Progress in the Biological Understanding and Management of Breast Cancer‐Associated Central Nervous System Metastases

Metastasis to the central nervous system (CNS) is a devastating neurological complication of systemic cancer. Brain metastases from breast cancer have been documented to occur in approximately 10%–16% of cases over the natural course of the disease with leptomeningeal metastases occurring in approximately 2%–5% of cases of breast cancer. CNS metastases among women with breast cancer tend to occur among those who are younger, have larger tumors, and have a more aggressive histological subtype such as the triple negative and HER2‐positive subtypes. Treatment of CNS metastases involves various combinations of whole brain radiation therapy, surgery, stereotactic radiosurgery, and chemotherapy. We will discuss the progress made in the treatment and prevention of breast cancer‐associated CNS metastases and will delve into the biological underpinnings of CNS metastases including evaluating the role of breast tumor subtype on the incidence, natural history, prognostic outcome, and impact of therapeutic efficacy.     

Curative liver resection for metastatic breast cancer.

AIMS: Hepatic resection is a standard procedure in the treatment of colorectal liver metastases. Liver metastases are frequent in breast cancer, but resectional treatment is rarely possible and few reports have addressed the results of surgical treatment for metastatic breast cancer. The aim of our study was to analyse the outcome of patients with metastatic breast cancer after resection of isolated hepatic secondaries and possibly to identify selection criteria for patients who may benefit from surgery. METHODS: Between 1984 and 1998, 90 patients with a history of breast cancer and suspected liver metastases were referred for surgical evaluation. Fifty-four patients also had extrahepatic disease or metastases from another primary tumour; multiple liver metastases were not amenable to surgical treatment in 20 patients. Five patients were treated by regional chemotherapy via an intra-arterial port catheter; after liver resection two patients were found to have liver metastases from intercurrent colorectal cancer. Thus only nine liver resections for metastatic breast cancer could be performed with curative intent. RESULTS: No patient died post-operatively after liver resection. In the follow-up period, four of the nine patients who were treated with curative intent received systemic chemotherapy. At a median follow-up of 29 months, four patients died from tumour recurrence. Five patients are currently alive. Five-year survival in the resection group was calculated as 51% (Kaplan-Meier estimate). Node-negative primary breast cancer and a long interval between treatment of the primary and liver metastases appeared to be associated with long survival after liver resection. CONCLUSIONS: These observations suggest that careful follow-up and adequate patient selection could offer some patients with isolated liver metastases from breast cancer a chance of long-term survival.     

Brain metastases in patients with breast cancer: new horizons

Brain metastases occur in as many as one third of patients with disseminated breast cancer. In this article, we discuss various presentations of brain metastases from breast cancer and review evidence that supports different treatment options. Because no prospective, randomized, controlled studies, to our knowledge, have focused solely on patients with brain metastases from breast cancer, we will first review retrospective studies of patients with brain metastases from breast cancer. Randomized studies of patients with brain metastases caused by multiple primary cancers will also be examined, and the conclusions from these studies will be extrapolated to patients with breast cancer. Because brain metastases from breast cancer occur in a variety of different clinical settings, ranging from a single metastasis without extensive extracranial disease to multiple brain metastases with widespread extracranial disease, treatment approaches must be tailored to the specific circumstances of each patient. For different clinical scenarios, neurosurgical resection, radiosurgery, and/or whole-brain radiation therapy may be appropriate treatment options. For patients with brain metastases from breast cancer that overexpresses HER2/neu, trastuzumab could alter the natural history of the non-central nervous system (CNS) disease. Therefore, HER2 status could also influence the treatment of brain metastases from breast cancer. Given the prevalence of brain metastases in patients with metastatic breast cancer in contemporary series, the rationale for clinical trials of CNS screening and prophylactic cranial irradiation will be discussed.     

Ethmoid sinus adenocarcinoma metastatic to breast

A young woman developed metastases to both breasts from an ethmoid sinus adenocarcinoma diagnosed 2 1/2 years earlier. Despite surgical excision of the breast metastases, postoperative radiotherapy to both breasts, and intensive chemotherapy, her breast metastases recurred in association with rapid progression of the disease in general. She died 1 year after the initial diagnosis of breast metastases. This case is the eighth report of a malignancy arising in the head and neck that metastasized to the breasts. The relevant literature is reviewed.     

Management of non metastatic phyllodes tumors of the breast: review of the literature

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior.The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity.Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials.     

