Van Nuys Prognostic Index Score Research Articles

Ipsilateral tumor recurrence risk in women with ductal carcinoma in situ: application of the Van Nuys Prognostic Index and the Memorial Sloan Kettering Cancer Center nomogram.

To apply the Van Nuys Prognostic Index (VNPI) and the Memorial Sloan Kettering Cancer Center (MSKCC) ductal carcinoma in situ (DCIS) nomogram to DCIS patients with known long-term outcomes. A retrospective review was performed of consecutive patients diagnosed with DCIS from 2007 to 2014. Included patients underwent breast-conserving surgery (BCS) and were followed with imaging for at least five years. For each patient, the VNPI and MSKCC nomogram risk estimates were determined. In addition, variables used in both models were compared between women with and without recurrences using the Wilcoxon signed-rank test and the Pearson's chi-squared test. Over the eight-year period, 456 women (average age 57 years, range 30-87) underwent BCS for DCIS. Thirty-one (6.8%) experienced an ipsilateral recurrence. The average VNPI scores were 7 (range 5-9) and 7 (range 4-10) for women with and without a recurrence (p = 0.14), respectively, with 4-6, 7-9, and 10-12 being the low, moderate, and high-risk groups, respectively. Per the MSKCC nomogram, the average five-year recurrence risks were 5% (range 1-12%) and 4% (range 1-38%) for women with and without a recurrence (p = 0.09), respectively. The recurrence risk-related variables were younger patient age, need for one or more re-excision surgeries, and use of endocrine therapy for 0 to less than five years after surgery. Ipsilateral tumor recurrence risk estimates based on the VNPI and MSKCC nomogram are similar between women with DCIS who did and did not have a recurrence, suggesting that more robust prognostic models are needed.

Will oncotype DX DCIS testing guide therapy? A single-institution correlation of oncotype DX DCIS results with histopathologic findings and clinical management decisions.

Given the increased detection rates of ductal carcinoma in situ (DCIS) and the limited overall survival benefit from adjuvant breast irradiation after breast-conserving surgery, there is interest in identifying subsets of patients who have low rates of ipsilateral breast tumor recurrence such that they might safely forgo radiation. The Oncotype DCIS score is a reverse transcription-PCR (RT-PCR)-based assay that was validated to predict which DCIS cases are most likely to recur. Clinically, these results may be used to assist in selecting which patients with DCIS might safely forgo radiation therapy after breast-conserving surgery; however, little is currently published on how this test is being used in practice. Our study examines traditional histopathologic features used in predicting DCIS risk with Oncotype DCIS results and how these results affect clinical decision-making at our academic institution. Histopathologic features and management decisions for 37 cases with Oncotype DCIS results over the past 4 years were collected. Necrosis, high nuclear grade, biopsy site change, estrogen receptor and progesterone receptor positivity <90% on immunohistochemistry, and Van Nuys Prognostic Index score of 8 or greater were significant predictors of an intermediate-high recurrence score on multivariate regression analysis (P<0.02). Low Oncotype DCIS scores and low nuclear grade were associated with lower rate of radiation therapy (P<0.008). There were seven cases (19%) with Oncotype DCIS results that we considered unexpected in relation to the histopathologic findings (ie, high nuclear grade with comedonecrosis and a low Oncotype score, or hormone receptor discrepancies). Overall, pathologic features correlate with Oncotype DCIS scores but unexpected results do occur, making individual recommendations sometimes challenging.

Comparison of predictive models for local recurrence of DCIS after breast conserving surgery.

