Ductal carcinoma in situ (DCIS) represents approximately 20% of new breast cancer diagnoses. DCIS is classified as non-invasive because the cancer cells are confined to milk ducts and have not spread beyond the duct walls to invade the surrounding tissue. If left untreated, at least a third of DCIS lesions will progress to invasive breast cancer. Even when treated, approximately 12% to 16% of women with DCIS are eventually diagnosed with invasive breast cancer. Nevertheless, it has been estimated that only 3% to 8% of women die of breast cancer within the first 20 years of receiving a diagnosis of DCIS. A small minority (0.5%) of women with DCIS eventually progress to stage IV breast cancer without ever being diagnosed with an in-breast invasive tumor.
The risk factors for DCIS recurrence (without any invasive breast cancer) are not identical to the risk factors for progression to invasive breast cancer. However, tamoxifen and aromatase inhibitors have both been found to reduce DCIS recurrence, as well as progression to invasive breast cancer among women with estrogen receptor positive (ER+) DCIS. Alcohol consumption is associated with increased risk of both DCIS and invasive breast cancer. The risk of DCIS recurrence or progression to invasive cancer continues for decades and requires active follow up that is likely to include additional diagnostic procedures. A tailored breast cancer diet is appropriate for those with DCIS to help improve outcomes, to the extent that this is possible through nutrition.
DCIS recurrence risk factors
DCIS can be eliminated with mastectomy, but this is considered overtreatment in many cases for a condition that is not life threatening and might not progress to invasive cancer. In fact, women who are treated for DCIS with mastectomy of the affected breast remain at ongoing risk of a recurrence of DCIS in the opposite breast. This is primarily because the risk factors that lead to the development of DCIS are for the most part still in place.
No radiation treatment following surgery to remove DCIS
Numerous studies have reported that relapse rates are considerably higher if radiotherapy is omitted. For example, one study reported that the rate of DCIS recurrence during the first 10 years after lumpectomy was 36% for women treated with surgery alone and 18% for women who received surgery plus radiation treatment. Another study found that the addition of radiation treatment to surgery for DCIS reduced the risk of any type of local recurrence by 48% during the first 15 years after diagnosis. Still another study reported that more than one fifth of cases of DCIS recurrence or progression to invasive breast cancer could be prevented if all women with DCIS who have breast conserving surgery also undergo radiation treatment.
However, a major 2015 study reported that while radiotherapy is associated with reduced recurrence in the same breast that DCIS was diagnosed, it does not appear to reduce breast cancer-specific mortality at 10 years. This suggests that radiation treatment is not worthwhile for low risk women. However, efforts to identify women who can safely treated for DCIS with surgery alone have not been entirely successful. A small percentage of women with small DCIS tumors with generally favorable characteristics will still experience a recurrence of DCIS.
Close or positive surgical margins
Surgeons normally attempt to remove a border of normal tissue along with a DCIS lesion so that any adjacent abnormal cells that might have migrated from the tumor are removed. Surgical margins are considered to be positive if the pathologist finds DCIS cells right up to the edge of the removed tissue. There is no consensus concerning the best minimum clear margin width for DCIS. The minimum standard of care is removal of the DCIS to clear margins (tumor not touching the inked surface). Many surgeons use a clear margin of 2 or 3 mm as a guideline, but some researchers have suggested that margins as wide as 1 cm are optimal. One long-term 2015 study reported that wider surgical margins were associated with lower likelihood of recurrence, but only among women not treated with radiation.
DCIS that forms a lump or thickening in the breast that can be felt by hand is more likely to recur than a lesion that cannot be detected manually.
High breast density
High breast density is associated with increased risk of DCIS recurrence.
HER2 positive DCIS
Each of the invasive breast cancer subtypes have been identified in DCIS, although there are differences in the proportion of each subtype. At least 30% of DCIS lesions overexpress HER2/neu (HER2+), a somewhat higher proportion than found in invasive breast cancer. HER2+ DCIS is associated with an increased risk of DCIS recurrence independent of tumor grade. Triple negative (ER-/PR-/HER2-) and other basal-like DCIS is rare. Triple negative or other HER2- subtypes are not associated with increased DCIS recurrence, although they are more likely than other subtypes to progress to invasive breast cancer.
Other DCIS characteristics
Other characteristics of DCIS associated with increased risk of recurrence are heightened Ki-67 antigen (a marker of proliferation), tumor size over 2.5 cm, predominantly solid architecture (affected breast ducts completely filled with cancer cells), extensive comedo necrosis (affected breast ducts plugged with dead cancer cells and associated debris, along with live cancer cells), and cancerization of lobules (DCIS which has extended “back” into the lobules). Although DCIS with microinvasion is associated with heightened risk of progression to invasive breast cancer, it does not appear to increase risk of DCIS recurrence.
The negative impact of DCIS recurrence has been underestimated because it takes as many as 15 years of follow up for the impact on survival to become apparent. This may have led to a tendency to de-emphasize the importance of radiation after breast conserving surgery in some cases. After all, radiation is a local treatment and any DCIS recurrence is likely be caught and treated. However, approximately one-third of DCIS recurrences are accompanied by invasive breast cancer outside the breast, which is not likely to be treated successfully. Therefore, preventing a recurrence of DCIS is important.
Risk factors for progression of DCIS to invasive breast cancer
Factors associated with progression to invasive breast cancer similar but not identical to those associated with recurrent DCIS.
