Breast Cancer Updates

Two recent advances in breast cancer treatment offer patients guidance and additional therapy options.

Expert Consensus Offers Welcome Guidance on Surgical Margins

By Shicha Kumar, MD, FACS

Breast/Endocrine Surgeon
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.


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.

Reference

  1. 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
Medical Oncologist
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.