Outcomes In Advanced Breast Cancer Research Articles

Innovative Surgical Approaches That Improve Individual Outcomes in Advanced Breast Cancer.

Breast cancer is the most common cause of cancer death in women and the second cause in the general population. The incidence has increased over time. Women in developing countries often present at an advanced stage where initial surgery is not feasible. Short disease-free intervals, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival. Surgery is an integral part of the therapeutic plan for locally advanced breast cancer. The integration of surgical care into the management of patients with advanced cancer has changed substantially with the use of neoadjuvant chemotherapy. Also, more recently, neoadjuvant endocrine therapy and targeted therapies offer new opportunities to downsize the tumor burden and transform the role of surgery for this population from palliation to largely curative intent. Innovative surgical approach to the primary tumor in metastatic disease may provide survival benefits and local control in some patients. Similar to systemic therapy, surgical therapy for secondary dissemination should be considered in certain cases for improved individual outcomes. Advances in reconstructive techniques have improved the quality of life of these patients.

Exploring adherence in patients with advanced breast cancer: focus on CDK4/6 inhibitors.

Treatment adherence is crucial for optimal outcomes in advanced breast cancer, but can be challenging due to various factors, i.e. patients' attitudes and behavior upon diagnosis, and complex therapies with high adverse effect rates. Our aim was to explore the adherence to oral anticancer medications (OAM) in women with advanced breast cancer, focusing on cyclin-dependent kinase 4 and 6 inhibitors (CDKI), and identify factors associated with the adherence. We conducted a cross-sectional study at the University Hospital Centre Zagreb, Croatia, involving women with stage IV advanced breast cancer receiving OAM. Data collection included a questionnaire assessing socio-demographic and clinical information, Beck Depression Inventory-II for depressive symptoms, Medication Adherence Report Scale (MARS-5) for adherence to OAM, and Beliefs about Medicines Questionnaire. Plasma concentrations of CDKI were confirmed by LC-MS/MS in three randomly selected participants. A total of 89 women were included. The most prescribed OAMs were anti-estrogen (71.3 %) and CDKI (60.9 %). MARS-5 scores (mean: 24.1 ± 1.6) correlated with CDKI plasma concentrations. Forgetfulness was the primary reason for non-adherence (25.9 %). Women receiving CDKI (p = 0.018), without depressive symptomatology (p = 0.043), and with more positive beliefs about medicines were more adherent (p < 0.05). This study enhances understanding of medication adherence in advanced breast cancer and identifies influential factors.

Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count With Clinical Outcomes in Advanced Breast Cancer in the MONARCH 2 Trial.

Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes. This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer that progressed on endocrine therapy. Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L). The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates. Tumor response and safety were also examined. NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response. The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS. Baseline NLR remained significant in the multivariate model (P < .0001). No unexpected differences in safety were observed by baseline NLR or ALC. Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status.

494P Proviral insertion in murine 1 (PIM1) kinase expression and clinical outcomes in advanced breast cancer (ABC)

494P Proviral insertion in murine 1 (PIM1) kinase expression and clinical outcomes in advanced breast cancer (ABC)

Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment.

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell-mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments.

Efficacy of Baseline Circulating Tumor Cells (CTCs) and Circulating Tumor DNA (ctDNA) for Evaluation of Tumor Heterogeneity and Clinical Outcome in Advanced Breast Cancer

Efficacy of Baseline Circulating Tumor Cells (CTCs) and Circulating Tumor DNA (ctDNA) for Evaluation of Tumor Heterogeneity and Clinical Outcome in Advanced Breast Cancer

Transcriptional Reprogramming Differentiates Active from Inactive ESR1 Fusions in Endocrine Therapy-Refractory Metastatic Breast Cancer.

