nab-Paclitaxel for the Treatment of Aggressive Metastatic Breast Cancer

Despite advances in early diagnosis, prevention, and treatment, breast cancer remains the second-leading cause of cancer-related deaths in women. The 5-year survival rate for patients with metastatic breast cancer (MBC) is just 24%. However, some forms of MBC appear to be more aggressive than others. Triple-negative breast cancer (TNBC; lacking overexpression of human epidermal growth factor receptor 2 [HER2] and expression of estrogen and progesterone receptors) and breast cancers that overexpress HER2 are the 2 biologically defined subtypes with the worst prognoses. Although a number of effective options have been developed for the treatment of HER2-overexpressing disease, TNBC remains a difficult-to-treat subtype. In addition to hormone receptor and HER2 status, multiple other factors are predictive of relatively poorer clinical outcomes, including visceral metastasis, short disease-free interval between the end of treatment for early-stage disease and diagnosis of MBC, and higher number of metastatic sites. There is an urgent need to improve therapy for patients with aggressive forms of breast cancer. Taxanes are considered among the most active classes of compounds against breast cancer. This review specifically examines the clinical trials in which nab-paclitaxel was used to treat patients with MBC and factors associated with poor prognosis.     

Survival Effect of Supportive Care Services for Turkish Patients with Metastatic Gastric Cancer

Background: Gastric cancer is the second most common cause of cancer- related deaths worldwide and ranks11th or 14th among all deaths. Patients with advanced disease require supportive care along with the medical and/or surgical treatment. Aim: To assess the need for palliative care for patients with advanced tumours along withstandard clinical therapy. Materials and Methods: Eighty-four patients with metastatic (stage 4) gastric cancer,including both patients who had received surgical treatment or not , were followed up in Bagcilar Training andResearch Hospital, Division of Medical Oncology between 2011 and 2014. They were categorised as supportivecare (-) (Group 1, n=37) and (+) groups (Group 2, n=47) and evaluated retrospectively. Results: Demographiccharacteristics of the patients were as follows: mean age, Group 1, 65.2±10.5 years, Group 2,63.7±11.3 years;male/female ratio, Group 1, 21/16, Group 2, 28/19; distribution of Eastern Cooperative Oncology Group(ECOG) performance scores of 0 and 1, Group 1, ECOG 0 (n=9) and 1 (n=14), Group 2, ECOG 0 (34) and 1(n=13) (p<0.0001); patients receiving second-line, Group 1 (n=7) and Group 2 (n=22) (p<0.008) or third - linechemotherapy,Group 2 (n=6) (p<0.02); mortality rates, Group 1, (n=28; 75.6%) and Group 2 (n=30; 63.8%);progression-free survival (PFS) rates, Group 1, 17.4±6 weeks, Group 2, 28.3±16.2 weeks; statistically significantoverall survival rates, Group 1, 20.8±8.2 weeks and Group 2, 28.3 ± 162 weeks (p<0.01). Conclusions: Thesupportive care team (medical oncologist, general surgeon, internal medicine specialist, algologist, psychiatristand radiologist) can play a role in the treatment of metastatic gastric tumours, with improvements shown interms of the performance status of cases, eligibility of patients to be on chemotherapy programmes for longerduration and overall survival rates in Turkey.     

