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Comparative Study
. 2003 Sep 15;89(6):1035-41.
doi: 10.1038/sj.bjc.6601173.

Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer

C D Archer  1 , M Parton, I E Smith, P A Ellis, J Salter, S Ashley, G Gui, N Sacks, S R Ebbs, W Allum, N Nasiri, M Dowsett
Affiliations
Comparative Study

Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer

C D Archer et al. Br J Cancer. .

Abstract

Patients undergoing primary chemotherapy for invasive breast cancer consented to a core biopsy of the invasive breast primary pre- and 24 h postchemotherapy. The resulting tissue was analysed for apoptosis, Ki67, ER and HER-2 using immunohistochemical techniques. These data were then used to evaluate the relationship between these biological markers and response to chemotherapy and overall survival. Response rate to chemotherapy in this group was 86%, 16 patients (25%) achieved a clinical complete response and 41 (63%) a partial response. Prechemotherapy there was a significant correlation between Ki67 and apoptotic index (AI), r=0.6, (P<0.001). A significant rise in AI (P<0.001), and fall in Ki67 (P=0.002) was seen 24 h following chemotherapy. No relationship was seen between pretreatment AI and clinical response, but higher Ki67 and growth index (Ki67/AI ratio, GI) did correlate with clinical response (both r=0.31, P<0.025). No correlation was seen between the change in AI or Ki67 at 24 h and clinical response or survival. Significant changes in apoptosis and proliferation can be demonstrated 24 h following chemotherapy, but these changes do not relate to clinical response or outcome in this study. Pretreatment proliferation and GI are however predictive of response to chemotherapy in breast cancer.

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Figures

Figure 1
Figure 1
Correlation of pretreatment Ki67 and AI scores. Each data point represents the scores for an individual tumour (rho=0.60, P<0.001).
Figure 2
Figure 2
The percentage change in Al (A), Ki67 (B) and GI (C) in core biopsies 24 h after chemotherapy (n=60). The scores have been divided to show a fall to the left of the line and a rise to the right, (A) AI, P<0.001, (B) Ki67, P=0.002, (C) GI P<0.001).
Figure 3
Figure 3
Scattergram illustrating the relationship between change in AI (A), Ki67 (B), GI (C) and clinical response. Each dot is a value for a tumour and the horizontal line is the median value. PD, progressive disease; NC, no change
Figure 4
Figure 4
Overall survival curves for patients according to pretreatment tumour growth indices (GI) (low GI<28.5 (median value) and high GI >28.5), and change in GI 24 h after chemotherapy (low change in GI <53.4 (median value), and high GI >53.4).
See this image and copyright information in PMC

References

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