Trends in utilization of hypofractionated whole breast irradiation (HF-WBI) in triple negative breast cancer (TNBC): a national cancer database (NCDB) analysis.

PURPOSE: We sought to identify trends over time with respect to the use of hypofractionated whole breast irradiation (HF-WBI) in women with triple negative breast cancer (TNBC) in the national cancer database (NCDB). METHODS: Trends in utilization of HF-WBI in women diagnosed with T1-2N0 TNBC in the NCDB between 2008 and 2013 were analyzed. Case-matched luminal A women were used for comparison. Variables included age, race, year of diagnosis, insurance status, income quartile, receipt of neoadjuvant chemotherapy, and institution (academic vs. community). Chi square, logistic regression, and multivariate analysis was performed. RESULTS: Utilization of HF-WBI among the 53,269 TNBC women identified steadily increased from 4.7% in 2008 to 14.0% in 2013 for women with TNBC compared to luminal A cancer whose utilization increased from 7.3 to 23.3% over the same time frame (p < 0.001). On univariate analysis, HF-WBI was associated with increasing age (p < 0.001), Medicare insurance (p < 0.001), race (p = 0.041), diagnosis after 2011 (p < 0.001), higher income quartile (p < 0.001), and treatment at academic institutions (p < 0.001). On multivariate analysis, age (p < 0.001, OR 1.038 per year), income quartile (p = 0.002, OR 1.061 per increase in quartile), treatment at an academic institution (p < 0.001, OR 1.78) significantly increased use of HF-WBI. CONCLUSIONS: Treatment at an academic center and year of diagnosis were most correlated with increased HF-WBI in T1-2N0 TNBC women in the NCDB from 2008 to 2013, followed by increasing age and income. Only 14% of T1-2N0 TNBC women received HF-WBI in 2013. Focus on increased utilization is needed for non-academic centers, lower income, and younger women.

Factors Influencing Management and Outcome in Patients with Occult Breast Cancer with Axillary Lymph Node Involvement: Analysis of the National Cancer Database.

BACKGROUND: Occult breast cancer (OBC) is rare and optimal local-regional (LR) management has not been defined. Using a patient registry database, we examine factors associated with treatment and outcomes in OBC. METHODS: Female patients with cT0 N1/2 M0 BC were selected from the National Cancer Database (2004-2013) and categorized into four treatment groups: MAST = mastectomy with axillary lymph node dissection (ALND) ± radiation (RT); RT + ALND = RT with ALND, no breast surgery; ALND = ALND alone; OBS = no breast surgery, RT, or ALND. Patient characteristics and overall survival (OS) were compared between groups, and multivariable analysis was used to identify factors associated with treatment and OS. RESULTS: Among 2.03 million BC cases, 1853 females (0.09%) with cT0 N1/2 M0 disease were identified and 1231 patients were categorized into a treatment group: MAST = 592, RT + ALND = 342, ALND = 106, OBS = 191. On logistic regression, care at an academic center was associated with a higher likelihood of RT + ALND compared with MAST (odds ratio 2.03, 95% confidence interval [CI] 1.50-2.74, p < 0.001). Patients treated with RT + ALND had significantly better OS on univariate survival analysis compared with patients treated with MAST (hazard ratio [HR] 0.475, 95% CI 0.306-0.736, p = 0.001). RT + ALND was independently associated with OS on multivariable survival analysis (HR 0.509, 95% CI 0.321-0.808, p = 0.004), after adjusting for covariates. CONCLUSIONS: Patients with OBC were more likely to undergo RT + ALND if they received care at an academic center. Patients treated with RT + ALND had significantly better OS compared with patients treated with MAST, after adjusting for covariates. This supports the use of RT + ALND as LR treatment for patients with OBC.

Weight loss with mindful eating in African American women following treatment for breast cancer: a longitudinal study.