No radiation treatment following surgery to remove DCIS
Generally speaking, progression of DCIS to invasive breast cancer is more likely if radiation is omitted. One large study found that by 15 years after breast conserving surgery for DCIS, almost one-third of the participants had developed either a recurrence of DCIS or invasive breast cancer in the same breast. Radiation treatment reduced this risk by 50%, equally divided between DCIS and invasive breast cancer. Radiation appeared to have a continuous protective effect against DCIS recurrences, but protected against invasive disease only during the first five years after radiation treatment. Again, evidence suggests that radiation could be omitted in women at low risk for progression to invasive breast cancer.
DCIS that forms a lump or thickening in the breast that can be felt by hand is more likely to progress to invasive disease than a lesion that cannot be detected manually. This means that DCIS found with a screening mammogram is normally less likely to progress that self-detected DCIS.
High breast density
High breast density is associated with increased risk of progression to invasive cancer in the breast treated for DCIS, as well as in the opposite, or untreated, breast. One study of 935 DCIS patients reported that women with the greatest area of mammographic breast density (top fifth of values) had more than twice the risk of invasive breast cancer in either breast compared to women with the smallest area of density (bottom fifth).
DCIS with microinvasion
DCIS with microinvasion has an elevated risk of progression to invasive breast cancer. Microinvasion refers to DCIS with an invasive component (beyond the ducts) of less than 1 or 2 mm. Microinvasion is found in 5 to 10% of DCIS cases. The incidence of microinvasion increases with the size and aggressiveness of the DCIS. The prognosis of DCIS with microinvasion appears to be intermediate between that of DCIS and invasive breast cancer. Unlike the majority of cases of DCIS without microinvasion, sentinel lymph node biopsy is appropriate for patients with microinvasion to evaluate the possible need for chemotherapy.
Concurrent LCIS and DCIS
DCIS that is found together with lobular carcinoma in situ (LCIS), the other type of noninvasive breast cancer, is associated with increased risk of progression to invasive breast cancer.
HER2 positive and triple negative DCIS
The type of DCIS is predictive of the type of invasive cancer that may eventually develop, suggesting than hormone receptor positive (ER+/PR+) DCIS is not likely to progress to aggressive breast cancer. On the other hand, DCIS with an aggressive subtype (such as HER2+ or triple negative) is more likely to progress to invasive breast cancer than ER+/PR+ disease and also to have aggressive (HER2+ or triple negative) characteristics when it does so.
African-American women who are diagnosed with DCIS have more than double the risk of progression to invasive breast cancer as non-Hispanic white women.
Other DCIS characteristics
Other characteristics of DCIS associated with increased risk of progression to invasive breast cancer are heightened Ki-67 antigen, overexpression of cyclooxygenase-2 (COX-2), and cancerization of lobules. Atypical ductal hyperplasia, which is not considered cancer, is a risk factor for both DCIS and invasive breast cancer. Generally speaking, microscopic pathology grading or nuclear grade does not reliably predict risk of progression.
Researchers are making progress in developing methods (including multigene and antibody signature tests) to predict the likelihood of DCIS recurrence or progression based on DCIS lesion characteristics.
Tamoxifen and aromatase inhibitors reduce progression to invasive breast cance
Tamoxifen and aromatase inhibitors have both been found to reduce both DCIS recurrence and progression to invasive breast cancer among women with estrogen receptor positive DCIS. One study reported that women with ER+ (ER+/PR+ or ER+/PR-) DCIS had approximately half the risk of progression to invasive breast cancer during the first 10 years after diagnosis if treated with tamoxifen for five years. No benefit was found for ER- (ER-/PR+ or ER-/PR-) DCIS.
Increased likelihood of additional screening and procedures
The risk of DCIS recurrence or progression to invasive cancer continues at least 20 years and requires active ongoing follow up. Some women face multiple additional diagnostic tests and invasive procedures over time after breast conserving treatment for DCIS. Patients need to be prepared psychologically and financially, as well as having enough flexibility in their work/family situations, to deal with this possibility.
One large 2012 study examined the rates of diagnostic mammograms and ipsilateral (in the same breast that was treated for DCIS) invasive procedures after breast conserving treatment. During the first 10 years, 31% of the women had diagnostic mammograms (which are more extensive than screening mammograms) and 62% had ipsilateral invasive procedures (e.g., needle biopsy, surgical biopsy, lumpectomy). The first six months after surgery to remove the DCIS lesions was particularly active. Excluding this early period, the annual rate of diagnostic mammograms was 4.3%; the corresponding rate of ipsilateral invasive procedures was 3.1%. Approximately 8.0% of the women experienced a recurrence of DCIS and 8.1% were diagnosed with invasive breast cancer during the follow-up period.
Radiation treatment might be associated with different pattern of recurrence
One controversial 10-year prospective study found that patterns of recurrence were different for women who had radiation treatment compared to those who did not. The study followed 1,000 patients with pure DCIS who underwent breast-conserving surgery with or without radiation. While women treated with radiation had a significantly lower DCIS recurrence rate than those who omitted radiation, they also experienced more invasive breast cancer recurrences (after a longer time from initial diagnosis to recurrence). This resulted in a small net lower breast cancer survival rate at 10 years for those who had radiation treatment. The average time to recurrence (DCIS or invasive breast cancer) for patients not receiving radiation was just under four years. For those receiving radiation, it was almost eight years. These findings need to be explained and confirmed with other studies.