Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.     

Mitoxantrone Plus Vinorelbine in Pretreated Patients with Metastatic Breast Cancer

Abstract

Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC).

Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was ≤2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m², D1+8 and mitoxantrone 10 mg/m² D8 every 21 days for 6 cycles.

All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths.

The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

Cyclin-Dependent Kinase 4/6 Inhibitors in Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR⁺) HER2⁻ breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation. We present a review of the currently available data and ongoing clinical trials that are evaluating the role of CDK4/6 inhibitors in neoadjuvant therapy of HR⁺ HER2⁻ early BC, and also illustrate translational aspects, such as the potential biomarkers of response to these new therapeutic agents.     

长春瑞滨联合顺铂治疗三阴性乳腺癌的临床观察

目的观察长春瑞滨联合顺铂治疗三阴性乳腺癌(TNBC)的疗效和毒副反应。方法入组27例TNBC患者,均给予长春瑞滨联合顺铂化疗,化疗2周期后评价疗效和毒副反应。结果 27例晚期TNBC中,CR 1例(3.7%),PR 8例(29.6%),SD 15例(55.6%),PD 3例(11.1%),总有效率为33.3%,疾病控制率为88.9%。主要毒副反应为骨髓抑制和消化道反应,均可耐受。结论长春瑞滨联合顺铂治疗TNBC疗效较好,毒副反应较轻。     

Cyclin-Dependent Kinase 4/6 Inhibitors Combined With Radiotherapy for Patients With Metastatic Breast Cancer

BackgroundThe cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. Data about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking.Patients and MethodsWe undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling.ResultsThirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site.ConclusionWe observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT.     

希罗达为主的联合方案治疗蒽环类耐药的复发转移性乳腺癌

目的 探讨希罗达为主的联合化疗方案治疗复发转移性乳腺癌的疗效及毒副反应.方法 42例复发转移性乳腺癌患者中,21例予以希罗达联合诺维本治疗;14例予以希罗达联合多西紫杉醇治疗;7例予以希罗达联合吉西他滨治疗.21 d为1周期,2周期后评价疗效.结果 41例可评价患者中,治疗后完全缓解(CR)8例,部分缓解(PR)16例,稳定(SD)9例,进展(PD)8例,有效率为58.54%.中位疾病进展时间为7.4个月,中位生存时间15.3个月.主要毒副反应为白细胞减少,其中Ⅲ～Ⅳ度占41.46%.结论 希罗达为主的联合化疗方案治疗复发转移性乳腺癌疗效确切,毒性反应可耐受.     

Patterns and Predictors of First-Line Taxane Use in Patients with Metastatic Triple-Negative Breast Cancer in US Clinical Practice

We investigated first-line (1L) treatment patterns and predictors of taxane use to better understand the evolving metastatic triple-negative breast cancer (mTNBC) treatment landscape. This retrospective analysis of the Truven Health MarketScan^® (Somers, NY, USA) Database included women with mTNBC who received 1L therapy within six months of diagnosis (January 2005–June 2015). Multivariate logistic regression models identified predictors of taxane use, adjusting for prognostic factors. A total of 2271 women with newly diagnosed mTNBC received 1L treatment during the study period. Half received a 1L taxane (53%), more often in combination than as monotherapy (58% versus 42%), though this varied by specific taxane. Nab-Paclitaxel monotherapy increased substantially after 2010. More recent treatment year (odds ratio, 2.16 (95% CI 1.69–2.76]) and number of metastases (≥3 versus 1: 1.73 (1.25–2.40)) predicted taxane monotherapy versus combination. Having a health maintenance organization versus a preferred provider organization plan predicted less nab-paclitaxel versus paclitaxel (0.32 (0.13–0.80)) or docetaxel (0.30 (0.10–0.89)) use. More recent index year (2011–2015 vs. 2005–2010) was the only predictor favoring nab-paclitaxel versus paclitaxel (2.01 (1.26–3.21)) or docetaxel (3.63 (2.11–6.26)). Taxane-containing regimens remained the most common 1L mTNBC treatments. Paclitaxel and nab-paclitaxel use changed substantially over time, with nab-paclitaxel use associated with insurance coverage.     

