Successful chemo-endocrine therapy for multiple bone metastases and myelophthisis caused by occult breast carcinoma

We report a 55-year-old postmenopausal woman with occult breast carcinoma with multiple bone metastases and myelophthisis in whom complete response (CR) was achieved with chemo-endocrine therapy. At the time of admission, she had anemia and left axillary lymph node enlargement, with extremely high levels of serum tumor markers and no breast mass on physical examination or on a mammogram. Roentgenograms and bone scintigrams showed multiple bone, lung, and pleural metastases. Bone marrow biopsy and aspiration cytology from the left axillary lymph node revealed an invasion of adenocarcinoma cells. On immunohistochemical staining, the cancer cells were positive for estrogen receptor (ER), progesterone receptor (PgR), and gross cystic disease fluid protein-15 (GCDFP-15). CR was induced with a combination chemotherapy of doxorubicin, cyclophosphamide, and 5-fluorouracil (CAF), and has been maintained with sequential docetaxel administration with endocrine therapy. Her performance status (Eastern Cooperative Oncology Group) improved from 4 to 0. This patient represents a very specific and rare case in whom a primary tumor could not be detected despite severe advanced breast carcinoma, and in whom CR was achieved by chemo-endocrine therapy. Received: October 21, 1999 / Accepted: July 28, 2000     

乳腺球蛋白在术前乳腺癌和腋窝淋巴结细针穿刺吸取组织中的表达及临床意义

目的 探讨乳腺球蛋白（mammaglobin,MAM）在术前乳腺癌及腋窝淋巴结细针穿刺吸取组织中的表达及临床意义.方法 对91例原发性乳腺癌行术前细针穿刺,将吸取的组织制备涂片,采用免疫组织化学方法（EnVision法）检测MAM表达,观察MAM表达与临床病理指标的关系.同时另收集15例原发性肺癌腋窝淋巴结转移患者,分析乳腺癌腋窝淋巴结转移、乳腺癌增生性淋巴结炎和肺癌腋窝淋巴结转移三者间术前腋窝淋巴结MAM表达的区别.统计分析采用χ2检验.结果 在91例原发性乳腺癌患者中MAM的阳性表达率为74.72%（68/91）.MAM的阳性表达与雌激素受体（ER）、孕激素受体（PR）、组织学分级、细胞学分级有关（P〈0.05）,与患者的年龄、肿瘤大小、淋巴结是否转移及HER-2状态无关（P〉0.05）.腋窝淋巴结观察结果显示,MAM在乳腺癌腋窝淋巴结转移患者中呈阳性表达,在乳腺癌增生性腋窝淋巴结炎和肺癌腋窝淋巴结转移患者中均为阴性表达.结论 MAM可表达于原发性和转移性乳腺癌,细针穿刺细胞学检查结合MAM的测定对乳腺癌的诊断及鉴别具有一定辅助判断价值.MAM阳性表达与ER、PR状态、细胞学分级、组织学分级有关,有利于了解肿瘤的生物学指标及判断预后.     

Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers.     

A case of occult breast carcinoma with irradiation therapy and axillary lymph node dissection

A 78-year-old woman was seen at the hospital for a swollen left axillary node. There was an elastic hard mass measuring 0.7 cm in diameter in the left axilla, but no breast mass was palpable in the bilateral breasts. Mammography did not reveal any tumor and calcification, and there was no abnormalities on breast ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). Aspiration biopsy cytology of the left axillary node revealed adenocarcinoma. Systemic examination failed to reveal primary lesion. Thus, to make the diagnosis, we enucleated the axillary nodule. Immunohistochemical staining for the excisional specimen revealed an estrogen receptor, progesterone receptor and gross cystic disease fluid protein-15 (GCDFP-15) was strongly positive, so we diagnosed it as an occult breast carcinoma. After obtaining her informed consent, the patient underwent left axillary lymph node dissection and irradiation therapy of the left breast. The patient has been disease-free under adjuvant chemoendocrine therapy. We treated the occult breast carcinoma with radiation therapy of the breast and axillary lymph node dissection, and provided a review of the literature.     