HER2-positive Breast Cancer Brain Metastases: Multiple Responses to Systemic Chemotherapy and Trastuzumab—a Case Report

Brain metastases from metastatic breast cancer typically occur in 10–15% of patients and are associated with survival of 3–6 months. Recent series have shown that women with HER2-postive metastatic breast cancer receiving the drug trastuzumab develop brain metastases more frequently than this, but also that continuation of trastuzumab after diagnosis of brain metastases in such patients is associated with extended survival. Authors have speculated that this is due to improved systemic control of disease; however, a possibility is that trastuzumab may have a beneficial effect on cerebral metastases themselves. We report the case of a woman with HER2-positive metastatic breast cancer who developed multiple brain metastases while on trastuzumab, in whom the addition of systemic chemotherapy to continued trastuzumab has produced multiple treatment responses associated with prolonged survival. This is the first report of its kind.     

Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases

Conflicting theories of epithelial carcinogenesis disagree on the clonal composition of primary tumors and on the time at which metastases occur. In order to study the spatial distribution of disparate clonal populations within breast carcinomas and the extent of the genetic relationship between primary tumors and regional metastases, we have analyzed by comparative genomic hybridization 122 tissue samples from altogether 60 breast cancer patients, including 34 tumor samples obtained from different quadrants of 9 breast carcinomas, as well as paired primary-metastatic samples from 12 patients. The median intratumor genetic heterogeneity score (HS) was 17.4% and unsupervised hierarchical clustering analysis comparing the genetic features to those of an independent series of 41 breast carcinomas confirmed intratumor clonal divergence in a high proportion of cases. The median HS between paired primary breast tumors and lymph node metastases was 33.3%, but the number of genomic imbalances did not differ significantly. Clustering analysis confirmed extensive clonal divergence between primary carcinomas and lymph node metastases in several cases. In the independent series of 41 breast carcinomas, the number of genomic imbalances in primary tumors was significantly higher in patients presenting lymph node metastases (median = 15.5) than in the group with no evidence of disease spreading at diagnosis (median = 5.0). We conclude that primary breast carcinomas may be composed of several genetically heterogeneous and spatially separated cell populations and that paired primary breast tumors and lymph node metastases often present divergent clonal evolution, indicating that metastases may occur relatively early during breast carcinogenesis.     

A case of secretory carcinoma of the breast in an adult

This report describes a case of secretory carcinoma of the breast in the adult. The patient, a 56-year-old female, had a tumor, 1 cm in size, in the upper outer quadrant of her left breast, and Patey's modified radical mastectomy was performed. No nodal metastases were found. Although secretory carcinoma of the breast has been called "juvenile carcinoma", 27 adult cases have been reported previously in the English and Japanese literature. It is reported to have a good prognosis but surgical therapy with an axillary node dissection is recommended, since axillary metastases have been found in approximately 30% of the recorded cases.     

乳腺癌内乳区淋巴结转移研究进展

 内乳区淋巴结的转移状况是乳腺癌的独立预后指标,也是乳腺癌分期的重要依据之一。内乳区淋巴结转移的患者预后较差。内乳区淋巴结的总体转移率为18 %～33 %,仅有内乳区淋巴结转移而无腋窝淋巴结转移的发生率为2 %～11 %,其转移受腋窝淋巴结状况、患者年龄、原发肿瘤的位置和特点等多因素影响。随着前哨淋巴结活检技术的不断发展,内乳区前哨淋巴结活检术可能以最小的风险评估内乳区淋巴结状况,并进一步完善乳腺癌的淋巴结分期,有助于为患者制定更为准确的个体化治疗方案。     

Local therapy and survival in breast cancer with distant metastases

This review article presents an evaluation of the effects of local therapy on survival of breast cancer patients with distant metastases along with a discussion of their relevance. Primary and recurrent breast cancers with distant metastases are systemic diseases with poor prognosis. However, several retrospective studies have demonstrated that surgical removal of the primary breast tumor has a favorable impact on the prognosis of stage IV breast cancer patients. Similarly, it has been reported that surgical resection of metastatic lesions in the lung as well as the liver yields unexpectedly promising results. The interaction of local treatment and systemic therapy may be important, because surgery and radiotherapy are only local treatments. However, it remains uncertain whether these encouraging findings are due to the surgical procedure itself or preoperative patient selection. Only a randomized prospective study can definitively show whether local treatment can prevent death from stage IV disease or recurrent breast cancer with distant metastases. Until data from prospective studies are available, clinicians must weigh retrospective experiences and clinical judgment in deciding whether to offer surgery or radiotherapy to these patients.     

