Progress in understanding fatigue associated with breast cancer treatment

Fatigue is one of the most common and distressing symptoms reported by cancer patients. This article reviews research that has examined the extent to which breast cancer patients experience fatigue during and following completion of chemotherapy and radiotherapy. The article also addresses methodological issues in the study of fatigue as well as the current status of efforts to prevent or relieve fatigue associated with breast cancer treatment.     

Weekly epirubicin in the treatment of gestational breast cancer (GBC)

Background GBC is a rare disease and chemotherapy in this setting lacks a standardized approach. Patients and Methods Patients 16–30 weeks pregnant with locally advanced/metastatic disease or with high risk of recurrence after surgery were evaluated. Results Twenty patients received weekly epirubicin 35 mg/m². Median maternal age was 37 years (23–42). Median gestational age at chemotherapy was 19 weeks. Thirteen patients were treated after surgery while 7 had locally advanced tumours of which one had liver metastases. Mean total epirubicin dose was 420 mg/m² with a median number of 12 administrations (4–16). No grade 3–4 toxicities were observed. No foetal adverse events were observed except 1 premature delivery at 28 weeks. Births were induced by caesarean section in 12 patients at a median gestational age of 35 weeks. No malformations were reported except 1 newborn with polycystic kidney. At a median age of 2 years, neurological, cardiological and immunological development was normal in all children as reported by their parents. In 7/20 patients with evaluable disease, five had an objective response. At a median follow-up of 38 months, 17 patients are alive; 14 are disease free. Conclusions Weekly epirubicin appears safe and effective with low foetal toxicity and could be considered in GBC. Fedro A. Peccatori and Hatem A. Azim Jr contributed equally to the work.     

Pregnancy and its role in breast cancer

Early full-term pregnancy is the only recognized factor able to prevent breast cancer. There are several hypotheses to explain the mechanisms of this protection, namely an altered hormonal milieu, a differentiation process or a switch in stem cell properties. To explore them, authors have been using animal models, mainly in rodents. Hormonal administration with estrogen and progesterone was the most widely used process to mimic the mammary changes during pregnancy. We have recently proposed that this enigmatic protective role of a full-term birth in breast cancer is carried out by tumor inhibition mediated by differentiated mammary epithelial cells. This explanation may give a new perspective of breast cancer prevention and treatment.     

Metronomic therapy and breast cancer: A systematic review

Metronomic therapy (MT) refers to repetitive, low doses of chemotherapy drugs.     

Pregnancy following breast cancer using assisted reproduction and its effect on long-term outcome

Introduction and aimsWe have previously shown that pregnancy is safe following breast cancer, even in endocrine sensitive disease. Yet infertility remains common following systemic treatment. To date, no study has evaluated the safety of assisted reproductive technology (ART) after breast cancer treatment. In this study, we evaluated the impact of ART on pregnancy and long-term outcomes of young breast cancer survivors.MethodsThis is a multi-centre retrospective study in which women who were diagnosed with breast cancer between 2000 and 2009, and had a pregnancy following breast cancer diagnosis were eligible. Patients were divided into two groups according to whether ART following primary systemic therapy was performed to achieve pregnancy. We evaluated the association between ART use and clinic-pathological characteristics, pregnancy outcome and long-term breast cancer outcome.ResultsA total of 198 patients were evaluated; of whom 25 underwent ART. No significant differences in tumour characteristics were observed between both groups, except for histological grade 3 tumours, which were fewer in the ART group (36% versus 59%, p = 0.033). Around 90% of patients received primary adjuvant chemotherapy and more than 50% had an endocrine sensitive disease. Patients in the ART group were older at diagnosis (31.4 versus 33.7 years, p = 0.009), at conception (38 versus 35 years, p < 0.001), and experienced more miscarriages (23.5 versus 12.6%, p = 0.082). Full term pregnancies were achieved in 77% and 76% of the spontaneous and ART groups, respectively. Mean follow-up between conception and last follow-up was 63 and 50 months in the spontaneous and ART groups, respectively with no difference in breast cancer outcome observed between the two groups (p = 0.54).ConclusionPregnancy using ART in women with history of breast cancer is feasible and does not seem to be detrimental to cancer outcome. Larger studies are needed to further confirm this observation.     

吉西他滨对复发性乳腺癌患者的化疗作用

 目的 探讨吉西他滨在乳腺癌化疗中的作用。方法 取得不同患者的乳腺癌组织标本，采用胶原酶消化法获取乳腺癌原代细胞，应用原代培养和MTT法检测各种化疗药物在体外对乳腺癌原代细胞的杀伤效果。结果 对原发性乳腺癌患者，紫杉类药物的疗效优于蒽环类药物和吉西他滨（P＜0.01）；对复发性乳腺癌患者，吉西他滨的疗效则明显优于蒽环类和紫杉类药物（P＜0.01）。结论 吉西他滨可以作为乳腺癌化疗的二线药物应用于复发性患者。     