PURPOSE: Women with higher body mass index (BMI) following breast cancer (BC) treatment are at higher risk of BC recurrence and death than women of normal weight. African American (AA) BC patients have the highest risk of BC recurrence and gain more weight after diagnosis than their white counterparts. The purpose of this study was to evaluate the association between a mindful eating intervention and weight loss in AA women following chemotherapy for BC. METHODS: A single-group 24-week longitudinal pilot study with repeated measures was conducted. AA women (N = 22, BMI = 35.13 kg/m(2), range = 27.08-47.21) with stage I-III BC who had finished active cancer treatment received a 12-week mindful eating intervention with individual dietary counseling and group mindfulness sessions, followed by bi-weekly telephone follow-up for 12 weeks. Linear mixed models were used to evaluate the effects of the intervention and of baseline mindfulness on the weight change over time. RESULTS: In the overall group (N = 22), MEQ scores increased over time (p = 0.001) while weight decreased over time (-0.887 kg, p = 0.015). Weight loss over time was associated with higher T1 MEQ scores (p = 0.043). Participants in the higher MEQ group (n = 11) at T1 experienced significant weight loss over time (-1.166 kg, p = 0.044), whereas those in the low MEQ (n = 11) did not lose weight. Participants who were diagnosed with stage 1 BC experienced significant weight loss over time (-7.909 kg, p = 0.014). CONCLUSIONS: This study suggests that a mindful weight loss program may be effective for weight reduction and maintenance in some AA women who have completed treatment for BC, particularly those diagnosed with stage 1 BC and with initially higher mindful eating behaviors. Mindful weight loss program is proposed as a promising way in which to reduce obesity-related conditions in AA BC survivors.

Trastuzumab-induced cardiomyopathy: incidence and associated risk factors in an inner-city population.

BACKGROUND: Although it is known that trastuzumab causes cardiotoxicity, its extent and reversibility are still in question. Earlier studies have not evaluated consecutive patients with reproducible nuclear ventriculography. OBJECTIVE: We sought to evaluate the baseline characteristics which predispose patients to increased risk of trastuzumab cardiotoxicity and to determine the natural history of the cardiotoxicity. METHODS AND RESULTS: Left ventricular ejection fraction (LVEF) was measured in 76 women aged 36-73 years who had been treated with trastuzumab at the University of Maryland Greenebaum Cancer Center. LVEF was determined at baseline and then 3, 6, 9, and 12 months after treatment initiation. Cardiotoxicity was defined as ≥ 16% decrease in LVEF or ≥ 10% decrease in LVEF to <50%. There were no differences in comorbidities, earlier treatment, or demographics between patients with and without trastuzumab-induced cardiomyopathy except that African Americans were more likely to develop decreased LVEF (P < .05). Twenty-one patients (28%) met criteria for cardiotoxicity. Four of those patients were continued on trastuzumab and 17 patients had therapy withheld at some point. Only 1 patient developed symptomatic heart failure requiring inpatient hospitalization. LVEF improved in most patients regardless of whether or not trastuzumab was continued. CONCLUSIONS: Decreased LVEF while undergoing trastuzumab therapy occurs frequently and is usually reversible. African Americans had a higher risk of developing decreased LVEF. These findings raise clinically important questions as to whether it is necessary to discontinue trastuzumab for asymptomatic decrease in LVEF and whether African Americans are more predisposed to a decrease in LVEF while receiving trastuzumab. Further studies carefully assessing LVEF should address these hypotheses.

In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy.

Cancer immunotherapy that deploys the host's immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically "cold" into "hot". In particular, after the ICIE treatment, the ratio of the CD8+ cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes "frostbite" of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8+ cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis.

Circulating Biomarkers in Breast Cancer.

Breast cancer management has progressed immensely over the decades, but the disease is still a major source of morbidity and mortality worldwide. Even with enhanced imaging detection and tissue biopsy capabilities, disease can progress on an ineffective treatment before additional information is obtained through standard methods of response evaluation, including the RECIST 1.1 criteria, widely used for assessment of treatment response and benefit from therapy.6 Circulating biomarkers have the potential to provide valuable insight into disease progression and response to therapy, and they can serve to identify actionable mutations and tumor characteristics that can direct therapy. These biomarkers can be collected at higher frequencies than imaging or tissue sampling, potentially allowing for more informed management. This review will evaluate the roles of circulating biomarkers in breast cancer, including the serum markers Carcinoembryonic antigen CA15-3, CA27-29, HER2 ECD, and investigatory markers such as GP88; and the components of the liquid biopsy, including circulating tumor cells, cell free DNA/DNA methylation, circulating tumor DNA, and circulating microRNA.

Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.

The circulating tumor cells (CTCs, the root cause of cancer metastasis and poor cancer prognosis) are very difficult to culture for scale-up in vitro, which has hampered their use in cancer research/prognosis and patient-specific therapeutic development. Herein, we report a robust electromicrofluidic chip for not only efficient capture of heterogeneous (EpCAM+ and CD44+) CTCs with high purity but also glutathione-controlled gentle release of the CTCs with high efficiency and viability. This is enabled by coating the polydimethylsiloxane (PDMS) surface in the device with a 10 nm gold layer through a 4 nm titanium coupling layer, for convenient PEGylation and linkage of capture antibodies via the thiol-gold chemistry. Surprisingly, the percentage of EpCAM+ mammary CTCs can be as low as ∼35% (∼70% on average), showing that the commonly used approach of capturing CTCs with EpCAM alone may miss many EpCAM- CTCs. Furthermore, the CD44+ CTCs can be cultured to form 3D spheroids efficiently for scale-up. In contrast, the CTCs captured with EpCAM alone are poor in proliferation in vitro, consistent with the literature. By capture of the CTC heterogeneity, the percentage of stage IV patients whose CTCs can be successfully cultured/scaled up is improved from 12.5% to 68.8%. These findings demonstrate that the common practice of CTC capture with EpCAM alone misses the CTC heterogeneity including the critical CD44+ CTCs. This study may be valuable to the procurement and scale-up of heterogeneous CTCs, to facilitate the understanding of cancer metastasis and the development of cancer metastasis-targeted personalized cancer therapies conveniently via the minimally invasive liquid/blood biopsy.

Metformin Bicarbonate-Mediated Efficient RNAi for Precise Targeting of TP53 Deficiency in Colon and Rectal Cancers.

Colon and rectal cancers are the leading causes of cancer-related deaths in the United States and effective targeted therapies are in need for treating them. Our genomic analyses show hemizygous deletion of TP53, an important tumor suppressor gene, is highly frequent in both cancers, and the 5-year survival of patients with the more prevalent colon cancer is significantly reduced in the patients with the cancer harboring such deletion, although such reduction is not observed for rectal cancer. Unfortunately, direct targeting TP53 has been unsuccessful for cancer therapy. Interestingly, POLR2A, a gene essential for cell survival and proliferation, is almost always deleted together with TP53 in colon and rectal cancers. Therefore, RNA interference (RNAi) with small interfering RNAs (siRNAs) to precisely target/inhibit POLR2A may be an effective strategy for selectively killing cancer cells with TP53 deficiency. However, the difficulty of delivering siRNAs specifically into the cytosol where they perform their function, is a major barrier for siRNA-based therapies. Here, metformin bicarbonate (MetC) is synthesized to develop pH-responsive MetC-nanoparticles with a unique "bomb" for effective cytosolic delivery of POLR2A siRNA, which greatly facilitates its endo/lysosomal escape into the cytosol and augments its therapeutic efficacy of cancer harboring TP53 deficiency. Moreover, the MetC-based nanoparticles without functional siRNA show notable therapeutic effect with no evident toxicity or immunogenicity.

Patterns of Failure in Triple Negative Breast Cancer Patients in an Urban, Predominately Black Population.

Triple negative breast cancers (TNBC) behave more aggressively than hormone-receptor positive breast cancers. They are also known preferentially to affect young black women, often leading to poorer outcomes compared with those for white women. We sought to evaluate the comprehensive patterns of failure associated with treatment for TNBC at an urban institution with a predominantly black population and to assess the impact of social determinants of health on treatment failure. A retrospective review of TNBC patients treated from 2005 to 2015 was conducted. Detailed patient, tumor, and treatment characteristics and information on patterns of failure were included. With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. Treatment failure was associated with insurance type and smoking status, as well as several tumor characteristics. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. In contrast to previous studies, we found that black women had higher overall survival than white women, but race was not associated with differences in recurrence patterns or with likelihood of treatment failure. Regardless of race, of the patients who recurred, 53% failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients and suggest a need for improved follow-up focusing on detecting locoregional failures. Multidisciplinary care is essential in the management of these patients at time of failure.

