When ‘Less is More’ in Breast Cancer Treatment

When ‘Less is More’ in Breast Cancer Treatment

The overtreatment of breast cancer has received much recent attention, with articles in The New York Times, The Wall Street Journal, Forbes, and other outlets tackling the issue. Recent studies have indicated that some commonly used breast cancer treatments, from the use of double mastectomy in women with early breast cancer to the use of mastectomy or radiation therapy in ductal in situ carcinoma (DCIS), are not always needed and may put patients at risk of adverse effects without sufficient potential for benefit.

Dr. Fatima Cardoso
“Overtreatment is one of the hottest discussions in breast cancer treatment today,” Fatima Cardoso, MD, of the Champalimaud Cancer Centre, in Lisbon, Portugal, told the ASCO Daily News. “The reason behind [overtreatment] is clear—we only have one shot at clearing this disease, and that is when it’s early,” Dr. Cardoso said.

However, Dr. Cardoso explained, the philosophy of “when in doubt, treat” is now being questioned, in particular with the advent of molecularly targeted therapy and tools that may allow more precise tailoring of therapy for individual patients. “We must do better at identifying who needs what type of treatment,” she said.

The latest evidence on overtreatment and the appropriate use of available therapies will be featured in the June 7 Education Session, “Less Is More: A Multidisciplinary Conversation on Treatment Options.” The session, chaired by Dr. Cardoso, will also include presentations by Laura Esserman, MD, MBA, of the University of California, San Francisco, and Eun-Sil Shelley Hwang, MD, MPH, of Duke University Medical Center.*

Optimizing Chemotherapy

During her presentation, Dr. Cardoso will discuss the current state of gene signatures and tumor burden for tailoring chemotherapy decisions in breast cancer. “We need good tools to be able to define who needs chemotherapy and who doesn’t,” Dr. Cardoso said. Chemotherapy is the treatment modality that patients are often most hesitant to use because of concerns about side effects, both short and long term. However, Dr. Cardoso said that for some patients, chemotherapy “is indispensable for achieving cure.” The challenge lies in distinguishing patients likely to benefit from chemotherapy from those who are not.

In recent years, researchers have identified gene signatures that are significantly associated with prognosis in patients with breast cancer. These gene signatures, several of which have been commercially developed, may help identify patients with higher-risk disease who are more likely to benefit from chemotherapy and those with lower-risk disease who may safely avoid it. Dr. Cardoso has been centrally involved in efforts to evaluate these tools, serving as a principal investigator of the MINDACT trial, one of the first large, prospective trials to validate the use of a genetic signature in a clinical setting.1

Dr. Cardoso will discuss the results of the MINDACT trial during her presentation. “We will be able to dissect the results and see how these tools can be applied in the clinic to determine which patients need to receive chemotherapy,” Dr. Cardoso said.

Optimizing Surgery and Radiation Therapy

During her presentation, Dr. Esserman will discuss the optimal use of surgery and radiation therapy in patients with breast cancer. Dr. Cardoso noted that some areas of the world have seen an increasing number of unnecessary mastectomies. “It’s important to clearly understand who needs a mastectomy and who can be safely treated with breast-conserving surgery,” she said.

Another important issue that will be discussed during the session is the appropriate use of axillary dissection. Although the procedure is sometimes necessary, it is associated with a risk of developing lymphedema, one of the most significant consequences of breast cancer surgery, Dr. Cardoso said. According to recent data, axillary dissection can be omitted in some circumstances, even when a sentinel lymph node tests positive, suggesting that some patients can be spared the risks associated with lymph node dissection.2

The appropriate use of radiation therapy is also an important consideration, Dr. Cardoso said, noting that surgery and radiation therapy are complementary, and overuse of either modality should be avoided.

Optimizing Management of DCIS

Dr. Hwang will discuss controversies in the treatment of DCIS during her presentation. Currently, there is somewhat of a contradiction in treatment approaches, Dr. Cardoso said, with some advocating for less-aggressive treatment in patients with invasive breast cancer yet a more aggressive approach for DCIS, even though DCIS is “not yet cancer and may never become cancer,” Dr. Cardoso said.

Dr. Cardoso noted that many cases of DCIS are lesions that are diagnosed via screening and may never become malignant. In patients with DCIS, “more mastectomies are being performed, and more radiation is being done. We should probably be avoiding most of these excessive treatments, especially excess mastectomy.”

Although overtreatment of DCIS is a concern, Dr. Cardoso noted that the optimal management of DCIS remains controversial, with some evidence supporting treatment rather than a watch-and-wait approach. However, the management of DCIS has not been well studied in prospective, randomized trials.

This will change with the undertaking of the prospective, randomized COMET trial.3 The trial will be headed by Dr. Hwang, along with Alastair M. Thompson, BSc(Hons), MB ChB, MD, FRCSEd, from The University of Texas MD Anderson Cancer Center, and Ann H. Partridge, MD, MPH, from the Dana-Farber Cancer Institute. Of the approximately 40,000 women who will be diagnosed with low-risk DCIS over a 4-year period at participating sites across the United States, approximately 5% are expected to participate in the trial.

COMET participants will be randomly assigned to receive guideline-concordant surgery with or without radiation or active surveillance consisting of a mammogram every 6 months for 5 years; patients in both groups can opt to receive endocrine therapy. The trial is being funded by the Patient-Centered Outcomes Research Institute, an independent nonprofit organization authorized by the U.S. Congress.

Dr. Cardoso emphasized the need to explain to patients the importance of such studies. She suggested that patients might be hesitant to enroll on a trial in which they may be randomly assigned to receive no treatment.

“That is hard to explain to a patient,” she said. “We need to involve patient advocates and discuss how we can explain these types of trials to patients and [help them understand] these are important questions.”  

– Melinda B. Tanzola, PhD