Chemotherapy of breast cancer: current views and results

The paper critically reviews major accomplishments achieved with the use of chemotherapy in the treatment of various stages of breast cancer. In spite of innumerable clinical trials, there is no evidence that in advanced breast cancer the addition of more drugs, either in concomitant, sequential or alternating fashion, to known effective combinations, was able to significantly improve the incidence and the magnitude of objective response or its median duration or survival. The addition of endocrine therapy to chemotherapy has failed so far to improve the most important end-point, i.e. total survival. Second-line chemotherapy is only moderately effective for a fairly short period of time. Thus, in women with advanced breast cancer excessive tumor cell burden and permanent drug resistance remain the major obstacles to obtaining complete remission and long-term disease free survival. In the adjuvant setting, the initial trials with combination chemotherapy have achieved consistent results, particularly in women with minimal axillary node involvement. Unless a woman has undergone a surgical breast-saving procedure, postoperative radiotherapy does not appear to play an important therapeutic role, either with or without concomitant or sequential chemotherapy. Present results would suggest that in advanced breast cancer little progress can be expected in the near future. Therefore, medical oncologists should focus on the correct application of established drug regimens, using a sequential flow of hormonal manipulations and cytotoxic chemotherapy. In high-risk groups, full dose adjuvant polydrug therapy given for a relatively short period of time appears to be at present the only means able to significantly decrease the failure rate following local regional treatment. Present consistent achievements, which appear devoid of important delay morbidity (e.g. cancerogenesis, chronic organ damage) will require further clinical research to identify more effective and less toxic treatments.     

Adjuvant therapy of breast cancer

The treatment of early-stage breast cancer includes the use of chemotherapeutic and hormonal agents. Both chemotherapy and hormonal therapy have been shown by large, randomized trials to offer a survival advantage. The most commonly used chemotherapeutic agents used in the United States are doxorubicin and cyclophosphamide (AC). However, 3 studies have suggested that there may be an advantage in the use of taxanes in the adjuvant treatment of breast cancer. Furthermore the use of dose dense chemotherapy, incorporating AC and paclitaxel, has shown very promising results. It is well established that tamoxifen, a selective estrogen receptor modulator (SERM), improves overall survival (OS) in women with hormone receptor (HR) positive breast cancer. However, the results from large multicenter, randomized trials, suggest the potential superiority of aromatase inhibitors, compared to tamoxifen or an advantage of sequencing tamoxifen followed by an aromatase inhibitor (AI). The role of ovarian suppression is still being investigated in patients who have received prior chemotherapy. Newer agents, such as the monoclonal antibody against the HER2/neu receptor, trastuzumab, are now being studied as adjuvant therapy in early-stage breast cancer. In the next few years, with the completion of several large randomized trials, we will be able to answer several questions, including the optimal way of incorporating AIs into adjuvant therapy, the long-term sequella of using trastuzumab in the adjuvant treatment of breast cancer and the role of ovarian suppression combined with an aromatse inhibitor in premenopausal women with breast cancer.     

含洛铂的联合方案治疗晚期乳腺癌的临床观察

目的 观察含洛铂的联合化疗方案治疗晚期复治乳腺癌的疗效及毒副反应。方法 收集2010年1月至2012年5月47例治疗后进展的晚期乳腺癌患者,给予含洛铂（30mg／m²）的联合化疗方案,3～4周为1个周期。至少化疗2个周期后评价疗效及毒副反应。结果 全组47例患者均可评价疗效和毒副反应。无1例获CR,PR 13例,SD 22例,PD 12例,有效率（RR）为27.7％,疾病控制率（DCR）为74.5％。ER或HER-2阳性表达者与其阴性表达者DCR比较,差异均无统计学意义（P＞0.05）。二线治疗者与三线及以上治疗者的RR比较,差异亦无统计学意义（P＞0.05）。至随访截止日期,36例疾病进展,中位疾病进展时间（TTP）为4.7个月（95％CI：4.1～5.3个月）。主要毒副反应为骨髓抑制、消化道反应及疲乏等,多为1、2级,经对症处理后均能缓解,无治疗相关性死亡。结论 含洛铂的联合方案治疗晚期复治乳腺癌疗效较好,毒副反应可耐受。     

妊娠期乳腺癌24例临床分析

目的研究妊娠期乳腺癌在诊断和治疗方面的特殊性。方法回顾性分析1985年至2002年间的妊娠期乳腺癌24例,Ⅰ期7例,Ⅱa期8例,Ⅱb期6例,Ⅲ期3例。11例在终止妊娠后行综合治疗,11例在妊娠中期接受乳腺癌改良根治术,分娩后行综合治疗。2例分娩后行综合治疗。结果终止妊娠和继续妊娠的5年生存率分别为54.5%和53.8%。5年总生存率为54.1%。结论终止妊娠不能提高妊娠期乳腺癌5年生存率。     

