Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy

Abstract

Summary Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation. but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with prinmary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

“…The same negative results were reported in the literature concerning p21 in the only report that dealt with patient age, 6 in all five studies concerning hormone receptor status, 59 -61,87,88 in one of three studies concerning lymph node status, 60 in one of two studies concerning tumor size, 60 in two of six studies concerning Scarff-Bloom grade, 59,60 and in three of six studies concerning p53. 59,61,89 The results were different concerning mitotic activity and in both studies that correlated p21 with mitotic activity. 61,89 p53 was correlated with histologic grade, hormone receptor status, mitotic activity, SPF, Ki-67, and cyclin A.…”

Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients

“…However, it has also been concluded that p53 mutation or accumulation predicts poor response to tamoxifen (14,48). The results in the present study demonstrated that the patients with both normal and altered p53 status appear to have a good response to tamoxifen.…”

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

“…Also, survival in patients with stable disease of greater than 6 months duration is similar to that of patients that achieve a PR to treatment (Manni et al, 1989). Others groups studying similar patients defined ÔresponseÕ as CR + PR + SD of more than 6 months duration (Wright et al, 1992;Klijn et al, 1993;Archer et al, 1995;Berns et al, 1995;Elledge et al, 1998), and most demonstrated that overexpression of c-erbB2 reduced the response rate to endocrine therapy in advanced breast cancer.…”

“…Two studies reported that c-erbB2 overexpression did not alter response to hormonal therapy (Archer et al, 1995;Elledge et al, 1998). The former was based on fewer than 100 patients and so lacked statistical power.…”