New adjuvant strategies for breast cancer: meeting the challenge of integrating chemotherapy and trastuzumab (Herceptin)

Abstract

Improvements in breast cancer treatment will arrive with better understanding of its biology and through biologically oriented therapeutic interventions as well as better identification of patient populations susceptible to benefit from classical therapies (endocrine and chemotherapy). Among the new chemotherapies, the taxanes have emerged as powerful agents in the treatment of metastatic breast cancer and a strong emphasis has been pursued into their development in the adjuvant setting. Two generations of adjuvant pivotal trials with taxanes have been developed. The first generation compared taxane/anthracycline regimens to nontaxane combinations or sequence regimens. The second generation of trials is presently being performed and contains taxanes in both arms, comparing their use in combination or in sequence. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) is the first biologic modifier with significant activity in advanced breast cancer patients amplifying the HER2 gene. As a consequence of these results, including improved survival in the metastatic setting, this agent has been very quickly considered for adjuvant development. However, the significant cardiac toxicity observed with trastuzumab/anthracycline combinations has led to two main strategies for integrating trastuzumab in the adjuvant setting: (1) addition of trastuzumab to mostly anthracycline-based programs (sequential approach); and (2) biology-oriented strategy based on synergism between trastuzumab and chemotherapy agents. Large-scale clinical research programs are presently being developed and will create a challenge for clinical researchers. The adequate scientific hypothesis, related to the pivotal studies of trastuzumab in the adjuvant setting, require large sample sizes (several thousand patients) and a very strict selection of the patient population (tumors amplifying the HER2 gene). Success in a timely fashion requires global collaboration, dedication to high-standard clinical research, and awareness of all available protocols by oncologists and patients with breast cancer.