Q2. What are the future works in this paper?
Perhaps a next step required to fully integrate Trastuzumab into the curative treatment algorithm for breast cancer patients is to fully evaluate its role as neo-adjuvant therapy and attempts are now being made to extend the benefit seen with adjuvant Trastuzumab as neoadjuvant treatment.
Q3. What is the role of the small molecule Lapatinib in the treatment of cancer?
(23)The small molecule Lapatinib acts by inhibiting the receptor tyrosine kinase activity of HER2 and also the EGFR (ErbB1) receptor.
Q4. How long has Trastuzumab been widely adopted as standard treatment?
One year of treatment, starting either with the taxane component of chemotherapy, or after chemotherapy, has been widely adopted as standard treatment across the world.
Q5. What is the potential benefit of an intracellular signalling blockade with small molecules?
(5) In particular, when considering the potential benefit of an intracellular signalling blockade with small molecules such as Lapatinib, is the possible relevance of the truncated HER2 receptor, p95, which results in constitutive activation and no extra-cellular target to which an antibody such as Trastuzumab can bind.
Q6. how much is trostuzumab effective in breast cancer?
Trastuzumab in metastatic breast cancerAs a single agent Trastuzumab can produce response rates up to 35% in selected metastatic breast cancer patients.
Q7. What is the role of Trastuzumab in the 45-50% of breast?
Regarding the role of Trastuzumab in the 45-50% patients(44) with HER2 positive tumours co-expressing HER2 and the oestrogen receptor (ER), pre-clinical evidence supports an interaction between their dependant signalling pathways.
Q8. What is the effect of Trastuzumab on cancer?
It has demonstrated activity in early phase trials when added to Trastuzumab for patients with disease progressing on Trastuzumab therapy, which incidentally provides further evidence of retained tumour sensitivity to anti-HER2 therapy even though resistance to Trastuzumab has developed.
Q9. What is the main barrier to concurrent administration of Trastuzumab and chemotherapy?
The main barrier to concurrent administration of Trastuzumab and chemotherapy is the high risk of cardiotoxicity with an anthracycline-Trastuzumab combination.
Q10. What is the next step to integrating Trastuzumab into the curative?
(56)Perhaps a next step required to fully integrate Trastuzumab into the curative treatment algorithm for breast cancer patients is to fully evaluate its role as neo-adjuvant therapy and attempts are now being made to extend the benefit seen with adjuvant Trastuzumab as neoadjuvant treatment.
Q11. What is the response rate of Trastuzumab in HER2 positive breast?
An impressive response rate of 46% was seen in a phase II trial testing this combination,(32) although concerns exist surrounding the potential combined cardiotoxicity of these two drugs.
Q12. What is the benefit of using Trastuzumab in breast cancer?
Page 8 of 18The clear benefit of using Trastuzumab in patients with advanced HER2 positive breast cancer quickly led to the initiation of a series of large trials testing the hypothesis that the use of Trastuzumab in HER2 over-expressing early breast cancer could improve disease-free survival.
Q13. What is the effect of Trastuzumab on the HER2 receptor?
(28) Another agent KOS-953 (17-AAG) inhibits the activity of heat shock protein 90 resulting in degradation and reduced expression of the HER2 receptor and has also produced responses in an early report from a phase II study.
Q14. What is the pragmatic treatment strategy for breast cancer?
Many argue that this is the most pragmatic treatment strategy in light of the absence of data confirming long term cardiac safety with the use of both an anthracycline and a taxane in the adjuvant treatment schedule.
Q15. Why is FISH widely held as the gold standard?
FISH is widely held as the gold standard not just because there is a good correlation between DNA copy number and protein levels, but also because routine fixation processes mean that protein levels as measured by IHC may not always be an accurate indicator of the level in vivo in the patient.
Q16. What is the main barrier to concurrent administration of Trastuzumab?
The MD Anderson centre conducted a randomised trial where patients either received Trastuzumab or not, concurrently with neo-adjuvant chemotherapy.
Q17. What is the main reason for the high rate of CNS involvement after Trastuzum?
(33)It is now well recognised that HER2 positive breast cancer has a high rate of CNS involvement, and cerebral metastasis as the site of progression after Trastuzumab is unexpectedly common.(34-37) The particular challenge facing us now is how best to control this disease, particularly when presenting in the setting of responding extra-cranial metastasis.
Q18. What is the way to reduce cardiotoxicity with Trastuzumab?
One potential strategy for minimising cardiotoxicity with anthracycline-Trastuzumab combinations may by the use ofPage 13 of 18liposomal doxorubicin and this topic has been recently reviewed in detail by Rayson et al.