autologous blood and marrow transplantation - Blog Science ...

Bewick et al.
pression in MBC, i.e., 20-57% of patients with MBC have elevated HER-2
plasma/serum concentration. 14-20,22-25
These HER-2 positive patients had a significantly
decreased OS and PFS following HDCT and ABSC transplantation (Table
2 and Fig. 1A and B). Therefore, the presence of elevated plasma HER-2 may be
an important prognostic factor that could be used to select more effective and
additional therapies for these patients (e.g., directly targeted treatments using
immunologic therapy).
It is still not certain whether patients with elevated levels of HER-2 would
benefit more from specific and/or increased dosages of chemotherapeutic agents as
suggested previously by some clinical studies. 31-34
Results from a study by Muss et
al. 31
suggest that patients with node positive early breast cancer who overexpress
HER-2 may benefit from higher doses of adjuvant chemotherapy particularly when
using doxorubicin. Results of this retrospective study indicate that increased
dosages of drugs used in HDCT do not significantly improve response and survival
in patients with MBC who overexpress HER-2. (Four of the five patients which
received an additional HDCT treatment were HER-2 positive.)
HER-2 overexpression has been observed to result in resistance to a wide
variety of drugs both in vitro and clinically. Correlations have been found between
HER-2 overexpression and resistance of breast tumor cells in vitro to a wide variety
of agents, including alkylating agents such as m-platinum and cyclophosphamide,
35
tumor necrosis factor, 36
and natural killer cells. 37
Several clinical
studies have also shown an association between HER-2 overexpression and drug
resistance to alkylating agents, anthracyclines, and CMF-like regimens. 31,38-
^ 0
Additional studies have shown a correlation of HER-2 overexpression with
tamoxifen 41-44
and hormone therapy 25
- 45
resistance in breast cancer. Alternatively,
the poor prognosis associated with HER-2 overexpression may occur as a result of
increased proliferation and metastasis as indicated by other studies. 13,2446
In
another recent study, HER-2 overexpression was described as having both
prognostic and predictive value with regard to adjuvant therapy in patients with
lymph node positive breast cancer. 47
Other biomarkers, e.g., estrogen receptor,
high S-phase fraction, p53 mutation, may also contribute estimating survivals. This
together with our finding could be of potential clinical relevance by making choices
to alternative or more aggressive treatments available to selected patients.
In conclusion, in our retrospective study, we are the first to identify a potential
prognostic factor relating to the overexpression of HER-2 in plasma using an EIA
method, in women with MBC undergoing HDCT and ABSC transplantation. These
data need confirmation in a larger prospective study including a multivariate
analysis to discriminate whether or not this biomarker is an independent prognostic
factor. Evaluation of PFS and OS will also require possible correlation with other
biomarkers, e.g., MDR1, MRP, Topo II(, p53, BAG-1, which are all included in a
prospective study currently underway.
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