Diagnosis and management of spinal metastases from breast cancer

Conclusions Metastases to the spine is a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life due to troublesome back pain and neurologic morbidity. It is not uncommon for spinal metastases to be an early and predominant manifestation of the patients systemic disease process. Although the breast cancer must be considered to be advanced, these patients will frequently have a reasonable functional status at the time of diagnosis of the spinal metastases. Accordingly, an aggressive approach of management should be considered in such patients so as to potentially achieve the most effective palliation. In the setting of breast cancer metastatic to the spine, radiation/systemic steroidal therapy remains the first line of management. The principle exception favoring primary surgical management is roentgenographic evidence of spinal instability related to the vertebral involvement by the metastatic process. The surgical team must also remain ready to intervene early with surgical decompression and spinal stabilization when any neurologic deterioration occurs during radiation therapy. When surgery is indicated, the anterior transthoracic approach to spinal metastases is an effective means of palliating these breast cancer patients.A team approach involving the spinal surgeon, thoracic surgeon and anesthesiologist optimizes the care of the patient requiring thoracic spinal decompression of metastatic disease. Involvement of the thoracic surgeon in these patients care can result in expeditious thoracic exposure of the pathologic area of concern and valuable contribution to the post-operative care of these unfortunate patients.     

脊髓转移癌的临床研究

脊髓转移癌（ISCM）在临床中并不常见,肺癌和乳腺癌是其最常见的原发肿瘤.患者主要表现为虚弱无力、感觉异常或缺失,可以累及任何节段的脊髓.核磁共振成像是目前ISCM最有效的无创检查手段.ISCM的最佳治疗方法尚存争议,目前主要以手术和放疗为主,整体预后较差,确诊后的中位生存时间大约为4～9个月.     

Metastatic tumors to the pancreas: The role of surgery

Pancreatic metastases from other primary malignancies are a rare entity. By far, the most common primary cancer site resulting in an isolated pancreatic metastasis is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. Only few data on the surgical outcome of pancreatic resections performed for metastases from other primary tumor have been published, and there are no guidelines to address the surgical treatment for these patients. In this study, we performed a review of the published literature, focusing on the early and long-term results of surgery for the most frequent primary tumors metastasizing to the pancreas. Results for the Literature’s analysis show that in last years an increasing number of surgical resections have been performed in selected patients with limited pancreatic disease. Pancreatic resection for metastatic disease can be performed with acceptable mortality and morbidity rates. The usefulness of pancreatic resection is mainly linked to the biology of the primary tumor metastasizing to the pancreas. The benefit of metastasectomy in terms of patient survival has been observed for metastases from renal cell cancer, while for other primary tumors, such as lung and breast cancers, the role of surgery is mainly palliative.     

Diabetes insípida central como primera manifestación clínica de un carcinoma colorrectal metastásico

Metastases of systemic tumours in the hypothalamus-pituitary region are reported to be around 1% to 4% of all intra-cranial metastases. Most of them are diagnosed when the primary tumour is operated-upon, or when widespread metastases occur. The metastasic infiltration of this region is usually asymptomatic and rarely recognised ante-mortem. The metastases rarely clinically manifest, but diabetes insipidus is the most frequent. Autopsy studies have shown breast and lung cancer are the mostfrequent cause of the metastases in this region. We present a clinical case of a patient presenting diabetes insipidus as the first manifestation of a metastasic colorectal cancer.     

A role for hepatic metastasectomy in stage IV melanoma and breast cancer: reestablishing the surgical modality

Historically, liver-related metastases associated with melanoma or breast cancer have portended a poor prognosis. Many affected patients are not considered for surgical resection based on the extent and multifocal nature of their disease. For this patient population, treatment includes systemic and/or regional therapy, local destruction (ablation/radiation), and embolization. Despite the best therapeutic regimens, prognosis remains poor. Advances in surgical technique and postoperative care have led to a resurgence in the use of metastasectomy, most notably seen in patients with colorectal-related liver metastases. With the potential for therapeutic durability and a small chance of cure, surgical resection may offer improved survival compared to other therapeutic modalities. This review summarizes the existing literature that addresses the topic of metastasectomy in patients with melanoma and breast cancer.     

Bilateral breast metastases from ewing sarcoma of the femur

We report a case of bilateral breast metastases from Ewing sarcoma of the femur. A 40-year-old woman presented with Ewing sarcoma of the left thigh, treated by complete surgical exeresis and chemotherapy. Secondary, a large tumor appeared in the left breast. Bone scintigraphy, chest, and abdominal computed tomographic scan were normal. A breast biopsy found a malignant tumor composed of small round cells consistent with the initial diagnosis. After the first cycle of chemotherapy, a tumor was discovered in the controlateral breast. After 5 cycles, residual tumors persisted in the 2 breasts. Tumor exeresis was performed and found bilateral breast metastases of Ewing sarcoma. Because of the early recurrence of the left breast tumor, segmentectomy of the right breast and left mastectomy were performed. The histopathological analysis confirmed Ewing sarcoma metastases in the left breast. Despite local radiotherapy, the clinical course was marked by lumbar bone metastasis, local chest evolution, and progression of the disease. Metastases to the breast by extramammary malignant neoplasms are unusual. Sarcoma is an extremely rare cause of breast metastases and our case is the first report of breast metastases from Ewing sarcoma.     