21 Background: Efforts have been made to identify women for whom radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) can be omitted. These include development of the Memorial Sloan-Kettering (MSK) nomogram, the Van Nuys Prognostic Index (VNPI), and the DCIS Score. We assessed correlation of the predictive qualities of these 3 approaches to determine risk of local recurrence (LR) and need for RT. Methods: We calculated VNPI score and used the MSK nomogram to determine LR risks for 48 women on whom DCIS Scores were available since January 2012. Given that the DCIS Score does not account for HT, MSK risks were calculated with and without its use. 10-year LR risks from DCIS Score reports were compared with MSK nomogram estimates using the Pearson correlation coefficient. These comparisons were done for MSK LR risks with and without HT. VNPI scores yield low, intermediate and high risk categories. To compare the 3 predictive models, each patient was assigned an RT recommendation per instrument. Two 10-year LR risk “thresholds” to recommend RT were used - 10 and 15% - to account for M.D. preference. Results: For LR risk, the MSK nomogram (excluding HT) and the DCIS Score showed weak positive correlation (R = 0.346, p &lt; 0.02), weaker when including HT (R = 0.179, p: 0.224). VNPI Score could not be calculated on 5 patients and they were excluded in comparisons involving VNPI. DCIS Score, using 15% LR risk as the RT recommendation threshold, and VNPI RT recommendations correlated in 72.1% of cases. Lowering the threshold to10% reduced the correlation to 32.6%. Comparison of the 3 approaches’ RT recommendations with a 15% threshold showed agreement in 65.1% (28/43) of cases, and a 10% threshold reduced the agreement to 18.6% (8/43). Conclusions: Our analysis shows some correlation between the MSK nomogram and the DCIS Score, more when HT is excluded. Lowering the threshold 10-year LR risk to recommend RT from 15 to 10% reduced agreement among the 3 instruments.

Is radiotherapy necessary for intermediate risk ductal carcinoma in situ after breast conserving surgery?

Identifying ductal carcinoma in situ (DCIS) patients at highest risk for recurrence after breast conserving surgery (BCS) remains a clinical concern. Subjecting all such patients to radiotherapy may be unnecessary. The Van Nuys Prognostic Index (VNPI) is a simple scoring system for predicting the risk of local recurrence in patients with DCIS. We reviewed patients with DCIS applying the VNPI score system. A total of 184 DCIS patients who underwent surgery at our institution between January 2003 and December 2011 were identified. Patients were not treated according to VNPI guidelines; rather, radiation therapy was applied at each surgeon’s discretion. All patients with hormonal receptor positive tumors were treated with hormonal therapy. Pathology reports were reviewed and VNPI scores of each DCIS calculated. Of the 184 patients, 52 (28.3%), 115 (62.5%) and 17 (9.2%) had low, intermediate and high VNPI scores, respectively. Six of the 184 patients (3.3%) developed ipsilateral local recurrence, five in the intermediate and one in the high VNPI score group. Of the five in the intermediate group, three (60%) were in patients with ER-negative tumors. VNPI score itself was not associated with recurrence (P = 0.145). Factors associated with recurrence included tumor size (hazard ratio [HR] 6.88), grade (HR 9.07) and hormone receptor status (HR 11.75). Radiotherapy did not significantly improve recurrence rates in patients with low and intermediate risk DCIS, especially in those with ER-positive tumors. Radiotherapy can be omitted in patients with ER-positive intermediate score DCIS and in patients with low score DCIS.

The consequence of undertreatment of patients treated with breast conserving therapy for ductal carcinoma in-situ

BackgroundThe use of clinical features to allocate adjuvant therapy in the treatment of ductal carcinoma in situ with breast-conserving therapy remains controversial. MethodsA review of patients with ductal carcinoma in situ treated with breast-conserving therapy was performed. The recurrence rate was examined in relation to patient age, tumor characteristics, Van Nuys Prognostic Index, and the receipt of prescribed adjuvant therapies. ResultsSix percent of patients (17 of 294) had developed local recurrences after a median follow-up period of 63 months. Fifty-nine percent of patients (91 of 154) with estrogen receptor–positive tumors did not receive prescribed tamoxifen. Thirty-one percent of patients (45 of 147) with Van Nuys Prognostic Index scores ≥7 did not receive recommended radiation therapy. Receipt of prescribed adjuvant therapy did not result in a decrease in the rate of local recurrence. Patient age was the only factor associated with local recurrence on univariate but not on multivariate analysis (P = .374). ConclusionsA low rate of local recurrence was achieved despite a large number of patients' not receiving prescribed adjuvant therapies.

