Is there a standard type and duration of adjuvant chemotherapy for early stage breast cancer?

SummaryAdjuvant chemotherapy clearly reduces the odds of subsequent breast cancer recurrence, metastases, and mortality. There are three main areas of interest regarding adjuvant chemotherapy: (1) Should everyone receive it? (2) Is there an optimal regimen for everyone or selected individuals at this time? And (3) Can we improve on existing regimens?A multitude of investigations from around the world have addressed the three questions raised above. Increasingly we are able to identify both those patients most likely to need adjuvant chemotherapy (prognosis) and, perhaps, those most likely to benefit from it (prediction). In this regard, web-based, multi-factorial calculators, best exemplified by Adjuvant!, permit a patient and her caregiver to estimate her absolute odds of benefit from chemotherapy, thus better informing women in their assessment of benefits and risks (http://www.adjuvantonline.com/index.jsp). The answer to the next question, whether there is an optimal regimen, dose, and schedule of adjuvant chemotherapy, is, frankly, “no™. Clinical research over the last four decades has strongly suggested the following principles:
• Combination chemotherapy appears to be superior to single agent, although ongoing clinical trials are re-addressing this issue.
• Multiple cycles of chemotherapy are superior to a single peri-operative course. Furthermore, there appears to be an optimal duration of therapy, although this has not been well-defined.
• “Modern™ chemotherapy including an anthracycline and a taxane appears to be superior to the CMF regimen. However, the “best” combination has not been proven.
• There is a dose response curve with increasing benefit up to an optimal dose level, but this curve appears to plateau. Further dose escalation, at least for cyclophosphamide, anthracyclines, and the taxanes, or very high doses of combination therapies which require bone marrow stem cell transplantation, is of little benefit.
• Dose-dense chemotherapy (every one or two weeks) may be superior to less frequent scheduling (every three weeks), although this strategy may be class or even agent specific.In summary, it is clear that adjuvant chemotherapy is beneficial for women with early stage breast cancer, and it is clear that selected regimens, based on specific agents, cumulative and cycle-specific dose, and schedule may affect the relative efficacy. It is not clear which patients are most likely to benefit from any adjuvant chemotherapy at all, or from specific strategies. Thus, at this time there is no single standard type or duration of adjuvant chemotherapy, and physicians should choose from regimens that have proven benefit as demonstrated in randomized Phase III trials.