You Have Nothing to Lose

Abstract

DOI: 10.1200/JCO.2014.60.5634 “Hey, Lee, it’s John. Do you have a couple of minutes?” “Of course,” I said. I already knew by his tone of voice where this conversation was going. John is a friend of a friend, and we had chatted at several social gatherings. He is a young executive on the advancement track. Having earned his MBA at a prestigious business school, he had already held significant finance jobs in two divisions at his company. He is a strategic thinker who handles numbers easily, an excellent leader, and a genuinely sincere guy. I run the cancer team for a large health plan. Although I know John from our informal meetings, this call could only mean one thing—his wife had breast cancer, or his child had a tumor. “It’s my wife, Jan. She’s been diagnosed with breast cancer.” The facts came easily from a man used to working with numbers. “The primary tumor was 2.1 centimeters. The lymph glands were negative for cancer. Her estrogen receptor is positive and the HER2 [human epidermal growth factor receptor 2] gene was 1 . Her Oncotype [Oncotype DX] score was 17. She’s scheduled for postoperative radiation therapy and antiestrogen therapy.” “But,” he then said. “We don’t know what to do.” I was surprised. When I considered all of those factors together, I was estimating that this woman’s benefit from additional treatment with adjuvant chemotherapy was extremely small. No one with breast cancer is guaranteed to have a cure, but I liked her odds. This couple should be uncorking their best bottle of wine in celebration. John was not celebrating. The first medical oncologist his wife had consulted had recommended 6 months of adjuvant chemotherapy, stating that it would improve her chances of a permanent cure. “The oncologist believed that Jan should be treated because of her T2 tumor size,” he said. “I’ve done some reading about adjuvant treatment, and from what I’ve read, the Oncotype score means that she won’t have any benefit from the chemotherapy.” I caught myself nodding in agreement as I watched my reflection in the office window. Researchers know that a small fraction of women with small tumors still relapse, although the overwhelming majority of them are cured with surgery and radiation. It is clear from other studies that women with larger tumors and positive lymph glands benefit from chemotherapy immediately after surgery— the cure rates are often improved by 50% compared with surgery alone. But women like Jan had little room for improvement because the cure rate with surgery was more than 90%. Still, a small fraction, approximately 10 of every 100, did relapse. Previously, among women with small tumors, there was not a way to identify those with poor risk and those who were already cured. Oncologists faced a dilemma. Should they treat all of these women to provide benefit for a few? The Oncotype DX test (Genomic Health, Redwood City, CA) was devised for exactly this situation, because it identifies the few women in this group who do benefit from additional treatment. The women with high scores were much more likely to experience recurrence than the majority of their fellow women, who had low scores although their tumors were the same small size. Jan had the numbers in her favor. I thought John was right. “So we sought a second opinion at one of the major cancer centers,” John said. “Whom did you see there?” I asked. John told me the name, and I smiled. I knew this man well from work we have done together in professional societies. I respected him as a physician and I liked him as a person. I was certain that with his input, the ambiguity about adjuvant chemotherapy would be resolved. “And what did he recommend?” I asked. “He recommended the same adjuvant chemotherapy. He admitted that the benefit would be small, if there was any benefit at all, but he finished by saying, ‘You have nothing to lose.’” I was stunned. There was definitely something to lose. Jan’s life would be turned upside down for 6 months while she and John rearranged their work schedules and found child care for her treatment days. She would lose her hair and battle the inevitable fatigue. I knew the numbers from our database at UnitedHealthcare. In the 2-year span from 2011 to 2012, there were 3,137 women in the company’s clinical registry who received adjuvant chemotherapy for breast cancer. Six of them died as a result of complications of that treatment. In the same cohort, 2,386 women were evaluated in emergency rooms JOURNAL OF CLINICAL ONCOLOGY A R T O F O N C O L O G Y VOLUME 33 NUMBER 14 MAY 1