Association of Serum Progranulin Levels With Disease Progression, Therapy Response and Survival in Patients With Metastatic Breast Cancer.

BACKGROUND: Progranulin (GP88) is a critical player in breast tumorigenesis. GP88 tumor expression is associated with increased recurrence and mortality, whereas GP88 circulating levels are elevated in patients with breast cancer compared with healthy individuals. We examined here the correlation between serum GP88 levels in patients with metastatic breast cancer (MBC) with overall survival and disease status determined as response to therapy or progression of disease. PATIENTS AND METHODS: An institutional review board (IRB)-approved study prospectively enrolled 101 patients with MBC at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. GP88 serum levels were correlated with patients' disease status determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and survival outcomes by Kaplan-Meier analysis and log rank statistics. RESULTS: Patients' survival was stratified by serum GP88 level. Patients with serum GP88 < 55 ng/mL had a 4-fold increased survival compared with patients with GP88 > 55 ng/mL. Examination of GP88 serum levels in association with disease status showed a statistically significant association between serum GP88 levels and disease progression or response to therapy while CA15-3 level was only associated to progression. CONCLUSION: The association of serum GP88 level with survival and disease status suggests the potential of using the serum GP88 test for monitoring disease status in patients with MBC. Measurement of serum GP88 levels in patients with MBC may have clinical value as a cost-effective adjunct to the management of patients with MBC with imaging.

Targeted Heating of Mitochondria Greatly Augments Nanoparticle-Mediated Cancer Chemotherapy.

Cancer is the second leading cause of mortality globally. Various nanoparticles have been developed to improve the efficacy and safety of chemotherapy, photothermal therapy, and their combination for treating cancer. However, most of the existing nanoparticles are low in both subcellular precision and drug loading content (<≈5%), and the effect of targeted heating of subcellular organelles on the enhancement of chemotherapy has not been well explored. Here, a hybrid Py@Si-TH nanoparticle is reported to first target cancer cells overexpressed with the variant CD44 via its natural ligand HA on the outermost surface of the nanoparticle before cellular uptake, and then target mitochondria after they are taken up inside cells. In addition, the nanoparticle is ultraefficient for encapsulating doxorubicin hydrochloride (DOX) to form Py@Si-TH-DOX nanoparticle. The encapsulation efficiency is ≈100% at the commonly used low feeding ratio of 1:20 (DOX:empty nanoparticle), and >80% at an ultrahigh feeding ratio of 1:1. In combination with near infrared (NIR, 808 nm) laser irradiation, the tumor weight in the Py@Si-TH-DOX treatment group is 8.5 times less than that in the Py@Si-H-DOX (i.e., DOX-laden nanoparticles without mitochondrial targeting) group, suggesting targeted heating of mitochondria is a valuable strategy for enhancing chemotherapy to combat cancer.

Bioinspired One Cell Culture Isolates Highly Tumorigenic and Metastatic Cancer Stem Cells Capable of Multilineage Differentiation.

Cancer stem cells (CSCs) are rare cancer cells that are postulated to be responsible for cancer relapse and metastasis. However, CSCs are difficult to isolate and poorly understood. Here, a bioinspired approach for label-free isolation and culture of CSCs, by microencapsulating one cancer cell in the nanoliter-scale hydrogel core of each prehatching embryo-like core-shell microcapsule, is reported. Only a small percentage of the individually microencapsulated cancer cells can proliferate into a cell colony. Gene and protein expression analyses indicate high stemness of the cells in the colonies. Importantly, the colony cells are capable of cross-tissue multilineage (e.g., endothelial, cardiac, neural, and osteogenic) differentiation, which is not observed for "CSCs" isolated using other contemporary approaches. Further studies demonstrate the colony cells are highly tumorigenic, metastatic, and drug resistant. These data show the colony cells obtained with the bioinspired one-cell-culture approach are truly CSCs. Significantly, multiple pathways are identified to upregulate in the CSCs and enrichment of genes related to the pathways is correlated with significantly decreased survival of breast cancer patients. Collectively, this study may provide a valuable method for isolating and culturing CSCs, to facilitate the understanding of cancer biology and etiology and the development of effective CSC-targeted cancer therapies.

Neratinib in Combination With Trastuzumab for the Treatment of Patients With Advanced HER2-positive Breast Cancer: A Phase I/II Study.

