Relationship of variations in tumor cell kinetics induced by primary chemotherapy to tumor regression and prognosis in locally advanced breast cancer

Abstract

The relationship of changes in 3H-thymidine labelling index (TLI) induced by primary chemotherapy to tumor response and relapse rate in 36 patients with previously untreated locally advanced breast cancer (LABC) was analyzed. All patients received primary chemotherapy (3 cycles FAC), followed by mastectomy and subsequent adjuvant chemotherapy (3 FAC alternated with 3 CMF). Tumor TLI was evaluated immediately prior to primary chemotherapy and at the time of mastectomy. Median pretreatment TLI was used to discriminate between tumors with a high or low proliferative rate. Clinical objective response to primary chemotherapy was 83% in patients with high TLI and 56% for those with low pretreatment TLI (p = 0.06). Primary chemotherapy induced a > or = 50% reduction of the proliferative rate in 83% and 39% of the tumors with high and low pretreatment TLI, respectively (p = 0.006). Patients were classified into 4 groups according to TLI values both before and after primary chemotherapy: patients who remained in the high TLI group after primary FAC had the highest response rate (100%) and the lowest 2-year relapse rate (20%). These data suggest that: a) improved response to aggressive cytotoxic treatment occurs in tumors with high TLI at diagnosis; b) there is a significant correlation between TLI changes induced by primary chemotherapy and pretreatment proliferative activity; c) patients who remain in the high TLI group after primary chemotherapy are more likely to benefit from subsequent adjuvant systemic therapy.

Chemotherapy Is More Effective in Patients with Breast Cancer Not Expressing Steroid Hormone Receptors

“…Conversely to the method used to choose an adjuvant systemic therapy regimen, the selection of preoperative therapy does not commonly take into account biological characteristics of the tumor. In fact, very few features were tested as predictors of preoperative treatment response indicators, including diameter of the tumor (20) and in very few patients MIB-1 increased expression (17,21) or proliferative index (22,23). A large experience on factors predicting response in the preoperative setting was published recently and is based on a retrospective analysis of the National Surgical Adjuvant breast and Bowel Project B-18 study (24).…”

Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer

“…Both primary endocrine (Clarke et al, 1993) and cytotoxic treatments (Daidone et al, 1991;Gardin et al, 1994) inhibit tumour growth. Tumour cell proliferation has been shown to be a prognostic marker in some reports (Remvikos et al, 1989;Bonetti et al, 1996;Chevillard et al, 1996), but data on its predictive value are conflicting.…”

Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi

“…Similarly, previous clinical trials assessing S-phase fraction by flow cytometry demonstrated better clinical response to primary chemotherapy in tumours showing a high S-phase fraction (Spyratos et al, 1992;O'Reilly et al, 1992;Belemboago et al, 1992;Remvikos et al, 1993). Surprisingly, the few clinical trials using the tritiated thymidine labelling index (TLI) as a method of assessing tumour proliferation did not show a significant difference for tumour response in tumours with a high TLI (Bonadonna et al, 1990;Daidone et al, 1991;Gardin et al, 1994 Predictive value of 'c-erbB-2 overexpression' Chemosensitivity and overexpression of c-erbB-2 in human breast carcinoma is a matter of controversy (for review see Klijn et al, 1993). In our series c-erbB-2 was not a predictive factor for chemotherapeutic-induced tumour reduction or tumour resistance.…”