The Safety of Using Liposomal Doxorubicin in Combination with Trastuzumab for the
Treatment of HER-2 Overexpressing Breast Cancer: A Systematic Review
Raksheeth Agarwal*, Oliver Emmanuel**
*Universitas Indonesia – (+62) 85777808310, raksheeth@hotmail.com
** Universitas Indonesia – (+62) 818635925, oliveremmanuel@hotmail.com
1. Introduction
Breast cancer is the most frequent form of cancer in women and is the second most frequent cancer
associated with death in patients. About 124.8 per 100,000 women are diagnosed with breast cancer
per year, and the number of deaths caused by breast cancer is 21.9 per 100,000 women per year.
About 12.3% of women will be diagnosed with breast cancer throughout their lives. Fortunately,
about 89.4% of women survive 5 years or more after being diagnosed with breast cancer.
(Surveillance, Epidemiology... n.d.). Common drugs used to treat Breast Cance r include doxorubicin,
and trastuzumab.
A more aggressive variant of this disease is called HER-2 overexpressing breast cancer. HER-2
membrane bound protein is a growth receptor that regulates the growth and proliferation of healthy
breast cells. HER-2 positive breast cancer means that there is overexpression of this growth factor
receptor in the cancer cells. The prognosis of HER-2 positive breast cancer is much worse than in
HER-2 negative breast cancer due to the excessive copies of the growth receptors increasing the
proliferation of cancer cells. (HER2 Status and Breast Cancer, n.d.)
In a study conducted by the MD Anderson Cancer Center, the five year recurrence-free survival rate
was 77.1% in those suffering HER-2 positive tumors in early stages and 93.7% in those with negative
HER-2 expression (Gonzales, et al. 2005)
Doxorubicin is a part of a group of cancer chemotherapy drugs known as anthracyclines. It is widely
regarded as one of the most effective and potent antineoplastic drugs, limited only by its potential
toxicity to non-cancerous cells. The most widely known systemic side effect of doxorubicin
administration is its associated cardiotoxicity. Doxorubicin has been classically used for the treatment
of various cancers, one of them being Breast Cancer. The known cytotoxic mechanisms of
doxorubicin include intercalation of DNA, inhibition of Topoisomerase II, and generation of free
radicals (Katzung & Trevor, 2013). Doxorubicin is able to diffuse passively across the cell membrane
and associate itself with cytoplasmic proteasomes. The drug-proteasome complex is then translocated