Fine Tuning of the Van Nuys Prognostic Index (VNPI) 2003 by Integrating the Genomic Grade Index (GGI): New Tools for Ductal Carcinoma In Situ (DCIS)

Ductal carcinoma in situ (DCIS) is considered a heterogeneous premalignant condition of the breast with a certain probability for progressing to malignancy. There is no standard of care. The updated Van Nuys Prognostic Index (VNPI) 2003 is a clinical tool in treatment decision making. This study assessed the prognostic value of the VNPI after integration of proliferative biomarkers (GGI and Ki-67). DCIS samples were divided into three VNPI subgroups (low risk [score 4-6], intermediate risk [score 7-9], high risk [score 10-12]) based on nuclear grade ± necrosis, tumor size, margin width, and age. Nuclear grade was substituted by the genomic grade index (GGI) to generate the VNPI-GGI and combined with the Ki-67 to generate the VNPI-Ki67. Disease-free survival was calculated by Kaplan-Meier survival plots with log-rank significance. Multiple regression analysis was carried out using Cox proportional hazard regression analysis. A total of 88 cases (median age 54 years) with representative tissue were identified out of 168 DCIS patients. Median follow-up was more than 5 years. Ten patients developed an ipsilateral recurrence of whom nine were invasive: six patients were classified in the VNPI subgroup 2 and three patients in the VNPI subgroup 3. One non-invasive recurrence (DCIS) was classified in the VNPI subgroup III. A statistical association was observed between a high VNPI score and a higher risk of recurrence (HR = 7.72 [95% CI 1.01-58.91], p = 0.049). Ki-67 did not improve the prognostic value of VNPI (HR = 6.5, [95% CI 0.80-53.33], p = 0.08). In contrast, the VNPI-GGI could identify more accurately high-risk DCIS patients with early relapses within 5 years (HR = 18.14 [95% CI 1.75-188], p = 0.015). GGI incorporated into the VNPI improved its prognostic value for DCIS, especially for identifying early relapses. This method should be validated and incorporated in future prospective clinical DCIS trials.

Decreased CD10 Expression Is Associated with a Higher Risk of Relapse in Ductal Carcinoma In Situ (DCIS).

Abstract Background: The Van Nuys Prognostic Index (VNPI) is the most widely used tool to predict local recurrence and guide therapy for DCIS. Nevertheless, many patients are still over-treated. Pre-clinical evidence indicates myo-epithelial cell (MEC) death in DCIS is a pre-requisite to tumor invasion. In this study we hypothesized that loss of CD10, (a marker of MECs), would be a surrogate for basement membrane disruption and tumor invasion. The aim of the present study was to retrospectively evaluate the prognostic value of CD10 in pure DCIS.Methods: CD10 expression was evaluated by qRT-PCR and immuno-histochemistry (IHC) using FFPE tissues on normal samples (N=11) and two independent pure DCIS populations: a training set (N=66) and a validation set (N=88).Results: MECs were the only cells that showed CD10 staining using IHC in normal and DCIS samples. All normal breast tissue samples demonstrated high expression levels of CD10 using both IHC and RT-PCR. In contrast, DCIS samples showed a wide range of CD10 expression levels: 1/3 of DCIS expressed high CD10 levels similar to those observed in normal breast tissue (high expression), whereas 2/3 expressed CD10 at a level below normal breast tissue (low expression). DCIS tumors with low CD10 mRNA levels were significantly associated with a higher risk of local relapse (HR= 2.49; [95%CI: 1.13-5.49], p=0.02). These results were validated in an independent dataset (HR= 1.805 [95%CI: 1.11-2.92], p=0.016). Of interest, no local relapses were observed in the high CD10 expression DCIS group. In multivariate analysis, CD10 expression by qRT-PCR was significantly associated with relapse (HR= 2.25, [95%CI: 1.24-4.09], p=0.008) in addition to VNPI score (HR: 2.03; [95%CI: 1.23-3.35], p=0.006).Conclusion: Decreased expression of CD10 in DCIS is associated with a higher risk of local relapse. These promising results are currently being validated in a larger patient series. Assessment of CD10 in addition to VPNI may lead to improved treatment tailoring for women with DCIS. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2112.

