Endocrine Therapy for Leptomeningeal Metastases from ER‐Positive Breast Cancer: Case Report and a Review of the Literature

Leptomeningeal disease is an uncommon complication of estrogen receptor positive breast cancer. While there is little consensus on the standard of care, recommendations from current clinical practice guidelines are to treat with intrathecal chemotherapy, necessitating invasive procedures and potentially resulting in a substantial incidence of serious complications and side effects. Here, we review all published evidence of the effectiveness of systemic hormonal therapy alone in treating this condition, with the advantage of requiring no invasive procedures and having virtually no serious complications or side effects. Evidence indicates that most hormonal therapies can penetrate the central nervous system and can be an effective treatment of endocrine sensitive breast cancer that is widely metastatic to the leptomeninges.     

Outcomes of breast cancer in patients who use alternative therapies as primary treatment

BACKGROUND: Some breast cancer patients opt for alternative treatments in place of conventional treatments. The lack of published data on the outcome of this strategy may contribute to this trend. METHODS: A chart review was performed of breast cancer patients who refused or delayed standard surgery, chemotherapy, and/or radiation therapy. Prognosis was calculated for recommended and actual therapy. RESULTS: Thirty-three patients were included in the analysis. Of 11 patients who initially refused surgery, 10 developed disease progression. Of 3 patients who refused adequate nodal sampling, 1 developed nodal recurrence. Of 10 patients who refused local control procedures, 2 developed local recurrences and 2 died of metastatic disease. By refusing chemotherapy, 9 patients increased their estimated 10-year mortality rate from 17% to 25%. CONCLUSIONS: Alternative therapies used as primary treatment for breast cancer are associated with increased recurrence and death. Homeopathy instead of surgery resulted in disease progression in most patients. These data may aid patients who are considering alternative therapies.     

Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer

The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease.The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy.However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research.This review focuses on current and emerging treatments for HR+ metastatic breast cancer.     

男性乳腺癌的综合治疗

男性乳腺癌是一种少见的疾病,其发病率呈上升趋势。由于难以开展大宗的临床研究,男性乳腺癌的治疗基本参照女性乳腺癌的研究数据。外科手术以全乳切除加腋窝淋巴结清扫或前哨淋巴结活检为主。多数男性乳腺癌激素受体为阳性,因此,应用他莫昔芬是标准辅助治疗方法。辅助放射治疗和化疗的适应证参照女性乳腺癌标准。内分泌治疗是转移性男性乳腺癌的主要治疗方法,化疗和抗人类表皮生长因子受体2（HER2）治疗对部分病人有较好疗效。     

70岁以上老年乳腺癌临床病理特点和治疗体会

目的探讨70岁以上老年乳腺癌患者的临床病理特点和治疗方式。方法回顾性分析2008年1月至2018年1月北京市第六医院外科收治的年龄大于70岁,且手术后病理明确诊断116例乳腺癌的临床资料。结果116例均为女性,平均年龄73岁,病程1周至5年,其中92例有伴发疾病。该组患者主要手术方式为乳癌改良根治术(乳房全切和腋窝清扫比例分别为70.2%和61.3%),术后病理浸润性癌占85.3%(99/116),其中黏液癌等特殊类型癌占6.9%(8/116),三阴乳腺癌占11.1%(11/99),HER2阳性乳腺癌占18.2%(18/99)。接受术后化疗者比例48.3%(56/116),内分泌治疗者55%(61/116)。术后中位随访时间44个月,术后复发率5.1%(5/99),乳腺癌相关死亡8例,伴发疾病相关死亡17例。结论老年性乳腺癌患者具有临床病理和分子生物学特点的特殊性,病程长,病期相对晚,伴发疾病较多,化疗耐受性差,内分泌治疗依从性较差,手术和内分泌治疗是主要和有效的治疗方法。     

Management of Ewing sarcoma family of tumors: Current scenario and unmet need

Ewing sarcoma family tumors(ESFT) are heter ogeneous,aggressive group of disease with peak incidence in adolescent and young adults. The outcome has been improved dramatically from 10% with surgery and radiotherapy alone to 65%-70% now, in localized disease, with the introduction of chemotherapy. Chemotherapy regimen evolved from single agent to multiagent with effort of many cooperative clinical trials over decades. The usual treatment protocol include introduction of multi-agent chemotherapy in neoadjuvant setting to eradicate systemic disease with timely incorporation of surgery and/or radiotherapy as local treatment modality and further adjuvant chemotherapy to prevent recurrence. Risk adapted chemotherapy in neoadjuvant and adjuvant setting along with radiotherapy has been used in many international collaborative trials and has resulted in improved outcome,more so in patients with localized disease. The role of high dose chemotherapy with stem cell rescue is still debatable. The outcome of patients with metastatic disease is dismal with long term outcome ranges from 20%-40% depending on the sites of metastasis and intensity of treatment. There is a huge unmet need to improve outcome further, more so in metastatic setting.Novel therapy targeting the molecular pathways and pathogenesis of ESFT is very much required. Here we have discussed the current standard of management in patients with ESFT, investigational targeted or novel therapies along with future promises.     

