Metastatic Breast Cancer Research Papers (original) (raw)

Aberrant activation of some members of human epidermal growth factor receptor (HER) family plays a key role in breast carcinogenesis. Lapatinib is an oral dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. Clinical data have shown that lapatinib is active in HER2-positive breast cancer as monotherapy, in combination with trastuzumab, and in trastuzumab-resistant patients. Phase I clinical trials have shown also that lapatinib is well tolerated, with mild diarrhea and skin rush as common toxic effects and low incidence of cardiotoxicity. Phase II and III clinical trials' data provide encouraging evidence of the clinical effectiveness of lapatinib in advanced or metastatic breast cancer and for its potential in patients with brain metastases. Interim results from the large, phase III trial in 392 patients showed that in combination with capecitabine lapatinib almost doubled time to progression when compared with capecitabine alone. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents [paclitaxel (Taxol), capecitabine and platinoids], hormonotherapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes are allowing us to bring patientspecific novel therapies such as lapatinib to the clinic.

Background: AMG 706 is an oral, investigational inhibitor of angiogenesis with direct antitumor activity, achieved by selectively targeting VEGF, PDGF and Kit receptors. Inhibition of the VEGF pathway in combination with chemotherapy has... more

- by P. Mainwaring
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- Metastatic Breast Cancer

1 From the Department of Nuclear Medicine (UT, CG, HWDY, HAM) and Division of Breast Medical Oncology (SD, MC), University of Texas MD Anderson Cancer Center, Unit 1263, 1515 Holcombe Blvd, Houston, TX 77030. Received March 27, 2007;... more

- by Culis Gamez
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- Radiology, Metastatic Breast Cancer, Bone Metastases, Medical and Health Sciences

Trastuzumab-DM1 (T-DM1) is an antibody-drug conjugate that uses trastuzumab to specifically deliver the maytansinoid antimicrotubule agent DM1 to HER2-positive cells. This first-in-human study of T-DM1 evaluated safety, pharmacokinetics,... more

- by S. Girish
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- Survival Analysis, Immunohistochemistry, Treatment Outcome, Risk assessment

The mouse 4T1 mammary carcinoma is a BALB/c-derived tumor that spontaneously metastasizes and induces immune suppression. Although >95% of wild type BALB/c mice die from metastatic 4T1 tumor even if the primary mammary tumor is surgically removed, >65% of BALB/c mice with a deleted Signal Transducer Activator of Transcription 6 (STAT6) gene survive post-surgery. STAT6-deficiency also confers enhanced immunity against spontaneously developing breast cancer since NeuT +/) mice that are STAT6deficient develop mammary tumors later and survive longer than NeuT +/) mice that are STAT6-competent. Rejection of metastastic disease and survival of STAT6deficient mice after removal of primary tumor involve three mechanisms: (1) The generation of M1 type macrophages that produce nitric oxide and are tumoricidal; (2) A decrease to normal in the elevated levels of myeloid suppressor cells that accumulate during primary tumor growth; and (3) CD8 + tumor-specific T lymphocytes. STAT6-deficient, but not wild type BALB/c, mice generate nitric oxide producing macrophages because they lack the STAT6 transcription factor which is necessary for signaling through the type 2 IL-4Ra complex, and which induces the production of arginase instead of nitric oxide. Keywords Tumor-induced immune suppression AE Immune surveillance AE M1 macrophages AE Metastatic breast cancer AE Cell-mediated tumor immunity Signal Transducer Activator of Transcription 6 deficient (STAT6-/-) mice have enhanced immunity to transplanted tumors This article is a symposium paper from the conference ''Tumor Escape and Its Determinants''

- by Pratima Sinha
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- Immunology, Breast Cancer, Biology, Medicine

Conclusions: BIBF 1120 in combination with mFOLFOX6, for first-line mCRC has a similar magnitude of efficacy and safety/tolerability profile but lower incidence of SAE in comparison to BEV. Detailed analysis of SAEs is ongoing. Funded by... more

- by T. Shahid
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- Metastatic Breast Cancer

A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m2, 5-fluorouracil 375 mg/m2, and L-leucovorin 100 mg/m2 on day 1, weekly. Patient characteristics were: median age 53 years (range 36–65); estrogen receptor (ER)

Evaluation of cancer biomarkers from blood could significantly enable biomarker assessment by providing a relatively non-invasive source of representative tumor material. Circulating Tumor Cells (CTCs) isolated from blood of metastatic... more

