Current approaches in treatment of triple-negative breast cancer

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Abstract

Triple-negative breast cancer (TNBC) is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American women. TNBC is a term derived from tumors that are characterized by the absence of ER, PgR, and HER2. So patients with TNBC do not benefit from hormonal or trastuzumab-based therapies. TNBCs are biologically aggressive, although some reports suggest that they respond to chemotherapy better than other types of breast cancer, prognosis remains poor. This is due to: shortened disease-free interval in the adjuvant and neoadjuvant setting and a more aggressive course in the metastatic setting.

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Most cited references 35

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Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

Roman Rouzier, Charles Perou, W Symmans … (2005)

Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.

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Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

William Gradishar, Sergei Tjulandin, Neville Davidson … (2005)

ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225). ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.

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Molecular classification and molecular forecasting of breast cancer: ready for clinical application?

James Brenton, Lisa A Carey, Ahmed Ashour Ahmed … (2005)

Profiling breast cancer with expression arrays has become common, and it has been suggested that the results from early studies will lead to understanding of the molecular differences between clinical cases and allow individualization of care. We critically review two main applications of expression profiling; studies unraveling novel breast cancer classifications and those that aim to identify novel markers for prediction of clinical outcome. Breast cancer may now be subclassified into luminal, basal, and HER2 subtypes with distinct differences in prognosis and response to therapy. However, profiling studies to identify predictive markers have suffered from methodologic problems that prevent general application of their results. Future work will need to reanalyze existing microarray data sets to identify more representative sets of candidate genes for use as prognostic signatures and will need to take into account the new knowledge of molecular subtypes of breast cancer when assessing predictive effects.

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Journal

Journal ID (nlm-ta): Cancer Biol Med

Journal ID (iso-abbrev): Cancer Biol Med

Journal ID (publisher-id): CBM

Title: Cancer Biology & Medicine

Publisher: Chinese Anti-Cancer Association

ISSN (Print): 2095-3941

Publication date (Print and electronic): June 2015

Publication date (Print): June 2015

Volume: 12

Issue: 2

Pages: 106-116

Affiliations

[1]Clinical Oncology and Nuclear Medicine, Mansoura University, Mansoura 35516, Egypt

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Correspondence to: Hend Ahmed El-Hadaad

E-mail: hend_am@ 123456mans.edu.eg

Article

Publisher ID: cbm-12-02-106

DOI: 10.7497/j.issn.2095-3941.2015.0030

PMC ID: 4493381

PubMed ID: 26175926

SO-VID: 27520a6c-6f8e-4e30-866d-582ed7265c53

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This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

Current approaches in treatment of triple-negative breast cancer

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Karger: Oncology

Most cited references 35

Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

Molecular classification and molecular forecasting of breast cancer: ready for clinical application?

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