Background: In breast cancer, HER-2 overexpression suggests s poor prognosis. Trastuzumab is a humanized monoclonal antibody with specificity to the HER-2 protein. We evaluated the safety and efficacy of combined trastuzumab and paclitaxel therapy in women with metastatic breast cancer.
Patients and Methods: Combination chemotherapy was given to patients with HER-2 overexpressing metastatic breast cancer. All patients had previously received one or more chemotherapy treatments. Patients received a loading trastuzumab dose of 4 mg/kg intravenously (i.v.), followed by 2 mg/kg maintenance dose at weekly intervals. A paclitaxel dose of 80 mg/m² was administered on the same day as the trastuzumab infusion.
Results: A total of 53 patients were examined. Seventy percent received two or more prior chemotherapy treatments for metastatic breast cancer, and 66.0% of patients had two or more metastatic sites. The overall response rate to our approach was 37.7%. Median time to progression was 12.0 months. Grade 3/4 neutropenia was seen in only 11.3% of patients. Peripheral neuropathy occurred in 65.1% of patients after seven treatments, requiring us to change to biweekly paclitaxel administration in 16 patients. Most of them were able to continue the treatment. Other toxicities were mild and tolerable.
Conclusion: Combined trastuzumab and paclitaxel therapy, administered as second-line or later treatment, produced lasting objective responses and was well tolerated by women with HER-2 overexpressing metastatic breast cancer. A major obstacle to continuing treatment was peripheral neuropathy. However, modifying the interval to every 2 weeks enabled us to continue the treatment. This combination chemotherapy was safely performed in our outpatient clinic.

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Background: It has been reported that 5'-deoxy-5-fluorouridine (5'-DFUR), the pro-drug of 5-FU, is effective treatment for breast cancer that express thymidine phosphorylase (dThdPase). Since oral cyclophosphamide (CPA) induces dThdPase, a synergistic effect can be expected by combining CPA with 5'-DFUR. We evaluated the usefulness of combination chemotherapy using CPA and 5'-DFUR in patients with relapsed breast cancer in this prospective phase II study.
Methods: Patients with relapsed, advanced breast cancer with evaluable lesions were given 5'-DFUR at 800 mg/day/body and CPA at 100 mg/day/body for 2 weeks, then underwent 2 weeks of drug withdrawal. This was considered one course of treatment. It was repeated until progressive disease (PD) was confirmed. The lesions were evaluated according to UICC criteria and compared with regard to the clinical status.
Results: Sixty-four patients with relapsed, advanced breast cancer were registered. Complete response (CR) was seen in 7 patients, partial response (PR) in 12 patients, no change (NC) in 25 patients, of whom 11 achieved long NC with the effect lasting for more than 6 months, and PD was seen in 20 patients. The response rate was 29.7%. The total number of CR, PR, and long NC cases was 30, which comprise-46.9% of the total 64 cases (the clinical benefit rate). As for adverse events, hematological toxicities were seen in 9 patients, with grade 3 toxicits was seen in 1 patient. All other adverse events were grade 1 or 2.
Conclusion: For those patients who achieved an effect more than NC, it was possible to continue the therapy for an average of 53 weeks. This treatment method is worth considering for patients who have metastatic breast cancer, that is not life threatening.

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Sappey's demonstration of the breast lymphatic vessels, showing the presence of a subareolar lymphatic plexus and few thick vessels originating from the breast itself, is famous. However, with the exception of such studies performed by injection methods, to the best of our knowledge there has been no demonstration of the entire distribution of the breast lymphatic vessels. D2-40 immunohistochemistry of semiserial sections (at 0.1-mm intervals) taken from the healthy breast of a 20-year-old female cadaver revealed that the lymphatic endothelial density was much higher in and along the mammary glandular tissues than in the overlying subcutaneous and deep fascial tissues. Thus, the extent of the subareolar lymphatic plexus is likely to have been overestimated by the injection method. Instead, networks of lymphatic vessels around the mammary glands were evident in the physiological state.

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We report a rare case of pseudo-Meigs' syndrome due to metastasis of breast cancer to both ovaries. A 34-year-old woman with exertional dyspnea was admitted to our hospital. Before entry the patient had undergone radical mastectomy for left breast cancer in June 1998. Resection and reconstruction of the chest wall for recurrence of the breast cancer had been performed in April 2001. Right pleural effusion was found on admission to our hospital in October 2002. Continuous thoracic drainage obtained 500-2000 ml of fluid per day. Cytologic results were both normal and benign, and cultures for bacteria and acid-fast bacilli were negative. During treatment of the pleural effusion, which proved to be cryptogenic and intractable, a huge pelvic tumor was found. The primary site was unknown. Surgery was performed in November 2002, and tumors were removed from both ovaries. The right pleural effusion vanished after surgery. Pseudo-Meigs' syndrome with metastasis of breast cancer to both ovaries was diagnosed. The patient died of cachexia related to the carcinoma in January 2005.

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Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a common microscopic lesion that is found at breast biopsy, and presents with proliferation of the stromal cells and slit-like pseudovascular spaces with endothelial-like spindle cells. In contrast, nodular PASH is relatively rare. We report here a case of nodular PASH with multiple palpable masses.
A 49-year-old woman who had experienced gradual enlargement of her breasts for 13 years noticed an elastic but firm palpable mass in her breast. We were able to detect 7 masses in her right breast and 2 in the left. Ultrasonography and mammography demonstrated nonspecific findings, and FNA and CNB did not establish a diagnosis. An excisional biopsy was performed, and the pathological findings revealed nodular PASH. Eighteen months after the excisional biopsy, the size of the nodules and the whole breast had decreased remarkably. While the possibility of a change in the hormonal background or the influence of drugs was considered, we were not able to reach a single specific conclusion regarding the pathogenesis.