Genomic analysis has recently identified multiple ESR1 gene translocations in estrogen receptor alpha-positive (ERα+) metastatic breast cancer (MBC) that encode chimeric proteins whereby the ESR1 ligand binding domain (LBD) is replaced by C-terminal sequences from many different gene partners. Here we functionally screened 15 ESR1 fusions and identified 10 that promoted estradiol-independent cell growth, motility, invasion, epithelial-to-mesenchymal transition, and resistance to fulvestrant. RNA sequencing identified a gene expression pattern specific to functionally active ESR1 gene fusions that was subsequently reduced to a diagnostic 24-gene signature. This signature was further examined in 20 ERα+ patient-derived xenografts and in 55 ERα+ MBC samples. The 24-gene signature successfully identified cases harboring ESR1 gene fusions and also accurately diagnosed the presence of activating ESR1 LBD point mutations. Therefore, the 24-gene signature represents an efficient approach to screening samples for the presence of diverse somatic ESR1 mutations and translocations that drive endocrine treatment failure in MBC. SIGNIFICANCE: This study identifies a gene signature diagnostic for functional ESR1 fusions that drive poor outcome in advanced breast cancer, which could also help guide precision medicine approaches in patients harboring ESR1 mutations.

Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

Identification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40 + and PD-1 + T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer were analyzed along of first line antineoplastic therapy. Subsequently, a comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients showed higher basal levels of myeloid derived suppressor cells (35.43, IR = 180.73 vs 17.53, IR = 16.96 cells/μl; p = 0.001) and regulatory T cells (32.05, IR = 29.84 vs 22.61, IR = 13.57 cells/μl; p = 0.001) in comparison with healthy women. Furthermore, an increase in the number of activated T lymphocytes (expressing OX40), a decrease of immune inhibitory cells (MDSCs and Tregs) and inhibited T lymphocytes (expressing PD-1) were observed along the treatment in patients with clinical benefit (p ≤ 0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be correlated with clinical evolution, at least in ABC.

Gaps in Care and Support for Patients With Advanced Breast Cancer: A Report From the Advanced Breast Cancer Global Alliance.

PURPOSEAlthough new therapeutic options continue to improve disease-related outcomes in advanced breast cancer (ABC), enhanced focus is needed to improve quality of life for patients currently living with ABC.METHODSIn November 2019, a multidisciplinary workshop to explore patient perceptions of their information and support needs was held at the ABC Global Alliance Annual Meeting in Lisbon, Portugal. Ninety-two attendees from 27 countries participated in the workshop.RESULTSSeveral key unmet needs were identified and discussed in the workshop, including the following: (1) Significant patient knowledge gaps exist related to the diagnosis and management of ABC, and the availability of patient-focused information to support these gaps in knowledge remains limited. (2) The development of meaningful relationships between patients and health care professionals, and the role of patients in decision making, is often overlooked for patients with ABC. (3) Multidisciplinary care approaches are crucial for patients with ABC; however, these often lack effective coordination. (4) Access to clinical trials for ABC also remains limited. (5) Caregivers, friends, and family members do not receive sufficient guidance to support patients with ABC and manage their own well-being.CONCLUSIONThe variety of unmet needs explored in the workshop demonstrates that patients with ABC still face considerable challenges related to quality of care and support, which will not be resolved until tangible action is taken. Issues highlighted in the workshop should be prioritized by working groups to shape the development of community-based solutions. There is a need for the global community to act proactively to maximize awareness of these ongoing unmet needs and existing resources, while socializing and building new initiatives and resources that will help to close these gaps for patients.

69TiP MADELINE Asia: A mobile app-based prospective observational study of patient reported outcomes in advanced breast cancer in Asia

69TiP MADELINE Asia: A mobile app-based prospective observational study of patient reported outcomes in advanced breast cancer in Asia

Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy.

