Expert Consensus Offers Welcome Guidance on Surgical Margins
Roswell Park Cancer Institute
When removing a breast tumor, a surgeon’s goal is to eliminate the cancer completely. To accomplish this we remove both the tumor and a narrow rim of healthy cells around it—an area called the surgical margin. But how much healthy tissue must be removed to effectively limit the likelihood that the tumor will return? Until now the answer has not always been clear.
In February 2015 the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) issued a joint statement describing how wide surgical margins should be to have the best chances of reducing recurrence in patients with early-stage breast cancers. The statement detailed the conclusions of a multidisciplinary panel that reviewed the results of 33 different studies involving more than 28,000 patients who received both breast-conserving surgery and whole-breast radiation to treat Stage I or Stage II breast cancer.
The joint statement provided the first clear guidance for surgeons, radiation medicine specialists, and patients on a few key points. First, it confirmed that cancer was more likely to recur in patients with “positive margins”—that is, cancer cells on the edge of the tissue specimen that had been surgically removed. This held true even if patients received additional radiation therapy or other treatment after surgery.
Second, although negative margins—no evidence of cancer on the edge of the surgically removed tissue—were strongly linked with a decrease in cancer recurrence, the panel found that a narrow margin was sufficient; there was no benefit in removing a wider rim of healthy cells around a breast tumor.
Because the majority of women with early-stage breast cancer opt for breast-conserving therapy, it is especially important for oncologists to have evidence-based guidelines for reducing the chances of recurrence while avoiding overtreatment. Among those women as many as 40 percent have been found to have positive margins and may have required additional surgery, which can be emotionally and physically challenging, worsen cosmetic outcome, delay other planned therapies, and increase healthcare costs.
Although these guidelines do not replace surgical judgment—and each patient’s case should be considered carefully and individually—this important, evidence-based guidance from two influential medical societies will help standardize one of the most common surgical procedures for breast cancer, giving patients their best protection against recurrence while reducing the consequences of additional treatments they do not need. In the past no consensus existed on what constitutes a negative margin, and decisions about the width of the area removed around the tumor and what additional treatment might be needed could be very different from center to center and from surgeon to surgeon.
The consensus statement from SSO and ASTRO means that more patients can choose breast conservation if medically appropriate for them and that fewer patients will need additional surgery after an initial lumpectomy. The panel’s strong and clear definitions can reassure breast cancer surgeons, radiation oncologists, and patients that we can reduce the number of operations a patient may need without compromising outcomes.
Shicha Kumar, MD, FACS*, is interim chief of breast surgery and an assistant professor of oncology in the Department of Surgical Oncology at Roswell Park Cancer Institute in Buffalo, New York. A member of the Society of Surgical Oncology and a Fellow of the American College of Surgeons, she is also an assistant professor of surgery at the University at Buffalo. To see a video interview with Dr. Kumar, go to [roswellpark.org/shicha-kumar](http://roswellpark.org/shicha-kumar).*
New Guidelines Increase Efficiency in Patient Care
By Angela Keleher, MD, FACS
Director of the Dyson Breast Center Director of Breast Surgery
Dyson Center for Cancer Care at Vassar Brothers Medical Center
Poughkeepsie, New York
The new standard of care for breast cancer surgery1 is an important advance for patients because before this study there was no clear consensus of how wide a negative margin had to be during breast-conserving surgery or lumpectomy to reduce the risk of recurrence. Many doctors wanted at least 2 millimeters (mm) of normal tissue between the edge of the cancer and the outer edge of the removed tissue. Other doctors considered 1 mm satisfactory. Only a few years ago, that margin was sometimes as much as 10 mm. In all of those cases, if the margin was less than what the doctor wanted, the patient was returned to the operating room to take more tissue until the adequate margin was achieved.
