Editor’s Note
	Visionary

Last fall I had the pleasure of interviewing legendary cancer research leader Dr Aron Goldhirsch for our sister series for medical oncologists. During this conversation about the International Breast Cancer Study Group that Aron heads, I happened to mention a little-noticed Italian study published in 2001 by Dr Francesco Boccardo. Aron perked up immediately at the mention of the paper. “Boccardo is a visionary,” he exclaimed. “He has always been two steps ahead of the rest of us.” Dr Goldhirsch’s comments about his colleague came to mind when I began to gear up for the 2003 San Antonio Breast Cancer Symposium. Our education group invited Dr Boccardo to participate in one of the “Meet the Professor” sessions we hosted during the conference, and he was gracious enough to accept.

As I stood in front of an audience poised to ask questions, I felt compelled to relate Aron’s accolades. Dr Boccardo took the podium, smiled and almost blushed. After a modest quip to offset his embarrassment, he answered the many questions from the audience in the cautious and very thoughtful manner for which he is known. Our “Meet the Professor” session took place one day after Boccardo had made a plenary presentation of a study that randomly assigned postmenopausal women on two to three years of adjuvant tamoxifen to either complete five years of therapy or be switched to anastrozole (Arimidex®).

Women who switched to the aromatase inhibitor had fewer relapses and longer survival. In the enclosed program, Dr Boccardo reviews the data demonstrating an advantage for anastrozole and his reflections on the many treatment strategies he has pioneered in the last two decades — five years of tamoxifen, tamoxifen in postmenopausal women, ovarian suppression in premenopausal women, chemotherapy plus tamoxifen, and now anastrozole after two to three years of tamoxifen.

Also during the San Antonio meeting, Dr Paul Goss presented the results of a study demonstrating an advantage to another aromatase inhibitor, letrozole (Femara®), compared to placebo after five years of tamoxifen. A third study has been subsequently published in the New England Journal of Medicine, documenting an advantage to switching to another aromatase inhibitor, exemestane (Aromasin®), after two years of tamoxifen.

In this program, Dr Craig Henderson comments that all of this accumulating evidence points in the same direction — aromatase inhibitors clearly seem superior to tamoxifen in postmenopausal women, and the role of tamoxifen in the adjuvant setting for these women (if any) will likely require redefinition. Dr Henderson and many other research leaders believe that the optimal strategy is to start with the most effective therapy; therefore, he uses up-front aromatase inhibitors.

While the aromatase inhibitor story is rapidly unfolding, this issue of our series also discusses two other research concepts that are worthy of attention. Seema Khan reviews a plethora of clinical research questions in breast surgery, but one of the most interesting to me was a paper she and her colleague, Monica Morrow, published on the role of primary breast surgery in women presenting with metastatic disease. To the surprise of many, this retrospective yet very convincing analysis of SEER data demonstrated a survival benefit in women who had their primary tumors resected.

This paper is just one of a number of recent data sets that focus greater attention on the importance of local tumor control with both surgery and radiation therapy in determining long-term outcome. Perhaps we will eventually see that the blacks and whites of Halsted and Fisher are actually more of a continuum of grays.

Finally, I interviewed the investigator who presented the most talked-about paper at the San Antonio meeting, Soonmyung Paik. His study of a genomic profiling assay of tumor tissue from participants in the classic NSABP-B-14 trial suggests that this new tissue assay may be able to identify a substantial fraction of women in whom the incremental gain from chemotherapy will be so small that it can be avoided.

Dr Paik also commented on two other current tissue assays that are critical in breast cancer management — HER2 and estrogen/progesterone receptor. Many studies have documented a wide variation in quality control in performance of these evaluations in community laboratories. The importance of accurate measurement of ER/PR in initial primary surgery has been known for two decades but the significance of HER2 has only recently been appreciated. Not only is this assay critical to entry in the current ongoing adjuvant trastuzumab (Herceptin®) trials, but oncologists consider this result in determining prognosis and selecting chemotherapy and endocrine treatment. Dr Paik discusses recent NSABP work clearly documenting that the volume of HER2 testing performed by a laboratory directly correlates with quality control.

The concept of a research “visionary” is interesting to consider. Obviously, endocrine “mavens” like Boccardo saw long before any of us the potential value of these agents. But the truth is that many promising research concepts will fail to live up to expectations. We all must hope that research leaders look past these failures and continue to pursue what their minds’ eyes see, so that we all can benefit from a new generation of treatment paradigms.

— Neil Love, MD

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