Editor's Note Dr Piccart’s mother

In 1990, I was honored to receive an invitation to Oxford University to attend and observe the second meeting of the Early Breast Cancer Trialists' Collaborative Group. The renowned research leaders who comprised this esteemed group had been invited by Richard Peto to hear the initial results of the second breast cancer overview. Peto has always been a bit of a maverick — he reminds me of the smart kid in school who diverts attention away from his intelligence and ability by getting into trouble. A perfect example of this mischievous inclination was our accommodations in Oxford. Peto had arranged for all the trialists — a group well-accustomed to high-end hotels — to stay in the Oxford dorms.

Similarly, he also sent out a questionnaire prior to the meeting asking everyone to predict what the data would demonstrate. During the two-day meeting he put up transparencies (he still doesn't like slides or PowerPoint) of these predictions, which he then gleefully destroyed one point at a time with his data. During the meeting, I met Peto and asked if he would allow me to interview him on his next trip "across the pond."

Some time after that, I noted that Sir Richard (actually, knighthood had not yet been bestowed) was giving the kick-off lecture at the New York Metropolitan Breast Cancer Group annual meeting. I inquired about an interview and Peto agreed to be recorded after his talk. For the New York recording — and all subsequent interviews he has done for this series — Peto refused an honorarium, but I also learned he would not specifically commit to when, where and even if we would definitely do the interview. I flew my production crew to New York, reserved a meeting room and set up a mini-recording studio anyhow.

Immediately after his lecture — which exceeded the allotted time limit by 30 minutes and might have gone longer were it not for moderator Larry Norton almost dragging Peto off the stage — I approached Sir Richard, who was chatting with Larry near the podium. Peto was up for the interview; however, he indicated that he would rather do it right there at the podium area. As our production people scrambled to get things set up, on an impulse, I asked Larry to join the recording session.

What followed was one of the most electrifying moments of my career. I felt like a high school basketball player shooting hoops with Michael Jordan and Shaquille O'Neal. For years, Larry would tell me that many people would approach him and comment on the exceptional quality of the program. It has been 14 years since that once-in-a-lifetime interview.

At the 2004 Miami Breast Cancer Conference, a similar unplanned and memorable event occurred. For quite some time I have been trying to interview Martine Piccart. We finally managed to arrange an appointment just after she completed her last lecture at the meeting and just before she was to return to Belgium. As Dr Piccart and I headed toward the interview room, we happened to pass Larry who was also in town serving as part of the conference faculty. Larry always arranges very tight flight schedules, and we had previously made the decision to delay our annual interview until ASCO where we would have more time together.

As we exchanged pleasantries, Larry mentioned that his flight was delayed and asked if I wanted to chat. Remembering the prior Peto-Norton extravaganza, I made the instantaneous decision to set up "round two," this time with Larry and Martine. The result — in this issue — was no less interesting than the interview with the original duo.

After Larry buzzed out to the airport, I continued chatting with Dr Piccart. Toward the end of the interview I decided to ask one of the questions that I love to ask pioneers in the field. I inquired why she entered the field of breast oncology. To my surprise, she told me that more than 20 years ago her mother was diagnosed with multiple node-positive breast cancer and received CMF for a year and then tamoxifen for 10 years. Miraculously, the tumor never recurred. But unfortunately, endometrial cancer was later diagnosed — perhaps as a consequence of the tamoxifen — and currently Martine's mother is being treated with an adjuvant aromatase inhibitor for a second primary tumor.

Listening to this story, and seeing the pain on Dr Piccart's face as she described the long year her mom spent on CMF, I thought about the ebb and flow of breast cancer research since finishing my fellowship in 1977. At that point, endocrine therapy was the "kinder, gentler" palliative therapy for metastatic disease. Most oncologists assumed it would never have an impact in the adjuvant setting, let alone for women at increased risk.

In 1985, Peto and the overview crushed that assumption, but the evidence of endometrial cancer that emerged in 1992 tempered our enthusiasm. By 2001 a new alternative was appearing — aromatase inhibitors (AIs) — in the form of ATAC and anastrozole. And a bit more than two years later, we are now also seeing evidence of the superiority of AIs after two and five years of tamoxifen.

In a 2001 San Antonio lecture right after Mike Baum presented the ATAC results, Craig Jordan quipped during a presentation, "Tamoxifen — the gold standard of breast cancer therapy... until yesterday." This prescient remark points directly to the fact that a new adjuvant player had started to make its way through the trials and tribulations of reaching acceptability.

Will this life cycle of a targeted treatment that starts out as palliative therapy for advanced disease and ends up having a dramatic impact on survival as adjuvant therapy exemplified in the story of Dr Piccart's mother and the AIs be repeated in breast cancer? Many observers believe that this can and will happen and that the leading candidate is trastuzumab. Maria Theodoulou comments in this edition on several major large adjuvant trials in women with HER2-positive tumors. The hope and expectation we all share is that these studies will demonstrate the same kind of meaningful impact that has already been shown with endocrine interventions in women with ER-positive tumors.

The excitement about HER2-positive disease management is also evident in Dr Piccart's discussion of women with liver-only metastases. She has referred a number of these patients for hepatic resection after significant treatment responses to trastuzumab. She also notes the increasing number of patients who have excellent peripheral disease control but CNS disease progression, and she speculates that this will be an important feature to analyze in the emerging adjuvant trastuzumab trial results.

Also in this program, Kent Osborne discusses the evolving research from his lab and others on the interconnection between pathways for HER2 and estrogen receptors. He suggests that a useful strategy to evaluate in clinical trials would be combining interventions that affect both systems. A number of ongoing and proposed studies are investigating this strategy, including an ECOG study combining trastuzumab and anastrozole.

As these and other critical research questions are addressed in ongoing clinical trials, physicians and patients must make difficult decisions in many situations for which suboptimal trial data exist. In 1982, the physician treating Dr Piccart's mother facing the grim prognosis of a woman with eight positive axillary nodes took a leap of faith with his patient and her daughter, and utilized a treatment strategy that was unproven at that time. Every oncologist considers and balances similar anecdotal success stories with unsuccessful cases as they make the next generation of challenging decisions.

Neil Love, MD
NLove@ResearchToPractice.net

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