CD10 expression and risk of relapse in DCIS

e22053 Background: DCIS is a heterogeneous malignant condition of the breast with no standard of care. The Van Nuys Prognostic Index (VNPI) is the most useful tool to predict local recurrence. However, assessment of the VNPI score is not easy and many women with DCIS are offered the same treatment. Experimental evidence has indicated that a local death of the myo-epithelial cells (MECs) in the DCIS is a pre-requisite to tumor invasion. In this study we hypothesized that loss of CD10, (a marker of MECs), would be a surrogate for basement membrane disruption and tumor invasion. The aim of the present study was to retrospectively evaluate the prognostic value of CD10 in DCIS. Methods: CD10 expression was evaluated by qRT-PCR and immuno-histochemistry (IHC) using FFPE tissues on normal samples (N=11) and two independent DCIS populations: a training set (N=66) and a validating set (N=88). Results: MECs were the only cells that showed a CD10 staining using IHC in normal and DCIS samples. All normal tissue samples demonstrated high expression levels of CD10 using both IHC and RT-PCR. In contrast, DCIS samples showed a wide range of CD10 expression levels. Of interest, 66% of DCIS showed lower expression values of CD10 compared to normal tissues. The group of DCIS with low expression of CD10 was statistically associated with higher risk of relapse [HR: 2.49 (CI.95%= 1.13–5.49), P= 0.02]. These results were independently validated in our validation set using both techniques (qRT-PCR: HR: 1.805 (CI.95%= 1.11–2.92), P= 0.02]; IHC [HR: 1.84 (CI.95%= 1.00–3.40), P= 0.05]. In multivariate analysis, CD10 remained significant (HR=2.25; [95CI: 1.24–4.09], p=0.008) together with VNPI [HR: 2.03 (CI.95%= 1.23–3.35), P= 0.006]. Conclusions: Decrease of CD10 expression in MECs is associated with higher risk of relapse in DCIS and it has the potential to improve DCIS management. These promising results are currently being validated in a larger patient's series. No significant financial relationships to disclose.

Prognostic Significance of Oncogenic Markers in Ductal Carcinoma In Situ of the Breast: A Clinicopathologic Study

Ductal carcinoma in situ (DCIS) is a heterogeneous malignant condition of the breast with an excellent prognosis. Until recently mastectomy was the standard treatment. As the results of the National Surgical Adjuvant Breast and Bowel Project-17 trial and the introduction of the Van Nuys Prognostic Index (VNPI) less radical therapies are used. Objectives are to identify clinicopathologic and biologic factors that may predict outcome. Cases of DCIS diagnosed in two Belgian University Centers were included. Paraffin-embedded material and Hematoxylin and Eosin stained slides of DCIS cases were reviewed and tumor size, margin width, nuclear grade, and comedo necrosis were assessed. Molecular markers (estrogen receptor, progesterone receptor, HER1-4, Ki67, and c-myc) were assayed immunohistochemically. Applied treatment strategies were correlated with the prospective use of the VNPI score. Kaplan-Meier survival plots were generated with log-rank significance and multiple regression analysis was carried out using Cox proportional hazards regression analysis; 159 patients were included with a median age of 54 years (range 29-78); 141 had DCIS and 18 DCIS with microinvasion. The median time of follow-up was 54 months (range 5-253). Twenty-three patients developed a recurrence (14.5%). The median time to recurrence was 46 months (range 5-253). Before the introduction of the VNPI, 37.5% of the DCIS patients showed a recurrence while thereafter 6.7% recurred (p < 0.005). Two recurrences occurred in the VNPI group I (7.1%); seven in the VNPI group II (8.5%) (median time to recurrence 66.3 months) and 14 in the VNPI group III (28.5%) (median time to recurrence 40.2 months) (disease-free survival [DFS]: p < 0.05). A Cox proportional hazards regression analysis indicated that tumor size, margin width, pathologic class, and age were independent predictors of recurrence, but none of the studied molecular markers showed this. Overexpression of HER4 in the presence of HER3 was found to be associated with a better DFS (p < 0.05). This study confirms the value of the VNPI score and questions the benefit of an aggressive approach in the low-risk DCIS lesions. Independent predictors for recurrence included size, margin width, pathologic class, and age, but none of the molecular markers were part of it. Overexpression of HER4 in the presence of HER3 was associated with a better DFS.