There are limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer, especially in patients treated with endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors. A pooled analysis of individual patient-level data from MONARCH 2 and 3 trials was performed. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2) and divided into 2 treatment groups: abemaciclib + ET vs placebo + ET. The primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate, adverse events according to BMI, and loss of weight (≥5% from baseline) during treatment. This analysis included 1138 patients (757 received abemaciclib + ET and 381 placebo + ET). There was no difference in PFS between BMI categories in either group, although normal-weight patients presented a numerically higher benefit with abemaciclib + ET (Pinteraction= .07). Normal and/or underweight patients presented higher overall response rate in the abemaciclib + ET group compared with overweightand/or obese patients (49.4% vs 41.6%, odds ratio = 0.73, 95% confidence interval = 0.54 to 0.99) as well as higher neutropenia frequency (51.0% vs 40.4%, P = .004). Weight loss was more frequent in the abemaciclib + ET group (odds ratio = 3.23, 95% confidence interval = 2.09 to 5.01). Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight or obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal and/or underweight patients compared with overweight and/or obese patients. More studies analyzing body composition parameters in patients under treatment with cyclin-dependent kinase 4/6 inhibitors may further clarify this hypothesis.

Impact of Prior Cancer History on the Clinical Outcomes in Advanced Breast Cancer: A Propensity Score-Adjusted, Population-Based Study.

PurposeDespite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain.Materials and MethodsPatients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS).ResultsA total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years.ConclusionPrior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.

P125 - Impact of prior cancer (pc) history on the clinical outcomes in advanced breast cancer (ABC): a population-based study

P125 - Impact of prior cancer (pc) history on the clinical outcomes in advanced breast cancer (ABC): a population-based study

Real-world patient- and caregiver-reported outcomes in advanced breast cancer.

Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor-positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (≥2l-pf), and second- or subsequent-line progressive disease (≥2l-pd). Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 ± 29.9 for 1l-pd vs. 68.2 ± 23.2 for 1l-pf, and 54.0 ± 23.6 for ≥2l-pd vs. 66.0 ± 22.1 for ≥2l-pf), lower mean utility values (0.64 ± 0.22 for 1l-pd vs. 0.73 ± 0.20 for 1l-pf, and 0.65 ± 0.25 for ≥2l-pd vs. 0.74 ± 0.18 for ≥2l-pf), and greater productivity loss (39.4 ± 27.7 for 1l-pd vs. 27.5 ± 30.1 for 1l-pf, and 37.6 ± 29.2 for ≥2l-pd vs. 32.0 ± 29.0 for ≥2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and ≥2l.

Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer

Purpose: Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% of breast cancers, as well as pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications of HRD signatures. Whereas BRCA1/2 mutations confer sensitivity to platinum-based chemotherapies, it is not yet clear whether mutation signatures can independently predict platinum response.Experimental Design: In this observational study, we sequenced tumor whole genomes (100× depth) and matched normals (60×) of 93 advanced-stage breast cancers (33 platinum-treated). We computed a published metric called HRDetect, independently trained to predict BRCA1/2 status, and assessed its capacity to predict outcomes on platinum-based chemotherapies. Clinical endpoints were overall survival (OS), total duration on platinum-based therapy (TDT), and radiographic evidence of clinical improvement (CI).Results: HRDetect predicted BRCA1/2 status with an area under the curve (AUC) of 0.94 and optimal threshold of 0.7. Elevated HRDetect was also significantly associated with CI on platinum-based therapy (AUC = 0.89; P = 0.006) with the same optimal threshold, even after adjusting for BRCA1/2 mutation status and treatment timing. HRDetect scores over 0.7 were associated with a 3-month extended median TDT (P = 0.0003) and 1.3-year extended median OS (P = 0.04).Conclusions: Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials. Clin Cancer Res; 23(24); 7521-30. ©2017 AACR.

Prognostic outcomes in advanced breast cancer: the metastasis-free interval is important