A case of cytokeratin 20-positive large-cell neuroendocrine carcinoma of the breast

We report a rare case of large-cell neuroendocrine carcinoma of the breast. A 63-year-old woman was admitted to our hospital with a firm mass in the right breast. Mammography revealed a high-density mass with specula, and ultrasonography showed a heterogeneous hypoechoic mass with irregular margin and posterior acoustical shadowing. She underwent breast-conserving surgery with axillary lymph node dissection. Histopathologically, the tumor consisted of large cells with polygonal and prominent nuclei and a small amount of eosinophilic cytoplasm, and these cells showed palisading arrangement with fibrous stroma. The tumor cells were positive for neuroendocrine markers such as NSE, synaptophysin, CD56 (NCAM), but not for chromogranin A. Interestingly, the tumor cells showed reactivity for cytokeratin 20 but not for cytokeratin 7. The immunostaining pattern is different from the usual adenocarcinoma of the breast. The patient received postoperative radiotherapy and was given adjuvant chemotherapy. She has remained disease-free for 44?months.     

Is It Contralateral Axillary Metastasis or Occult Breast Cancer?: A Confusing Case Report

We report the case of a 43-year-old woman with primary left breast cancer presenting metastatic lymphadenopathy in the contralateral axilla. This patient represents a diagnostic and therapeutic challenge because primary breast cancer, occult contralateral breast cancer, and extra-mammary primary lesion can all be the source of the contralateral axillary metastasis. Left breast-conserving surgery, left sentinel lymph node biopsy, right breast mass excision, and right axillary lymph node dissection were performed. Immunohistochemical analysis revealed that the left breast cancer specimen was positive for estrogen receptor (ER) and progesterone receptor (PR), but negative for human epidermal growth factor receptor 2 (HER2). In contrast, the right axillary lymphadenopathy specimen was negative for ER and PR, but positive for HER2. Further investigation revealed no evidence of occult primary cancers or extra-mammary tumors. After surgical intervention, the patient was treated with adjuvant chemotherapy, adjuvant radiation therapy, and targeted therapy with trastuzumab. Two years after diagnosis, she is free of disease and presently being treated with tamoxifen.Key Words: Breast carcinoma, Occult primary tumor, Contralateral axillary lymph node metastasis, Immunohistochemistry     

Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up.

PURPOSE: To evaluate the detection of epithelial cells in bone marrow of breast cancer patients as an indicator of metastatic disease. PATIENTS AND METHODS: Between 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer patients during primary surgery. Specimens were stained immunocytochemically for epithelial cells expressing cytokeratins or the epithelial membrane antigen. The long-term outcomes of these patients were analyzed in this study. RESULTS: In 166 of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These patients were designated BM+. The rate of tumor recurrence or cancer-related death was significantly higher in BM+ patients than in BM- patients. Multivariate analysis using the Cox regression model revealed BM status as a prognostic parameter independent of tumor size and axillary lymph node status. However, tumor size and axillary lymph node status were clearly superior prognostic parameters. CONCLUSION: Disseminated epithelial cells in BM are associated with poor clinical outcome in breast cancer patients. However, the presence of these cells is not a sufficient parameter to predict growing metastases in the majority of patients, suggesting that epithelial cells in the BM of breast cancer patients at the time of surgery have limited metastatic potential. The role of these cells needs to be further evaluated.     

Correlation of Bcl-2 and p53 expression in primary breast tumors and corresponding metastatic lymph nodes

BACKGROUND: The p53 tumor suppressor gene product participated in G1 cell cycle arrest or cell death. Loss of function was associated with poor outcome in patients with breast carcinoma. bcl-2 prevented apoptosis induced by c-myc or growth factor deprivation. High bcl-2 expression in breast tumor tissue specimens appears to be associated with favorable prognostic factors. However, Bcl-2 and p53 expression in primary tumor tissue specimens versus metastatic lymph node specimens in breast carcinoma has not been studied. The current study compared Bcl-2 and p53 expression in primary breast carcinoma tissue specimens with Bcl-2 and p53 expression in axillary lymph node specimens. METHODS: Primary breast tumor and corresponding axillary metastatic lymph node tissue specimens were obtained from 60 patients with breast carcinoma. They were evaluated for the presence of Bcl-2 and p53 expression by immunohistochemistry using standard methods. RESULTS: Bcl-2 expression in primary tumor tissue specimens (53%) was correlated with Bcl-2 expression in metastatic lymph node specimens (50 %; Pearson correlation = 0.656). p53 expression in primary tumor specimens (72%) was correlated with p53 expression in metastatic lymph node specimens (60 %; Pearson correlation = 0.800). A significant inverse correlation also was found between p53 and Bcl-2 expression in primary breast tumor tissue specimens (Pearson correlation = -0.310). CONCLUSIONS: The current study suggested that Bcl-2 and p53 expression in axillary metastatic lymph node specimens is correlated with Bcl-2 and p53 expression in the primary tumor tissue specimens. The prognostic and predictive value of Bcl-2 and p53 expression in axillary lymph node metastasis in patients with breast carcinoma needs to be further evaluated in larger trials with longer follow-up.     

