Reduced dose anthracycline post-breast cancer surgery has no effect on outcome

Jul 20 2008

Canadian researchers have discovered that there is a low risk of adverse effect from reducing post-op chemo by up to 25%, according to findings published in the online journal ecancermedicalscience.

The study, undertaken at the British Columbia Cancer Agency, Vancouver, found that women with early stage breast cancer treated with up to 4 courses of standard adjuvant anthracycline showed no relationship between dose intensity and clinical outcome, despite nearly a decade of follow-up.

Between 1990 and 1995, 484 patients were assessed in 4 groups: 1- all cycles delivered at full dose and on time; 2- one single dose reduction or dose delay; 3- >1 dose reduction or dose delay; and 4- <2 cycles of chemotherapy delivered. With an average follow-up of 9.6 years, the researchers found no significant differences in relapse-free survival, breast cancer-specific survival, or overall survival between the 4 groups.

Reductions in the dose intensity (DI) of adjuvant anthracycline based chemotherapy in early stage breast cancer are frequently required due to treatment toxicity or poor tolerance, but the implications of a minimal reduction in DI on clinical outcome remain uncertain. Side effects from the therapy can include nausea, fever, weight fluctuations, low white blood cell count and general fatigue.

Lead author Dr Anna Tinker noted that "while there is a breadth of chemotherapy options (e.g. anthracycline based, anthracycline and taxane based, dose dense) the anthracycline based regimen remains a commonly used form of chemotherapy. It may be considered as the sole treatment modality in low risk, endocrine non-responsive disease, or more often, it will form part of a treatment plan such as AC for 4 cycles followed by a taxane, with or with out subsequent hormone therapy or trastuzumab. Therefore, it is important to understand the possible impact of dose modifications of AC therapy on clinical outcomes".

Recognising a threshold effect of both cumulative dose and dose intensity of anthracyclines, and in light of emerging evidence that dosing schedules may impact on outcome in women with node positive breast cancer, oncologists are often concerned that any single dose modifications or delays will compromise clinical benefit. Oncologists are known to utilise haematopoietic growth factors if dose reductions or delays in adjuvant anthracycline based chemotherapy have been required. Recent data also suggests that chemotherapy dose intensity may be particularly important for patients with ER(-) disease.

However, this retrospective population-based analysis of women with early stage breast cancer treated with up to 4 courses of standard adjuvant AC has not identified a relationship between DI and clinical outcome. When endocrine responsiveness was considered no difference in outcome was appreciated between the 4 groups.