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Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?

Koukourakis MI, Giatromanolaki A, Galazios G, Sivridis E - Br. J. Cancer (2003)

Bottom Line: We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy.In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively).Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr

ABSTRACT
Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10-20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angiogenesis, cancer cell proliferation, steroid receptor expression, c-erbB-2 oncoprotein overexpression, p53 protein nuclear accumulation or bcl-2 antiapoptotic protein expression, can predict failure of local therapy. We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy. In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively). In multivariate analysis, the microvessel density and the c-erbB-2 status were independent and significant factors related to local relapse (P=0.001, t-ratio 3.36 and P=0.02, t-ratio 2.26, respectively). Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression. High angiogenesis, however, was linked with local relapse regardless of the radiotherapy regimen.

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Kaplan–Meier survival curves stratified for radiotherapy schedule (conventional vs HypoARC).
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fig1: Kaplan–Meier survival curves stratified for radiotherapy schedule (conventional vs HypoARC).

Mentions: Out of 31 patients treated with HypoARC, four (12.9%) relapsed locally vs seven out of 40 (17.6%) of patients treated with CRT. The LRFS of patients treated with HypoARC or CRT is plotted in Figure 1Figure 1


Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?

Koukourakis MI, Giatromanolaki A, Galazios G, Sivridis E - Br. J. Cancer (2003)

Kaplan–Meier survival curves stratified for radiotherapy schedule (conventional vs HypoARC).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376345&req=5

fig1: Kaplan–Meier survival curves stratified for radiotherapy schedule (conventional vs HypoARC).
Mentions: Out of 31 patients treated with HypoARC, four (12.9%) relapsed locally vs seven out of 40 (17.6%) of patients treated with CRT. The LRFS of patients treated with HypoARC or CRT is plotted in Figure 1Figure 1

Bottom Line: We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy.In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively).Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr

ABSTRACT
Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10-20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angiogenesis, cancer cell proliferation, steroid receptor expression, c-erbB-2 oncoprotein overexpression, p53 protein nuclear accumulation or bcl-2 antiapoptotic protein expression, can predict failure of local therapy. We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy. In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively). In multivariate analysis, the microvessel density and the c-erbB-2 status were independent and significant factors related to local relapse (P=0.001, t-ratio 3.36 and P=0.02, t-ratio 2.26, respectively). Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression. High angiogenesis, however, was linked with local relapse regardless of the radiotherapy regimen.

Show MeSH
Related in: MedlinePlus