p53 expression,growth, and spontaneous metastasis of the human GI 101 breast carcinoma in athymic nude mice

The human GI 101 breast carcinoma cell lines produces spontaneous metastasis to the lungs when xenografted subcutaneously in female athymic nude mice. To establish the time-course of tumor growth and distant metastasis to the lungs and axillary lymph nodes, 5 mm3 of tumor tissue was implanted in the subaxial region of female athymic nude mice. Micrometastases in the lung were first detected 3 weeks after tumor implantation. The incidence of lung metastasis and the number of tumor emboli were correlated with the volume of the primary tumors. Ipsilateral axillary lymph node metastasis was observed within 17 weeks, indicating that metastasis to the lymph node is a later event. Unlike pulmonary micrometastases which were in the form of clusters of four to six tumor cells, metastasis to the lymph nodes were in nodules of poorly differentiated and larger tumor cells. Immunohistochemistry evaluation of p53 oncoprotein in the primary and metastatic tumor cells showed different patterns of subcellular accumulation. Cytoplasmic staining was mainly detected in the primary and secondary tumor cells disseminated to the lungs. In contrast, nuclear staining was only detected in tumor cells infiltrated to the axillary lymph nodes. There was no gain of loss of positivity of p53 accumulation (i.e., qualitative measurements) as the tumor grew in size. The data indicate that the GI 101 tumor cells could be used as a useful model for studying the malignant progression of hormone-independent breast cancer, antimetastatic drugs, and early events in tumor metastasis.     

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

Carcinome neuroendocrine à grandes cellules du sein : à propos d’un cas et revue de la littérature

Neuroendocrine carcinoma with large cells is a slightly different tumor from the high rank of malignity. We report a case of breast localization in a 28-year-old patient. It is a locally advanced classified T4dN1M0 tumor that required neoadjuvant chemotherapy. The clinical answer was 75% of the level of the tumor. A standard surgery mastectomy with axillary lymph node dissection was realized, followed by external radiotherapy. The anatomopathologic and the immuno-histochimical study of the operational part confirmed the diagnosis of neuroendocrine carcinoma with large cells expressing the progesterone receptor. The patient is subjected to adjuvant hormonal treatment. After a 12 months retreat, a complete remission is maintained. Considering the scarcity of neuroendocrine carcinoma with large cells of the breast, the therapeutic standard is not yet available and the forecast remains difficult to determine.     

Stromal sarcoma with features of giant cell malignant fibrous histiocytoma

We report a case of primary giant cell malignant fibrous histiocytoma (GCMFH) of the breast. A 56-year-old Japanese woman presented with a firm mass in the right breast. Mammography and ultrasonography revealed a well-circumscribed and lobulated mass in the upper outer quadrant of the right breast, indicative of a benign breast tumor or mucinous carcinoma. Magnetic resonance imaging revealed a restricted breast tumor without intraductal spread. Computed tomography and bone scintigraphy found no sites of distant metastases. Fine needle aspiration biopsy showed several clusters of atypical cells associated with numerous multinucleated giant cells. Breast-conserving surgery with axillary lymph nodes dissection was performed. Histological examination showed primary GCMFH of the breast. No metastases were identified in any of the 15 left axillary lymph nodes resected and surgical margins were free from tumor cells. The tumor was negative for both estrogen and progesterone receptor. Neither adjuvant chemoendocrine therapy nor postoperative radiotherapy was given, and the patient has remained disease free for 30 months postoperatively. To our knowledge, only 30 cases of primary MFH of the breast have been reported in the literature.     

Prognosis in breast cancer utilizing histologic characteristics of the primary tumor.