Neoadjuvant chemotherapy of breast cancer

The use of neoadjuvant chemotherapy in the treatment of breast cancer has been evolving during the past two decades. Fisher's group accomplished the scientific rationale in mouse models in the 1970s. The Milan group was the first to use neoadjuvant therapy in locally advanced breast cancer and also determined that adjuvant sequential doxorubicin with cyclophosphamide/methotrexate/fluorouracil (CMF) offered improved survival when compared to alternating CMF with doxorubicin. Other groups (M. D. Anderson and NSABP) have evaluated similar doxorubicin-based neoadjuvant therapies in locally advanced breast cancer (LABC) and in early disease. These studies have shown an increase in breast-conserving therapy (BCT) and an increase in pathologic complete response (pCR) when neoadjuvant therapy was used. Due to anthracycline resistance, taxanes were added to the doxorubicin-based neoadjuvant chemotherapy regimen with an increase in BCT and pCR than when an anthracycline regimen was used alone. Overall survival has yet to be determined when comparing an anthracycline-based regimen to the same regimen with the addition of a sequential taxane. Therefore, a combined treatment of an anthracycline/cyclophosphamide/taxane regimen is the recommended neoadjuvant chemotherapy for patients with breast cancer.     

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男性乳腺癌是一种少见的疾病,其发病率呈上升趋势。由于难以开展大宗的临床研究,男性乳腺癌的治疗基本参照女性乳腺癌的研究数据。外科手术以全乳切除加腋窝淋巴结清扫或前哨淋巴结活检为主。多数男性乳腺癌激素受体为阳性,因此,应用他莫昔芬是标准辅助治疗方法。辅助放射治疗和化疗的适应证参照女性乳腺癌标准。内分泌治疗是转移性男性乳腺癌的主要治疗方法,化疗和抗人类表皮生长因子受体2(HER2)治疗对部分病人有较好疗效。     

Could biological aggressivity markers of breast cancer alter the therapeutic course? Preliminary results

The aim of this study is to justify an individual therapeutical attitude in breast cancer, related to diversity of breast tumors, aggressiveness grade and metastatic potential. Between January 2000--December 2001, 150 patients were admitted with breast cancer (stage II and III) and underwent surgery in our department. We selected 75 cases in our study. In 51 (68%) cases the first therapeutical method was surgery, in 15 (20%) cases surgery was performed after chemotherapy, in 2 (2.66%) cases after radiotherapy and after chemotherapy and radiotherapy in 7 (9.33%) cases. We evaluated several classical factors and new immunohistochemical markers with an important value for diagnosis, prognosis and therapy: oestrogen and progesterone receptors, c-erb B2, pS2 and p53 proteins, von Willebrand factor. Several factors had a predictive role regarding the response to chemotherapy. These predictive factors will improve the histopathological diagnosis. The oncoproteins and hormonal receptors also will evaluate with more accuracy the metastatic risk and will assure a better therapy decision.     

复发转移乳腺癌(附34例报告)

目的　探讨复发转移乳腺癌的临床病理特点 ,最佳治疗方法和治疗效果。方法　对3 4例复发转移乳腺癌病人 ,采取化疗 ,结合手术 ,放射治疗 ,术后继续化疗。结果　 2 3例伴有内脏转移的 2个部位以上复发转移病人 ,经化疗病灶缩小明显 (PR) 7例 ,病情稳定 (SD ) 8例 ,病情进展(PD) 8例 ,临床获益 (CR PR SD) 65 % (15 / 2 3 )。 1年生存率 65 % ,11例局部复发化疗后病灶缩小 (PR) 10例 ,病情进展 (PD) 1例 ,临床获益 90 % (10 / 11) ,2年无瘤生存率 90 %。结论　伴有内脏转移的复发转移应以化疗为主 ,病灶缩小者 ,局部手术切除 ,放疗 ,术后继续化疗。显著延长生存时间。局部复发无内脏转移 ,也应先化疗 ,再手术 ,可减少远隔器官转移。     

MRI在乳腺癌综合治疗中的应用价值及评价

随着乳腺癌个体化、规范化综合治疗理念的推广,乳腺MRI在综合治疗中的作用日益受到重视。伴随乳腺MRI临床应用开展和研究的深入,其在乳腺癌的诊断、保乳治疗、新辅助化疗(NAC)以及随访监测中的应用价值得到评估。乳腺MRI对肿瘤范围的精确显示为多种治疗方式的合理应用、评估及监测治疗效果等方面具有重要价值,对乳腺癌综合治疗起着不可替代的作用。     

Trends and Novel Approaches in Neoadjuvant Treatment of Breast Cancer

Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.     

