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

Abstract

Patients undergoing primary chemotherapy for invasive breast cancer consented to a core biopsy of the invasive breast primary preand 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 ¼ 0.6, (Po0.001). A significant rise in AI (Po0.001), and fall in Ki67 (P ¼ 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 ¼ 0.31, Po0.025). 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.

Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

“…However, investigations that have studied the importance of apoptosis in human solid tumors have been sparse. Studies of cervical cancer have found the baseline apoptotic index of the malignant cells to be prognostic of clinical response to chemotherapy (26) and overall survival (27). The determination of baseline apoptotic index in breast cancer has been investigated but without definitive indication on the appropriate therapeutic implications of these information (26,27).…”

“…Studies of cervical cancer have found the baseline apoptotic index of the malignant cells to be prognostic of clinical response to chemotherapy (26) and overall survival (27). The determination of baseline apoptotic index in breast cancer has been investigated but without definitive indication on the appropriate therapeutic implications of these information (26,27). Therefore, determining the importance of therapy-induced apoptosis in solid tumors currently remains a relatively unexplored area of clinical research.…”

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

“…It is also worth noting that the tumour morphology after treatment will be determined by factors in addition to proliferation, such as cell loss. In this respect, although Ki67 is a primary marker of proliferation, it can also be a secondary reflection of cell death (Archer et al, 2003).…”

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].…”