- by Mark Lackner and +4
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- Breast Cancer, Multidisciplinary, Lung Cancer, Mutation Detection

BACKGROUND. This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial... more

- by Patricia Fobair
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- Group Therapy, Cancer, Randomization, Treatment

Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in... more

- by Ebrahim S . Delpassand,MD
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- Ophthalmology, Treatment, Comparative Study, Toxicity
- by Ajay Pandita
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- Breast Cancer, Multidisciplinary, Lung Cancer, Mutation Detection

BACKGROUND: Existing reports of utility values for metastatic non-small cell lung cancer (NSCLC) vary quite widely and are not all suitable for use in submissions in the UK. The aim of this study was to elicit UK societal based utility values for different stages of NSCLC and different grade III-IV toxicities commonly associated with chemotherapy treatments. Toxicities included neutropenia, febrile neutropenia, fatigue, diarrhoea, nausea and vomiting, rash and hair loss. METHODS: Existing health state descriptions of metastatic breast cancer were revised to make them suitable as descriptions of metastatic NSCLC patients on second-line treatment. The existing health states were used in cognitive debrief interviews with oncologists (n = 5) and oncology specialist nurses (n = 5). Changes were made as suggested by the clinical experts. The resulting health states (n = 17) were piloted and used in a societal based valuation study (n = 100). Participants rated half of the total health sta...

- by Megan Stafford
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- Demography, Psychometrics, Quality of life, Lung Cancer

Background Treatments with survival benefi t are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare... more

- by Seth Seegobin
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- Lancet, Aged, Survival Rate, Metastatic Breast Cancer

Living with advanced cancer is oftentimes fraught with anxiety and fear as well as physical symptoms, such as pain, fatigue, and dyspnea. 1-3 Psycho-behavioral interventions, specifically expressive-supportive therapy, guided imagery, mindfulness meditation, and relaxation training, have been effective at relieving symptoms and enhancing a sense of well-being in these patients. 4-8 Music therapy (MT) is an established health profession in which music is used within a therapeutic relationship to address physical, emotional, cognitive, and social needs of individuals. 9 It has been investigated in medical settings through both descriptive and experimental studies. A meta-analysis of 97 medical and dental studies revealed an overall effect size (ES) of 0.88 for music versus non-music conditions, an ES of 0.57 overall for patients with cancer, and an ES of 1.40 for studies where patient-preferred music was used. 10 A more recent meta-analysis reviewed the results of 19 randomized controlled studies and cited significant effects of music on anxiety, mood, and comfort during a variety of medical care routines, with less evidence of efficacy during painful procedures. Qualified music therapists use music in the clinical oncology setting as a complementary or integrative therapy to assist cancer patients in coping with illness and to ameliorate symptoms associated with their condition or treatment. The evidence to support the use of MT with oncology patients is evolving. Much of this work has been with children who have cancer and has used guided imagery with music. Additionally, several studies have demonstrated improved treatment-related symptoms for adults undergoing chemotherapy and radiation therapy. 24-31 Quality of life and mood were improved in patients with various cancer diagnoses and at different stages in two ABSTRACT This study examined the effects of music therapy (MT), immediate and over time, on patients' psychological functioning, quality of life, and physiologic stress arousal. This intervention, whereby patients use music strategies to cope with cancer-related stressors, is based on a transactional stress-coping framework.

- by Suzanne Hanser
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- Integrative Medicine, Quality of life, Music Therapy, Prospective studies

This article describes a team-based approach to the development of a comprehensive codebook for multiple researchers to use during content analysis of the transcripts of the expressive writings of women (in this study, N = 89) with metastatic breast cancer. The codebook structure was developed iteratively by reaching a consensus on the analysis of shared transcripts to create an all-encompassing set of codes, with definitions, inclusion and exclusion criteria, and exemplar text from the transcripts. The Qualitative Solutions and Research International NVivo software program was used to maintain an electronic database of the consensus analysis of transcripts, information about each code, and a detailed log about the process of developing the codebook. The team ultimately created a comprehensive codebook that contained 27 codes with definitions, inclusion and exclusion criteria, and example text. The codes were verified by each team member through reanalysis of a set of shared transcripts that had been previously coded using an earlier version of the codebook. The team met to discuss individual coding and reached a consensus on the final version of the codebook. No new code was identified during the reanalysis, and there was fairly uniform agreement on the coding. The final version of the codebook will be used to guide each team member's individual analysis of the remaining (74) transcripts, which will be divided among the team. Periodic meetings are planned to discuss the individual analysis and to resolve any issue associated with using the codebook. As new codes are identified and agreed upon by the team, they will be added to the codebook. A team-based approach can facilitate the development of a practical and accurate codebook to guide the analysis of a large amount of qualitative data. D