Metastatic disease of the breast and local recurrence of breast cancer

Breast cancer is a major health problem worldwide with over 1 million new cases diagnosed each year. The aim of treatment is to achieve good loco-regional control, provide appropriate adjuvant therapy and treat potential micro-metastasis. Early detection with breast screening and better treatment options have improved outcome. However approximately 40% of patients will suffer a recurrence and still 35–40% will eventually present with metastatic disease. Metastatic disease is incurable with the median survival being 2–3 years. Several therapies have been shown to maintain a good quality of life whilst prolonging survival. In certain sub-groups of breast cancer, that is, human epidermal growth factor receptor 2 (HER2)-positive cancer the advent of trastuzumab has improved survival rates. A multidisciplinary team approach is essential to obtain the diagnosis and plan the appropriate treatment. The diagnosis of metastatic disease brings distress to patients and their relatives and support should be available from palliative care teams.     

激素抵抗性前列腺癌(附39例报告)

目的探讨激素抵抗性前列腺癌的诊断和治疗,以提高其诊治水平。同时比较中国人和欧美人激素抵抗性前列腺癌生存期的差异。方法回顾性分析1995年6月～2004年10月39例激素抵抗性前列腺癌患者的临床资料。结果确诊激素抵抗性前列腺癌时,38例血PSA值较最低点均有不同程度升高,血PSA值0．2ng/ml～200ng/ml,平均(51．16±54．71)ng/ml,其中有4例血PSA值一直在4ng/ml以下,升高很少,主要靠转移灶来诊断。化疗是主要的治疗方法,常用的有磷酸雌二醇氮芥,磷酸雌二醇氮芥 足叶乙甙,环磷酰胺 足叶乙甙,磷酸雌二醇氮芥 环磷酰胺等。PSA有效率为44．4%～57．8%,平均有效时间3,8月～7．5月,软组织灶有效率为28．6%～50%。39例中已死亡21例,这21例诊断激素抵抗性前列腺癌后,中位生存期为16个月。结论绝大多数激素抵抗性前列腺癌患者可用PSA诊断和随访,但极少数患者PSA变化很小,需用癌灶和症状来随访。化疗是治疗激素抵抗性前列腺癌的主要方法,有一定的疗效。本组患者生存时间似较欧美患者长。     

转移性肝癌介入治疗的疗效及影响预后的因素

目的 探讨转移性肝癌介入治疗的疗效及影响预后的因素。方法 ３６例中,原发癌灶切除者１７例,未切除者１９例,肝动脉化疗栓塞治疗１９例,肝动脉化疗药物灌注治疗者１７例。结果 原发癌灶切除组半年生存率,较未切除者具有显著性差异。肝动脉化疗栓塞治疗组半年生存率,较肝动脉化疗药物灌注治疗组,具有高度显著性差异。结论转移性肝癌患者,应尽可能切除原发癌灶,并给全身化疗,免疫治疗及原发癌灶的选择性动脉化疗药物灌注     

Pilot Trial of Alternating Paclitaxel and Doxorubicin in Advanced Breast Cancer

Abstract: Studies combining paclitaxel and doxorubicin in the treatment of metastatic breast cancer have shown dose-limiting toxicities and raised questions relating to the risk of cardiac toxicities. This pilot trial evaluates an alternating approach to assess safety and feasibility of paclitaxel alternating with doxorubicin as chemotherapy for recurrent breast cancer. Twelve patients with measurable or evaluable breast cancer who had received no more than one prior chemotherapy (either as adjuvant therapy or therapy for metastatic disease) and no prior anthracycline- or taxane-containing chemotherapy were included. Paclitaxel was administered at 200 mg/² as a continuous 24-hour intravenous infusion alternating with doxorubicin at 75 mg/m² intravenously, administered every 21 days for a maximum of 10 cycles of therapy. Objective responses were observed in seven of 12 patients (58%) (three complete responses and four partial responses). Objective responses were seen in lymph node, visceral, soft tissue, and bony sites of metastases. The median duration of response was 9.6 months (range 1.4–20.6). A total number of 102 cycles of therapy were administered with 8 of 12 patients tolerating all 10 cycles (median of 10 cycles per patient, range 2–10). Adverse effects included mild myalgias, arthralgias, and peripheral neuropathies. Cardiac toxicities included asymptomatic sinus tachycardia, sinus bradycardia, and nonspecific T-wave abnormality. One patient experienced left ventricular failure. There were no serious hypersensitivity reactions. Paclitaxel cycles resulted in lower granulocyte nadirs than doxorubicin cycles. There were no significant differences in thrombocytopenia between the two agents. The feasibility of administering paclitaxel and doxorubicin in alternating cycles was demonstrated. This was a well-tolerated regimen with results supportive of safety in administration in an alternating regimen.     

