Moderate neutropenia with adjuvant CMF confers improved survival in early breast cancer

Abstract

Despite the extensive literature clearly demonstrating the survival benefit for adjuvant chemotherapy in women with operable breast cancer, there are few data confirming this in routine practice. Some studies have suggested that not all women gain to the same extent, with older women showing a smaller benefit and lower doses achieving poorer outcomes. We therefore reviewed the case notes of 750 women treated over a 15-year period at The Edinburgh Cancer Centre with the same intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) regimen, to identify patient- and treatment-related factors influencing outcome in routine practice. The actuarial 10-year survival for these women was 59.3%, with the anticipated poorer outcome for those with more involved ipsilateral axillary nodes, higher grade and ER-negative tumours. There was no evidence that a lower delivered dose intensity or older age at presentation resulted in a poorer survival. Of particular interest was the observation that 45% of patients who had grade 2/3 neutropenia had a 10% absolute survival advantage over those with no neutropenia (P<0.001). This strongly suggests that some degree of neutropenia has more influence on outcome than age or delivered dose intensity.

Figure 1

Breast-cancer-specific overall survival for all 750 patients treated with three-weekly i.v. CMF.

Figure 2

Breast-cancer-specific overall survival by number of involved axillary nodes (P<0.0001).

Figure 3

Breast-cancer-specific overall survival by number of courses of CMF administered (P=0.009).

Figure 4

Breast-cancer-specific overall survival by average dose intensity for patients completing six courses of CMF chemotherapy (P=NS).

Figure 5

Breast-cancer-specific overall survival by maximum recorded grade of neutropenia (P<0.001 for grade 2 and 3 combined vs grades 0, 1, and 4 combined).