Metastatic and triple-negative breast cancer: challenges and treatment options

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Abstract

The major current conventional types of metastatic breast cancer (MBC) treatments include surgery, radiation, hormonal therapy, chemotherapy, or immunotherapy. Introducing biological drugs, targeted treatment and gene therapy can potentially reduce the mortality and improve the quality of life in patients with MBC. However, combination of several types of treatment is usually recommended. Triple negative breast cancer (TNBC) accounts for 10–20% of all cases of breast carcinoma and is characterized by the low expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). Consequently, convenient treatments used for MBC that target these receptors are not effective for TNBC which therefore requires special treatment approaches. This review discusses the occurrence of MBC, the prognosis and predictive biomarkers of MBC, and focuses on the novel advanced tactics for treatment of MBC and TNBC. Nanotechnology-based combinatorial approach for the suppression of EGFR by siRNA and gifitinib is described.

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Breast cancer metastasis: markers and models.

Britta Weigelt, Johannes Peterse, Laura J van 't Veer (2005)

Breast cancer starts as a local disease, but it can metastasize to the lymph nodes and distant organs. At primary diagnosis, prognostic markers are used to assess whether the transition to systemic disease is likely to have occurred. The prevailing model of metastasis reflects this view--it suggests that metastatic capacity is a late, acquired event in tumorigenesis. Others have proposed the idea that breast cancer is intrinsically a systemic disease. New molecular technologies, such as DNA microarrays, support the idea that metastatic capacity might be an inherent feature of breast tumours. These data have important implications for prognosis prediction and our understanding of metastasis.

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Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer.

Kimberly Blackwell, Harold J Burstein, Anna Storniolo … (2010)

Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC). Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab. The primary end point was progression-free survival (PFS). Secondary efficacy end points included overall response rate (ORR), clinical benefit rate (CBR; complete response, partial response, and stable disease for >/= 24 weeks), and overall survival (OS). In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the combination of lapatinib with trastuzumab was superior to lapatinib alone for PFS (hazard ratio [HR] = 0.73; 95% CI, 0.57 to 0.93; P = .008) and CBR (24.7% in the combination arm v 12.4% in the monotherapy arm; P = .01). A trend for improved OS in the combination arm was observed (HR = 0.75; 95% CI, 0.53 to 1.07; P = .106). There was no difference in ORR (10.3% in the combination arm v 6.9% in the monotherapy arm; P = .46). The most frequent adverse events were diarrhea, rash, nausea, and fatigue; diarrhea was higher in the combination arm (P = .03). The incidence of symptomatic and asymptomatic cardiac events was low (combination therapy = 2% and 3.4%; monotherapy = 0.7% and 1.4%, respectively). Despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC.

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Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer.

G Budd, Massimo Cristofanilli, Mathew Ellis … (2006)

The presence of >or=5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival. One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined approximately 4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory. Interreader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and >or=5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and or=5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P=0.0039). Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.

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Author and article information

Contributors

Tamara Minko: 848-445-6348 , minko@rci.rutgers.edu

Journal

Journal ID (nlm-ta): Drug Deliv Transl Res

Journal ID (iso-abbrev): Drug Deliv Transl Res

Title: Drug Delivery and Translational Research

Publisher: Springer US (New York )

ISSN (Print): 2190-393X

ISSN (Electronic): 2190-3948

Publication date (Electronic): 5 July 2018

Publication date PMC-release: 5 July 2018

Publication date (Print): 2018

Volume: 8

Issue: 5

Pages: 1483-1507

Affiliations

[1 ]ISNI 0000 0004 1936 8796, GRID grid.430387.b, Department of Pharmaceutics, Ernest Mario School of Pharmacy, , Rutgers, The State University of New Jersey, ; 160 Frelinghuysen Road, Piscataway, NJ 08854-8020 USA

[2 ]ISNI 0000 0004 1936 8796, GRID grid.430387.b, Rutgers Cancer Institute, ; New Brunswick, NJ 08903 USA

[3 ]ISNI 0000 0004 1936 8796, GRID grid.430387.b, Environmental and Occupational Health Sciences Institute, Rutgers, , Rutgers, The State University of New Jersey, ; Piscataway, NJ 08854 USA

Article

Publisher ID: 551

DOI: 10.1007/s13346-018-0551-3

PMC ID: 6133085

PubMed ID: 29978332

SO-VID: 7026bda7-f51c-46be-a5bc-8508bcd9354a

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;

Award ID: CA138533

Award Recipient : Tamara Minko

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: liposomes,egfr,sirna,gefitinib,combinatorial treatment of breast cancer

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: liposomes, egfr, sirna, gefitinib, combinatorial treatment of breast cancer

Metastatic and triple-negative breast cancer: challenges and treatment options

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Neuropharmacology and Therapy

Most cited references 211

Breast cancer metastasis: markers and models.

Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer.

Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer.

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