The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ

BackgroundDebate regarding the benefit of radiotherapy after local excision of ductal carcinoma in situ (DCIS) continues. The Van Nuys Prognostic Index (VNPI) is thought to be a useful aid in deciding which patients are at increased risk of local recurrence and who may benefit from adjuvant radiotherapy (RT). Recently published interim data from the Sloane project has showed that the VNPI score did significantly affect the chances of getting planned radiotherapy in the UK, suggesting that British clinicians may already be using this scoring system to assist in decision making. This paper independently assesses the prognostic validity of the VNPI in a British population.Patients and methodsA retrospective review was conducted of all patients (n = 215) who underwent breast conserving surgery for DCIS at a single institution between 1997 – 2006. No patients included in the study received additional radiotherapy or hormonal treatment. Kaplan Meier survival curves were calculated, to determine disease free survival, for the total sample and a series of univariate analyses were performed to examine the value of various prognostic factors including the VNPI. The log-rank test was used to determine statistical significance of differential survival rates. Multivariate Cox regression analysis was performed to analyze the significance of the individual components of the VNPI. All analyses were conducted using SPSS software, version 14.5.ResultsThe mean follow-up period was 53 months (range 12–97, SD19.9). Ninety five tumours were high grade (44%) and 84 tumours exhibited comedo necrosis (39%). The closest mean initial excision margin was 2.4 mm (range 0–22 mm, standard deviation 2.8) and a total of 72 tumours (33%) underwent further re-excision. The observed and the actuarial 8 year disease-free survival rates in this study were 91% and 83% respectively. The VNPI score and the presence of comedo necrosis were the only statistically significant prognostic indicators (P < 0.05).ConclusionThis follow-up study of 215 patients with DCIS treated with local excision and observation alone is one of the largest series in which rates of recurrence are unaffected by radiation therapy, hormone manipulation or chemotherapy. It has afforded us the opportunity to assess the prognostic impact of patient and tumour characteristics free of any potentially confounding treatment related influences. The results suggest that the VNPI can be used to identify a subset of patients who are at risk of local recurrence and who may potentially benefit from RT.

259 Patients with DCIS of the breast applying USC/Van Nuys prognostic index: a retrospective review with long term follow up

