Breast cancer with cartilaginous and/or osseous metaplasia

We report a rare case of breast cancer with cartilaginous and/or osseous metaplasia. A 59-year-old woman had a large lump in her left breast, which had enlarged gradually over a period of 2 years. Mammography, ultrasonography and aspiration cytology suggested phyllodes tumor with carcinoma. She underwent wide excision and sentinel lymph node biopsy. Because of the existence metastatic tumor cells in the sentinel lymph node on frozen section, sequential axillary lymph node dissection was conducted consequently. Histologically, the tumor consisted of invasive ductal carcinoma and spindle-cell carcinoma, including cartilaginous metaplasia. Adjuvant chemotherapy and whole-breast irradiation were performed. However, she died of multiple metastases to the liver 2 years after surgery. Breast cancer with cartilaginous and/or osseous metaplasia belongs to a special type of invasive carcinoma, and the incidence is very low. We here present our case and a review of the literature.     

Massive mucinous carcinoma of the breast untreated for 6 years

 We report a patient with a massive mucinous carcinoma of the breast that had been untreated for 6 years. A 47-year-old premenopausal woman presented with a large right-breast mass. Although she had noticed a lump in the right breast 6 years previously, she had not sought treatment. The tumor had enlarged gradually and become ulcerated. With a diagnosis of advanced breast cancer with skin invasion, she underwent right mastectomy with a free skin graft. No lymph node metastases or distant metastases were detected. The histologic diagnosis of the tumor was pure mucinous carcinoma of the breast with no component of ordinary invasive ductal cancer. She has been well without evidence of tumor recurrence for 7 years after the surgery. The prognosis for mucinous carcinoma of the breast has been recognized as relatively good. The results in our patient are consistent with the biological behavior of this carcinoma. Received: August 29, 2002 / Accepted: December 12, 2002 Correspondence to:F. Yoneyama     

A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma.     

Positron emission tomography and sentinel lymph node dissection in breast cancer

Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.     

Contralateral uptake and metastases in sentinel lymph node mapping for recurrent breast cancer

BACKGROUND AND OBJECTIVES: Sentinel lymph node mapping as a constitutive component in the staging process for invasive breast cancer continues to gain acceptance. We have identified two patients with recurrent invasive breast cancer in whom contralateral sentinel lymph node uptake and metastases, respectively, were detected. Such findings have not been previously reported in our review of the medical literature between 1966 and October 2004. METHODS: Sentinel lymph node mapping was performed on two patients with recurrent invasive breast cancer at our institution. At the time of their index diagnosis, both had received breast conserving surgery and an axillary lymph node dissection with post-operative radiotherapy (RT). All lymph nodes and margins of resection were without tumor. Both patients remained with no evidence of disease for years until routine serial screening mammography was interpreted as suspicious. Each underwent a stereotactic biopsy of the ipsilateral breast corresponding to the mammographic abnormality. Pathology confirmed invasive ductal carcinoma. Both patients refused the recommended salvage mastectomy. PRINCIPAL RESULTS: During a second attempt at breast conservation, sentinel lymph node mapping--which is typically contraindicated for patients with prior axillary surgery--revealed contralateral axillary uptake for both patients. The respective contralateral sentinel node was excised with pathology revealing no tumor in one case, and a microscopic focus of metastatic carcinoma in the second case. MAJOR CONCLUSION: Some patients may benefit from sentinel lymph node mapping prior to salvage mastectomy. Identifying uptake in a contralateral sentinel lymph node may change the multi-disciplinary management of recurrent invasive breast cancer to include a contralateral axillary dissection, chemotherapy, and/or RT to the contralateral axilla.     