A study was made of the inter-relationships and prognostic significance of structural characteristics found in primary breast cancers and their associated axillary lymph nodes. The prognostically favorable characteristics included the following. For the primary tumor: nuclear differentiation of the cancer cells, diffuse lymphoid cell infiltrations (LI) and perivenous lymphoid cell infiltrations (PVI). For the axillary lymph nodes: sinus histiocytosis (SH). Perivenous lymphoid cell infiltrations (PVI) in the primary tumor are found to be as important a prognostic factor as SH in the axillary lymph nodes; these two characteristics are found to be positively associated. Evaluation of the nuclear grade (NG), LI, and PVI in the primary tumor allows for the definition of association with cancer cells having a low (anaplastic) nuclear grade, and to be positively associated with follicular hyperplasia (FH) in the lymph nodes. We also found a positive association between the cellular responses to areas of in situ carcinoma and the cellular responses to accompanying invasive breast breast cancer tissue. They also provide a prognostic system for classifying breast cancer patients on the basis of the microscopic characteristics of the primary tumor and surrounding breast tissue. The latter system should be of value in comparing the therapeutic benefits of various treatments.     

Primary neuroendocrine carcinoma of the breast: a case report

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.     

Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland

A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 × 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin–eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.     

前哨淋巴结阳性早期乳腺癌非前哨淋巴结的组织学检测及临床意义

目的：研究早期乳腺癌患者前哨淋巴结(SLN)阳性时非前哨淋巴结(NSN)转移的可能性及其临床意义。方法：对84例SLN阳性接受乳癌根治术的早期乳腺癌患者的NSN及HER-2免疫组化等进行检测，分析NSN转移的发生率及相关临床因素。结果：SLN阳性患者NSN转移的检出率是48．8％(41／84)，NSN转移与原发肿瘤的大小、SLN转移灶的大小及HER-2的表达状况有关，原发肿瘤直径小于1cm及SLN转移灶小于1mm时NSN无转移，NSN的阳性率随原发肿瘤及SLN转移灶直径的增大而提高，HER-2蛋白阳性者NSN转移率高。结论：原发肿瘤直径小于1cm且SLN转移灶小于1mm时的早期乳腺癌患者可免于腋窝清扫，反之亦然；HER-2阳性患者NSN转移率较高，应考虑腋窝清扫。     

Expression of epidermal growth factor receptors in four histologic cell types of lung cancer

Lung cancer tissues from 68 patients were examined for epidermal growth factor (EGF) receptor levels and EGF receptor gene copy numbers. Histologic cell types of these lung cancer tissues included squamous-cell carcinoma (n = 30), adenocarcinoma (n = 28), large-cell carcinoma (n = 4), and small-cell carcinoma (n = 6). Tissues of squamous-cell carcinoma exhibited exceptionally high 125I-EGF binding activity, and those of small-cell carcinoma showed no EGF binding activity. Southern blot hybridization analysis revealed EGF receptor gene amplification in the squamous-cell carcinomas with high EGF binding activity. The EGF receptor levels in squamous-cell carcinomas and adenocarcinomas were compared with their pathological staging grouping and pathological findings, including degree of differentiation, diameter of tumor, and lymph node metastasis. However, unlike previous reports on breast and bladder cancers, there was no obvious correlation between these pathological characteristics and the EGF receptor levels of lung cancer.     

乳腺癌伴神经内分泌分化及其与nm23、pS2等预后因素的关系

目的　研究乳腺癌中神经内分泌分化情况 ,及其与nm 2 3、pS2基因及淋巴结转移的关系。 方法　采用免疫组化S P法 ,对 5 8例乳腺癌手术标本用神经内分泌抗体NSE、Sy、CgA进行测定 ,观察其表达情况 ;同时进行nm 2 3、pS2基因检测并与淋巴结转移情况共同分析。结果　 5 8例乳腺癌患者中NSE、Sy、CgA 3种抗体同时表达阳性者 14例 ,占 2 4% ,电镜下观察发现肿瘤细胞中有神经内分泌颗粒。NE阳性者nm 2 3、pS2表达水平均低于NE阴性者 ,而NSE阳性者淋巴结转移率 ( 5 7% ,8/14 )较NE阴性者 ( 2 7% ,12 /4 4)高 (P <0 .0 5 )。结论　乳腺癌伴神经内分泌分化是肿瘤异质性的表现 ,是乳腺癌的 1种特殊类型 ,具有与一般类型乳腺癌不完全一致的生物学行为 ,在乳腺癌术后治疗方案的决策上应重视