Editor’s Note
	Are we moving quickly enough?

Every healthcare professional who has witnessed the human havoc of breast cancer has hope that future advances will relegate the disease to the paradigm of pneumococal pneumonia. However, until a “penicillin-like” cure appears, there will be many, many frustrating moments as reflected by Dr Muss.

Occasionally, in interviews for this series, I query research leaders about their coping mechanisms for the frequent heartbreaking moments in breast cancer medicine. Another guest for this issue of Breast Cancer Update, Dr Clifford Hudis, summarized his coping mechanism as “lots of time on the Stairmaster® and participation in clinical research.”

After 25 years in oncology and a succession of ASCO meetings that seem to only report baby steps in the overwhelming challenges of this disease, it is easy to feel a sense of disappointment. However, the lead interview of this issue focuses on a patient treated seven years ago by Dr Debu Tripathy. In comparing the therapy this woman received then to how she might be treated today, a somewhat different perspective emerges.

This young woman — presenting with a node-positive, HER2-positive, ER/PRnegative primary tumor — was treated with four cycles of adjuvant AC. Dr Tripathy notes that today this patient would likely be treated with a taxane-containing adjuvant regimen and, perhaps of even greater importance, she would have had the option to enroll in one of a number of major cooperative group trials evaluating trastuzumab in the adjuvant setting.

In fact, when this woman relapsed with metastatic disease in 1996, she was enrolled in the pivotal randomized trial by Slamon et al comparing chemotherapy alone to chemotherapy plus trastuzumab. The rapid pace of clinical research is evident, when one considers that just a few years after this study demonstrated an advantage to adding trastuzumab in metastatic setting, the NSABP, Intergroup and the newly formed BCIRG all had implemented adjuvant trastuzumab trials.

Dr Tripathy’s case highlights another major conceptual development in clinical research in the last few years — specifically, the attention to the impact of post-trial therapy in studies of metastatic disease. This patient actually progressed on the treatment to which she was randomized (paclitaxel alone), as well as the crossover therapy mandated in the study (paclitaxel plus trastuzumab).

However, she subsequently had a remarkable complete response to trastuzumab plus vinorelbine. Dr Tripathy notes the irony in this woman’s relatively long survival being the result of third-line therapy initiated after the trial’s major randomizations.

In the previous issue of Breast Cancer Update, Dr Joyce O’Shaughnessy commented on the impact of post-trial therapy on the results of the X-T versus T trial that evaluated the biochemically synergistic combination of capecitabine and docetaxel. She noted that while the patients randomized to X-T had longer survival than those who received docetaxel alone, patients who received capecitabine after docetaxel also had excellent outcomes. This brings up the question of what might have been demonstrated with a third arm of capecitabine followed by docetaxel on progression.

Compared to 10-15 years ago, trials in the metastatic setting are currently planned not only to improve treatment options, but perhaps even more importantly, to delineate strategies to be tested in the adjuvant setting. Just as the chemotrastuzumab approach moved quickly to the earlier disease setting, X-T is now being evaluated in both adjuvant and neoadjuvant trials.

The timetable on moving therapies through the breast cancer continuum is rapidly accelerating. In this issue, Dr Rowan Chlebowski, who authored the first ASCO Technology Assessment on breast cancer chemoprevention, provides insights on the second version of this futuristic document. He notes that, in the last seven years, we have progressed from initial randomized trials of aromatase inhibitors in advanced disease, to studies that will explore this strategy in high-risk women.

Is this coalescence of an integrated breast cancer clinical research strategy a cause for optimism or simply more hype? Having just returned from Oxford, England, where Sir Richard Peto presented preliminary unpublished results from the first international meta-analysis on early endocrine therapy of prostate cancer (about 17 years after a similar analysis in breast cancer), we can at least state that breast cancer is at the vanguard of oncologic research in solid tumors. On the other hand, for physicians like Dr Muss, on the front line of this disease, there unfortunately will be many more dark personal moments before definitive answers are attained.

— Neil Love, MD

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