Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy

Abstract

Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.

Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells

“…Bcl-2 protein expression is elevated in tissue samples from patients with residual breast tumor after the completion of treatment (Ellis et al, 1998), which indicates that Bcl-2 may be associated with chemoresistance in breast cancer cells. Interestingly, we found that 435B cells are more resistant to chemotherapyinduced apoptosis than parental 435 cells.…”

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

“…Reactivity was detected by an ABC -peroxidase -antiperoxidase (PAP) method, and scored according to the method described by Going (1994). A change of 440% between different paired biopsies was taken as being meaningful (Ellis et al, 1998;Iqbal et al, 2002) and a value of o1% was regarded as indicating a lack of proliferation.…”

The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer

“…Although these studies have produced partially conflicting results, it is apparent that higher pre-therapy proliferation is associated with a better response and that a significant fall in Ki67 occurs following neoadjuvant chemotherapy [6,7]. We have previously shown for neoadjuvant endocrine therapy, that Ki67 assessment performed in samples already exposed to therapy more accurately predicts outcome than its assessment in pretherapy biopsies, but this is not known for chemotherapy [8].…”