BACKGROUND: Despite the availability of several human epidermal growth factor receptor 2 (HER2)-directed treatments, many HER2-positive (HER2+) breast cancers eventually progress because of primary or acquired resistance. PATIENTS AND METHODS: A 2-part, open-label, multicenter phase I/II study was conducted to determine the recommended dose of neratinib when administered with trastuzumab (part I), and to assess the antitumor activity of this combination in women with locally advanced or metastatic HER2+ breast cancer previously treated with at least 1 prior trastuzumab-based regimen (part II). Patients received oral neratinib (160 or 240 mg/d) once daily plus intravenous trastuzumab 4 mg/kg (loading dose) then 2 mg/kg weekly. Diarrhea prophylaxis was not permitted. The primary endpoint in part II was investigator-assessed 16-week progression-free survival (PFS). RESULTS: Forty-five patients received neratinib plus trastuzumab (part I: neratinib 160 mg/d, n = 4; neratinib 240 mg/d, n = 4; part II: neratinib 240 mg/d, n = 37). In part I, there were no dose-limiting toxicities and the recommended neratinib dose was 240 mg/d. In part II, the 16-week PFS rate was 44.8% (90% confidence interval, 28.8%-59.6%), and the median PFS was 15.9 weeks (95% confidence interval, 15.1-31.3 weeks) in 28 evaluable patients. Three patients had durable clinical benefit lasting 9.4 to 9.7 years. Diarrhea was the most common adverse event (grade 3, n = 7 [15.6%]; grade 4, n = 0). No clinically significant cardiac toxicity was seen. CONCLUSIONS: Neratinib in combination with trastuzumab was well-tolerated and had encouraging antitumor activity in patients with advanced trastuzumab-pretreated HER2+ breast cancer. Durable responses can be achieved in some patients.

Enhanced cancer therapy with cold-controlled drug release and photothermal warming enabled by one nanoplatform.

Stimuli-responsive nanoparticles hold great promise for drug delivery to improve the safety and efficacy of cancer therapy. One of the most investigated stimuli-responsive strategies is to induce drug release by heating with laser, ultrasound, or electromagnetic field. More recently, cryosurgery (also called cryotherapy and cryoablation), destruction of diseased tissues by first cooling/freezing and then warming back, has been used to treat various diseases including cancer in the clinic. Here we developed a cold-responsive nanoparticle for controlled drug release as a result of the irreversible disassembly of the nanoparticle when cooled to below ∼10 °C. Furthermore, this nanoparticle can be used to generate localized heating under near infrared (NIR) laser irradiation, which can facilitate the warming process after cooling/freezing during cryosurgery. Indeed, the combination of this cold-responsive nanoparticle with ice cooling and NIR laser irradiation can greatly augment cancer destruction both in vitro and in vivo with no evident systemic toxicity.

Prevalence and risk of skeletal complications and use of radiation therapy in elderly women diagnosed with metastatic breast cancer.

OBJECTIVE: Real-world data regarding patient factors associated with the occurrence of spinal cord compression (SCC) or pathological fracture (PF), or need for bone surgery (BS), or use of radiation therapy (RAD) (i.e. skeletal complications and radiation therapy; SCRT) are limited for women with metastatic breast cancer (BCa). Given the substantial clinical and economic burden of these events in advanced BCa, we conducted the present study to understand the prevalence and identify the risk factors associated with these events among elderly women presenting with de novo metastatic BCa. METHODS: Using linked Surveillance, Epidemiology, and End Results and Medicare data, we identified women with incident metastatic BCa diagnosed during 2005-2009. Associations between patient demographics and select clinically relevant factors, and SCRT were examined using the Cox proportional hazards model, accounting for death as a competing risk. RESULTS: Of 3,731 Medicare beneficiaries with incident metastatic BCa, 1,808 (48.5%) experienced at least one SCRT event during a median follow-up of 13.2 months; a majority (69%) experienced a subsequent SCRT event. The proportions of women who had RAD, PF, BS, and SCC were: 32%, 28%, 8%, and 4%. Older women (80+ years), or those with more comorbid conditions (CCI≥2) had a statistically significant lower risk of SCRT (HR 0.78 [CI: 0.67-0.92, p<0.01]; HR 0.77 [CI: 0.67-0.89, p<0.01], respectively), primarily due to lower frequency of radiotherapy (p<0.01). Compared to Caucasians, African Americans had lower risk of SCRT (HR 0.70 [CI: 0.60-0.82, p<0.01]), as well as all SCRT subtypes defining this group except for SCC, which was the same for both race groups. CONCLUSION: This study highlights that certain patient characteristics and clinical factors are associated with the risk of spinal cord compression or pathologic fractures, or need for bone surgery or radiation among women with metastatic BCa. In future studies, it will also be important to consider the clinical and economic burden based on these components of skeletal complications and radiation therapy use in order to guide and improve the management of women with advanced BCa.