Breast cancer bone metastasis in femur: surgical considerations and reconstruction with Long Gamma Nail.

AIM: The femur is the most common long bone involved in metastatic breast cancer. Several studies have been published on the surgical management of metastatic disease of the femur. However, only few studies have been published specifically on the outcomes following reconstruction of femoral metastasis from breast cancer using a third generation intramedullary nail. The aim of this study is to review the outcomes after intramedullary surgical stabilization of femoral metastases from breast cancer. This is often associated with significant bone destruction. METHODS: A retrospective study of 18 femoral metastatic lesions in 15 patients treated with a Long Gamma Nail over a 6-year period was carried out. Pain relief, mobilization status and implant related complications were the main outcome measures analyzed. RESULTS: Thirteen out of 15 patients had complete pain relief and all patients regained their preoperative mobilization status with or without walking aids. There were no implant failures or perioperative deaths. Four (26%) patients developed minor complications. Ten patients died with an average survival of 9 months and five patients are alive with an average survival of 32 months. CONCLUSION: Stabilization of femoral metastases due to breast cancer with Long Gamma Nail is a safe and effective method with acceptable risks.     

74例乳腺癌骨转移的临床预后因素分析

目的:探讨乳腺癌骨转移的临床特征并分析其预后因素。方法:回顾74例乳腺癌骨转移好发部位、病灶特点、发生时间、激素受体分布情况等并用COX比例风险模型进行乳腺癌骨转移预后因素分析。结果:乳腺癌骨转移好发部位在胸部与脊柱,尤其是肋骨和腰椎,几乎均为溶骨性病灶。骨转移平均发生时间为术后33.4个月。骨转移患者中激素受体阳性率比例较高。COX比例风险模型分析显示雌激素受体状况、病理类型和初发单/多发骨转移情况是影响乳腺癌骨转移预后的独立因素。结论:雌激素受体状况、病理类型和初发单/多发骨转移情况是影响乳腺癌骨转移预后的独立因素。对乳腺癌骨转移规律的认识有助于临床诊断和治疗。     

Breast masses in males with carcinoma of the prostate.

Breast masses in male patients who have prostatic carcinoma may represent gynecomastia secondary to estrogen therapy, metastasis of the prostatic carcinoma to the breast, or a primary carcinoma of the breast. Accurate diagnosis of this lesion by biopsy and, if possible, histochemical determination of acid phosphatase is essential to determine prognosis and treatment. The patient with breast metastases from a primary prostatic carcinoma will survive on the average only 4 mo. However, in the patient with prostatic carcinoma, surgical treatment for a primary breast carcinoma may extend survival considerably.     

Biology and surgical management of Breast Cancer

The surgical treatment of breast cancer has been a source of controversy. The controversy arises from the differences in physicians' philosophies regarding the biology of breast carcinoma. Traditionally, surgeons have emphasized the potential therapeutic value of regional lymph node dissection, maintaining that adequate loco-regional treatment is of prime concern in patients with localized tumors. On the other hand, medical oncologists have always stressed the systemic nature of cancer. However, breast cancer is a very heterogeneous disease with an enormous range of different biologic characteristics, and new information is continually becoming available on the natural history of breast cancer. Therefore, we should seek a more rational theory based on the clinical evidence which can explain the biologic characteristics of breast cancer. We have proposed a new spectrum hypothesis as follows: (a)tumor cells traverse lymphatics to lymph nodes by direct extension, and there is an orderly pattern in the early stage of lymph node metastases; (b)regional lymph nodes are able to trap tumor cells but are ineffective or incomplete barriers to tumor cell spread; (c)regional lymph nodes have biologic importance, and a positive lymph node is an indicator of a host-tumor relationship that correlates with the subsequent appearance of distant disease; (d)lymphatic and hematogenous dissemination occur not serially, but in a parallel fashion; (e)many palpable invasive breast cancers are a systemic disease, but non-invasive or minimally invasive breast cancers are likely to be a local disease; (f)early detection and treatment of in-breast cancer improves survival, but variations in regional therapy are unlikely to have a major influence on survival.