J. Michael Dixon, MBChB, MD
Professor of Surgery, Consultant Surgeon,
University of Edinburgh
Clinical Director of the Edinburgh Breast Unit,
Western General Hospital,
OBTN: You’ve spoken around the world about the diagnosis and treatment of breast cancer for a number of years. Would you be able to encapsulate what you feel are the major advancements that have occurred within the past few years?
I think there are a number of advances. Number one is that we’re diagnosing cancer at an earlier stage. That’s partly due to screening, but it’s also due to better patient education, women coming forward with small lumps, better investigative tools, better radiology, better image-guided core biopsies, etc.
The second big advance is in treatment. More patients are now receiving breast-conserving surgery, and the surgery now produces much better cosmetic outcomes. We now understand that big surgeons don’t need to make big incisions—that is, surgeons don’t need to remove the cancer with a lot of surrounding tissue. There has been a dramatic movement away from routinely removing all the axillary nodes with the advent of sentinel node biopsy. That’s been a major improvement. It has improved the speed with which patients recover after surgery. Because most of the patients are node-negative, they can have a sentinel node biopsy as their only axillary node procedure. This reduces the number of women who get significant arm problems and lymphedema after surgery. More recently, we’ve learned that perhaps some women with positive nodes after sentinel lymph node biopsy don’t need an axillary lymph node dissection even if they do have one or two positive sentinel lymph nodes.
The other advance in treatment is in systemic therapy. For hormonal therapy, we have the aromatase inhibitors that have demonstrated superiority over tamoxifen in postmenopausal women. In chemotherapy, there has been wider use of taxanes and anthracyclines compared with standard cyclophosphamide, methotrexate, and 5-fluorouracil regimens. Then, of course, there is the discovery of anti-HER2 drugs with Herceptin or, recently, with lapatinib, and pertuzumab.
Could you summarize the main points of your presentation at the 10th International Congress on the Future of Breast Cancer and put that into perspective in terms of the lessons learned in endocrine therapy over the course of the past 5 years?
The first lesson we’ve learned is that neoadjuvant endocrine therapy is very effective therapy in older women with larger cancers. For women who have a lot of other morbidities, you can treat these patients with a drug like letrozole or anastrozole alone, and that’s probably the only treatment they’re going to require. It at least controls their breast cancer until the time of their death. So, the first thing is that these new drugs alone are sufficient treatment.
The second thing we’ve learned is that endocrine therapy works differently than chemotherapy in how it shrinks the cancer. It’s a lot slower. The treatment duration that’s required to shrink the cancer down to a size where you can perform breast-conserving surgery can be years—rather than a few weeks, which is the case for neoadjuvant chemotherapy. In other words, you might give 4 to 8 cycles of neoadjuvant chemotherapy over a period of 12 to 24 weeks, whereas neoadjuvant endocrine therapy is given over a period of 9 to 10 months
We also find that in neoadjuvant endocrine therapy the cancer implodes and shrinks from the center. It produces a central scar and pulls the cancer inward. That’s great news for the surgeon because if you’ve got a 4-cm cancer and it implodes, you end up with a 1-cm cancer by the time you’re finished with endocrine therapy.
How do these differences (ie, endocrine therapy vs chemotherapy) impact your surgical approaches in treating these patients?
The patterns of response to neoadjuvant chemotherapy aren’t the same. Neoadjuvant chemotherapy is sort of like a shotgun approach. You pull the trigger and 90% of the cancer disappears, but the same area of the breast is affected. So, when the surgeon operates and removes the cancer that may be left, he or she often finds that the area of breast involvement is still very extensive.