Aggressive Subsets of Metastatic Triple Negative Breast Cancer

BackgroundRelative to other metastatic breast cancer subtypes, metastatic triple-negative breast cancer (mTNBC) has a shorter duration of response to therapy and worse overall survival. Among patients with mTNBC, it is hypothesized that inflammatory breast cancer (IBC) and young women have particularly aggressive phenotypes. We investigated clinical and cell-free DNA (cfDNA) characteristics of inflammatory-mTNBC and young-mTNBC.Patients and MethodsWe evaluated 158 patients with mTNBC who were stratified into 3 groups: (1) IBC; (2) patients aged 45 years or younger at primary diagnosis without IBC (non-IBC young); and (3) patients over age 45 at diagnosis without IBC. We evaluated clinicopathologic characteristics, sites of metastasis, survival outcomes, and the fraction of DNA in circulation derived from tumor (TFx).ResultsAnalysis of metastatic sites revealed that young patients without IBC had the most frequent lung metastases (P = .002). cfDNA analyses of first sample showed that TFx was highest in the non-IBC young group but not elevated in the IBC group (analysis of variance P = .056 for first TFx). Individually, median overall survival from metastatic diagnosis for the IBC group was 15.2 months; for the non-IBC young group, 21.2 months, and for the non-IBC over 45 group, 31.2 months. Patients with IBC and young patients without IBC had worse prognosis relative to patients over 45 without IBC (log-rank P = .023).ConclusionsAmong patients with mTNBC in this single-institution cohort, patients with IBC and young patients without IBC had significantly worse overall survival compared with patients over 45 without IBC. Young patients without IBC had significantly higher cfDNA TFx, whereas patients with IBC did not have elevated TFx despite a poor prognosis. These findings demonstrate that further analyses of mTNBC subsets are warranted.     

长春瑞滨联合希罗达对蒽环类/紫杉类治疗后复发转移性乳腺癌的疗效观察

目的探讨长春瑞滨联合希罗达方案对蒽环类/紫杉类治疗后晚期复发转移乳腺癌的近期疗效和不良反应。方法40例应用蒽环类/紫杉类治疗后复发转移性乳腺癌患者,长春瑞滨25 mg/m²,静脉快速滴入,第1、8天;希罗达1 000 mg/m²,早晚两次餐后30 min口服,连用14天,21天为1周期,每例患者至少接受2周期的治疗。结果40例患者完全缓解（CR）3例,部分缓解（PR）16例,病情稳定(SD)14例,病情进展（PD）7例,总有效率47.5%,临床获益率为70%,中位疾病进展时间(TTP)为8.5月。常见不良反应为骨髓抑制、消化道反应、手足综合征、神经毒性,少数患者出现口腔炎、头晕、乏力和胸闷等。结论长春瑞滨联合希罗达方案对紫杉/蒽环类治疗后复发转移乳腺癌疗效确切。治疗过程中患者耐受性好,不良反应轻。     

去甲长春花碱联合顺铂治疗转移性乳腺癌

目的：观察去甲长春花碱（vinorelbine,NVB)联合顺铂（cisplatin,DDP)治疗转移性乳腺癌的疗效及不良反应,方法：采用NVB25mfg/m^2d1.8DDP30mg/m^2d1-3,每3周重复一次,共用2－4周期。结果：40例患者中有效率45％（18／40）,CR2．5％（1／40）,PR42．5％（17／40）,主要剂量限制不良反应是白细胞减少（Ⅲ、Ⅳ度27．5％）,结论：NVB联合DDP治疗转移性乳腺癌有较好的疗效,且阿霉素和／或泰素治疗失败的患者亦有较好的疗效,不良反应中耐受。     

Effect of Surgery at Primary and Metastatic Sites in Patients With Stage IV Breast Cancer

BackgroundThere is no clear evidence of a survival benefit of resection of the primary tumor, or distant site resection (metastasectomy) in patients with stage IV breast cancer.Patients and MethodsThis retrospective analysis of stage IV breast cancer using the National Cancer Database. To evaluate variables associated with surgery at the primary site, we used univariate analyses followed by multivariate logistic regression. Consequently, we evaluated the impact of lumpectomy, mastectomy or metastasectomy on survival by conducting multivariate Cox regression survival analyses on the following groups: all stage IV patients; a subset of those with only one metastatic site; and another subset with metastasis to multiple distant sites.ResultsA total of 54,871 stage IV breast cancer patients were included in this analysis. Variables associated with the use of surgery at the primary were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N stage, extent of metastasis, and year of diagnosis. Survival analysis showed that both lumpectomy (median overall survival [OS], 45 months) and mastectomy (median OS, 44 months) were associated with better OS compared to no surgery (median OS, 22 months). The statistical effect was larger in the subgroup with metastasis to one site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit.ConclusionIn patients with metastasis to only one site, metastasectomy was associated with better OS when that site was the liver, lung, or brain.     

