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Treatment options for breast cancer resistant to anthracycline and taxane.

ABSTRACT: Breast cancer is the most common noncutaneous malignancy among every major ethnic group of women in the United States. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Moreover, even when these agents can be used in the metastatic setting, treatment failure occurs in most cases, and as a result the 5-year survival rates of patients with metastatic breast cancer are low. This outcome underscores the need for new, effective treatments of metastatic breast cancer and has led to investigation of novel ways to overcome the problem of drug resistance. This article reviews the current treatment options for breast cancer resistant to anthracycline and taxane and provides recommendations for disease management. Published sources for this review were found by searching PubMed (https://www.ncbi.nlm.nih.gov/pubmed) and congress Web sites.

SUBMITTER: Moreno-Aspitia A

PROVIDER: S-EPMC2688627 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Treatment options for breast cancer resistant to anthracycline and taxane.

Moreno-Aspitia Alvaro A Perez Edith A EA

Mayo Clinic proceedings 20090601 6

Breast cancer is the most common noncutaneous malignancy among every major ethnic group of women in the United States. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Moreover, even when these agents can be used in the metas ...[more]

PMID: 19483170

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Project description:CONTEXT:Prediction of high probability of survival from standard cancer treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE:To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN, SETTING, AND PATIENTS:Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu)-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens (then endocrine therapy if estrogen receptor [ER]-positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. MAIN OUTCOME MEASURES:Distant relapse-free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years). RESULTS:Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy. CONCLUSION:A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.

Project description:Importance:Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence. Objectives:To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality. Design, Setting, and Participants:An observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019. Exposures:Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis. Main Outcomes and Measures:The primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method. Results:The mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55). Conclusions and Relevance:Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.

Project description:Objective:This study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy. Materials and Methods:Transcriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes. Results:We found a significant correlation of an expression module with distant relapse-free survival (HR = 0.213, 95% CI [0.131-0.347], P = 4.80E-9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients. Conclusion:We used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

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Treatment options for breast cancer resistant to anthracycline and taxane.

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Treatment options for breast cancer resistant to anthracycline and taxane.

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