October 1, 2008 (Vol. 28, No. 17)
Battles in the War on Cancer Are Being Won
A recent Point of View article in GEN had a pessimistic outlook about whether a reported decline in cancer deaths is a true indicator of progress in the fight against this disease. I have a more optimistic outlook, and hopefully, this response will be a ray of hope for readers who may, themselves, be involved in a personal struggle with breast cancer or know someone who is.
When I attended my first cancer conferences in the late 1970s, there were bewildering panel discussions about therapeutic options for breast cancer patients. I specifically recall the presentations of four experts entrenched in debates with four opposing opinions about the same conditions, and I was glad not to have to choose which view I would personally accept.
The medical decision-making at that time was based on tumor size, lymph node involvement, and estrogen receptor status for the tumor. In fact, the view until quite recently was that if you had breast cancer, you would die from breast cancer.
In the early 1980s, I was privileged to begin a three-decade association with the multidisciplinary Henrietta Banting Breast Centre at Women’s College Hospital, University of Toronto. The early imaging radiologists of this institution accepted the U.S. Health Insurance Plan reports of reduced breast cancer mortality following mammography, and starting in the mid-1960s, implemented routine screening mammography for women beginning at age 35 years.
Any reason was a good reason to get a baseline mammogram and maintain regular screening mammograms. The results of this program—along with the introduction of other innovative therapeutic strategies—led to early reports of notable breast cancer survival for women with small invasive tumor sizes, generally detectable only with mammography and the increased detection of noninvasive breast cancer, ductal carcinoma in situ.
This work led to my fascination with the idea of competing risks in breast cancer patients, that the removal of breast cancer death for a substantial number of patients should lead to the observation of a substantial number of other deaths. If a woman has breast cancer detected and good treatment at an early point in its natural history, while it is noninvasive or at a small-size of invasive cancer, one would hope that such a woman would survive breast cancer to die of another disease. We found that this proved to be the case— about 50% of women diagnosed with breast cancer at 65 years or older died of another cause.
A recent report of results from a National Cancer Institute of Cancer Phase III trial evaluating five years of maintenance letrozole therapy and being disease-free after five years of tamoxifen indicated that nonbreast cancer deaths accounted for 60% of the 252 known deaths (72% for those 70 years or older, and 48% for those <70 years). The caveat is that a woman would need to be eligible for hormonal therapy, with hormone-receptor positive tumor.
Younger women, who tend to have hormone-receptor negative disease and shorter survival, were excluded from the trial. However, the majority of breast cancer is detected in older women, who have proportionately more hormone-receptor positive disease. Thus, the potential for death from other causes becomes increasingly important in older patients with breast cancer. The common diagnosis of breast cancer makes the ramifications important.
Breast cancer is a complex heterogeneous disease with a long natural history. Prospective breast cancer studies—especially in the adjuvant setting—may take a decade or more from inception to completion, during which multiple aspects of therapeutics may change.
Progress has been incremental in the multiple domains of earlier detection, surgery, adjuvant radiotherapy, chemotherapy, and hormonal therapy, and lately prognostic and predictive biomarkers that may inform about therapeutic options. Together with all these elements, substantive progress is noticeable. There is an increased prospect that a woman may survive breast cancer to die of another cause. It is now time for an increased medical awareness that such is the situation.
Judith-Anne W. Chapman, Ph.D. (JChapman@ ctg.queenssu.ca), is a senior biostatistician at National Cancer Institute of Canada’s Clinical Trials Group.