Metastatic breast cancer is a heterogeneous disease with a diverse clinical course. There have been limited studies regarding prognostic outcomes in patients with de novo metastatic breast cancer versus those with metastatic recurrence, with controversial observations. In this study, we sought to examine the difference in survival outcomes among patients with advanced breast cancer stratified based on metastasis-free interval (MFI) and to further explore the role of systemic therapy in these patient groups. Of 569 consecutive patients with stage IV breast cancer between 1998 and 2013, 201 had de novo metastatic disease (metastasis at diagnosis) and 368 developed metastatic recurrence, including 168 with an MFI≤24 months and 200 with an MFI>24 months. In the 492 patients who received systemic therapy, de novo metastasis was an independent favorable prognostic factor for overall survival after metastasis when compared with metastatic recurrence irrespective of MFI. Compared with the patients with metastatic recurrence with an MFI≤24 months, those with an MFI>24 months had a superior survival outcome, although it did not reach statistical significance by multivariate analysis. In contrast, de novo metastatic breast cancer was associated with a worse prognosis when compared with recurring metastasis in the patients who did not receive systemic treatment. These findings provide more insight into the natural history of advanced breast cancer, thus necessitating further investigation into the molecular mechanism of drug resistance.

A real-world retrospective study of apatinib plus chemotherapy in metastatic breast cancer.

e12507 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical outcome in advanced breast cancer(ABC). Apatinib is an orally administered tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), which exhibited objective efficacy in metastatic breast cancer(MBC). We performed a retrospective observational analysis to evaluate the efficacy and safety of apatinib plus chemotherapy in the real-world practice of patients with MBC. Methods: Patients who have failed at least one prior chemotherapy regimen for metastatic disease were included in this study. The primary endpoint was progression free survival(PFS). Secondary end points included objective response rate(ORR), clinical benefit rate(CBR), overall survival(OS) and safety. Data analysis included association between clinicopathological characteristics or treatment choice and PFS. Results: Of the 23 patients analyzed, 14(60.9%) received plant-derived anticancer agents combined therapy and 9(39.1%) combined with non-plant-derived agents. Objective response rate(ORR) was 34.7% and clinical benefit rate(CBR) reached 52.2% on last tumor assessment. With a median follow-up of 9.0 months, the estimated median PFS and OS were 5.4 months (95%CI 3.5-7.3) and 8.2 months (95%CI 4.7-11.7), respectively. Toxicities were tolerable or could be clinically managed.The most frequently observed adverse events (AEs) of all grade were hypertension, myelosuppression, hand-foot syndrome, proteinuria, fatigue and gastrointestinal reaction. The most common grade 3/4 treatment-related AEs were myelosuppression(39.1%) and gastrointestinal reaction(17.4%). Conclusions: In this retrospective observational study, combination of apatinib with chemotherapy demonstrated clinically relevant efficacy and tolerability in metastatic breast cancer.

Abstract OT3-03-01: MADELINE: A prospective observational study of mobile app-based patient reported outcomes in advanced breast cancer

Abstract BACKGROUND: There have been few studies evaluating the day-to-day effects of advanced breast cancer (ABC) and its treatment on patients in a real-world setting.Palbociclib is a novel CDK4/6 inhibitor approved in the US for hormone-receptor positive, human epidermal growth factor receptor negative (HR+, HER2-) ABC/metastatic breast cancer (MBC) in combination with letrozole as initial endocrine based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. With the introduction of this first-in-class drug it is important to understand the experiences of patients initiating ABC therapies including palbociclib in real-world settings and to document the management of these therapies. A smartphone-based mobile application has been developed to collect patient-reported outcome (PRO) data to assess the impact of ABC and associated treatment on symptoms, functioning and quality of life (QOL) as reported by patients. The application is further designed to provide patients initiating palbociclib with a virtual community to connect to others enrolled in the study for peer support. Additionally, clinical data on therapy management (e.g. dose modifications, interruptions, discontinuations, adverse event management and monitoring) will be obtained from patients' medical records to explore the association between patient reported functioning and neutropenia. Study Design: A prospective, observational, non-interventional study. PROs collected via a mobile application and clinical data via case report forms completed by investigator. Eligibility Criteria: Women with HR+/HER2– ABC receiving palbociclib in combination with letrozole or fulvestrant as per US label (Group 1) orapproved therapies for ABC other than palbociclib (Group 2). No comparison is intended between the 2 groups. Specific Aims: The primary goals are to describe changes in patients' general health status as measured by monthly administration of the 12-Item Short Form Health Survey, describe changes in patients' psychological distress as measured by monthly administration of the Center for Epidemiological Studies Depression Scale, and describe the extent to which ABC and its treatment are associated with changes in patients' lives in terms of symptoms, functioning and QOL as measured by daily and weekly administration of targeted patient-reported questions. Additionally, for patients who are employed at baseline, time lost from work in relation to breast cancer and its treatment will be quantified.Data from patients' medical records will be used to document changes in therapy as well as the incidence, severity, and duration of neutropenia. The association between patient reported functioning and neutropenia will also be assessed. Finally, real-world monitoring patterns will be assessed. Statistical Methods: Descriptive statistics will be used to summarize all endpoints. Meta-data regarding use of virtual community resources will be explored for relationships to PRO data. Present Accrual and Target Accrual: Approximately 450 patients from up to 30 US sites will be enrolled. Study duration will be approximately 12 months assuming 6 months of recruitment. It is expected the study will start enrollment Q3 2016. Sponsor: Pfizer. Citation Format: McRoy LL, Mitra D, Hollis K, Kaye JA, Zelnak A, Cheyl J. MADELINE: A prospective observational study of mobile app-based patient reported outcomes in advanced breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-03-01.