Breast magnetic resonance imaging (MRI) surveillance in breast cancer survivors.

PURPOSE: As the breast cancer survivor population increases, the topic of screening these women for recurrences is increasingly relevant. In our institution, we use both breast MRI and mammography in the surveillance of breast cancer survivors, although little data exists on the use of MRI in this setting. We present a retrospective analysis of our experience and compare the sensitivity and specificity of MRI vs. mammography in this setting. METHODS: We identified women under 65 with a history of breast cancer and at least one follow-up MRI performed along with a mammogram done within 6 months of the MRI. We compared the outcomes of MRI and mammography in terms of biopsies performed as well as in detection of new cancers. RESULTS: Of 617 charts reviewed, 249 patients met inclusion criteria, with 571 paired MRI/mammogram results. There were 27 biopsies performed due to MRI findings alone, 10 done due to mammographic findings alone, and 15 done based on abnormalities seen on both imaging modalities. There were 8 malignancies identified based on an abnormal MRI, 3 detected on both MRI and mammography, and none identified via mammography alone. Overall, MRI had a sensitivity of 84.6% (the 95% CI 54.6-98.1) and a specificity of 95.3% (the 95% CI 93.3-96.9); mammography a sensitivity of 23.1% (the 95% CI 5.0-53.8), and a specificity of 96.4% (the 95% CI 94.5-97.8). CONCLUSIONS: Breast MRI is a useful surveillance modality in breast cancer survivors and may be more sensitive at detecting recurrences than mammography alone in this population.

Update on taxane development: new analogs and new formulations.

The taxanes (paclitaxel and docetaxel) represent an important class of antineoplastic agents that interfere with microtubule function leading to altered mitosis and cellular death. Paclitaxel (Taxol(®)) was originally extracted from a yew tree (Taxus spp., Taxaceae) a small slow-growing evergreen, coniferous tree. Due to the initial scarcity of paclitaxel, docetaxel (Taxotere(®)) a semisynthetic analog of paclitaxel produced from the needles of European yew tree, Taxus baccata was developed. Docetaxel differs from paclitaxel in two positions in its chemical structure and this small alteration makes it more water soluble. Today, paclitaxel and docetaxel are widely prescribed antineoplastic agents for a broad range of malignancies including lung cancer, breast cancer, prostate cancer, Kaposi's sarcoma, squamous cell carcinoma of the head and neck, gastric cancer, esophageal cancer, bladder cancer, and other carcinomas. Although very active clinically, paclitaxel and docetaxel have several clinical problems including poor drug solubility, serious dose-limiting toxicities such as myelosuppression, peripheral sensory neuropathy, allergic reactions, and eventual development of drug resistance. A number of these side effects have been associated with the solvents used for dilution of these antineoplastic agents: Cremophor EL for paclitaxel and polysorbate 80 for docetaxel. In addition, reports have linked these solvents to the alterations in paclitaxel and docetaxel pharmacokinetic profiles. In this review, we provide preclinical and clinical data on several novel taxanes formulations and analogs which are currently US Food and Drug Administration (FDA)-approved or in clinical development in various solid tumor malignancies. Of the new taxanes nab-paclitaxel and cabazitaxel have enjoyed clinical success and are FDA-approved; while many of the other compounds described in this review are unlikely to be further developed for clinical use in daily practice. Furthermore, the successful clinical emergence of novel nontaxane microtubule-targeting chemotherapy agents such as epothilones and eribulin is liable to further restrict the development of novel taxanes.