The Advantages and Disadvantages of Adjuvant Chemotherapy for Breast Cancer
Data presented at the San Antonio Breast Cancer Symposium show that basically all women with HER2+ breast cancers benefit from adjuvant chemotherapy/Herceptin due to their worse prognosis. In my mind, however, there is no more controversial area in breast cancer than in which patients truly benefit from receiving adjuvant chemotherapy, among women who are (1) postmenopausal and (2) have small, low grade, node negative, ER+ and Her2- breast cancers which generally have a high cure rate, made higher with hormonal therapy. How much will adjuvant chemotherapy help?
This is a situation where I'm on the side that we clearly overtreat women with good prognosis cancers for a very small, if it even truly exists, increase in the chance of cure. Adjuvant!
Online is a computer program used by most breast oncologists to predict the benefit of chemotherapy. Much of the time it is useful, particularly for node positive breast cancer. There are several reasons, though, why I think it overestimates the benefit of adjuvant chemotherapy in small, node negative, ER+ breast cancers in postmenopausal females. It does not segregate the breast cancers biologically, nor does it necessarily incorporate the Her2 negative status or growth fraction (e.g. Ki67). It is based in part on best available data, but not complete data.
It is interesting how switching between less aggressive to more aggressive chemotherapy regimens can make it seem like there is an increase in cure rate for these patients, when no clinical trial data would support this.
Lastly, the computer program is, in fact, a series of mathematical models that extrapolates (i.e. estimates based on mathematical formulas) a potential benefit of adjuvant chemotherapy. This extrapolation may not be accurate in this patient population.
Several randomized clinical trials did show a benefit to adjuvant chemotherapy in these women, but if I recall, these trials used adriamycin/cytoxan at a time when we did not subset by HER2 positivity - therefore women who are ER+ Her2- may not have derived any benefit. All the benefit in these trials may have been amongst the HER2+ breast cancer patients, who now would be offered Herceptin/Chemotherapy. And the current favorite regimen for these women is taxotere/cytoxan rather than adriamycin cytoxan. Supporting the "no chemotherapy" position are several randomized clinical trials in recent years showing that these women get no increase in their cure rate from chemotherapy. One I recall did not even show any variation in benefit as the size of the cancer increased, and an accompanying editorial by breast oncologists at Johns Hopkins provided very interesting commentary.
It is for these reasons that I read with great interest an article by Hassett and others that examined how frequently academic breast oncologists offered chemotherapy to these patients. They looked at how frequently women with these good prognosis breast cancers were given adjuvant chemotherapy at eight prominent academic medical institutions. The basic summary of this article was that there was a fair amount of disagreement among the experts. The range of women offered chemotherapy varied from roughly 40% to 80% depending on which of the eight academic medical centers the patient was seen at. So in this situation, with a difficult decision where the answer is unknown, even the experts disagree....