Patient-reported outcomes in advanced breast cancer: inside the label and approval documents

Patient-reported outcome (PRO) measures are used in clinical research and practice for the assessment of disease-related symptoms and impacts as well as treatment-related side effects, from the patient perspective. However, a systematic examination of the role of PROs in metastatic breast cancer treatment approvals is lacking. A review of FDA labels and historical drug approval documents for metastatic breast cancer treatments was conducted to determine how PROs had been used or pursued to support labeling claims. In the historical drug approval documents, PROs were often being implemented by sponsors, and regulatory reviewers noted several issues limiting their suitability to support label claims. The findings suggest there is much room for improvement in how sponsors develop, implement, and report PRO measurement strategies as part of drug approval.

A European Organisation for Research and Treatment of Cancer randomized, double-blind, placebo-controlled, multicentre phase II trial of anastrozole in combination with gefitinib or placebo in hormone receptor-positive advanced breast cancer (NCT00066378)

BackgroundPreclinical data suggest that epidermal growth factor receptor (EGFR) inhibitors (e.g. gefitinib) can delay endocrine resistance in breast cancer. A double-blind, placebo-controlled, phase II trial investigated whether adding gefitinib (G) to anastrozole (A) would improve outcome in advanced breast cancer (ABC). MethodsPostmenopausal pre-treated hormone receptor-positive ABC patients (locally recurrent or metastatic) were 1:1 randomized to A (1 mg/d) plus G 250 mg/d or plus placebo (P). Patients who had prior treatment with an aromatase inhibitor in metastatic setting or with trastuzumab, anti-EGFR or anti-VEGF agents were excluded. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal. Progression-free survival (PFS) rate at 1 year was assessed according to Response Evaluation Criteria in Solid Tumours, version 1.0. ResultsOf 108 planned patients, 71 were recruited (36 in A/G and 35 in A/P). The trial closed prematurely due to slow recruitment; 31 patients had prior chemotherapy and 53 prior endocrine therapy (all except one received tamoxifen); 60% in adjuvant and 16% in metastatic setting received tamoxifen; 59 patients had visceral disease. Median follow-up was 18 months. PFS rate at 1 year was 35% for A/G and 32% for A/P arm. Objective responses were six (22%) in the A/G and nine (28%) in the A/P arm. Median duration of response was 13.8 and 18.6 months in the A/G and A/P arms, respectively. Fatigue (35%), diarrhoea (31%), rash (32%), dry skin (27%), and arthralgia/myalgia (27%) were the commonest adverse events in the A/G arm. ConclusionsThis phase II study, although prematurely closed, did not show a signal that adding G to A improves PFS at 1 year and its use is not supported. Gastrointestinal and skin toxicities were more pronounced with G resulting in premature therapy interruption in almost 1 in 3 patients (ClinicalTrials.gov number, NCT00066378).