- by Marsha Fonteyn
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- Nursing, Content Analysis, Qualitative Research, Nursing Research

Background: Routine adjuvant administration of trastuzumab (T) has been implemented in most centers, but its economic impact has not yet been well examined. Methods: A Markov model was constructed based on clinical data of the Herceptin Adjuvant (HERA) and the Finland Herceptin (FinHer) trials. Costs from the perspective of a Swiss health care provider were calculated based on resource use. Results: On the basis of HERA data, our model yielded an overall survival rate of 71.8% for the T group versus 62.8% for the control group [risk ratio (RR) = 0.87) after 10 years and 62.9% versus 52.7% (RR = 0.84) after 15 years. Costeffectiveness resulted in 40505 Euros (EUR) per life years gained (LYG) after 10 years and 19673 EUR per LYG after 15 years. For the FinHer regimen, overall survival after 10 and 15 years resulted in 81.8% versus 66.1% (RR = 0.81) and 73.6% versus 57.0% (RR = 0.77). Costs of 8497 EUR per patient could be saved after 10 years and 9256 EUR after 15 years compared with the control group.

- by Konstantin Dedes
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- Economics, Australia, Breast Cancer, Pharmacoeconomics
- by Seema Khan and +1
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- Breast Cancer, Metastatic Breast Cancer

ErbB2, a metastasis-promoting oncoprotein, is overexpressed in $25% of invasive/metastatic breast cancers, but in 50%-60% of noninvasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3z in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3z overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3z overexpression reduced cell adhesion by activating the TGF-b/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition. Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3z had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.

- by William Muller
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- Breast Cancer, Cell Migration, Cell Adhesion, Transcription Factors

Background: Treatment options for patients with metastatic breast cancer (MBC) include a rapidly expanding repertoire of medical, surgical and supportive care measures. Design: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. Results: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated.

- by Peter Schmid
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- Evidence Based Medicine, Clinical Trial, Quality of life, Mastectomy

In spite of advances in treatment strategies, about 25%-40% of patients with breast cancer still eventually develop metastatic disease that is largely incurable. Treatment goals vary from symptom control to lengthening survival, mainly on the basis of patient age and performance status, tumor biology, site and extent of disease, and prior therapies. In particular, breast cancer molecular characterization allows for the identification of breast cancer subtypes with distinct biological features, a distinct clinical course, and distinct treatment sensitivity.

- by Valentina Conte
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- Metastatic Breast Cancer, ADJUVANT THERAPY, Oncologist

Background A multicenter, phase II study was conducted to evaluate the efficacy and safety of the Japanese intermittent 4-week regimen of capecitabine in patients with advanced/metastatic breast cancer.

- by Kenjiro Aogi
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- Breast Cancer, Treatment Outcome, Japan, Aged

Abstracts study of 100 adult asthmatics. RESULTS: The table reports outcomes over a 10-year period. Results were driven by the impact of ICS on quality of life, rather than on mortality. Findings were stable over most input data ranges. However, at efficacy levels below 3% and toxicity rates greater than 2.9%, the cost-effectiveness estimate exceeded $100,000/QALY. CONCLUSION: Results suggest that inhaled steroids deliver good comparative value in mild-to-moderate adult asthma. More research is needed, however, on the impact of ICS toxicity on patient preferences.

- by Ahmad Arafat
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- Molecular Biology, Palliative Care, Breast Cancer, Quality of life

Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer.

- by Lourdes Calvo
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- Molecular Biology, Drug Discovery, Cancer treatment, Metastatic Breast Cancer

전이성 유방암 치료의 주된 목적은 질병의 완화이며, 이를 위한 방법으로 주로 항암화학요법과 항암호르몬 요법을 사용한다. 전이성 유방암의 치료를 위한 항암화학제제로서 단독적 파클리탁 Purpose: The aim of this study was to determine the incremental effectiveness (the differences in progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness of Genexol-PM compared to Paclitaxel when these drugs were used as treatment for patients with metastatic breast cancer. Methods: In the absence of any comparative direct evidence of the relative efficacy of Paclitaxel and Genexol-PM in this setting, a meta-analysis was conducted to determine the effects of the Paclitaxel on the health outcome. The decision tree model was constructed to evaluate the two treatment regimens. All the costs are in 2008 Korean Won (KW) and they were evaluated according to the 3rd party payer perspective, and the direct nonmedical and indirect costs were excluded. Results: When compared with Paclitaxel, Genexol-PM was shown to increase the re-sponse rate and the time to progression for patients with metastatic breast cancer. Although the overall treatment costs of Genexol-PM were slightly higher than those of Paclitaxel, Genexol-PM was associated with a delayed time to progression of 4.78 months per patient. The incremental cost effectiveness ratio for Genexol-PM versus Paclitaxel was KW 2,295,228 per year gained, which is far below the per capita GDP or the threshold of the willingness-to-pay in Korea. Conclusion: Compared with Paclitaxel, Genexol-PM for treating metastatic breast cancer is within the acceptable range of the cost-effectiveness ratio for medical intervention.

- by Sangjin Shin
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- Breast Cancer, Cost effectiveness, Metastatic Breast Cancer, Cost Benefit Analysis

Introduction Proteasome inhibition provides an attractive approach to cancer therapy and may have application in the treatment of breast cancer. However, results of recent clinical trials to evaluate the effect of the proteasome inhibitor Bortezomib (Velcade ® , also called PS-341) in metastatic breast cancer patients have shown limited activity when used as a single agent. This underscores the need to find new and more efficacious proteasome inhibitors. In this study, we evaluate the efficacy of the novel proteasome inhibitor BU-32 (NSC D750499-S) using in vitro and in vivo breast cancer models.

- by Hareesh Nair
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- Clinical Trial, Flow Cytometry, Breast Cancer, Cell Cycle
- by Banu çaycı
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- Breast Cancer, Multivariate Analysis, Therapy, Connective tissue

Nitric oxide (NO), a gaseous free radical that is
synthesized in organisms by nitric oxide synthases, participates
in a critical fashion in the regulation of diverse
physiological functions such as vascular and neuronal
signal transduction, host defense, and cell death regulation.
Two major pathways of NO signaling involve production
of the second messenger guanosine 30,50-cyclic monophosphate
(cGMP) and posttranslational modification
(PTM) of redox-sensitive cysteine thiols of proteins. We
recently clarified the physiological formation of 8-nitroguanosine
30,50-cyclic monophosphate (8-nitro-cGMP) as
the first demonstration, since the discovery of cGMP more
than 40 years ago, of a new second messenger derived
from cGMP in mammals. 8-Nitro-cGMP is electrophilic
and reacts efficiently with sulfhydryls of proteins to produce
a novel PTM via cGMP adduction, a process that we
named protein S-guanylation. 8-Nitro-cGMP may regulate
electrophilic signaling on the basis of its electrophilicity
through induction of S-guanylation of redox sensor proteins.
Examples include S-guanylation of the redox sensor
protein Kelch-like ECH-associated protein 1 (Keap1),
which leads to activation of NF-E2-related factor 2 (Nrf2)-
dependent expression of antioxidant and cytoprotective
genes. This S-guanylation-mediated activation of an antioxidant
adaptive response may play an important role in
cytoprotection during bacterial infections and oxidative
stress. Identification of new redox-sensitive proteins as
targets for S-guanylation may help development of novel
therapeutics for oxidative stress- and inflammation-related
disorders and vascular diseases as well as understanding of
cellular protection against oxidative stress.

- by Abu Muhammad
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- Breast Cancer, Breast Cancer Research, Metastatic Breast Cancer

Women with metastatic breast cancer (MBC), a life-threatening illness, stand to benefit a great deal from online support groups, but none have been studied specifically within this population. The present mixed-method study was carried out to determine which therapeutic factors occurred in online MBC support groups, and to see how such factors might have acted to benefit participants. Participants were 20 women with MBC who participated in online peer support groups. Most reported benefiting in some way from their groups. Six therapeutic factors theorized to be helpful in online support groups and cancer support groups were present in the groups studied: group cohesiveness, information exchange, universality, instillation of hope, catharsis, and altruism. However, although participants reported being able to discuss many other concerns freely, they had difficulty discussing death and dying, which are critical issues for this category of women with BC.

- by Ruvanee Vilhauer
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- Health Psychology, Palliative Care, Self Help Group, Psychosocial Research

A genomic profile of somatic mutations revealed using
NGS diagnostics is essential for implementing precision
medicine in patients with MBC. Even when a mutation is
not currently actionable, it may become druggable in the
near future because of the fast-evolving technology and
drug development milieu. As to the time and manner of
incorporating NGS molecular results into clinical practice,
it is no longer a question of why, but instead when and how
to interpret the NGS results which may be a game-changer
in the management of patients with MBC.

Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. The majority of patients with metastatic breast cancer who initially respond to trastuzumab develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients still relapse despite trastuzumab-based therapy. In this review, we discuss potential mechanisms of antitumor activity by trastuzumab, and how these mechanisms become altered to promote therapeutic resistance. We also discuss novel therapies that may improve the efficacy of trastuzumab, and that offer hope that the survival of breast cancer patients with HER2-overexpressing tumors can be vastly improved.

Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells . Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL,

- by Michelle Martínez-Montemayor and +1
- •
- Nutrition and Dietetics, Cell Adhesion, Apoptosis, Western blotting
- by Nilufer Guler and +2
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- Magnetic Resonance Imaging, Breast Cancer, Immunohistochemistry, Medical Oncology

The treatment of metastatic breast cancer (MBC) is complex and relates at a fundamental level to the fact that MBC represents multiple diseases. Important differences in patterns of recurrence, time to progression (TTP), and overall survival (OS) exist by breast cancer biologic subtype. Differences in tumor biology dictate clinical behavior and should be considered in the selection of an appropriate therapeutic strategy in the metastatic setting. For women with endocrine-responsive breast cancer, the decision to initiate chemotherapy for metastatic disease generally occurs much later in the natural history of the disease compared with women with hormone receptor-negative MBC.

- by Robert Carlson
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- Metastatic Breast Cancer, Disease Progression, Antineoplastic Agents
- by Bilal Abuasal
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- Organic Chemistry, Breast Cancer, Wound Healing, Mice

The role of the breast care nurse was developed in the UK and is now being adopted internationally. Although evidence is available to suggest that the role is beneficial in the care of women with primary breast cancer, it is emerging that women with metastatic breast cancer do not receive the same level of support. This study aimed to develop an understanding of the role of the breast care nurse in the provision of care for patients with metastatic breast cancer. A cross-sectional survey of 276 breast care nurses in the UK found that 91% of breast care nurses stated that they provided care for patients with metastatic disease and 81% provided ongoing information and support. However 57% of breast care nurses acknowledged that the provision of care for this population was inadequate and many reported feeling ill equipped to care for women with progressive disease. Care pathways for this patient group are unstructured and ill defined complicating the efforts of breast care nurses to identify and provide care for them. In conclusion, the current nursing service for women with metastatic breast cancer is inadequate but many breast care nurses are working to address this.

- by Deborah Fenlon
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- Nursing, Oncology Nursing, Great Britain, Patient Care Team

Purpose: The combination of bolus doxorubicin followed by a 3-h infusion of paclitaxel has high antitumor activity in patients with metastatic breast cancer, but is limited by unexpected cardiac toxicity. In contrast, the administration of the two drugs 16 h apart has similar antitumor activity but less cardiac toxicity. The purpose of this study was to compare the pharmacokinetics of these drugs when doxorubicin administration preceded paclitaxel by 30 min or by 24 h. Patients and methods: Women with locally advanced breast cancer were treated with doxorubicin (60 mg/m 2 i.v. bolus) followed 24 h later by paclitaxel (200 mg/m 2 i.v. over 3 h) for six cycles (four before and two after surgery). In one of the ®rst two cycles doxorubicin preceded paclitaxel by 30 min instead of 24 h, with plasma sampling for pharmacokinetic analysis up to 48 h. Determination of drug levels in plasma was done by HPLC. Results: A total of 28 patients were included. No clinical cardiac toxicity was observed but ®ve patients discontinued doxorubicin-paclitaxel treatment after four cycles because of a decrease in LVEF of at least 15% from baseline or to less than 50%. While paclitaxel pharmacokinetics were not changed, there was a 30% and an 80% increase in the AUC 0±24h for

- by José Morais
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- Drug interactions, Heart, Cancer Chemotherapy, Paclitaxel

The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US
Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1
and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated.

- by 郭集慶 Victor C Kok
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- Breast Cancer, Chemotherapy, Medical Oncology, Breast Cancer Research
- by Vladimir Moiseyenko
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- Metastatic Breast Cancer

Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( &amp;amp;amp;amp;amp;lt; 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.

- by Dimosthenis Skarlos
- •
- Polymorphism, Kinetics, Breast Cancer, Monoclonal Antibodies

front-line chemotherapy, the patient received high-dose chemotherapy with granulocyte colony-stimulating factor (G-CSF) stimulated autologous peripheral blood stem cell We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and (PBSC) transplantation. The conditioning regimen consisted of: cyclophosphamide 2 g/m 2 in 5% dextrose injec-facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autolog-tion USP (D5W) 500 cc i.v. over 2 h on days −6 to −4, thiotepa 240 mg/m 2 in 0.9% sodium chloride USP 250 cc ous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to i.v. over 4 h on days −6 to −4, and BCNU 150 mg/m 2 in D5W 500 cc i.v. over 2 h on days −6 to −4. Day 0 rep-pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of resented the day of transplantation. During the infusion of BCNU, the patient developed a unilateral frontal crushing BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symp-headache, circumoral paresthesia, photophobia, and facial flushing. The patient was treated with propoxyphene 130 toms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome mg p.o. and hydromorphone 1 mg i.v. which relieved the pain. Laboratory values were within normal limits. Sub-should be considered when administering high-dose BCNU infusions. sequent doses of BCNU were pre-medicated with hydromorphone 0.5 mg i.v. and hydrocortisone 50 mg i.v. The

- by Cindy Ippoliti
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- Cytokines, Face, Headache, Flushing

Background: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.

- by Joseph Hibbeln and +1
- •
- Group Therapy, Social Support, Treatment Outcome, Group Psychotherapy
- by Ramon Colomer and +1
- •
- Breast Cancer, Single Nucleotide Polymorphism, Metastatic Breast Cancer

162 The Breast tion of oestrone in breast tissues. We have synthesized EIMPT, a steroidal competitive inhibitor of oestrone sulphatase activity. In intact MCF-7 breast cancer cells in culture, ElMPT inhibited oestrone sulphatase activity in a dose-dependent mamter. The sulphatase activity in the absence of ElMPT was 89.4 +I-5.2, 23.5 +I-3.0 and 3.6 +I-0.2 fmol/2Oh006 cells respectively. Using 1OuM ElMPT, 96% inhibition of oestrone sulphatase activity was achieved. In contrast, Danazol, reported to inhibit the sulphatase, only inhibited oestrone sulphatase by 40% when tested at the same concentration. Furthermore, ElMPI was resistant to metabolism to oestrone in the presence of liver or placental microsomes. The development of inhibitors of oestrone sulphatase represents a novel therapeutic strategy to oestrogen-dependent breast cancer.

- by Lars Bastholt
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- Breast, Clinical Sciences, Metastatic Breast Cancer

Purpose This phase II study was designed in order to evaluate efficacy and safety of the combination of vinorelbine (VNB), fluorouracil (FU) and leucovorin (LV) in patients with metastatic breast carcinoma (MBC) previously treated with anthracyclines and taxanes. Methods From 12/2003 to 12/2007, 51 women (median age 59) were treated. Performance status (PS) (ECOG) was 0-2 (median 0). The chemotherapy consisted of VNB 25 mg/sqm on day 1 added to FU and LV (following De Gramont schedule) on day 1 and 2. Treatment was repeated every 14 days. 518 cycles of CT were administered (median 12). Most common sites of metastatic spread were: bone, liver, lymph nodes, lung. Results We recorded three cases of G4 neuthropenia and in one case it was febrile; no others G4 toxicities were seen. G3 toxicities were more common, especially neuthropenia (8 patientss) asthenia (4) mucositis (2) and Hand-Foot Syndrome (2). Overall response rate was 27.5% (14 patients had a PR) and disease control rate was 76.5%; 12 patients experienced disease progression. Median time to progression (TTP) was 7.70 months and overall survival (OS) was 18.70 months. Conclusions Results demonstrate that the ViFL regimen has substantial activity in patients with MBC already treated with anthracyclines and taxanes. The combination may be considered a valid choice for the treatment of MBC. Better survival results were seen in patients with visceral metastases than bone involvement. The low response rate shows that the ViFL regimen is not suitable for the neoadjuvant setting.

- by Alessandro Comandone
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- Cancer, Survival Analysis, Disease Control, Aged

Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFjB activation by IKKa/b kinases, which results in impaired IjB degradation, NFjB translocation and NFjB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFjB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFjB activity by gallic acid, which results in potent inhibition of NFjB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFjB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFjB activity in the cancer-inflammation network.

- by Dagmar García-Rivera
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- Western blotting, Signal Transduction, Phytotherapy, Cancer Therapy