scholarly journals Advancements in the Treatment of Metastatic Breast Cancer (MBC): The Role of Ixabepilone

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Massimo Cristofanilli
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Safety Data ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
Epothilone B ◽  
Metastatic Setting

Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

2014 ◽  
Vol 10 (01) ◽  
pp. 25
Author(s):  
Bernardo L Rapoport ◽  
Simon Nayler ◽  
Georgia S Demetriou ◽  
Shun D Moodley ◽  
Carol A Benn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Treatment Options ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Pathologic Diagnosis ◽  
Metastatic Setting

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumors, both clinically and pathologically. These cancers are characterized by the lack of expression of the hormone receptors estrogen receptor (ER) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2(HER2)gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant, and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomized trials. Numerous studies have now shown that TNBC has significantly higher pathologic complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathologic diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant, and metastatic setting, including an assessment of future directions of treatment.

The role of taxanes in HR+ve/HER2-ve metastatic breast cancer (MBC) patients (pts) from adjuvant to metastatic setting in the clinical practice: Results from GIM13-AMBRA study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1055-1055
Author(s):  
Giorgio Mustacchi ◽  
Marina Elena Cazzaniga ◽  
Emanuela Romagnoli ◽  
Filippo Montemurro ◽  
Michele De Laurentiis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Clinical Practice ◽  
Molecular Subtypes ◽  
Metastatic Breast ◽  
Metastatic Setting ◽  
Patterns Of Behavior ◽  
Treatment Table

1055 Background: The molecular subtypes of BC have individual patterns of behavior, prognosis and sensitivity to treatment, with subsequent implications for the choice of, or indeed role, for adjuvant (Adj) and metastatic chemotherapy (CHT). Taxanes (T) play a central role in chemotherapy for BC. However, previous studies have reported that T are relatively ineffective in patients with Luminal (HR+ve) BC compared with other subtypes. Aim of the present analysis is to describe the use of T in the clinical practice in Italy in HR+ve pts. Methods: AMBRA is a longitudinal cohort study, aiming to describe the choice of first and subsequent lines of treatment in HER2-ve MBC pts receiving at least one CHT (SABCS 2016, P5-15-07 & P5-14-09) in the years 2012-2015. For the present analysis, we focused on the use of T from the AdJ to the metastatic setting. Results: So far, 791/1500 pts have been registered into the study, 651 of them (82,3%) evaluable with HR+ MBC. Main characteristics are: Mean age 52 years; pN: UK 64 (9.8%) N+=405 (62.2%); Adj CHT=397 (61 %), mean DFI=96,99 months. T were used in 60.3% of the cases in the Adj setting, alone or in combination with other drugs, mainly anthracyclines (82.6%), with a mean DFI of 56.9 months. In the metastatic setting, across 1st to 3rd line, 460 pts (70.6%) received T, alone (49.7%) or in combination with Bevacizumab (38.2%), or other CHT drugs (11.9%). Details of the use of T in MBC are described in the table below. Conclusions: T have been used in more than 60% of cases of Luminal tumours in the Adj setting. In this population DFS is significantly shorter as compared with the non-T treated luminal population, as previously suggested by different Authors. Re-challenge with T is very frequent across different lines for MBC. Paclitaxel is the most used T, Docetaxel the less used and Nab-paclitaxel, labelled for MBC only, shows an increasing use from 1st-to 3rd line of treatment. [Table: see text]

Disease progression of metastatic breast cancer by first relapse site after definitive radiotherapy.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 36-36
Author(s):  
Kenshiro Shiraishi ◽  
Keiichiro Tada ◽  
Jiro Kawamori ◽  
Atsushi Fukuuchi ◽  
Tsunehiro Nishi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Definitive Radiotherapy ◽  
Distant Relapse ◽  
Metastatic Setting ◽  
Metastatic Relapse ◽  
First Relapse

36 Background: Bone metastasis as initial distant relapse is commonly considered to have better prognosis than other sites in metastatic breast cancer. To elucidate true clinical course of metastatic disease, it is essential that we prospectively manage patients since primary setting. Methods: Overall, 3,417 patients with breast cancer treated with mastectomy (n = 379, 11.1%) or breast-conserving surgery (n = 3,029, 88.6%) followed by definitive radiotherapy at two institutions in Center of Tokyo between 1980 and 2014 were included in the study. Information on all patients was prospectively collected and rigorously-controlled. Initial metastatic relapse sites included bone, brain, and other (mainly visceral). Intrinsic subtypes of tumor were classified as luminal A, luminal-human epidermal growth factor receptor 2 (HER2), luminal B, triple negative, and HER2 identified by routine immunohistochemistry and histological grade. Cumulative incidence rates of overall survival (OS) for each affected site after metastatic relapse were estimated according to Kaplan-Meier method. Results: Median follow-up time for living patients was 113 months. A total of 370 patients experienced metastatic progression as first relapse event. Median duration of OS after initial metastatic relapse was 69 month in all subtypes. No difference was seen in OS among five subtypes after initial bone or brain relapse. Meanwhile, OS of luminal subtypes after initial other-site relapse was better than that of triple negative and HER2 subtypes (P = .003). Notably, OS rates of bone and non-bone/brain metastasis groups as initial relapse site were almost identical (P= .626). Conclusions: We find no difference in mortality after metastatic relapse between bone and other site except for brain metastasis as initial relapse in breast cancer patients following definitive radiotherapy in our cohort without primary metastatic setting. Careful consideration is needed for initial distant relapse regardless of which site is involved. However, prognosis of metastatic breast cancer after definitive radiotherapy is favorable based on real world data, attributable mainly to improved systemic therapy and modern multidisciplinary approach.