A case of non-palpating breast cancer with huge lymph node metastasis

We report a case of non-palpating breast cancer with huge lymph node metastasis. The patient was a 58-year-old woman who had a huge tumor at her right armpit. The tumor was 4 cm in diameter. Aspiration biopsy cytology for the tumor was performed. The diagnosis is Class V. Mammography showed an ill-defined mass at her right breast. Ultrasonography revealed a low echoic mass at the C area of her right breast. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 cycles of CEF (E: 60 mg/tri-weekly) plus 12 cycles of paclitaxe (l80 mg/weekly). After chemotherapy, she received muscle preserving mastectomy plus axillary lymph nodes dissection. In histopathology, there were no carcinoma cells in resected breast tissue and resected lymph nodes. Therefore, the effect of chemotherapy was diagnosed as a pathological complete response. After operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 6 years.     

A case of advanced accessory breast cancer effectively treated with trastuzumab and paclitaxel

A 53-year-old woman was admitted for left axillary mass. The computed tomography showed an invasive mass in the left axilla and left supraclavicular lymph node swelling. Histological findings of axillary mass revealed infiltrating ductal carcinoma of scirrhous type. We diagnosed advanced accessory breast cancer, and the patient was treated by combination chemotherapy with paclitaxel and trastuzumab. The lesions disappeared after 4 courses of chemotherapy and was clinically diagnosed as complete response(CR).     

Neoadjuvant endocrine therapy with anastrozole significantly downstaged an elderly breast cancer woman with locally-advanced breast cancer which became operable

A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.     

A case of breast carcinoma with cartilaginous and osseous metaplasia

We report a case of a 49-year-old Japanese woman diagnosed with breast carcinoma with osseous and cartilaginous metaplasia with a poor outcome. Histological examination revealed invasive ductal carcinoma with undifferentiated sarcomatous components including chondrosarcomatous areas. Osseous metaplasia was also noted in a very limited area. Neither axillary lymph node metastases nor vessel invasion were observed. Immunohistochemical examination was negative for estrogen receptor, progesterone receptor and HER2 overexpression. Stage II A T2N0M0 carcinoma was diagnosed postoperatively. Five months after the operation, she developed lung metastases. Although she received systemic chemotherapy, the lesions increased in number and grew rapidly. She died of pulmonary distress 5 months after relapse.     

Two cases of recurrent breast cancer with regional lymph node metastases showing a complete response to trastuzumab and paclitaxel treatment

We report two cases of recurrent breast cancer with regional lymph node metastases that responded completely to treatment with trastuzumab and paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer, underwent mastectomy and axillary lymph node dissection in July 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic and blood vessels, negative nodal status (0/11), negative ER/PgR status, and overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin and cyclophosphamide were administered from January 2003; however, they were not effective. The patient showed a complete response after three months of chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in September 2003. She has maintained a complete response for two and a half years and was not administered any further treatment as of February 2006. Case 2: A 59-year-old woman, who presented with right breast cancer, underwent mastectomy and axillary lymph node dissection in May 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological grade 2, positive invasion to the lymphatic and blood vessels, negative nodal status (0/5), positive ER and uncertain PgR status, and overexpression of HER 2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a right supraclavicular lymph node metastasis was noted in October 2004. Treatment with exemestane was not effective. However, a complete response was observed with trastuzumab and paclitaxel for four months. She has maintained a complete response for six months and was not administered any further treatment as of February 2006.     

A case of advanced breast cancer with multiple lung and liver metastases successfully treated with multi-disciplinary therapy

We report a case of advanced breast cancer with multiple lung and liver metastases (T4bN1M1) achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was a 63-year-old woman with slight jaundice who had ascites and an ulcerative breast lump with multiple lung and liver metastases. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although the ascites and the jaundice disappeared after chemotherapy, the response for breast tumor, metastatic sites in the lung and the liver were less satisfactory. Fifteen-months later, she received radiation therapy so that metastasis in the brain was recognized. But she had no neurological symptoms. Multi-disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.     