The role of chemotherapy in the treatment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC)

ObjectiveUrothelial cell carcinoma of the upper urinary tract (UUT-UCC) is a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. This review highlights the main chemotherapy regimens available for UUT-UCCs based on the recent literature.Materials and methodsData on urothelial malignancies and UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; urothelial carcinomas; upper urinary tract; carcinoma; transitional cell; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors; and survival.ResultsNo evidence level 1 information from prospective randomized trials was available. Because of its many similarities with bladder urothelial carcinomas, chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. Most teams have proposed a neoadjuvant or an adjuvant treatment based either on the combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) or on gemcitabine/cisplatin (GC). These regimens have been shown to prolong survival moderately. All recent studies have included limited numbers of patients and have reported poor patient outcomes after both neoadjuvant and adjuvant chemotherapy. Regarding metastatic UUT-UCCs, vinflunine has demonstrated moderate activity in these patients with a manageable toxicity. Interestingly, specific molecular markers [microsatellite instability (MSI), E-cadherin, HIF-1α, and RNA levels of the telomerase gene] can provide useful information that can help diagnose and determine patient prognosis in patients with UUT-UCC.ConclusionChemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. However, there is no strong evidence that chemotherapy is effective due to the rarity of the disease and the lack of data in the current literature. Thus, physicians must take into account the specific clinical characteristics of each individual patient with regard to renal function, medical comorbidities, tumor location, grade, and stage, and molecular marker status when determining the optimal treatment regimen for their patients. The ongoing identification of the oncologic mechanisms of this type of cancer might pave the way for the development of specific treatments that are targeted to the characteristics of each patient's tumor in the future.     

Implications of Anthracycline‐Resistant and Taxane‐Resistant Metastatic Breast Cancer and New Therapeutic Options

Abstract: Patients with advanced or metastatic breast cancer commonly develop disease resistant to chemotherapy (typically anthracyclines and taxanes), which presents a major obstacle to therapy and leaves few effective treatment options. Drug resistance can occur due to various mechanisms including modification of drug efflux membrane transporters such as P‐glycoprotein, as well as alterations in β‐tubulin. The novel epothilone B analog, ixabepilone, which has low susceptibility to various drug‐resistance mechanisms, has demonstrated preclinical activity in drug‐resistant breast cancer. The clinical activity of ixabepilone was evaluated in metastatic breast cancer patients with highly pretreated and/or resistant/refractory disease. Results were reviewed from three phase II trials in which ixabepilone was administered as monotherapy and one phase III trial that evaluated ixabepilone in combination with capecitabine. As a single agent, ixabepilone demonstrated activity in women who were heavily pretreated and resistant to an anthracycline, a taxane, and/or capecitabine. The combination of ixabepilone and capecitabine was significantly more active than capecitabine alone in patients with prior treatment or resistance to anthracyclines and taxanes. Treatment‐related adverse events were generally low grade except for grade 3/4 toxicities, including neutropenia (53–54%) and reversible peripheral sensory neuropathy (14–16%). Ixabepilone has significant activity in patients with heavily pretreated metastatic breast cancer who are disease resistant or refractory to anthracyclines and taxanes. Further clinical evaluation of this agent in patients with drug‐resistant breast cancer and in specific patient subsets is warranted.     

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??Interpretation of the ASCO practice guideline??Chemotherapy and targeted for women with HER2-Negative (or unknown) advanced breast cancer GAO Guo-xuan??LIU Yin-hua.Breast Disease Center??Peking University First Hospital??Beijing 100034??China
Corresponding author??LIU Yin-hua??E-mail??liuyinhua@medmail.com.cn
Abstract In October 2014 Journal of Clinical Oncology??it published the Chemotherapy and Targeted for Women With Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer??ASCO Practice Guideline.Recommendations include??Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary (eg??immediately life-threatening disease).Single agent is preferable to combination chemotherapy??and longer planned duration improves outcome but must be balanced against toxicity.There is no single optimal first-line or subsequent line chemotherapy??and choice of treatment will be determined by multiple factors including prior therapy??toxicity??performance status??comorbid conditions??and patient preference.The role of bevacizumab remains controversial.Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer.