Expression of HER2neu in ductal carcinoma in situ is associated with local recurrence.

Determination of the risk of recurrence after local excision of ductal carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on immunohistochemical staining to oestrogen receptor (ER), progesterone receptor (PR) and HER2neu improved risk prediction in invasive breast cancer, but few studies have evaluated if molecular classification of DCIS predicts local recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to determine if molecular classification predicts local recurrence after breast-conserving therapy for DCIS. We reviewed the records of patients with DCIS treated between 1987 and 2000, carried out a pathology review and immunohistochemical staining for ER, PR and HER2neu and categorised cases into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu-), luminal B (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER-, PR-, HER2neu+), triple negative (ER-, PR-, HER2neu-)]. We evaluated the association between the molecular subtype and the development of local recurrence. In total, 180 cases of DCIS were included in the study (luminal A, n=113; luminal B, n=25; HER2neu type, n=29; triple negative, n=13). The median follow-up time was 8.7 years. We observed higher rates of local recurrence among luminal B (40%) and HER2neu type (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On multivariable analysis, HER2neu overexpression was associated with an increased risk of local recurrence (hazard ratio=1.98; 95% confidence interval: 1.11, 3.53, P=0.02). HER2neu expression in DCIS is a significant predictor of local recurrence, whereas luminal A and triple negative phenotypes are associated with relatively low risks of local recurrence.

Han K ，Nofech-Mozes S ，Narod S ，Hanna W ，Vesprini D ，Saskin R ，Taylor C ，Kong I ，Paszat L ，Rakovitch E ... -  《-》

The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast: a study of a large cohort of patients treated with surgery alone.

A number of conventional histopathologic features have been associated with recurrence of ductal carcinoma in situ (DCIS) after surgery alone and are included in the Van Nuys Pathologic Classification and Prognostic Index. To the authors' knowledge, very little is known regarding the prognostic significance of the many biologic markers that have been studied in DCIS in the past decade. Clinical and pathologic data were analyzed from 151 patients who underwent wide local excision alone for DCIS that was diagnosed by mammography or as an incidental finding between 1982 and 2000. Using local disease recurrence as an endpoint, the authors sought to determine the prognostic significance of a large number of histopathologic parameters as well as biologic markers (estrogen receptor [ER], progesterone receptor [PR], p53, HER-2/neu, Ki-67, p21, and bcl-2), as determined by immunohistochemical staining of contemporary or archival tissue. With a median follow-up of 65 months, 42 recurrences were reported to occur between 11 months and 97 months after definitive surgery. In a univariate analysis, tumor size, Van Nuys pathologic classification, and degree of necrosis demonstrated significant correlations with the rate of recurrence. Tumor size, necrosis, nuclear grade, and comedonecrosis were found to be associated significantly with the time to disease recurrence. None of the biologic markers demonstrated a significant association with the rate of recurrence or the time to disease recurrence. In a multivariate analysis, only large tumor size (Van Nuys 2 or 3) and higher degrees of necrosis (Van Nuys 2 or 3) were found to be associated significantly with both the rate of recurrence and the time to recurrence. No biologic marker showed a significant correlation with recurrence. Using Classification and Regression-Tree Analysis and Tree-Structured Survival Analysis, PR > 3.5% and bcl-2 < 97.5% were associated with a higher recurrence rate in the subgroup of patients with small tumor size (Van Nuys size 1) and higher degrees of tumor necrosis (Van Nuys 2 or 3). The current results confirmed the value of conventional histopathologic parameters, as outlined in the Van Nuys classification system, in predicting local recurrence of DCIS. Using traditional logistic analyses, no significant correlation was found between a variety of biologic markers and disease recurrence.

Cornfield DB ，Palazzo JP ，Schwartz GF ，Goonewardene SA ，Kovatich AJ ，Chervoneva I ，Hyslop T ，Schwarting R ... -  《CANCER》

Improved outcomes of breast-conserving therapy for patients with ductal carcinoma in situ.

Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2(+) DCIS. We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR(+)HER-2(-), 27 were ER/PR(+)HER-2(+), 6 were ER(-)/PR(-)HER-2(+), and 6 were ER(-)/PR(-)HER-2(-). On univariable analysis, HER-2(+)was significantly associated with Grade III, ER(-)/PR(-), central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2(+). In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated with HER-2(+)DCIS included more extensive DCIS, Grade III, ER(-)/PR(-), central necrosis, comedo subtype, and postmenopausal status. Further follow-up and additional studies are required to confirm these results.

Halasz LM ，Sreedhara M ，Chen YH ，Bellon JR ，Punglia RS ，Wong JS ，Harris JR ，Brock JE ... -  《-》

Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy.

Nguyen PL ，Taghian AG ，Katz MS ，Niemierko A ，Abi Raad RF ，Boon WL ，Bellon JR ，Wong JS ，Smith BL ，Harris JR ... -  《-》

Is there a low-grade precursor pathway in breast cancer?

King TA ，Sakr RA ，Muhsen S ，Andrade VP ，Giri D ，Van Zee KJ ，Morrow M ... -  《-》