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We encountered two cases of ductal adenoma of the breast. In the first case, a 32-year-old woman presented with a two-year history of a left breast lump. Previous ultrasonography had demonstrated three tumors which were thought to be most likely fibroadenoma. On excisional biopsy of the largest , intraoperative pathological examination of frozen sections was suspicious for ductal carcinoma with a differential diagnosis of intraductal papilloma or intraductal papillary carcinoma. Ductal adenoma was diagnosed after pathological examination of the permanent sections.
The second case was a 64-year-old woman who presented with a hard lump in her left breast. Mammography and ultrasonography demonstrated images typical of carcinoma. Aspiration biopsy cytology (ABC) repeated twice was reported as “ indeterminate” . Excisional biopsy was later done. Ductal adenoma (sclerosing papilloma) with hemorrhagic infarction was diagnosed.
It is noteworthy that ductal adenoma have clinical and histopathological features that should be differentiated from carcinoma, especially when the tumor is accompanied by secondary changes such as hemorrhage or infarction.

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A case of ductal carcinoma in situ (DCIS) that was treated by partial mastectomy is reported. The operation was performed after accurate estimation of cancer spread by three-dimensional computed tomography (3D-CT). The patient was a 39-year-old woman without a palpable lump who had a bloody nipple discharge. Ultrasonography showed distended mammary ducts with intraductal components. Fine needle aspiration cytology revealed ductal carcinoma. Galactography showed two subsegmental ducts and peripheral branches in the upper-inner quadrant of the right breast. 3D-CT depicted a well enhanced segmental-clumped lesion including two subsegments of a duct lobular system shown in galactograms. DCIS was diagnosed and partial mastectomy following the video assisted thoracoscopic surgery (VATS) marker insertion was performed, after cancer spread was accurately diagnosed by 3D-CT guidance. DCIS resected by minimally sufficient partial mastectomy with negative surgical margins was diagnosed histopathologically.

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We reconstructed a large chest wall defect, resulting from the resection of a locally advanced breast carcinoma, using an external oblique myocutaneous flap. The patient, a 58-year-old Japanese woman, presented with an inoperable breast carcinoma (StageIV). Combination chemotherapy with cyclophosphamide (CPA) and epirubicin hydrochloride (EPI) resulted in a reduction in size of both the primary tumor and the metastatic lesions. However, the patient continued to experience purulent discharge accompanied by an unpleasant odor, as well as contact bleeding from the residual breast lesion. To address these complaints, we removed much of the remaining tumor surgically. The resulting skin defect measured 440 cm² and was covered using an external oblique myocutaneous flap. The patient's postoperative course was excellent, and she was still alive and well after 40 months of chemotherapy. This case is a demonstration of the effectiveness of the external oblique myocutaneous flap for the coverage of large ipsilateral chest wall defects.

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We present a case of low-grade angiosarcoma of the breast.
A 26-year old woman presented with a lump in the left breast. An elastic hard and ill-defined tumor, 80× 50 mm in size, was palpated in the upper region of her left breast. Mammography showed a dense lesion with poorly defined boarder. Ultrasonography showed a hyper-and hypo-echoic lesion with an unclear border, but no definite tumor. Fine needle aspiration cytology showed no evidence of malignancy. Therefore, she was followed with a diagnosis of mastopathy.
Six months later, the lump got enlarged. A contrast-enhanced MRI of the breast was performed. It showed a 100× 60 mm enhancing vascular mass. Most parts of the tumor enhanced remarkably at the early phase, and prolonged enhancement was recognized at the late phase. Core needle biopsy was performed, and a possible angiosarcoma was diagnosed.
It is not easy to diagnose the mammary angiosarcoma. MRI may contribute to the accurate diagnosis and play an important role regarding this entity.

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An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest® (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.

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We present a rare case of invasive right breast carcinoma in a 72-year-old woman with Behç's disease (BD). A radical modified right mastectomy and axillary lymphadenectomy were performed and postoperative hormonal therapy with the aromatase inhibitor anastrozole was administered for adjuvant therapy. At 10 months follow-up the patient remains disease free. Malignancies associated with BD are very uncommon. The pathological findings showed small vessel vasculitis and lobulitis of the breast in association with invasive carcinoma.

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We report a case of isoechoic axillary lymph node metastasis of mucinous carcinoma (so-called pure mucinous carcinoma) of the breast. A 47-year-old premenopausal woman was referred to our hospital with a 2 years history of mass and distortion of her left breast and with recent worsening of her symptoms. Ultrasonography demonstrated a well-circumscribed mass, about 5 cm in diameter, which was isoechoic compared to the surrounding fat tissue. Distal enhancement was also recognized. A left axillary ultrasonographic scan demonstrated four nodules, which were indistinct because of their isoechogenicity compared to the surrounding tissue. Based on a preoperative diagnosis of mucinous carcinoma of the left breast with left axillary lymph nodes metastases, left mastectomy and left axillary nodal dissection were performed. Mucinous carcinoma with axillary lymph node metastases was diagnosed histologically. The lymph node metastases showed histological findings identical to those of the primary tumor, which was considered to be the reason for their isoechogenicity. Although lymph node metastasis of mucinous carcinoma of the breast is rare, ultrasonographers should perform careful scanning when the primary breast mass is suspicious for mucinous carcinoma, because lymph node metastases of mucinous carcinoma can be more indistinct and difficult to detect than those of other types of breast cancer.

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Wrong:Kiyoshi Nishimura,
Right:Reiki Nishimura,

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