Cristina Olcese

Relationship Between Margin Width and Recurrence of Ductal Carcinoma In Situ: Analysis of 2996 Women Treated With Breast-conserving Surgery for 30 Years

OBJECTIVE Our goal was to investigate, in a large population of women with ductal carcinoma in situ (DCIS) and long follow-up, the relationship between margin width and recurrence, controlling for other characteristics. BACKGROUND Although DCIS has minimal mortality, recurrence rates after breast-conserving surgery are significant, and half are invasive. Positive margins are associated with increased risk of local recurrence, but there is no consensus regarding optimal negative margin width. METHODS We retrospectively reviewed a prospective database of DCIS patients undergoing breast-conserving surgery from 1978 to 2010. Univariate and Cox proportional hazard models were used to investigate the association between margin width and recurrence. RESULTS In this review, 2996 cases were identified, of which 363 recurred. Median follow-up for women without recurrence was 75 months (range 0-30 years); 732 were studied for ≥10 years. Controlling for age, family history, presentation, nuclear grade, number of excisions, radiotherapy (RT), endocrine therapy, and year of surgery, margin width was significantly associated with recurrence in the entire population. Larger negative margins were associated with a lower hazard ratio compared with positive margins. An interaction between RT and margin width was significant (P < 0.03); the association of recurrence with margin width was significant in those without RT (P < 0.0001), but not in those with RT (P = 0.95). CONCLUSIONS In women not receiving RT, wider margins are significantly associated with a lower rate of recurrence. Obtaining wider negative margins may be important in reducing the risk of recurrence in women who choose not to undergo RT and may not be necessary in those who receive RT.

Fibroepithelial Lesions in the Breast of Adolescent Females: A Clinicopathological Study of 54 Cases

Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992–2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow‐up information were obtained from electronic medical records. Forty‐eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African‐American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high‐power fields (HPFs) (range, 0–6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow‐up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.

Atypical Ductal Hyperplasia Bordering on Ductal Carcinoma In Situ Interobserver Variability and Outcomes in 105 Cases

Background. The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are “borderline” breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. Methods. We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. Results. A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantly with lesion size and nuclear grade. There was diagnostic agreement by all 5 pathologists in 30% of cases, 4 pathologists in 42%, and 3 pathologists in 25%. At a median follow-up of 37 months, 4 (3.8%) patients developed subsequent ipsilateral breast carcinoma (2 invasive, 2 DCIS); all 4 cases had MajDx of ADH. Conclusions. Borderline ADH/DCIS represents an entity for which reproducible categorization as ADH or DCIS cannot be achieved. Furthermore, histologic features of borderline lesions resulting in MajDx of ADH vs. DCIS are not prognostic for risk of subsequent breast carcinoma.

Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ

The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast‐conserving surgery (BCS).

Association of MRI and locoregional recurrence (LRR) rates in ductal carcinoma in situ (DCIS) patients treated with or without radiation therapy (RT).

57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. METHODS All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. RESULTS 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. CONCLUSIONS We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text].

Recurrence rates for ductal carcinoma in situ: Analysis of 2,996 patients treated with breast-conserving surgery over 30 years.

32 Background: Randomized trials of radiation after breast-conserving surgery (BCS) for DCIS found substantial rates of recurrence, with half of recurrences invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed, and are largely attributed to systemic therapy improvements. Here we examine recurrence rates after BCS for DCIS over 3 decades at one institution. METHODS We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978-2010. Cox proportional hazard models were used to investigate the association between treatment period and recurrence, controlling for other variables. RESULTS 363 (12%) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0-30 years); 732 were followed for ≥ 10 years. The 5-year recurrence rate for 1978-1998 was 13.6% versus 6.6% for 1999-2010 (hazard ratio [HR] 0.62, p < 0.0001). After controlling for age, family history, presentation (radiologic vs clinical), nuclear grade (non-high vs. high grade), necrosis, number of excisions ( ≤ 2 vs ≥ 3), margin status (positive/close vs negative), radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, and adjustment for 7 other factors, the decrease in recurrence rates was limited to those without radiation (HR 0.62, p = 0.003); there was no decline in recurrence rates among those receiving radiation (HR 1.13, p = 0.6). CONCLUSIONS Recurrence rates for DCIS have fallen over time. Increases in screen-detection, negative margins, and use of adjuvant therapies only partially explain the decrease. The unexplained decline is limited to women not receiving radiation, suggesting it is not due to changes in radiation efficacy, but may be due to improvements in radiologic detection and pathologic assessment. The lower recurrence risk observed for DCIS patients treated in more recent years is important for patient education, especially in view of the widely reported recent increase in use of mastectomy.