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

2014 ◽  
Vol 10 (01) ◽  
pp. 35 ◽  
Author(s):  
Bernardo L Rapoport ◽  
Simon Nayler ◽  
Georgia S Demetriou ◽  
Shun D Moodley ◽  
Carol A Benn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Treatment Options ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Cancers ◽  
Metastatic Setting

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumours, both clinically and pathologically. These cancers are characterised by the lack of expression of the hormone receptors oestrogen receptor (OR) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2 (HER2) gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomised trials. Numerous studies have now shown that TNBC has significantly higher pathological complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathological diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant and metastatic setting, including an assessment of future directions of treatment.

Treatment of Metastatic Breast Cancer

2014 ◽  
Vol 12 (5S) ◽  
pp. 759-761 ◽  
Author(s):  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
Annual Conference ◽  
Her2 Positive ◽  
Treatment Regimens ◽  
New Strategies

Many newer agents in combination are being studied in the front-line treatment of women with HER2-positive metastatic breast cancer (MBC), but the story in the endocrine arena is more about the wise use of new strategies to overcome endocrine resistance, because no new antihormonal agents have been approved in the past decade. During his presentation at the NCCN 19th Annual Conference, Dr. William Gradishar explored what’s new in the treatment of MBC, focusing primarily on enhancing the effect of endocrine therapy to overcome resistance with newer targeted agents such as everolimus, reevaluating the role of rebiopsy on disease progression and measuring circulating tumor cells as a surrogate of response to treatment, and reviewing the effective treatment regimens for HER2-positive disease.

scholarly journals A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S32783 ◽  
Author(s):  
Simon B. Zeichner ◽  
Hiromi Terawaki ◽  
Keerthi Gogineni
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Symptomatic Disease ◽  
Metastatic Setting ◽  
Epidermal Growth ◽  
New Treatment

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Dose-response analysis of efficacy from phase I single-arm trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15209-e15209
Author(s):  
Peter A. Kaufman ◽  
Sonia Pernas Simon ◽  
Miguel Martin ◽  
Marta Gil-Martin ◽  
Patricia Gomez Pardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Response ◽  
Dose Escalation ◽  
Phase 1 ◽  
Single Agent ◽  
Safety Data ◽  
Metastatic Breast ◽  
Response Analysis ◽  
Metastatic Setting

e15209 Background: Balixafortide (B) is a potent, selective antagonist of the chemokine receptor CXCR4. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in metastatic breast cancer (MBC). Efficacy and safety data were published recently from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC1. We report the final efficacy analyses from this trial, including assessment of dose-response. Methods: In this single-arm, dose escalation trial, patients (pts) received E + increasing doses of B using a 3+3 design in 3 parts: Part I (cohorts received low E doses); Part II (dose-escalation cohort for B [1−5.5mg/kg] + 1.4mg/m2 E); Expanded Cohort (EC; 5.5mg/kg B + 1.4mg/m2 E) to confirm safety and efficacy. Results: At entry, all 56 women (age range 33−82 years) were HER2-negative (IHC and/or FISH), CXCR4 positive. The majority were Caucasian. Most pts were heavily pre-treated in the metastatic setting (line of chemotherapy on study: 29% 2nd line, 50% 3rd line, 21% 4th line). 75% were hormone receptor positive and 23% had triple negative breast cancer. Conclusions: A consistent dose response effect for B + E was suggested in heavily pretreated pts with HER2 negative MBC across all efficacy endpoints. A comparison of these efficacy results, and particularly response data, with single agent data for E in similar populations2, 3 showed that pts in the EC had a more profound benefit observed consistently throughout all efficacy endpoints. Further data and analysis will be forthcoming for presentation. 1. 3 patients from Part II also included in EC because they received the B dose selected for EC (5.5mg/kg). 2. Part I was an initial safety run-in with lower E doses, and so is not included in the table. 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24 2. Cortes J et al. Lancet. 2011; 377: 914−923 3. Kaufman PA et al. J Clin Oncol. 2015; 33: 594−601. Clinical trial information: NCT01837095 . [Table: see text]

scholarly journals The Evolution of Radiation Therapy in Metastatic Breast Cancer: From Local Therapy to Systemic Agent

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jessica M. S. Jutzy ◽  
Jeffrey M. Lemons ◽  
Jason J. Luke ◽  
Steven J. Chmura
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Metastatic Breast Cancer ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Tumor Biology ◽  
Metastatic Breast ◽  
Local Therapy ◽  
Metastatic Setting

Radiation therapy is a mainstay of treatment in early and locally advanced breast cancer but is typically reserved for palliation of symptomatic lesions in patients with metastatic breast cancer. With new advances in the field of tumor biology and immunology, the role of radiation in the metastatic setting is evolving to harness its immune-enhancing properties. Through the release of tumor antigens, tumor DNA, and cytokines into the tumor microenvironment, radiation augments the antitumoral immune response to affect both the targeted lesion and distant sites of metastatic disease. The use of immunotherapeutics to promote antitumoral immunity has resulted in improved treatment responses in patients with metastatic disease and the combination of radiation therapy and immunotherapy has become an area of intense investigation. In this article, we will review the emerging role of radiation in the treatment of metastatic disease and discuss the current state of the science and clinical trials investigating the combination of radiation and immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document