多西紫杉醇联合米托蒽醌治疗晚期乳腺癌

目的:评定多的紫杉醇联合米托蒽醌治疗晚期乳腺癌临床疗效及不良反应。方法:52例病人均有病理学诊断及可评价客观指标。采用多西紫杉醇75mg/m~2d1,静脉滴注1小时,用多西紫杉醇前1天口服地塞米松10mg,连续3天。米托蒽酿14mg/m~2d1化疗。21～30天为1周期,2周期评价疗效。结果:52例病人可评价疗效和不良反应。CR 6例,PR 32例,NC 10例,PD 4例,有效率73.08％,不良反应主要为白细胞减少Ⅲ度占32.69％,Ⅳ度占25.00％;脱发Ⅱ度占44.23％,Ⅲ度占21.15％;腹泻Ⅱ度占32.69％,Ⅲ度占21.15％。结论:多西紫杉醇联合米托蒽醌治疗晚期乳腺癌有效率较高,不良反应可以耐受。     

Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations

The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy. The US Government’s right to retain a non-exclusive, royalty free license in and to any copyright is acknowledged.     

Changes in serum hydroxyvitamin D levels of breast cancer patients during tamoxifen treatment or chemotherapy in premenopausal breast cancer patients

BackgroundWe investigated the effect of breast cancer adjuvant treatment on vitamin D status, as measured by serum hydroxyvitamin D (25OHD).MethodsPremenopausal patients (n = 483) diagnosed with non-metastatic breast cancer in 2009 at Asan Medical Center had serum 25OHD levels prospectively analysed at diagnosis and 6 and 12 months after surgery. We excluded patients who took vitamin D supplements or received neoadjuvant chemotherapy. Vitamin D sufficiency was defined as a serum level of ⩾30 ng/ml, insufficiency as 20–29 ng/ml and deficiency as <20 ng/ml.ResultsCompared with baseline serum 25OHD, patients who received chemotherapy had decreased serum 25OHD levels at 6 months (–5.52 ng/ml, p = 0.003) and 12 months (–1.24 ng/ml, p = 0.517) and patients who received anti-hormone therapy had significantly increased serum 25OHD levels at 6 months (+3.00 ng/ml, p = 0.681) and 12 months (+6.47 ng/ml, p = 0.002, respectively). Among patients who received chemotherapy, 49.5% were vitamin D sufficient at diagnosis but only 26.9% were sufficient 6 months after finishing chemotherapy and this percentage increased to 45.2% at 12 months.ConclusionsVitamin D levels decrease during chemotherapy but recover after treatment ends. Anti-hormone therapy with tamoxifen causes serum vitamin D levels to increase. Whether the increased serum vitamin D affects the antitumour effect of the tamoxifen has yet to be determined.     

可手术乳腺癌新辅助化疗364例临床分析

目的：探讨新辅助化疗对可手术乳腺癌的治疗作用、方案、周期数以及生物学指标与疗效的关系。方法：364例新辅助化疗的乳腺癌患者,治疗前肿瘤穿刺活检或术后标本均检测生物学指标ER、PR、C-erbB-2、Ki-67、p53。患者采用FAC、TE、NP方案化疗,每3～4周1次,共1～4个周期,化疗结束后10～14天手术。疗效按UICC实体瘤疗效评定标准进行评价,并统计患者5年生存率。结果：TE方案有效率及病理缓解率高于FAC方案及NP方案（P〈0．05）,其5年生存率也高于后两方案（P〈0．05）;新辅助化疗2周期以上的有效率高于2个周期（P〈0．05）,但平均生存时间无显著差异（P〉0．05）;C-erbB-2阴性、p53阳性、ER／PR阴性患者的有效率高（P〈0．05）;Ki-67表达结果不影响治疗的有效率（P〉0．05）;以上生物学指标表达的不同情况5年生存率之间无显著差异（P〉0．05）。结论：可手术乳腺癌术前应给予2个周期以上TE方案化疗;生物学指标中C-erbB-2阴性、p53阳性、ER／PR阴性的患者有效率高。     

Integrated gene expression profile predicts prognosis of breast cancer patients

Gene expression data has in recent years demonstrated the superior capacity to predict the prognosis of breast cancer patients unreceiving adjuvant chemotherapy comparing to the information available from traditional clinical and pathological sources. Meanwhile, adjuvant chemotherapy can significantly improve survival of breast cancer. It would be inappropriate to ignore its effect on prognosis. We hypothesized that an integrated gene expression profile can predict the prognosis of breast cancer patients receiving chemotherapy. Therefore, we screened the specific gene markers and constructed an integrated 24-gene signature by low-density microarray including the “poor signature” and genes related to resistance to chemotherapy. The gene signature stratified correctly patients into good prognosis group and poor prognosis group. In addition, the Kaplan–Meier analyses for disease-free survival as a function of the 24-gene signature showed highly significant differences between the two groups (Log Rank test P < 0.0001 = Univariate and multivariate Cox’s proportional-hazards regression analyses indicated that the signature represents the strongest independent prognostic factor for breast cancer patients. When compared with single signature, such as Oncotype DX™ and 70 poor signature, the integrated signature showed more predominant power of predication in breast cancer patients receiving chemotherapy. Such integrated signature will critically aid clinical decision making at the level of individualization for most breast cancer patients receiving chemotherapy. Lian-Fang Li and Xiaojing Xu have contributed equally to this work.