Implementation of a Multidisciplinary Model of Care for Women With Metastatic Breast Cancer: Challenges and Lessons Learned

IntroductionThe present study examined the feasibility and effects of integrating a multidisciplinary team (MDT) model of care for women with metastatic breast cancer (MBC) into a large Australian cancer center. The challenges encountered and lessons learned are described.Patients and MethodsIn the present prospective, longitudinal, mixed-methods implementation study, the MDT model included face-to-face consultations with a breast care nurse and social worker, followed by a MDT case discussion and face-to-face delivery of a personalized management plan. Data were collected to describe the cohort of women living with MBC who had attended a specialist breast cancer service and their supportive care needs.ResultsA total of 62 women with median age of 60 years (interquartile range [IQR], 37-82 years) participated. The median interval from the first breast cancer diagnosis was 5.7 years (IQR, 2.0-11.6 years), and the median interval from the diagnosis of MBC was 2.0 years (IQR, 0.9-3.6 years). The MDT care model required new resources and cross-sector participation. However, the participants indicated a preference for personalized needs assessment and care planning at the diagnosis of MBC.ConclusionsThe results highlight the challenges of implementing and evaluating an MDT care model for women with MBC. The model coordinated MDT collaboration to strengthen the delivery of complex care plans. Investment in cross-sector partnerships to optimize care coordination for women with MBC was needed.     

Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast Cancer

Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.     

Irinotecan as a Palliative Therapy for Metastatic Breast Cancer Patients after Previous Chemotherapy

Background: This analysis was conducted to evaluate the efficacy and safety of irinotecan based chemotherapyfor treatment of patients with metastatic breast cancer (MBC) who experienced disease progression after one tothree chemotherapy regimens, including at least one anthracycline- or taxane-based. Methods: Clinical studieswere identified using a predefined search strategy. Pooled response rates (RR) to treatment were calculated.Results: As irinotecan based regimens, 5 clinical studies which including 217 patients with refractory MBC wereconsidered eligible for inclusion, with irinotecan, cisplatin, capecitabine, or TS-1. Systemic analysis suggestedthat, in all patients, pooled RR was 48.8% (106/217) with irinotecan based regimens. Thrombocytopenia andleukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatmentrelated deaths occurred. Conclusion: This systemic analysis suggests that irinotecan based regimens are beneficialand safe for treating patients with MBC after other chemotherapy.     

miRNA-29在正常乳腺、原发性乳腺癌及转移性乳腺癌组织中的表达意义

目的 探讨微小RNA-29 (miRNA-29)在正常乳腺、原发性乳腺癌以及转移性乳腺癌组织中的表达,并分析miRNA-29、基质金属蛋白酶-2(MMP-2)在疾病发生与进展中的作用.方法 选取286例乳腺癌患者,其中原发性乳腺癌205例,转移性乳腺癌81例,同期选取150例无乳腺疾病的健康妇女为对照组.采用RT-PCR检测miRNA-29与MMP-2表达水平.结果 三组乳腺标本中miRNA-29与MMP-2水平比较差异均具有统计学意义(P＜0.05),其miRNA-29与MMP-2表达呈负相关性,而肿瘤大小、病理分期、HER-2及ki-67均与miRNA-29表达具有密切相关性(P＜0.05).结论 miRNA-29与乳腺癌的发生、发展与转移等过程均具相关性,明确其表达水平有助于病情评估及临床治疗.     

Eribulin Monotherapy in Patients Aged 70 Years and Older With Metastatic Breast Cancer

Purpose.

Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients.

Methods.

Data were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m² as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50–59 years, 60–69 years, ≥70 years).

Results.

Overall, 827 patients were included in the analysis (<50 years, n = 253; 50–59 years, n = 289; 60–69 years, n = 206; ≥70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia).

Conclusion.

Eribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups.     

Economic Analysis of Psychosocial Group Therapy in Women with Metastatic Breast Cancer

Purpose

Metastatic breast cancer is associated with psychological distress in one-third of patients. We examined the impact of group psychosocial support on health care costs in metastatic breast cancer. Psychosocial interventions have been shown to reduce psychological distress in these patients. In other diseases, depression and anxiety have been associated with higher health care system resource utilization.

