Ductal Carcinoma In Situ (DCIS)

In the last several decades, the incidence of Ductal Carcinoma In Situ (DCIS) has increased dramatically, due largely to screening mammography.   The diagnosis was relatively rare before the early 1980's and the widespread use of mammography.  Today, approximately one woman is diagnosed with DCIS for every four women diagnosed with invasive breast cancer (Allegra, 2010).

DCIS represents a range of abnormal cells present within the breast or milk ducts.  Unlike invasive breast cancer the abnormal cells have not invaded neighboring tissues.  Although DCIS is a risk factor for invasive breast cancer, the natural history of DCIS and the likelihood that DCIS will progress to invasive disease is unknown. There is no available data on DCIS that is left untreated.  However, a review of autopsy records showed that somewhere between 9% and 15% of women have undetected DCIS at death (Welch, 1997). This supports the idea that a proportion of DCIS occurrences will not progress into invasive cancer or become life-threatening. The problem is that we do not know how to identify this proportion yet.

How best to treat DCIS, and even whether to consider it cancer, remain controversial. 

Controversy Over Treatment

DCIS is typically treated like early-stage invasive breast cancer – with breast-conserving surgery (BCS) and radiation therapy (RT), or mastectomy, and often hormonal therapy.  But the survival rate is high - at ten years after diagnosis 96 to 98% of women are alive (Allegra, 2010).  So the issue becomes whether there are patients who could get by with less treatment, or no treatment at all.  The problem is that there currently is no definitive way to distinguish between those cases that will remain within the milk ducts and may even disappear (Zahl, 2008), and those that will become invasive.

Radiation

For many years, the customary treatment of DCIS was mastectomy.  With the local and distant recurrence rates so low after mastectomy, between 1-2%, a more conservative approach was introduced: breast-conserving surgery (BCS) combined with radiation therapy (RT).  Studies in early breast cancer show the outcomes for mastectomy vs. BCS and RT to be similar, but no randomized controlled trials comparing the two methods for DCIS have been carried out.

Now, whether or not RT is necessary after breast conserving surgery is being debated. Retrospective studies showed that patients with DCIS treated with BCS alone experienced low rates of local recurrence (Harris, 2009). These studies raised important questions about the need for RT in the conservative management of DCIS. 

Four prospective randomized trials showed an approximately 50% reduction in local recurrence when RT was added after surgery, but no differences in overall survival (Bijker, 2006; Fisher, 2001; Holmberg, 2008; Houghton, 2003).  None of these trials were able to identify a subset of patients who derived no benefit from RT. 

Controversy remains over how complete the excisions were in these trials, and how it was defined.  Some argue that if adequate margins (tissue that contains no evidence of the abnormal cells) are achieved than RT may not be necessary, but the definition of margins varies among these studies.

These randomized trials along with other observational studies have not provided strong evidence that BCS plus RT is more or less effective than BCS alone (Virnig, 2010).  Breast cancer mortality after DCIS diagnosis is very low; as a result, few studies have included a sufficient number of cases to support identification of a mortality benefit.  At this time, the scientific and medical community cannot quantify the impact of local invasive recurrence on long-term survival after DCIS diagnosis.  Breast conserving surgery with adjuvant radiotherapy may benefit some women, though the absolute impact may be small.

Several staging systems have been developed and tested retrospectively to identify a subset of patients with such a low risk of recurrence that RT can safely be omitted, but there is still no consensus or recommendations on a reliable system for prediction.

Tamoxifen

Tamoxifen is the only Food and Drug Administration-approved drug for reducing the risk of local recurrence in patients with DCIS.  Results from randomized clinical trials demonstrate that tamoxifen reduces the risk of recurrence of DCIS or invasive breast cancer in the opposite breast, although no survival benefit has been shown.

In a double-blind prospective study, 1,804 women were randomized to BCS, RT and placebo, or BCS, RT and tamoxifen for five years.  Women in the tamoxifen group had fewer recurrences at 5 years than did those on a placebo (8.2% vs. 13.4%).  This means that for every 100 women taking tamoxifen in the study, approximately 8 developed either DCIS again or invasive breast cancer vs. approximately 13 women out of every 100 women who were taking placebo (Fisher, 2001).

Another study of 1,701 women found that after an average follow-up of four and a half years, tamoxifen decreased the risk of developing DCIS again by approximately one-third, but did not lower the risk of developing invasive breast cancer in the same breast (Houghton, 2003).

Active Surveillance

Is active surveillance an option?  Active surveillance involves close monitoring with treatment if there is any progression.  Some physicians do recommend active surveillance as an option with DCIS, although it is a hard sell until there are randomized controlled trials comparing active surveillance with current treatments. There may be a subset of women who can be monitored after biopsy in lieu of surgery or other therapies. Tumor size, margin status, biological factors, age, patient preference, grade, and mammographic density may all be relevant factors in such decision-making.  Randomized clinical trials or comparative effectiveness research is needed to compare the outcomes from standard treatment and more conservative management.

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