Adjuvant chemotherapy in breast cancer: An expiration date?

Monday, June 20, 2011
One issue that confronts medical oncologists is the explanation of benefits from chemotherapy, especially in women newly diagnosed with breast cancer. Clinical trials have demonstrated the survival benefit of multi-agent chemotherapy with the commonly reported hazard ratio used to explain such benefits, and the assumption that this benefit is sustained over the time a patient is alive (ie, it is proportional). For example, if a treatment is associated with an improvement in survival, with a hazard ratio of 0.75, the general assumption is that the relative benefit of 25% will be realized one, two, three, five, and ten years following treatment.

In a commentary published in the Journal of Clinical Oncology, Ismail Jatoi and colleagues question whether or not the assumption above is true.1 Citing both trials and overviews on the adjuvant treatment of breast cancer, they make the credible observation that adjuvant treatment results in a non-proportional benefit; that adjuvant therapy helps by reducing recurrence and risk of death, but only in the first 4 years after diagnosis. In essence, they suggest that the benefits of treatment are not static (or "proportional") but rather lessen as time goes on. In other words, the benefits of chemotherapy may have an expiration date.

While facetiously stated, it is also not entirely accurate. One of the overviews cited by Jatoi is performed by the Early Breast Cancer Trialists Group (EBCTG) and Jatoi acknowledges one of the most important findings reported: that the benefits of treatment on breast cancer mortality is sustained over 15 years. While the magnitude of the benefit may fluctuate, the benefit is still seen.

So, How do we go about communicating this information? Well, the highest risk of death following diagnosis is within the first 4 years. This is essentially the same time frame where adjuvant chemotherapy works, so in my opinion, the discussions on the benefits of adjuvant chemotherapy still ring as true. In a period of critical risk, treatment can be given. This is still very heartening news. In addition, the follow-up on adjuvant clinical trials is limited by the practical factors involved in clinical research: to power a study to overall survival takes more participants than one powered for relapse free survival, and if that endpoint was extended to 15 years, even more patients may be required.

For now, we must engage patients in an open and honest discussion and do our best with the information provided. We can use tumor characteristics to gauge risk of relapse without treatment, data on chemotherapy to personalize the individual benefits, and acknowledge that treatment benefits are most realized early as opposed to life-long. Ultimately, every decision related to cancer and its treatment must remain as it has always been- a decision based on informed judgment representing the collaboration between the patient and her team.

1. I Jatoi, et al. J Clin Oncol 2011; Published on line, May 2011.

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