Methods

Data on health care system resources utilization were collected as part of a Canadian multicenter randomized controlled trial of a supportive-expressive group support in metastatic breast cancer. Costs were obtained from one tertiary care hospital in Toronto. A cost minimization analysis was conducted since there was no survival difference; the primary endpoint of the study. Cost-effectiveness analyses were conducted for mood and pain.

Results

Total health care utilization costs (including costs of the group therapy intervention) for the intervention and control groups were $31,715 and $28,189, respectively per patient. The difference in total costs between groups ($3,526) was not statistically significant (P = 0.53). The cost-effectiveness analysis for mood showed the intervention group to have an increased cost of $5,550 per patient for an effect size of 0.5 on the POMS scale. The corresponding cost for pain was $4,309. An exploratory analysis on patients who were more distressed at baseline showed a non-significant decrease in cost in favor of the intervention arm (difference of $3,911 P = 0.66).

Conclusion

Psychosocial intervention, in the form of supportive-expressive group support for metastatic breast cancer, does not lower health care system resource utilization.     

Phase II Study of Paclitaxel and Dasatinib in Metastatic Breast Cancer

Background

Overexpression and activation of tyrosine kinase Src has been linked to breast carcinogenesis and bone metastases. We showed the feasibility of combining the SRC inhibitor dasatinib with weekly paclitaxel in patients with metastatic breast cancer (MBC) and herein report the subsequent phase II trial.

中等剂量卡培他滨单药治疗转移性乳腺癌的疗效及安全性

目的观察中等剂量［2 000 mg/(m²·d)］卡培他滨治疗转移性乳腺癌的疗效和不良反应。方法卡培他滨单药治疗43例转移性乳腺癌,2000 mg/(m²·d),d1～14,每3周为1周期。结果43例患者平均行8周期卡培他滨治疗,客观缓解率（CR+PR）为18.6%,临床获益率（CR+PR+SD）为86.0%。整体的中位无进展生存期（PFS）为7.1月（95%CI：5.8～8.4）,在一线治疗、二线治疗和三线及以上治疗亚组中差异无统计学意义,分别为7.1月、6.1月和8.1月（P=0.390）。在蒽环类药物与紫杉类药物治疗均失败的患者中,PFS明显缩短（6.1月 vs.7.1月,P=0.038）。大于65岁的患者PFS显著延长（8.1月 vs.6.1月,P=0.045）。主要不良反应为手足综合征19例（44.2%）。结论中等剂量［2 000 mg/(m²·d)］卡培他滨单药治疗转移性乳腺癌安全、有效。     

吉西他滨联合顺铂治疗HER2阳性转移性乳腺癌疗效观察

目的 观察吉西他滨（GEM）联合顺铂（DDP）在治疗既往使用过蒽环类和或紫杉醇类、HER2阳性转移性乳腺癌的疗效与安全性。方法 64例分为观察组（GP方案）和对照组（NP方案）各32例。GP方案：GEM1000mg／m^2静脉点滴第1、8天，DDP80mg／m^2分成3次，静脉点滴，第1、2、3天。NP方案：长春瑞滨（NVB）30mg／m^2静脉点滴，第1、8天，DDP与观察组相同。21天为1个周期，每例2个周期。结果64例均可评价疗效和毒性反应。观察组CR2例、PR15例、SD5例、PD10例，总有效率（CR＋PR）为53，1％，中位肿瘤进展时间（TTP）4．8个月，毒性反应中恶心呕吐和白细胞下降发生率高，血小板降低明显。对照组中无CR，PR9例、SD10例、PD13例，总有效率为28．1％，TTP4．1个月，毒性反应是恶心呕吐和白细胞下降及静脉炎。两组总有效率比较有显著性差异（P〈0．05）。结论 GEM加DDP联合治疗HER2阳性转移性乳腺癌有效安全，毒副反应轻，患者能耐受，为蒽环类和（或）紫杉醇类治疗失败并HER2阳性的患者提供了有效的治疗方案。