ER-/PR- Treatment & Recurrence Risk

My first question is whether anyone knows the literature on this and if the majority of people with receptor negative DCIS have recurrence (i.e., are we at significant risk of recurrence regardless of other risk factors such as grade, size, necrosis and clean margins)?

The answer is a big fat "NO", the majority of people with DCIS who are ER-/PR- do not have a recurrence.   

Reading this board, you might think that recurrences are very common. They aren't. The numbers vary but I believe on average the recurrence rate after a lumpectomy for DCIS (usually accompanied by radiation) is in the range of 8% - 12%.  The recurrence rate for those who have ER-/PR- DCIS might be higher but even at that, the majority of ER-/PR- women do not have a recurrence.

As for HER2 status, while it is known that HER2+ invasive cancer is more aggressive than HER2- invasive cancer, there is no such definitive understanding of how HER2 status affects those with DCIS.  Herceptin, which is the drug used to treat HER2+ invasive cancer, is not approved for those who have DCIS (although there are 3 clinical trials underway).

Here is a recent article that summarizes much of the DCIS research on this topic: Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review  http://www.jcancer.org/v02p0232.htm

About ER-/PR- status, it says:

"We identified 16 studies (2,470 total patients) that evaluated the relationship between ER expression and risk of local recurrence (Table 9). Four of these studies revealed an association between ER-negative DCIS and risk of local recurrence."  This means that 12 studies did not find that ER- DCIS is more likely to recur than ER+ DCIS.  Of the studies that did find a higher recurrence rate, 3 seem to have results that may be muddied by other issues (a majority of many patients with close margins, lumpectomy without radiation).  Here is a summary of one study that is a bit cleaner:

"In the third study that found a relationship between ER-negative DCIS and risk of local recurrence, Roka et al evaluated 132 patients with DCIS treated with breast-conserving surgery without (n=33) or with whole-breast radiotherapy (n=99) and found that patients with ER-negative DCIS were more likely than those with ER-positive DCIS to have a local recurrence (12.2% vs. 3.7%, Table 9) [23]. This study provides clinically useful information in that it gives an absolute difference between the rates of local recurrence in patients with ER-negative and ER-positive DCIS treated with surgery and radiotherapy: about 8.5%." 

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About HER2 status, this article says:

"We identified 15 (2,365 total patients) studies that evaluated the relationship between HER2 expression and local recurrence in DCIS. Eleven of these studies revealed no significant correlation between HER2 and disease recurrence. "  The results here are a bit too complicated and varied to summarize however I will say that in a couple of the studies, the combination of ER- and HER2+ was determined to be associated with a greater recurrence risk.  One of these studies did not have statistically significant results; the other did but this was a study where the patients were not treated with radiation.

Lots of data; no clear results.  But overall, back to the question, most women with DCIS do not have a recurrence, whatever their hormone status.  Personally if there was one factor that I would be focussed on, it would be margin size.  The larger the margins, the lower the recurrence rate - and I believe that is true whatever the hormone status.