A Comparison of Tumor Biology in Primary Ductal CarcinomaIn SituRecurring as Invasive Carcinoma versus a NewIn Situ

Abstract

Introduction. About half of all new ipsilateral events after a primary ductal carcinoma in situ (DCIS) are invasive carcinoma. We studied tumor markers in the primary DCIS in relation to type of event (invasive versus in situ). Methods. Two hundred and sixty-six women with a primary DCIS from two source populations, all with a known ipsilateral event, were included. All new events were regarded as recurrences. Patient and primary tumor characteristics (estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, and Ki67) were evaluated. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses. Results. One hundred and thirty-six of the recurrences were invasive carcinoma and 130 were in situ. The recurrence was more often invasive if the primary DCIS was ER+ (OR 2.5, 95% CI 1.2–5.1). Primary DCIS being HER2+ (OR 0.5, 95% CI 0.3–0.9), EGFR+ (OR 0.4, 95% CI 0.2–0.9), and ER95−/HER2+ (OR 0.2, 95% CI 0.1–0.6) had a lower risk of a recurrence being invasive. Conclusions. In this study, comparing type of recurrence after a DCIS showed that the ER−/HER2+ tumors were related to a recurrence being a new DCIS. And surprisingly, tumors being ER+, HER2−, and EGFR− were related to a recurrence being invasive cancer.

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

“…Despite the fact that Zhou et al 77 did not discern true DCIS outgrowths from new primary breast lesions, their findings remain very interesting: patients with ER-negative HER2-positive primary DCIS presented significantly more often with an in situ "recurrence," whereas ER-positive HER2-negative primary DCIS presented significantly more often with an invasive "recurrence." 77 This might seem contradictory, as HER2 is associated with poor prognosis in invasive breast cancer. This apparent paradox is indirectly supported by other studies.…”

“…HER2 amplification and its concurrent protein overexpression might act as a driver for intraductal clonal proliferation, instead of being a driver of cancer cell invasion. This hypothesis may explain the observations of Zhou et al ., and it may also explain the paradoxical observation of HER2 overexpression being much more common in DCIS than in invasive carcinoma . Nevertheless, a nested case–control study identified HER2 as a marker for progression to invasive carcinoma, and therefore additional investigations remain warranted to clarify the role of this intriguing receptor …”

“…Unfortunately, these authors did not investigate the clonal relationship between the primary DCIS lesion and its corresponding recurrence, since they regarded all ipsilateral new events as de facto recurrences. 77 Establishing whether a "recurrence" is either a new second primary tumor or an outgrowth of the initial DCIS lesion is essential for the success of this research strategy. To determine the clonal relationship between the primary DCIS lesion and the second breast event, morphological features such as nuclear grade and DCIS growth pattern can be studied, complemented by immunohistochemistry to assess the expression of ER, progesterone receptor (PR) and HER2.…”

“…To the best of our knowledge, this alternative strategy has been applied only once before. Zhou et al investigated a series of 266 women with primary pure DCIS and a known ipsilateral breast event: 136 of these so‐called recurrences were invasive carcinoma and 130 were DCIS. Unfortunately, these authors did not investigate the clonal relationship between the primary DCIS lesion and its corresponding recurrence, since they regarded all ipsilateral new events as de facto recurrences .…”

“…Zhou et al investigated a series of 266 women with primary pure DCIS and a known ipsilateral breast event: 136 of these so‐called recurrences were invasive carcinoma and 130 were DCIS. Unfortunately, these authors did not investigate the clonal relationship between the primary DCIS lesion and its corresponding recurrence, since they regarded all ipsilateral new events as de facto recurrences . Establishing whether a “recurrence” is either a new second primary tumor or an outgrowth of the initial DCIS lesion is essential for the success of this research strategy.…”