乳腺浸润性导管癌腋窝淋巴结转移的相关因素分析

目的研究乳腺浸润性导管癌腋窝淋巴结转移的相关因素,探讨利用乳腺及腋窝彩色多普勒超声结合肿瘤病理学检查分析预测乳腺浸润性导管癌的腋窝淋巴结转移情况。方法回顾性分析175例经过病理证实的乳腺浸润性导管癌患者,所有患者术前行乳腺及腋窝彩色多普勒超声检查,术后对肿瘤行病理检查。统计分析采用x2检验、Logistic回归分析及绘制ROC曲线。结果175例病例中,病理证实腋窝淋巴结转移者107例,肿瘤直径、肿瘤血流分级、腋窝淋巴结个数、淋巴结纵横比、淋巴结皮质最大厚度、淋巴结血流分型、肿瘤组织学分级、Ki67抗原和c—erbB-2阳性表达是影响腋窝淋巴结转移率的因素（P〈0．050）。最终进入模型的因素有淋巴结纵横比、肿瘤直径、淋巴结皮质最大厚度、肿瘤组织学分级Ⅱ、Ⅲ级及Ki67抗原阳性表达。ROC曲线下面积是0．964。结论淋巴结纵横比小、淋巴结皮质最大厚度I〉3mm、肿瘤直径≥2cm、肿瘤组织学分级高和Ki67抗原阳性提示较高的腋窝淋巴结转移率。     

A case of advanced breast cancer with multiple organ metastases successfully treated by tamoxifen]

A 66-year-old postmenopausal woman presented in June 1991 with a giant ulcerated left breast tumor. She had discovered the tumor two years previously, but had never visited any medical institution. She was diagnosed as advanced breast cancer with multiple lung metastases, bone metastasis, and both supraclavicular lymph node metastases by physical examination, fine needle aspiration cytology, chest X-P, and bone scintigraphy. Incisional biopsy, performed to confirm the histological type of breast cancer and to evaluate estrogen and progesterone receptor (ER and PgR) status, revealed solid-tubular carcinoma. Both ER and PgR were highly positive at 322.6 and 228.0 fmol/mg protein, respectively. Therefore, endocrine therapy was chosen to treat this advanced breast cancer patient, although she had multiple organ metastases. Twenty mg of Tamoxifen a day was administered per os. After treatment with tamoxifen, the size of ulceration started to decreased and the dyspnea caused by multiple lung metastases was reduced. Eight weeks after, she showed partial response (PR) determined from the size of the ulceration and chest X-P. She has been maintaining PR for more than 9 months. Thus, Tamoxifen was shown to be very effective for this case of advanced breast cancer with multiple organ metastases.     

Microinvasive breast carcinoma with extensive involvement of level III axillary lymph nodes: a case report

A 44-year-old woman presented with a right huge axillary mass. Both mammography and ultrasonography revealed a primary cancer of 2.8 cm maximum diameter in the right breast and metastases in the axillary lymph nodes, both being confirmed by aspiration cytology as ductal carcinoma. Right standard radical mastectomy with level III axillary lymph node dissection was carried out. Pathologically, the tumor was diagnosed as ductal carcinoma in situ with microinvasion (DCISM), histologic grade 3. The area of stromal invasion measured 1 mm at its widest point. Sixteen of the 17 resected axillary lymph nodes contained metastases, including six level III lymph nodes. Immunohistochemical studies of the tumor revealed overexpression of p53 protein, but not that of c-erbB-2 protein. The frequency of lymph node metastases from DCISM is reported to be very low. Therefore, the present case with extensive involvement of level III lymph nodes was unusual.      

Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an advanced breast cancer with multiple liver metastases

A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral axillary lymph node swelling and multiple liver metastases as detected on CT scan (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor and overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi-weekly 9 courses), was given. Tumor markers became negative 4 months later, and multiple liver nodules, breast tumor and axillary nodes completely disappeared 9 months later. Breast surgery was avoided, and CR was maintained more than 8 months only with bi-weekly trastuzumab. From the standpoint of the patient's convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a promising treatment choice for metastatic breast cancer.     

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.     

