Special Report II
In 1976, mammography (MMG) became a standard cancer screening strategy to detect breast cancer at an earlier stage in hopes of reducing mortality. Unsurprisingly, the incidence of ductal carcinoma in situ (DCIS), an early form of breast cancer, increased markedly from 7 cases per 100,000 women before the implementation of screening MMG to 56 per 100,000 women three decades afterwards in the late 2000s. Now, DCIS accounts for 20-25% of newly diagnosed breast cancers, more commonly detected on MMG as microcalcifications before presenting as a palpable mass. In 2015 alone, there were roughly 50,000 new DCIS diagnoses in the United States. The increased incidence of DCIS, however, has only been coupled with a marginal reduction in women presenting advanced breast cancer, raising concern for overdiagnosis of breast cancer.
DCIS is a type of non-invasive cancer contained within the basement membrane of the mammary ducts. An estimated 20- 30% of DCIS cases progress to invasive carcinoma, meaning 70-80% of cases do not. A number of predictive radiological and biologic markers have been explored for prognostication, such as nuclear grade, histologic type, size, and estrogen receptor (ER) status and more recently, molecular markers progesterone receptor, HER2, Ki67, and p16 expression. However, further research is needed to better understand the difference between DCIS that will progress to invasive disease in a clinically relevant timespan and those that will not.
Due to the concern of disease progression, the conventional treatment has been surgical removal of breast tissue with or without adjuvant radiation therapy and systemic therapy. With the current treatment strategy, prognosis for DCIS is extremely favorable with 10-year cumulative breast cancer death rate of 1.4-2.8%. Unfortunately, surgical treatment is not without risks. Even with the improvement in surgical techniques, like breast conserving partial mastectomies as opposed to mastectomies for certain surgical candidates, surgical treatment of DCIS is associated with potential complications, such as chronic incisional pain, breast fibrosis, breast lymphedema, chronic breast cellulitis, and poor patient reported outcomes (PRO) (i.e. negative body image). Treatment is also associated with depression and does not necessarily resolve patients’ fears of recurrence. Favorable prognosis for low grade DCIS raises concerns for overtreatment with potentially unnecessary surgical and radiation treatment, thus much interest has been generated in improving treatment strategies. How can the extremely favorable prognosis of current treatment strategies for DCIS be maintained, while reducing the number of patients receiving surgical treatments and associated morbidity?
At the American Society of Clinical Oncology (ASCO) Conference Annual Meeting on June 1-5, 2018 in Chicago, IL, landmark TAILORx results, a clinical trial assigning individualized options for treatment (Rx), were presented. The result demonstrates the Oncotype DX Breast Recurrence Score® test definitively identifies the 70% of women with early-stage breast cancer who receive no benefit from chemotherapy, and the 30% of women for whom chemotherapy benefit can be life-saving result of the TAILORx.
Dr. Hwang is a world-renowned expert in early-stage breast cancer and participated on DCIS studies, and currently the chief of breast surgical oncology at Duke Cancer Institute. Her extensive work includes basic science research to identify biological markers for better prognostication, clinical trials of less invasive systemic treatments, patientcentered research around their perceptions and experiences, and collaborative work on diagnostic imaging. Recently, she completed the CALGB40903 trial that looked at endocrine therapy with letrozole alone, as opposed to surgery for ER-positive DCIS. The primary outcomes of interest were changes in total MRI volume at 3 months and 6 months, which showed statistically significant reduction in volume. Further reports should follow regarding radiographic-pathologic correlation and reduction in Ki67 expression to help identify potential non-operative candidates who could be treated with endocrine therapy alone.
Currently, she is the principal investigator for an exciting and potentially groundbreaking COMET study. This is a prospective randomized trial powered for non-inferiority comparing conventional therapy to active surveillance (AS) consisting of biannual MMG and endocrine therapy for low-risk, ER-positive DCIS patients. The primary outcome is the rate of ipsilateral invasive cancer in 2 years. The secondary outcomes include quality of life outcomes, such as anxiety, depression, decisional regret, and body image. Two other prospective randomized trials, LORIS trial and LORD trial, also look at active surveillance as a non-inferior strategy for low-risk DCIS. Between the three trials, we should expect to be introduced to innovative ways we treat DCIS.
Andrew Siyeon Seong, MD, ME
Resident Physician, University of Washington Medical Center Department of Surgery
Dr. Seong is a resident physician at the University of Washington Medical Center Department of Surgery. He graduated from the Robert Larner College of Medicine at the University of Vermont and studied mechanical engineering at Cornell University for his Bachelor’s and Master’s degree.