Case Study Adjuvant Therapy Advances - Amy

Academia versus Efficacy

An exchange between Blumenschein and an “Ivy League” academician demonstrates the principles that each saw as unbreakable. They were consulting on a 28-year-old woman who 4 months postpartum was diagnosed with a T1N0 breast cancer 2 months after a mass was detected in her right breast. The cancer was triple negative (HER2-, ER-, and PR-). The patient chose preoperative chemotherapy and in August 2003 was started by her primary oncologist on AC 34 followed by Taxol 34 without the effect of this chemotherapy on her fertility having been discussed.

There was a measurable preoperative response to both AC and Taxol. However, a 0.7 cm focus of cancer remained in the breast after surgery and one node was positive on review of pathology. At this point, she selfreferred to Blumenschein for a second opinion. With the advantage of the pathology report, Blumenschein pointed out that the axillary nodes seen on a mammogram obtained in August 2003 suggested that quite possibly the patient was T3N1 on starting adjuvant therapy and that this change in diagnosis would have made a different therapy program more appropriate for her. The prolonged interval from detection to starting 5 months of chemotherapy and the delay to late consolidation treatment were additional concerns. Yes, the patient was a candidate for breast radiation
therapy but, before she began, Blumenschein suggested the way to insure the best possible outcome would be to repeat induction therapy with TAC 34, giving the Adriamycin by continuous infusion, followed by consolidation with 2 or 3 courses of FUMEP. Further action was then deferred until the patient could consider this recommendation.

The next day, the patient’s father entered the fray. He asked to see a peer-reviewed paper supporting the need to return to chemotherapy after she had just completed a similar regimen. The need for literature support is a frequent weak point in the real world of clinical decision making. So Blumenschein knew his recommendation was sunk when he needed a publication to back it up. Real-world clinical decisions taken for a particular patient often cannot be defended by citing academic publications in which a randomized controlled clinical trial has been conducted in a group of patients who are exactly similar to the individual patient being considered.

The patient’s Ivy League physician also vetoed Blumenschein’s recommendation. At the time, it was considered unlikely that breast cancer recurrences would remain sensitive to Adriamycin, and there was a growing concern within the oncology community about limiting the cumulative Adriamycin dose in order to minimize cardiac toxicity. Furthermore, she had not heard of using complex chemotherapy combinations such as MCCFUD and FUMEP as consolidation regimens in the adjuvant therapy of breast cancer patients and would not consider their use unless there was a creditable randomized trial which demonstrated them to be safe and effective. She expressed very strong feelings about the need for physicians to practice “evidence-based medicine,” and even questioned the need to give Adriamycin by continuous infusion.

Unfortunately, the patient’s decision to stop systemic chemotherapy at this point probably lowered her chance of tumor eradication to less than 20%, whereas plunging ahead might have allowed a 50% chance of tumor eradication. A final blow was the rejection of Blumenschein’s recommendation to give the patient Lupron1 with each course of chemotherapy in an attempt to preserve ovarian function in a fertile 28-year-old woman who was receiving aggressive chemotherapy. In this case, Dr. Ivy League was aware of the concept and, in fact, her study group was evaluating its use in this situation in a randomized trial. However, Amy was not eligible to be included in the study, so she did not raise the issue with her or discuss the matter in any way.

Amy never regained her menstrual cycle, her cancer reappeared, and she was never cured. When Dr. Alfred DiStefano, who was one of Dr. Blumenschein’s colleagues at both MDA and ACC, reviewed this case he made the following comment. “It is a shame to see someone so obviously intelligent and concerned for the welfare of her patients paralyzed into inaction and confined to the ‘standard of care’ by lack of the statistical anomaly of randomization. In my opinion this standard represents the ‘average’ at best and ‘mediocre’ at worst. Randomized trials are not needed to guide most of the things that we do every day. Experience and observation are still the prime tools of the art of medicine. Otherwise
we could be replaced by assembly line robots!”