Every year in early December, a large international meeting of virtually everyone interested in breast cancer is held in San Antonio. The tens of thousands of women and men who attend include people living with breast cancer, advocates, caregivers, pharmaceutical and biotech companies, basic scientists, and nonprofit organizations focused on breast cancer education and research. There are many other cancer conferences, but for many this huge gathering is the highlight of the year: you can get up to date on all aspects of research, catch up with the science, and get a glimpse of coming attractions. Here’s what got me thinking at this year’s meeting:
The Role of Surgery
As I listened to this year’s presentations, I was struck by the relatively small role surgery has in the curative treatment of breast cancer. Chemotherapy or a therapy that targets HER2 are now often given before surgery—a procedure called neoadjuvant treatment— to treat patients with tumors that are triple negative or HER2-positive. Giving treatment before surgery allows a doctor to see how much the tumor shrinks. If it shrinks a lot, it’s a sign the cancer responds to that type of treatment. If it doesn’t, it’s a sign other treatments are needed.
New HER2 Targeted Therapy
Just days after new data from the HER2CLIMB trial was presented at San Antonio, the U.S. Food and Drug Administration announced it was granting breakthrough therapy designation for tucatinib in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for locally advanced or metastatic HER2-positive breast cancer. The trial found that treating patients with tucatinib, Herceptin and Xeloda resulted in a median progression free survival (PFS) of 7.8 months compared to 5.6 months for Herceptin and Xeloda alone. It also showed improved PFS in patients with brain metastases. Tucatinib, a tyrosine kinase inhibitor that targets HER2, is the first HER2-targeted therapy found to cross the blood-brain barrier and slow the growth of brain metastases.
Evaluating the Best Dose
I attended an interesting presentation that focused on assumptions researchers make when determining the best dose of a drug to use in a clinical trial. We used to believe that early clinical trials should identify the maximum tolerated dose of a drug, because we assumed more was always better. But this may not necessarily be true. The Monarch 2 study, which compared the effectiveness of the hormone therapy fulvestrant (Faslodex) alone to Faslodex plus the CDK4/6 inhibitor abemaciclib (Verzenio) in women with hormone-sensitive, HER2-negative advanced breast cancer, was one example the presenters discussed. Early clinical trials found the maximum tolerated dose of Verzenio was 200 mg, which the researchers assumed would be best. But later studies showed a 150mg dose was equally effective. Similarly, the Paloma-2 trial showed that using a dose lower than the maximum tolerated dose of the CDK4/6 inhibitor pablociclib (Ibrance) resulted in the same survival benefits but with less toxicity.
Continuing the theme of reduced doses, Dr. Andrea De Censi an oncologist at the University of Genoa in Italy presented his “baby tam” study, which compared three years of a low dose of tamoxifen to a placebo after surgery in 500 women with atypical hyperplasia or LCIS. The low dose of tamoxifen decreased the recurrence of these breast precancerous lesions by 50%, with limited side effects.
Women Rise Up
This year’s meeting also included a debate on how to determine when mastectomy or lumpectomy are the best surgical option. It was a good idea. But as Karuna Jaggar, the executive director of Breast Cancer Action, publicly pointed out, the organizers had failed to include any women among the experts debating the topic. Needless to say, the audience was not receptive and it did not go over well—and this is unlikely to happen again. Fortunately, many of the other panels included women of all ages, who were presenting or moderating and there were many women in the audience asking questions—so we have made progress!
The Neighborhood Matters
Finally, I was very excited to see support for one of my pet theories: the neighborhood that surrounds the cancer cells is as important as the cancer itself. When you look at cancer from this perspective, it creates new treatment opportunities. That’s because if the environment is helping the cancer cells grow, you can think about ways to change the environment so that it’s no longer hospitable to the cancer cells.
Dr. Joseph Sparano, an oncologist at Albert Einstein College of Medicine in New York, gave a great talk about how the neighborhood, or tumor microenvironment, affects the risk of recurrence. He proposed a tumor microenvironment of metastasis (TMEM) that includes microanatomic structures that provide an on ramp for tumor cells to get into the blood stream or lymph system and then spread to other parts of the body. After studying tumors from 600 patients, Sparano and his team developed a scoring system to predict the risk of early recurrence. This MetaSite Score provides prognostic information about early recurrence that can be used along with information obtained about the tumor by the pathologist and the recurrence score from Oncotype DX, to help oncologists guide their treatment recommendations. In other words, metastatic spread depends on both the neighborhood and the cancer cells, and this score is another way to predict it.