With these new guidelines, many patients will avoid going back to the operating room for a greater margin. The study shows that none of the different margins—1, 2, or even 10 mm—reduced risk or changed the type of radiation therapy needed. Wider margins also do not matter for cancers with different biological characteristics. Rather than zeroing in on how wide the margin is, now the patient and her caregivers can focus on the other treatments for breast cancer to reduce recurrence. They can move forward with their systemic and local therapies without delay from additional operations. Ultimately, this new standard of care will benefit our patients so they can focus their attention on healing and not on whether the cancer has been adequately removed.
Angela Keleher, MD, FACS, is director of the Dyson Breast Center and director of breast surgery at the Dyson Center for Cancer Care at Vassar Brothers Medical Center in Poughkeepsie, New York. She earned her medical degree at the University of Illinois at Chicago and is certified by the American Board of Surgery. Dr. Keleher is a proud member of the American Society of Breast Disease, the American Society of Breast Surgeons, and the Society of Surgical Oncology.
- Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in Stages I and II invasive breast cancer. International Journal of Radiation Oncology, Biology, Physics. 2014;88(3):553-64. doi: 10.1016/j.ijrobp.2013.11.012.
New Oral Medications Offer Additional Options
By Sarah Schweber, MD
Memorial Sloan Kettering Commack
Positive results from two key clinical trials have generated excitement about a new class of oral medications to treat breast cancer: cyclin-dependent kinase (CDK) 4/6 inhibitors. These agents work by blocking signals that tell breast cancer cells to divide. Two recently reported trials showed that combining the CDK 4/6 inhibitor Ibrance® (palbociclib) with standard anti-estrogen therapies improved outcomes in patients with Stage IV hormone-positive, HER2-negative breast cancer.
The PALOMA-1 trial enrolled patients who had not received any prior treatment for Stage IV breast cancer. Ibrance plus Femara® (letrozole) doubled the duration of cancer control when compared with Femara plus an inactive placebo. Based on these encouraging results, a larger, confirmatory study of this combination is ongoing.
In the PALOMA-3 trial, Ibrance plus Faslodex® (fulvestrant) more than doubled the duration of cancer control compared with Faslodex plus an inactive placebo. All patients on PALOMA-3 had progressed on a previous anti-estrogen therapy. A third had also received prior chemotherapy.
Ibrance was generally well tolerated in both studies. The most commonly reported side effect was low white blood cell count. Most patients were able to complete their prescribed treatment.
These results suggest that we will soon have more non-chemotherapy options for patients with advanced hormone-positive breast cancer. Most patients with hormone-positive breast cancer initially respond to anti-estrogen therapies but eventually develop resistance. The combination of the oral mTOR inhibitor everolimus with Aromasin® (exemestane) was the first regimen proven to overcome resistance in some patients and is now one option available in the clinic. CDK 4/6 inhibitors are on track to become a second option.
Two clinical trials with the CDK 4/6 inhibitor abemaciclib in combination with standard anti-estrogen therapies are open at many Memorial Sloan Kettering locations. In addition to demonstrating the efficacy of this treatment strategy, researchers hope to identify tumor characteristics that will predict which patients will be most likely to respond. Memorial Sloan Kettering researchers are also investigating other novel agents for the treatment of advanced hormone-positive breast cancer. PI3K inhibitors and new anti-estrogen therapies will be studied in current and upcoming clinical trials.
These studies represent a very exciting time in breast cancer research. We have learned so much about the cellular signaling pathways that promote tumor growth and the techniques for developing drugs to target particular signaling molecules. These results are an example of how we put this knowledge together to bring new treatments to patients. I would encourage patients to consider participating in clinical trials to help us move forward in this work.
Sarah Schweber, MD is a board-certified medical oncologist at Memorial Sloan Kettering Commack whose practice focuses on caring for patients with breast and gynecologic cancers. She works as part of a team to provide state-of-the-art care to patients in a supportive environment, and feels privileged to be part of a dedicated group of medical oncologists, radiation oncologists, surgeons, radiologists, and nurses. In her practice, she follows evidence-based principles and works with patients to develop individualized treatment plans. Dr. Schweber earned her medical degree at University of New York Downstate College of Medicine.