The Van Nuys Prognostic Index (VNPI) is a simple score for predicting the risk of local recurrence (LR) in patients with Ductal Carcinoma In Situ (DCIS) conservatively treated. This score combines three independent predictors of Local Recurrence. The VNPI has recently been updated with the addition of age as a fourth parameter into the scoring system (University of Southern California/ VNPI). Our database consisted of 408 women with DCIS. Applying the USC/VNPI we reviewed retrospectively 259 patients who were treated with breast conserving surgery with or without radiotherapy (RT). Of these patients 63.5% had a low VNPI score, 32% intermediate and 4.5% a high score. In the low score group, the majority of the patients underwent Conservative Surgery (CS) without RT while in the intermediate group, almost half of the patients received RT. Eighty-three percent (83%) of the patients with high VNPI were treated with Conservative Surgery plus RT. Nodal assessment by Sentinel Lymph Node Biopsy was obtained in 32 patients since 2002. Twenty-one Local Recurrences were observed (8%) with a mean follow up of 130 months: sixteen were invasive. No statistically significant differences in Disease Free Survival were reached in all groups of VNPI score between patients treated with Conservative Surgery or Conservative Surgery plus RT. However it was noted that the higher the VNPI score, the lower was the risk of local recurrence in the group treated additionally with RT, even though it was not statistically significant. Further analysis included those patients treated with Conservative Surgery alone and followed up. Disease-free survival (DFS) at 10 years was 94% with low VNPI and 83% in both intermediate and high score (P < 0.05). No significant differences were observed in the subgroups of VNPI. The Local Relapse rate after Conservative Surgery alone, increased with tumor size, margin width, and pathology classification (P < 0,05), while age was not found to be a significant factor. Lesions with only mammographic appearances are associated with lower DFS but it did not reach significance (P = ns), while assumption of estrogenic hormones and familial history of breast cancer are significant factors associated with a higher risk of local recurrence. After multivariate analysis including seven clinical and pathological factors, the only significant predictors of local recurrence remained margin width of surgical excision, previous therapy with estrogens (contraceptives or Hormone Replacement Therapy) and the Van Nuys pathologic classification. The overall survival breast cancer specific was 99% and no differences were observed between groups (P = ns). The comparison of patients treated with a total mastectomy and those conservatively treated showed a significantly better local relapse free survival rate obtained with mastectomy (98.2% vs. 89.7% at 10 years P = 0.02). However, the overall cause-specific survival did not prove any better outcome (98.7% in both groups). Of the 32 patients who underwent a Sentinel Lymph Node Biopsy, four were found to have micrometastases and all of them had a previous Directional Vacuum Assisted Biopsy. Although in our series there is not a significant difference in LR rates by the parameter of age, the new USC/VNPI is still a simple and reliable scoring system for therapeutic management of DCIS. We did not find any statistically significant advantage in groups treated with the addition of RT. Obtaining wide surgical margins appears to be the strongest prognostic factor for local recurrence, regardless of other pathological factors or the addition of adjuvant radiation therapy. However, only prospective randomized studies can precisely predict the risk of LR of conservatively treated DCIS. The clinical significance of Sentinel Lymph Nodes micrometastases Immuno-Histo-Chemistry-detected found in DCIS patients remains uncertain. However, we hypothesize that the anatomical disruption after preoperative biopsy procedures increases the likelihood of epithelial cell displacement and the frequency of IHC-positive Sentinel Lymph Nodes, both of which are directly proportional to the degree of manipulation.

Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: a phase II clinical study

Background This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). Methods Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. Results The mean follow-up period was 9.5 months (range, 1–24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1–40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% ≥7 mm. No serious adverse events were reported. The infection rate was 4.0%. Conclusions Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.

Ductal carcinoma in situ of the breast and heparanase-1 expression: A molecular explanation for more aggressive subtypes

Ductal carcinoma in situ of the breast (DCIS) forms a heterogeneous group of lesions with varying invasive potential. This study tested whether heparanase-1 (HPR1), an endoglycosidase that specifically degrades the heparan sulfate (HS) proteoglycans in the breast extracellular matrix, was associated with the most aggressive DCIS subtypes. Fifty-seven DCIS specimens and 10 normal breast specimens were examined for HPR1 expression using immunohistochemical staining. Twenty-seven arbitrarily selected specimens were also examined for HS deposition by immunofluorescence staining, confirming HPR1 activity. Patient medical records were obtained to explore a possible association between biologic potential using Van Nuys Prognostic Index (VNPI) and HPR1 expression. Twenty-one (75%) of 28 comedo and microinvasive DCIS specimens stained HPR1 positive; 4 (14%) of 29 other subtypes (papillary, cribriform, and solid subtypes) stained HPR1 positive on immunohistochemistry (p = 0.003). Among 27 DCIS stained for HS, we found that 8 (67%) of 12 HPR1-negative DCIS had intact HS deposition in the extracellular basement membrane; none of the 15 HPR1-positive DCIS stained HS positive. Six (86%) of seven DCIS with VNPI scores 8 to 9 and 14 (50%) of 28 DCIS with VNPI scores 5 to 7 were HPR1 positive; only 3 (17%) of 18 DCIS with VNPI scores 3 to 4 were HPR1 positive. Median VNPI score in patients with HPR1-positive DCIS was 7 (range 3 to 9), compared with 4.5 (range 3 to 7) in patients with HPR1-negative DCIS (p < 0.001). HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane of the DCIS. HPR1 expression was associated with a higher VNPI score. These observations suggest that HPR1 expression in DCIS can play an important role in development of DCIS into an invasive breast cancer.

Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery.

