose (18-FDG) with high accuracy, and they contribute to decisions regarding diagnosis, staging, recurrence, and treatment response. Here, we report a case of false-positive metastatic lymph nodes that were diagnosed by PET/CT and ultrasonography in a 48-year-old breast cancer patient who had undergone mastectomy. The tumors, which were oval shaped and resembled lymph nodes, were detected by ultrasonography. PET/CT revealed high uptake of 18-FDG in the tumors. To investigate the proposed recurrence and to re-evaluate the biology of the recurrent tumors, a tumor was removed from the brachial plexus of the patient. Histological findings revealed it to be a schwannoma. All imaging modalities including PET/CT failed to distinguish benign tumors from metastatic lymph nodes in the brachial plexus. After resection of the schwannomas, the patient complained of a slight motor disorder of the second finger on the right hand. Hence, it is important to consider a false-positive case of lymph node metastasis in a breast cancer patient following mastectomy.

Successful treatment of leptomeningeal metastases from breast cancer using the combination of trastuzumab and capecitabine: a case report.

We report a case of metastatic breast cancer with leptomeninges and multiple bone metastases that showed an excellent response to the combination of trastuzumab and capecitabine; therapeutic effect was evaluated by MRI at follow-up. A 44-year-old woman underwent modified radical mastectomy in February 1997. In April 2003, a tumor at the right basis cerebri and multiple bone metastases were noted, and in October 2003, she underwent enucleation of the tumor. Histopathologically, the tumor was consistent with a basal skull metastasis from breast cancer. In March 2004, the patient began to experience pain, weakness, and paresthesia of both legs. She was diagnosed, with leptomeningeal metastasis (LM) from breast cancer using MRI. In December 2005, the combination of trastuzumab and capecitabine administered as sixth-line treatment was very effective for LM. Although it is generally very difficult to diagnose LM and assess the therapeutic effect with MRI, in this case, it was possible. To our knowledge, there has been no report in the literature describing the combination of trastuzumab and capecitabine for LM from breast cancer. Although the mechanism underlying the efficacy of this combination is still unknown, the treatment would be worth trying because of its few side effects in extensively treated patients with LM from breast cancer. To confirm the antitumor efficacy of trastuzumab and capecitabine, however, further investigations are required.

Churg-Strauss syndrome manifesting as perforation of the small intestine: report of a case.

We report a case of Churg-Strauss syndrome (CSS) causing perforation of the small intestine. A 51-year-old woman was admitted with an asthma attack and paralysis of both legs. Intravenous predonisolone (40 mg) was given to relieve her asthma. Laboratory data on admission showed leukocytosis with hypereosinophilia and a high level of serum IgE. Neurological examination also revealed mononeurutis multiplex. Based on these findings, we diagnosed CSS, and oral corticosteroids were continued. On the 20th day after admission, she suffered sudden abdominal pain. Abdominal X-ray showed free air in the abdomen, suggesting perforation of the gastrointestinal tract. Emergency laparotomy revealed generalized peritonitis caused by a perforated ulcer of the ileum. The resected specimens contained a perforation and multiple nonperforated ulcers with an irregular shape on the mucosal surface. Histopathological examinations revealed angiitis of the small vessels surrounded by eosinophilic infiltration and granuloma, consistent with CSS. Considering the high risk of perforation of the gastrointestinal tract, including the small intestine, during corticosteroid treatment in patients with CSS, any abdominal pain or discomfort must be investigated carefully.

Situs inversus totalis with malignant lymphoma of the stomach: report of a case.

Situs inversus totalis is a rare congenital anomaly that often occurs concomitantly with other disorders. We report a case of situs inversus totalis with malignant lymphoma of the stomach, which was successfully treated by surgery followed by chemotherapy and irradiation. The patient was a 51-year-old woman who present with colicky pain in the left upper quadrant of her abdomen. Chest X-ray showed a right-sided heart, and ultrasonography and computed tomography (CT) of the abdomen showed a situs inversus totalis with multiple gallstones in the gallbladder. Tree-dimensional reconstructed CT of the abdomen showed no other malformations coexisting with situs inversus totalis, but a barium upper gastrointestinal series found an inverted stomach and an elevated tumor with ulceration in the center, localized in the antrum of the stomach. First, we performed a cholecystectomy, followed by a total gastrectomy with dissection of the lymph nodes and splenectomy, and Roux-en-Y reconstruction. Histopathological examination confirmed a diagnosis of malignant lymphoma of the stomach (diffuse large B-cell type) with metastasis to the regional lymph nodes. Chemotherapy using the CHOP regimen was given three times, starting 1 month postoperatively. A followup CT scan showed enlargement of one lymph node around the abdominal aorta and irradiation was delivered to the area of the inverted Y in the abdomen. At the time of writing, 10 months after surgery, the patient is well with no signs of recurrence and leading a normal life. Careful preoperative assessment is very important for determining the most appropriate surgical procedure in patients with situs inversus totalis associated with a malignancy.