中等剂量卡培他滨单药治疗老年转移性乳腺癌的临床观察

目的：观察中等剂量卡培他滨单药治疗老年转移性乳腺癌的疗效和毒副反应。方法单药卡培他滨治疗39例老年转移性乳腺癌患者,每天2000 mg·m-2,分2次口服,连用14 d,休息7 d,每21 d为1周期,直到疾病进展,最多行6周期治疗。结果全组39例老年转移性乳腺癌患者中,PR 9例,SD 25例,PD 5例,总有效率23.1％,肿瘤控制率87.2％,中位肿瘤进展时间7.6个月。毒副反应有：Ⅰ、Ⅱ度手足综合征14例（35.9％）,Ⅰ、Ⅱ度骨髓抑制9例（23.1％）,Ⅰ度腹泻2例（5.1％）,Ⅰ度消化道反应1例（2.6％）。结论中等剂量卡培他滨单药治疗老年转移性乳腺癌安全有效,值得临床广泛推广。     

Second-Line Chemotherapy with Mitoxantrone as a Single Agent in Metastatic Breast Cancer

Summary

Ninety-three evaluable patients with metastatic breast cancer previously treated with chemotherapy, received mitoxantrone as a single agent (14 mg/m², by rapid intravenous infusion, once every 3 weeks). Patients received a median of 7 courses (range 2 to 18), with a mean cumulative total dose of 133 mg (range 36 to 342). A complete response (CR) was achieved in 2 patients (2%). Partial response (PR) was observed in 23 patients (25%). The overall response rate (CR + PR) was thus 27%, with a median duration of 9 months (range 3 to 18). Responses were observed in all metastatic sites, except for brain and peritoneum. Stabilization (S) occurred in 26 patients (28%). The remaining 42 patients (45%) showed clear progression of their metastatic disease while on therapy. The actuarial 24-month survival for the whole group was 13%, increasing to 29% in responders (CR + PR), as compared with only 10% for non- responders (S + P; P<0.0001). Mitoxantrone was generally well tolerated; nausea, vomiting and hair loss were mild. Nine out of 625 treatment cycles resulted in leukopenic fever with uneventful recovery. All patients had serial MUGA scans; 3 patients (cumulative total doses of 200, 250 and 342 mg, respectively) developed a significant drop in the left ventriculur ejection fraction. Clinical evidence of congestive heart failure was observed in one patient who had received prior doxorubicin-based adjuvant chemotherapy. Mitoxantrone seems to be as effective as other drugs given singly or in combination as second-line chemotherapy in patients with metastatic breast cancer. Its low morbidity makes its use attractive in this setting.     

贝伐单抗联合多西他赛化疗方案对转移性乳腺癌患者的临床疗效

目的 探讨贝伐单抗联合多西他赛化疗方案对转移性乳腺癌患者的临床疗效.方法 入组87例患者依据随机数字表法随机分为观察组(45例)和对照组(42例).观察组采用贝伐单抗联合多西他赛化疗,对照组采用卡培他滨联合多西他赛化疗.2组均以21 d为1周期,共化疗3周期.对比分析2组总有效率、生活质量以及不良反应.结果 观察组有效率(64.45%)显著高于对照组(40.47%),差异有统计学意义(P<0.05);观察组生活质量改善率(68.89%)高于对照组(40.48%),差异有统计学意义(P<0.05);观察组胃肠道反应、骨髓抑制、手足综合征等不良反应发生率均低于对照组,差异有统计学意义(P均< 0.05);2组1 a生存率比较差异无统计学意义(P>0.05).结论 贝伐单抗联合多西他赛化疗方案对转移性乳腺癌患者临床疗效显著,可明显改善患者生活质量,降低不良反应发生率,值得进一步推广应用.     

The Impact of Real-World Alternative Dosing Strategies of Palbociclib on Progression-Free Survival in Patients with Metastatic Breast Cancer

