Adjuvant Therapy for Breast Cancer: Current Approaches and Strategies for a Better Future

Worldwide, breast cancer is by far the most frequent cancer affecting women, with over 1 million new cases each year, and the leading cause of female cancer-related deaths. During the past decade, substantial progress has been made in the treatment of breast cancer, due to focused collaborative efforts in education, practice, and research.

Mortality rates for women with breast cancer in the United States and other industrialized countries are decreasing for the first time, largely as a result of advances in the adjuvant treatment of early-stage disease. These advances have been credited to the introduction of newer, more effective agents, as well as the application of the principles of combination chemotherapy and hormonal therapy, and the introduction of targeted therapies based on the biology of the disease. Some of these strategies have been excellently summarized by Dr. Sledge in this issue of the journal, with many advances becoming a reality due to the leadership and lifelong dedication of physicians such as Dr. Martin Abeloff.

Shifting Research Aims

Dose escalation, dose intensity, dose density, and drug sequencing have all been investigated with the aim of optimizing therapeutic strategies. However, approximately 20% to 85% of patients diagnosed with early breast cancer (depending on initial stage, tumor biology, and treatment strategy) are still expected to develop recurrent and/or metastatic disease. Reasons for this outcome may include inadequate surgery or treatment, drug resistance, and/or evolution of tumor cells resistant to initial treatment. The problem is magnified in the setting of metastatic breast cancer, where > 70% of patients die within 5 years despite the availability of newer detection methods and therapies.

New and future strategies in the adjuvant setting are focusing on the identification of tumor and host (patient) profiles, and also on the development of sensitive monitoring methods to accurately and effectively tailor and modify therapeutic strategies. Research into the use of systemic adjuvant therapies has therefore shifted away from using risk as the sole determinant of benefit, to also evaluating predictors of therapeutic benefit for the individual patient.

Prognosis can be only modestly determined via clinical stage, but as molecular profiling of genes and proteins that may affect outcome (prognosis and response to therapy) becomes part of standard of care, our prognostic capabilities are undergoing a true revolution. In addition to tumor profiles, important patient factors now need to be considered, including pharmacogenetics, life expectancy, performance status, and end-organ (liver, renal, and cardiac) function. Another important area is cancer-based quality-of-life research, designed to gain insight into the impact of disease and treatment on clinical outcomes, in an effort to enhance the cancer patient’s well-being in both the short and long terms.

Conclusions

Further improvements in patient life expectancy and quality of life will depend not only on the principles described above, but also on education of medical personnel, government employees, and patients, so that optimal options and therapies are considered and discussed with all patients-independent of socioeconomic position or race. Dedication and focus related to the possibilities for a better future will allow us to follow the example of pioneers such as Dr. Abeloff; to evaluate and utilize the best science, and the best methodology for introduction of this science into translational research, and then bring new preventive and therapeutic strategies to optimize outcomes of persons at risk or who develop breast cancer.

As a parting note to Dr. Abeloff and his family: It is remarkable how great an influence a single person-in this case, a physician/scientist with the highest ethical standards-can have on the lives of others. Thanks for the example and the guidance.

-Edith A. Perez, MD

The main article can be found here: The New Millennium for Adjuvant Therapy in Breast Cancer.