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TARGETED THERAPY The 1980’s saw the discovery of the Cerb2 or Her2/neu gene by Dennis Slamon and others. Approximately 20% of breast cancer patients have Her2/ neu positive cancer. This is associated with reduced survival and time to relapse. Slamon’s discovery provided an important opportunity to evaluate the concept of targeted cancer therapy and in 1998, Trastuzumab, the first humanized antibody targeting a cancer related gene was approved by the FDA for Her2/ neu – positive MBC. Eight years later, it was approved in the adjuvant setting. Another drug, Lapatinib, which inhibits the intracellular tyrosine kinase domains of EGFR and Her2 receptor, was added to the armamentarium of Her2 positive breast cancer in the 2008.


women with oestrogen receptors and positive breast cancer regardless of age. In 1998 Bernard Fisher reported that


tamoxifen reduced the incidence of breast cancer by 45% in high-risk women; this was the first successful chemoprevention trial in breast cancer. Treatment with tamoxifen reduced the risk of death by 14% in women younger than 50 and by 27% in those 50 years of


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age and older. The late 1990’s saw the introduction of a new class of drugs called aromatase inhibitors. These drugs are currently available for hormone positive breast cancer in post-menopausal women. Though overall survival has not been reported, time to disease recurrence and time to distant recurrence, and reduction in the incidence of contralateral breast cancer all favour the use of AI’s.


SYSTEMIC CHEMOTHERAPY Breast cancer is a relatively chemo- sensitive disease and chemotherapy in both the adjuvant and metastatic setting is used very widely. Another major contributor to the improvement in breast cancer survival has been the institution of systemic chemotherapy in the adjuvant as well as the metastatic setting since the 1970’s. Randomized trials have addressed many fundamental questions related to adjuvant chemotherapy. The two major trials, which had an impact on the care of women with breast cancer and the design of future strategies, were the NSABP trial using Melphalan and the trial by Bonnadonna using CMF. CMF quickly became the standard of care for node positive breast cancer. In recent years, anthracyclines and taxanes have become the backbones of treatment as many trials incorporating these agents have had a great impact on survival. The new century brought with it the use of antiangiogenic agents to control cancer. This concept dates back to 1971 with the discovery by Judah Folkman that angiogenesis plays a major role in tumour growth and metastases. Bevacizumab, a humanized monoclonal antibody that targets the VEGF became the first antiangiogenic agent approved by the FDA in 2004 for colon cancer. Approved in early 2008 for metastatic breast cancer, its use is currently under review by the FDA.


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