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September 9, 2015

Ductal Carcinoma In Situ: the Goldilocks of Treatment?

A commentary by Drs. Shaveta Vinayak and Ruth Keri on "Breast Cancer Mortality after a Diagnosis of Ductal Carcinoma In Situ" by Narod, et al., JAMA Oncology, 2015 

The management of ductal carcinoma in situ (DCIS) or stage 0 breast cancer has been under debate for many years.  Most of the patients with DCIS present without any symptoms and it is usually diagnosed by screening mammography.  As screening mammography has become more prevalent, the incidence of DCIS has also increased. DCIS has long been thought to be a precursor lesion for invasive cancer, hence the reason for aggressive treatment. The overarching goal of treatment of DCIS with the combination of surgery, radiation treatment, and endocrine therapy, is to reduce the risk of recurrence, including invasive cancer.  Currently, we do not have a good understanding of which patients go on to develop invasive cancer and therefore, the combination of our treatments may be over-treating or under-treating some of our patients.  So, what is the right treatment for patients with DCIS?  As we’ve learned over time for invasive cancer that one treatment does not fit all, similarly we need to develop approaches to individualize treatments for patients with DCIS.  Do all patients need breast radiation treatment after surgery?  A registration study (ECOG 5194) showed that patients with relatively favorable DCIS (low/intermediate grade) had lower invasive events with surgical excision alone (no radiation), compared to patients with unfavorable DCIS (high grade).  However, it is still not known which patients benefit the most from use of tamoxifen or aromatase inhibitors for reducing the risk of developing invasive cancer.

The recently published article by Narod and colleagues in JAMA Oncology, underscores the need for personalized treatment for DCIS.  As noted in this large observational study of more than 100,000 women with DCIS with a 20-year follow-up, the risk of dying from breast cancer is low (3.3% at 20 years). However this does not hold true for all patients.  Among patients with DCIS, women under the age of 35 and black women were at higher risk of dying from breast cancer.  Why would that be the case?  It is possible that the small number of patients that develop DCIS under the age of 35 have a different biology of DCIS, which increases the risk of progression to invasive cancer.  The authors also evaluated the well-established DCIS pathologic characteristics that are considered to be high risk, such as hormone receptor negativity, high grade, large tumor size, and comedonecrosis.  Not surprisingly, these were all associated with increased mortality following DCIS.  As noted in previous studies, including randomized trials (NSABP B-17), radiation treatment after surgery reduces the risk of developing invasive cancer, but does not alter the risk of dying from breast cancer.  Given that the Narod report was an observational study that relied on the data captured in the Surveillance, Epidemiology, and End Results (SEER) database, some of the limitations of the study included lack of central pathology review, information on margin status after surgery and adjuvant use of endocrine therapy.  These factors may impact outcomes from DCIS. 

This paper raises important questions regarding management of DCIS. Do we need to continue treating everyone with multimodality treatment if reducing the risk of developing invasive cancer does not impact survival?  Or, do we abort the current standard of using all therapies for all of our patients with DCIS?  Well, the answer is somewhere in the middle, but we need a higher level of evidence to support a change in clinical practice.  We know that all DCIS are not created equal but we don’t know which patients with DCIS are destined to progress to invasive cancer.  We are still lacking the tools to guide these precise treatment decisions for patients with DCIS, but further molecular understanding will pave the way! Identifying the molecular heterogeneity amongst premalignant lesions that portend poor outcomes is the subject of PQ6 in the NCI’s Provocative Questions Initiative.  Addressing this issue for DCIS would have a major impact on treatment decisions for patients with such lesions. Since none of the current treatments come without a cost, potentially long-term, we need to help our patients carefully consider risks and benefits in the management of DCIS, and provide them with the tools to reach personalized decisions for their care.    

We thank Drs. Janice Lyons and Robert Shenk for their insightful comments on this article.