The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma

Abstract

S_ary The use of chemotherapy as a form of primary treatment for breast cancer is increasing and, as a result, more resection specimens contain tumours which have been exposed to cytotoxic drugs. We have studied the effects of chemotherapy on the tumour morphology and various biological features of breast carcinoma in a group of 35 patients. These were a group who responded to treatment in a clinical study of the use of primary chemotherapy designed to reduce tumour bulk prior to surgery. Characteristic morphological changes, temporally related to the administration of cytotoxic agents, are seen. The malignant cells become enlarged with vacuolated cytoplasm and vesicular nuclei containing prominent nucleoli; occasionally the nuclei were angular and hyperchromatic. These features are interpreted as degenerative in nature. In 15 cases sufficient material was present in the pretreatment biopsies to compare the grade of the tumours before and after chemotherapy: changes were found in six tumours. Cytotoxic drugs do not induce a consistent pattern of change in the proliferation and apoptotic indices of individual tumours, but there is a tendency to reduce proliferative activity over all the tumours as a group. It was also found that chemotherapy is capable of modifying the expression of the oncoproteins c-erbB-2 and p53 in a minority of cases of breast cancer, usually resulting in an acquisition of immunoreactive oncoprotein. It is important to be aware of these effects when studying breast carcinomas removed after chemotherapy.

HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy

“…Breast cancer cells that survive adjuvant treatment may undergo genetic changes resulting in either a loss or gain of expression of some biological markers. 27 The greater genetic instability of these cells during the disease progression and as consequence of adjuvant endocrine therapy 28,29 and/or chemotherapy 30 could also explain the greater frequency of discordance in HER-2 status between primary tumour and local recurrence or metastasis highlighted in groups C and D with respect to group A.…”

Profiles of brain metastases: Prioritization of therapeutic targets

“…It has been suggested that the loss of hormone receptor expression is due to dedifferentiation of the metastatic tumor29 or the selection of cytogenetically unique clones that have an enhanced propensity to metastasize to distant sites 30, 31. Alternatively, the loss of hormone receptor expression in breast cancer patients may represent selection bias as a result of treatment 32. Brain metastasis is a late event in hormone receptor‐positive breast cancer.…”

Breast Cancer With Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis

“…During disease progression, this particular clone evolves, expands, and forms metastatic deposits that are genetically different from the majority of cells in the primary tumor [34]. Prior treatment such as chemotherapy may also elicit changes in HR status [35]. It is certainly possible that in a small percentage of cases, the discordance is solely the result of suboptimal reproducibility of the measurement methods.…”