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,
patient-centered 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.