The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors and lymph node metastases of breast cancer

The aim of this study was the analysis of Ki-67, Bcl-2 and Bak expression in primary tumor and axillary lymph node metastases of breast cancer as well as an attempt to assess preoperative chemotherapy influence on the mentioned markers with regard to changes in the morphological appearance of the primary tumor and its metastases. Immunohistochemical examinations of Ki-67, Bcl-2 and Bak expression were conducted on sections collected from 135 patients treated surgically on invasive ductal breast cancer. Sixty-four of these patients were administered preoperative chemotherapy, whilst on 71 patients the surgery was performed without initial chemotherapy. In the group of patients without preoperative chemotherapy positive correlation in Ki-67 and Bcl-2 expression between primary tumors and lymph node metastases (p<0.0001, r=0.707; p<0.0001, r=0.604, respectively) was observed. In the group of patients after chemotherapy positive correlation between primary tumors and lymph node metastases in case of Bcl-2 and Bak proteins (p<0.04, r=0.424; p<0.02, r=0.478, respectively) was observed. It was also found that preoperative chemotherapy has an influence on the expression of proteins connected with proliferation and apoptosis and thus, it can influence neoplastic process biology. It does not have any significant impact on the proapoptotic Bak protein expression either in primary tumor or in lymph node metastases of breast cancer. However, it is related to lower expression of antiapoptotic Bcl-2 protein (p<0.0005) and of Ki-67 proliferation marker (p<0.03) in primary tumors, which indirectly indicates a beneficial influence of preoperative chemotherapy on the primary tumor. Concurrently, the influence of neoadjuvant therapy on lymph node metastases seems to be relatively small, which can limit its effectiveness.     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.      

Unknown primary carcinoma, diagnosed as inflammatory breast cancer,and successfully treated with trastuzumab and vinorelbine

Occult breast cancer presenting with axillary lymph node metastases is uncommon, and inflammatory breast cancer (IBC), as a subtype, is quite rare. Here we describe a case of IBC, which arose as an unknown primary carcinoma; the patient presented with axillary lymph node metastasis, and was successfully treated with trastuzumab and vinorelbine. Specifically, a 55-year-old woman presented with right axillary lymphadenopathy. Although she underwent various examinations, the primary site of the disease was not revealed. Axillary lymph node dissection was performed, and the lesion was diagnosed as a poorly differentiated adenocarcinoma. The patient chose to be treated by alternative medicine. About 6 months later, she was referred to our hospital, due to marked bilateral neck and axillary lymph node swelling. She presented withdiffuse right breast enlargement, redness, and peau d’orange. Computed tomography (CT) of the breast showed skin thickening and swelling of the right breast.F-18 Fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG uptake in the right breast. The patient was clinically diagnosed with IBC. Because overexpression of the human epidermal growth factor receptor 2 (HER2) was found in the specimen from her right axillary lymph node, she was treated with trastuzumab and vinorelbine. Two months after the start of chemotherapy, CT revealed a complete response in the lymph nodes, and the skin thickening and parenchymal edema of the right breast had improved. FDG-PET was also performed at this time, and revealed no FDG uptake in either the right breast or the lymph nodes.     

The benefits and limitations of sentinel lymph node biopsy

Opinion statement The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Staging is based on tumor size and on the presence of lymph node metastases. The number of lymph nodes, although prognostic, no longer impacts treatment options. Sentinel lymph node (SLN) mapping and dissection is a more sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer, providing prognostic information, with less surgical morbidity than with axillary lymph node dissection (ALND). When analyzed by an experienced pathologist with serial sectioning and immunohistochemical evaluation, SLN is the most accurate detection tool used in staging of breast cancer. In many centers that use these staging principles, ALND is no longer performed for histologically negative axillary SLNs. In addition, this technique may also be therapeutic because in most patients, the SLN is the only positive axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who have a high risk of invasive carcinoma, such as those with large tumors, a mass, or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the cases. Women with locally advanced breast cancer may derive great benefit from a minimally invasive approach to the axilla because the extent of nodal involvement is unlikely to change further treatment. For clinically palpable nodes, ALND should be performed for therapeutic and local control. The use of sentinel node mapping in pregnancy is controversial. Vital blue dye is contraindicated in pregnant patients, although some have used radioactive colloid alone to map this subgroup of patients.