S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer

Abstract

Summary Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.

Cyclin A as a Predictive Factor for Chemotherapy Response in Advanced Head and Neck Cancer

“…Supporting this, our present and other results published previously (30) identify a direct association between high levels of CA and Ki-67, a cell proliferation marker. Proliferating cells are more sensitive to chemotherapeutical agents, and a positive correlation between proliferation rate and quality of prognosis after chemotherapy treatment has already been noted in other malignancies such as breast cancer, melanoma, and lymphoma (31)(32)(33). Moreover, in vitro experiments have shown that CA correlates with the sensitivity of human cancer cells to the cytotoxic effect of 5-fluorouracil (34), further supporting our observations.…”

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

“…Despite this, no correlation between cyclin A activity and response rate, TTP and OS calculated from the start of chemotherapy was found. A previous study from a randomised trial comparing adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) to radiotherapy in primary breast cancer showed that the benefit from chemotherapy was more pronounced among patients with tumours with a high S-phase fraction (Stal et al, 1994). Thus, the strong contrast between the adverse prognostic impact of a high proliferation rate from diagnosis of the disease, but not after start of aggressive chemotherapy, may indicate that chemotherapy has improved the course of the disease, especially in highly proliferating tumours.…”

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients

“…A similar correlation between a high proliferation rate and improvement of prognosis by CT has previously been noted in other malignancies including breast cancer, melanoma and lymphoma. (Joensuu et al, 1994;Stål et al, 1994;Hahka-Kemppinen et al, 1997).…”