Editor’s Note
	Talmudic scholar

The first time I chatted with Craig Henderson was on a chilly Boston afternoon in 1986 in a pre-Starbucks era coffee shop. Sipping espresso, I needed every available caffeine molecule to follow the man's circuitous but fascinating train of thought.

At that time Craig was the resident breast cancer maven at Dana-Farber, and he and several other semi-maverick researchers had just turned breast cancer research on its ear. A recent NIH consensus conference had just blessed tamoxifen as adjuvant therapy for postmenopausal women, mainly based on Richard Peto's spectacular presentation of the first international breast cancer meta-analysis.

I have a grainy video of Peto's talk, which could realistically be labeled as one of the major turning points of contemporary oncology research. His eyes studiously avoid the attendees as he pushes them to focus on the data contained in his slides. However, he sneaks glances at the audience hoping to see if they follow.

Craig, Mike Baum and Peto were the ringleaders of the overview movement, which held its first trialists meeting at Heathrow Airport just a few months before the consensus conference. Like most great ideas, the basis for the overview was simple: modest improvements in important outcomes in common diseases with substantial mortality have great public health significance. In order to detect modest advances, large numbers of the key events must be measured - in this case breast cancer mortality. Thus the overview was born.

The Boston "coffee talk" was the first in a series of brain-numbing conversations I have had with Craig over the years, many of which have appeared in this audio series. Editing these serpentine and usually lengthy dialogues is like deconstructing a Russian novel. Craig once told me that he likens his and other research leaders' insatiable interest in breast cancer research minutia to the zeal of Talmudic scholars inspecting each word of the ancient text looking for hidden meaning. He often cites unplanned subset analyses of trials I haven't even heard of, and in this issue he educated me on the many variations of FAC, CAF and FEC like a wine connoisseur describing vintage Bordeaux.

The great thing about these conversations is that at the center of these volcanic data eruptions are usually some very simple, highly practical patient care strategies. No one has to agree with these conclusions - and I always receive a couple of emails from oncologists whose buttons are pushed by Craig's viewpoints - but I personally find his "pearls" very enlightening.

This most recent interview includes at least two such nuggets:

These two studies seem to have affected many research leaders who previously recommended up-front tamoxifen in spite of very encouraging efficacy and tolerability data from the 47-month follow-up of the ATAC study presented more than a year ago and published last November. It will be interesting to see if the ASCO Technology Assessment group comments on the new Canadian and Italian data.

The clinical research strategy of searching for modest improvements in outcome by either meta-analysis or launching huge studies like ATAC has perhaps had an unexpected outcome on individual breast cancer patients and their physicians. Today, we can say with reasonable confidence to women with even a 10 percent risk of relapse that systemic therapy can further lower that risk by a couple percentage points.

This has created vexing decisions not commonly seen in other areas of cancer care. One can now debate the advisability of, for example, receiving adjuvant chemotherapy for a one or two percent improvement in relapse rate or whether a woman should receive anastrozole or tamoxifen for a similar marginal gain, albeit with perhaps reduced toxicity.

In that regard, we have enclosed a report from a unique "Breast Cancer Patient Perspectives" project that we implemented last year to bring patients' opinions and thoughts into our audio series and other educational efforts. This monograph includes results from anonymous keypad polling of more than 700 breast cancer survivors at three town meetings. These women were presented with common adjuvant treatment decisions, and a nationally respected faculty of breast cancer research leaders discussed their take on the risk-to-benefit ratios of a variety of interventions, including clinical trial participation.

This initiative was in no way a scientific study but rather a living demonstration of the heterogeneity of patient perspectives on situations for which multiple acceptable evidence-based treatment options exist. As our CME group moves forward, we hope that the experience gained through this project and others like it will allow us to serve as a communication conduit for the key constituents in the breast cancer crucible - "Talmudic scholars" like Craig Henderson and other research leaders, community-based clinicians and the women who struggle daily with this disease.

-Neil Love, MD

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