Editor’s Note

ANOTHER STEP FORWARD

Recently, I had the interesting opportunity to deliver a presentation about the history of breast cancer clinical research to an unusual audience — a gathering of prostate cancer research leaders who were struggling with the clinical applicability of emerging data on the adjuvant use of the antiandrogen, bicalutamide. The maturity of these data paralleled the adjuvant tamoxifen data that was available to medical oncologists in the early 1980’s. Through my lecture, I attempted to illustrate the potential road ahead for the adjuvant therapy of prostate cancer.

One of the urologists asked why breast cancer research was so far ahead of prostate cancer in the design and implementation of phase III randomized clinical trials. Since the incidence and mortality of these two cancers are similar, it was a fair question. My initial response related to the power of breast cancer advocacy groups to promote funding for research.

Yet another, perhaps equally important factor is the leadership of numerous visionary breast cancer investigators who have continuously challenged our sometimes tenaciously-held paradigms and forced us to find objective answers to important clinical questions. Of course, Dr Bernard Fisher leads the list of breast cancer “movers and shakers”. His personal saga and legacy are legendary.

There are many other important figures who have extended the breast cancer research frontier, including a provocative and controversial self-described “iconoclastic Brit” who has been a frequent guest on this series since his first interview during the 1990 NIH Consensus Conference.

Dr Michael Baum has always challenged us to examine our prejudices and preconceptions, and it was no surprise that on December 10, 2001, he presented at the San Antonio Breast Cancer Symposium perhaps the most exciting new data set in breast cancer research in more than a decade.

In the early 1990’s in an English pub, Dr Baum and his colleagues first outlined the concept for the ATAC trial on the back of an envelope. This study eventually became the largest cancer treatment trial ever conducted, and one of my favorite interview questions for guests on Breast Cancer Update this past year was, “What do you think the ATAC trial will show in its first data analysis?”

In an interview during the Miami Breast Cancer Conference in March 2001, Dr Baum predicted there would be no difference in the initial analysis of the three treatment arms (anastrozole, tamoxifen, and the combination). His prediction was based on the inclusion of a substantial number (about 15%) of women with ER-negative and ER-unknown tumors. These women were likely to be the first group of early relapsers. However, part of the excitement associated with well-conducted clinical research is being presented with pleasant surprises. It would not be an exaggeration to state that many of the “standing room only” San Antonio attendees were stunned by the ATAC results.

In the enclosed audio interview and print supplement, Dr Baum reviews these historic data. As with all of our programs, the transcripts of Dr Baum’s interview, relevant journal articles, and protocol web links are found at BreastCancerUpdate.com. Briefly, “the headline news” includes a significant improvement in efficacy and tolerability for anastrozole compared to both tamoxifen and the combination of tamoxifen and anastrozole. In this early analysis, perhaps the most surprising finding is 58% fewer second breast cancers in women treated with anastrozole compared to those receiving tamoxifen. The ATAC results have generated considerable discussion about the rationale for new trials using anastrozole in highrisk women and DCIS.

Just last year, an NIH Consensus Conference advocated the use of adjuvant tamoxifen in all patients with estrogen receptor-positive cancers, regardless of age, menopausal status, or recurrence risk. During the interview, Dr Baum described with amusement a lecture he had just attended by Dr Craig Jordan (another regular Breast Cancer Update guest) who began his presentation by saying, “Tamoxifen, the gold standard of endocrine therapy... until yesterday!” The enclosed program contains two other interviews documenting the rapid evolution of breast cancer clinical research, particularly that of targeted systemic therapy. Dr Mark Pegram takes us to the cutting edge of HER2 biology and reviews how the UCLA group — headed by Dr Dennis Slamon — is utilizing trastuzumab in clinical research and practice.

In particular, Dr Pegram enthusiastically endorses routine use of the FISH assay to determine HER2 status. He refers to a San Antonio presentation, by Dr Robert Mass, that conclusively demonstrates the superiority of the FISH assay relative to the IHC assay in identifying women likely to benefit from trastuzumab.

Finally, Dr Robert Livingston describes the design of an important new adjuvant Intergroup trial based in part upon Dr Joyce O’Shaughnessy’s presentation at last year’s San Antonio meeting, reporting a response rate and survival advantage for capecitabine/docetaxel compared to docetaxel alone in metastatic breast cancer. The proposed Intergroup adjuvant trial is just one of several new trials designed to evaluate the capecitabine/docetaxel combination in the adjuvant and neoadjuvant setting. The rapid incorporation of clinical trial results into the design of future studies is another example of the flexibility and efficiency we have come to expect of the breast cancer research infrastructure.

Often an outsider’s perspective enhances our appreciation for what we have obtained. As my prostate cancer colleagues gazed with envy at the progressively massive number of patients in the Early Breast Cancer Trialists’ Collaborative Group, I realized that thousands of breast cancer patients and researchers have set a lofty clinical research standard for oncology and medicine. This collaboration has now resulted in a 25% reduction in breast cancer mortality in the last decade, and hopefully, new steps forward — like ATAC — will further reduce the death rate in the future.

—Neil Love, MD

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