The Van Nuys Prognostic Index (VNPI), an algorithm based on tumour size, tumour grade, presence of necrosis and excision margin width, is claimed to predict local recurrence after breast-conserving surgery for ductal carcinoma in situ (DCIS). The aim of this study was to examine the validity of the VNPI in a UK population. Clinicopathological data, including VNPI subgroups, for 237 patients who had breast-conserving operations for DCIS were examined. Multivariate data analysis was performed using a Cox regression model to examine the independence and relative importance of different variables in predicting recurrence, and to compare the data with those used in derivation of the VNPI. The median follow-up was 47 months. There were 37 ipsilateral local recurrences. Excision margin width (P < 0.001) and tumour grade (by Van Nuys grading (P = 0.014) or simple nuclear grading (P = 0.004)) were the only independent risk factors for local recurrence. Excision margin width had three times more power than grade in predicting local recurrence. Subgrouping data by VNPI score predicted recurrence-free survival (P < 0.001), but stratified 78 per cent of patients into a group with a moderate risk of local recurrence. Excision margin width is the most important predictor of local recurrence after breast-conserving surgery for DCIS. The VNPI lacked discriminatory power for guiding further patient management.

Six of the Best, Breast 09

Aims: The Van Nuys prognostic index (VNPI) is a numerical algorithm based on tumour features and recurrence data from a large series of DCIS patients. It attempts to quantify easily measured prognostic factors in a reproducible fashion separating DCIS patients into three groups. The value of the VNPI will be determined by its reproducibility in other institutions. Methods: A total of 700 DCIS patients were identified from a prospective audit. Clinical and pathological data were assessed and a VNPI score was assigned to each woman retrospectively. Patients with a high score (8 or 9) usually had undergone mastectomy and were not considered in this analysis. Results: Median follow up was 5.8 years. A total of 423 patients underwent BCT. One hundred and seventy-nine women (42.4 per cent) received DXT. In the BCT group, 80 patients had a score of 3 or 4 with 8 LR (10 per cent). In the BCT/DXT group, 42 patients had a score of 3 or 4 with 1 LR (3 per cent). When a score of 4 was considered alone recurrences were 14 per cent (BCT alone) and 3 per cent (BCT/DXT). In the group with scores of 5, 6 or 7, 115 patients underwent BCT alone with 49 (42 per cent) recurrences. Seventy-six patients underwent BCT/DXT with nine (9 per cent) recurrences. Conclusion: In this study, the VNPI remains useful in predicting recurrence and guiding therapies. An intermediate score in the BCT alone group in this analysis had a high chance of local recurrence. Adjuvant DXT reduced the recurrence rate. In contrast to other studies, BCT alone patients with a low VNPI (3 or 4) appeared to benefit from adjuvant DXT.

The importance of complete excision in the prevention of local recurrence of ductal carcinoma in situ.

Mastectomy probably represents over-treatment for the majority of women with screen detected ductal carcinoma in situ (DCIS) and breast-conserving surgery is now widely advocated. In this study, biopsy cavity shavings were used to ensure complete excision in 129 women undergoing breast-conserving surgery for screen detected DCIS. A margin was considered clear if DCIS was > 1 mm from any margin of excision and shavings were clear. Patients with involved margins (DCIS at resection margin) underwent re-excision, irrespective of shaving status. After re-excision, 101 women (78%) had clear margins and 28 (22%) close margins (DCIS < or = 1 mm from resection margin). Cavity shavings were histologically clear of DCIS in all cases. Ipsilateral DCIS recurrence occurred in 12 (9.3%) patients. Two recurrences also contained invasive carcinoma. The median time to diagnosis was 14 months and all recurrences occurred at the site of the previous biopsy. Seven recurrences were detected at the first annual mammogram, four at the second and one at the third. Ipsilateral recurrence was related to margin status; only 2 out of 101 (2%) patients with clear margins recurred, compared with 10 out of 28 (36%) patients with close margins. Local recurrence and close margin status both correlated with a high modified Van Nuys prognostic index score. Our results indicate that local relapse represents residual DCIS rather than true recurrence in the majority of cases. Cavity shavings have proved ineffective in ensuring complete excision. We now ensure a minimum 10 mm margin of excision around all screen-detected DCIS lesions.