Background: Palbociclib, a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, in combination with letrozole or fulvestrant has been demonstrated to prolong the progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. In efforts to mitigate neutropenic toxicities, oncologists in real-world practice have prescribed alternative dosing strategies with palbociclib, yet the implication on PFS is unknown. Methods: We conducted a retrospective, observational chart review of all female patients at our clinics with HR+, HER2- metastatic breast cancer receiving palbociclib in combination with either letrozole or fulvestrant with a first dose initiated between June 2016 and December 2018 and followed their disease course until 30 April 2020. Results: The median PFS for all clinic patients receiving palbociclib and letrozole (n = 63) was 40.8 months (95% confidence interval (CI) 25.6–not estimable) and 16.97 months (95% CI 8.57–not estimable) for patients receiving palbociclib and fulvestrant (n = 11). We identified seven alternative dosing strategies prescribed by oncologists, the most prevalent being prescribing palbociclib for three weeks on and two weeks off (n = 8). The Kaplan–Meier curves for PFS in patients receiving letrozole and palbociclib prescribed alternative dosing strategies appear to diverge from monograph dosing early in the treatment. Many patients prescribed palbociclib using alternative dosing strategies continued to be observed even by the 18-month timepoint. The prevalence of grade 4 neutropenia was lower for patients on palbociclib with letrozole, suggesting a possible mitigation of severe neutropenia with alternative dosing strategies. Conclusions: We conclude that alternative dosing strategies used by oncologists such as prescribing palbociclib for three weeks on, two weeks off may achieve comparable disease control while mitigating neutropenic toxicities when compared to standard monograph dosing recommendations, prolonging treatment tolerability and adherence. Further large-scale studies are needed to confirm these results for future clinical adoption.     

环磷酰胺联合多西紫杉醇治疗转移性乳腺癌临床观察

目的 观察环磷酰胺联合多西紫杉醇治疗既往接受过多程化疗的转移性乳腺癌患者的近期疗效和毒副反应.方法 26例接受过多程化疗的转移性乳腺癌患者接受环磷酰胺联合多西紫杉醇方案化疗,环磷酰胺:600 mg/m2,d1;多西紫杉醇37.5 mg/m2,d1.8,21 d为1个周期,3个周期后评价疗效和毒副反应.结果 26例患者总...     

贝伐珠单抗联合紫杉类药物一线治疗局部复发或转移性乳腺癌患者的安全性及疗效

[目的]研究贝伐珠单抗联合紫杉类药物一线治疗Her-2阴性的局部复发或转移性乳腺癌患者的安全性和疗效。[方法]32例Her-2阴性的复发或转移性乳腺癌患者,一线接受贝伐珠单抗联合紫杉类方案的化疗,直至疾病进展或不良反应不能耐受或患者要求出组。研究者选择化疗方案：贝伐珠单抗15mg／kg静滴d1,多西他赛75mg／m^2,静滴d1,21d为一个周期;或贝伐珠单抗10mg／kg静滴d1,15紫杉醇80mg／m^2,静滴d1,8,15,为一个周期。每3个周期评价疗效。[结果]32例可评价疗效和副作用,PR16例,SD15例,PD1例,总有效率50％,中位TTP为7.25个月。3级以上不良反应为阴道出血、粒细胞下降以及腹泻。[结论]贝伐珠单抗联合紫杉类药物治疗晚期乳腺癌不良反应可以耐受,具有一定疗效。     

Real-World Clinical Outcomes of Ribociclib in Combination with a Non-Steroidal Aromatase Inhibitor and a Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal HR+/HER2− Advanced Breast Cancer Patients: An Italian Managed Access Program

Ribociclib plus an aromatase inhibitor and ovarian function suppression is the preferred first-line option for pre-/perimenopausal women with hormone receptor-positive/human epidermal growth factor receptor-2-negative advanced or metastatic breast cancer. We opened an italian managed access program (MAP) that permitted access to ribociclib to selected patients and allowed to collect informative results on the clinical impact of the therapy. The MAP (April 2018–May 2020) included 64 premenopausal patients, with characteristics similar to those of the MONALEESA-7 trial. Of 57 patients with a known response, 48 (84.2%) achieved a clinical benefit (i.e., complete response, N = 7 (12.3%); partial response, N = 17 (29.8%); stable disease, N = 24 (42.1%)), while 9 (15.8%) experienced tumor progression. Some patients (N = 15–23.4%) needed ribociclib dose reduction because of adverse events. Thereafter, the treatment was well tolerated, and no new safety signals emerged. Our study is the first reported Italian real-world evidence of ribociclib effectiveness in premenopausal HR+/HER2− advanced breast cancer patients. Response and clinical benefit rates were particularly encouraging compared with those of the ribociclib group of MONALEESA-7. Our work confirms that ribociclib in combination with endocrine therapy is highly effective in the treatment of premenopausal HR+/HER2− advanced breast cancer patients with an expected safety profile.     

Perioperative Screening for Metastatic Disease is not Indicated in Patients with Primary Breast Cancer and no Clinical Signs of Tumor Spread

Background. Is a perioperative metastatic screening program indicated in patients presenting with primary operable breast cancer and no signs of distant metastases? Patients and methods. The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analyzed in 1076 patients with an operable breast cancer and no clinical signs of metastases. Results. Staging examinations revealed 30 (2.8%) distant metastases, 130 (12.1%) suspect findings and excluded metastases in 916 (85.1%) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4%) and excluded them in 123 (94.6%) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing pathological tumor size (pT ≤q 2.0 cm: 1.6%, pT 2.1–5.0 cm: 3.0%, respectively pT > 5.0 cm: 15.1%; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.9%, pN1–3+: 1.8%, pN4–9+: 4.0%, pN ≥ 10+: 18.7%; p < 0.001). Due to false positive findings 123 (11.4%) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1076 patients saves costs of at least Euro 259,367.68. Conclusions. In breast cancer patients without clinical signs of tumor spread perioperative screening for metastases is not warranted because of low frequency of metastases, false positive findings, missing therapeutic consequences and high costs.     

艾素联合希罗达治疗使用蒽环类失败的复发转移性乳腺癌18例临床观察

目的观察艾素联合希罗达治疗蒽环类失败复发转移性乳腺癌的临床疗效和毒副反应。方法艾素75mg／m^2，静脉滴注1h，第1天；希罗达2000mg／m^2分2次口服，连续服用2周；用艾素前1天开始口服地塞米松8mg，每天2次，连续3d。每21d为1周期，至少应用2周期后评价疗效。结果全部18例可评价疗效，平均化疗4个周期。完全缓解（CR）4例，部分缓解（PR）6例，稳定（SD）4例，进展（PD）4例，有效率55．6％（10／18）。疾病进展时间（TTP）7．5个月，中位生存时间（MST）12．5个月。最常见的毒副反应为粒细胞减少，其中Ⅲ-Ⅳ度占50．O％，其次为手足综合征，Ⅱ-Ⅲ级占22，2％。结论艾素联合希罗达治疗使用蒽环类失败复发转移性乳腺癌疗效确切，毒副反应可耐受。     

Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage

Background: The overexpression of the human epidermal growth factor receptor-2 (HER2) gene is present in 20~25% of breast cancer (BC) patients, contributing to an inferior prognosis. Recent clinical trials showed that pyrotinib has promising antitumor activities and acceptable tolerability for those patients (ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03080805","term_id":"NCT03080805"}}NCT03080805 and {"type":"clinical-trial","attrs":{"text":"NCT02422199","term_id":"NCT02422199"}}NCT02422199). Therefore, this study aims to assess the cost-effectiveness of pyrotinib plus capecitabine versus lapatinib plus capecitabine for patients with HER2-positive metastatic BC after prior trastuzumab. Methods: A lifetime-partitioned survival model was established to evaluate health and economic outcomes with different treatment strategies. The primary outcome was the incremental cost-effectiveness ratio (ICER). Data were derived from the published literature, clinical trials, expert opinions, and other local charges. Sensitivity analyses were performed to assess the robustness of the findings. Scenario analyses were developed to make further evaluations. Results: The pyrotinib regimen had significant advantages over the lapatinib regimen after enrolling in the National Reimbursement Drug List (NRDL), with cost savings of USD 15,599.27 and a gain of 0.53 QALYs. Meanwhile, before enrolling in NRDL, the pyrotinib regimen afforded the same QALYs at a higher incremental cost of USD 45,400.64 versus the lapatinib regimen, producing an ICER of USD 85,944.79 per QALY. Scenario analyses yielded similar results. Sensitivity analyses suggested stability in the cost-effectiveness findings. Conclusions: Compared to lapatinib plus capecitabine, the pyrotinib plus capecitabine enrolled in NRDL is a cost-effective alternative second-line treatment for patients with HER2-positive metastatic BC in China.     

Aromatase Inhibition and Capecitabine Combination as 1st or 2nd Line Treatment for Metastatic Breast Cancer - a Retrospective Analysis

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) andcapecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysisof a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AIwith capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancertreated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI wereevaluated and outcomes were compared with those of women treated with capecitabine in conventional dose orAI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55%had visceral disease. No significant difference was observed between the three groups according to clinical andpathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-linetreatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabineand Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival didnot show any significant differences among combination and monotherapy groups. The most common adverseevents for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) andgrade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combinationtreatment with capecitabine and AI used as a first line or second line treatment was safe with much loweredtoxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advancedbreast cancer to confirm these findings.