The value of the Van Nuys Prognostic Index in ductal carcinoma in situ of the breast: a retrospective analysis

The Van Nuys Prognostic Index 1996 (VNPI), based upon tumor size, pathological grade and tumor margins, is a guideline for the treatment of ductal carcinoma in situ (DCIS). It was thought to strongly decrease overtreatment. In 2003, age was added to the index as a fourth prognostic factor. We examined changes in treatment modality after applying the VNPI retrospectively and investigated if the addition of age to the Index causes a shift in treatment. The influence of each prognostic factor on disease-free survival (DFS) was calculated. We performed a retrospective file study of DCIS patients treated between 1985 and 2003 at the University Hospital, Antwerp. Patients were assigned a Van Nuys Score 1996 and 2003. The influence of tumor size, pathological grade, tumor margins and age on DFS was calculated with the Kaplan-Meier method and the log-rank test. We identified 104 DCIS cases with a median follow-up of 36 months. Twelve patients showed recurrence (11.5%), of whom seven were invasive (58%). Seventeen of the 29 women diagnosed before 1997 were undertreated according to the VNPI 1996 and six of them showed recurrence. The remaining three recurrences were correctly treated. Seventy-five patients diagnosed after 1997 were all treated according to the VNPI 1996 and only three had a recurrence. The introduction of age caused no significant shift in treatment modalities. Significant differences in DFS were seen between large (>41 mm) and small (<15 mm) tumors (p = 0.0074), old (>60 years) and young (<40 years) patients (p = 0.024) and Van Nuys Subgroup 2 and 3 (p = 0.04). Tumor margins and pathological grade showed no significant difference in DFS. The VNPI can be a useful tool in the treatment of DCIS. However, this Index is not evidence-based, using a relatively small retrospective series of patients. The validity of the modified VNPI must be prospectively confirmed with large numbers of DCIS patients.     

The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast

BACKGROUND: The original Van Nuys prognostic index (VNPI) was introduced in 1996 as an aid to the complex treatment decision-making process for patients with ductal carcinoma in situ (DCIS) of the breast. This update adds patient age to the previous predictors of local recurrence in breast preservation patients. METHODS: A prospective database consisting of 706 conservatively patients with DCIS was examined using multivariate analysis. Four independent predictors of local recurrence (tumor size, margin width, pathologic classification, and age) were used to derive a new formula for the University of Southern California (USC)/VNPI. RESULTS: In all, 706 patients with pure DCIS were treated with breast preservation. There was no statistical difference in the 12-year local recurrence-free survival in patients with USC/VNPI scores of 4, 5, or 6, regardless of whether or not radiation therapy was used (P = not significant). Patients with USC/VNPI scores of 7, 8, or 9 received a statistically significant average 12% to 15% local recurrence-free survival benefit when treated with radiation therapy (P = 0.03). Patients with scores of 10, 11, or 12, although showing the greatest absolute benefit from radiation therapy, experienced local recurrence rates of almost 50% at 5 years. CONCLUSIONS: Ductal carcinoma in situ patients with USC/VNPI scores of 4, 5 or 6 can be considered for treatment with excision only. Patients with intermediate scores (7, 8, or 9) should be considered for treatment with radiation therapy or be reexcised if margin width is less than 10 mm and cosmetically feasible. Patients with USC/VNPI scores of 10, 11, or 12 exhibit extremely high local recurrence rates, regardless of irradiation, and should be considered for mastectomy, generally with immediate reconstruction or reexcision if technically possible.     

Contralateral breast cancer risk and endocrine therapy use in patients with ductal carcinoma in situ treated with unilateral mastectomy in the modern era

BackgroundIn patients with ductal carcinoma in situ (DCIS), the risk of developing contralateral breast cancer (CBC) and the role of adjuvant endocrine therapy (ET) in decreasing CBC risk is not well understood.MethodsA retrospective review was performed on patients with DCIS who underwent a unilateral mastectomy (UM) from 2000 to 2010. CBC incidence, time to CBC and disease free survival were evaluated for women who took ET versus those who did not.Results176 patients underwent a UM for DCIS, 72% were ER positive and 16% of patients took ET. At a median of 12 year follow up, 15 patients experienced CBC. Women over 63 years had highest incidence of CBC. CBC risk was not different between those who took ET versus those who did not.ConclusionThe overall incidence of CBC was 9% in our DCIS cohort and was not significantly different among patients who took ET versus those who did not.     

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast

Background: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. Methods: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. Results: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate;P=.07, for multivariate) and initial presentation (P=.05, for univariate;P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. Conclusions: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.     

Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status

As our knowledge of ductal carcinoma in situ (DCIS) continues to evolve, treatment decision-making has become increasingly complex and controversial for both patients and physicians. Treatment options include mastectomy, and breast conservation with or without radiation therapy. Data produced from the randomized clinical trials for DCIS has provided the basis for important treatment recommendations, but are not without limitations. In this article, we review our prospectively collected database consisting of 1036 patients with DCIS treated at the Van Nuys Breast Center and the USC/Norris Comprehensive Cancer Center. We review the use of the USC/Van Nuys Prognostic Index, a clinical algorithm designed to assist physicians in selection of appropriate treatments, and examine the impact of margin status as a sole predictor of local recurrence.     

Postoperative Tamoxifen for ductal carcinoma in situ: Cochrane systematic review and meta-analysis

This review aimed to assess the effects of postoperative Tamoxifen following surgical resection of ductal carcinoma in situ (DCIS). Data on local DCIS recurrence, new invasive carcinoma, distant disease, mortality and adverse effects were extracted from randomised controlled trials (RCTs) comparing Tamoxifen after surgery for DCIS (regardless of oestrogen receptor (ER) status), with or without adjuvant radiotherapy. Meta-analysis was performed using the fixed-effect model and the results expressed as relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs). Two RCTs which recruited 3375 women were included. Tamoxifen after surgery for DCIS reduced recurrence of ipsilateral DCIS (HR 0.75; 95% CI 0.61-0.92) and contralateral DCIS (RR 0.50; 95% CI 0.28-0.87). Contralateral invasive cancer was reduced (RR 0.57; 95% CI 0.39-0.83), and there was a trend towards decreased ipsilateral invasive cancer (HR 0.79; 95% CI 0.62-1.01). The number needed to treat in order for Tamoxifen to have a protective effect against all breast events is 15. There was no evidence of a difference in all-cause mortality (RR 1.11; 95% CI 0.89-1.39). Only one trial involving 1799 participants followed-up for 163 months (median) reported on adverse events with no significant difference in event rate between Tamoxifen and placebo groups, but there was a non-significant trend towards more endometrial cancer in the Tamoxifen group. This review concludes that while Tamoxifen after local excision for DCIS, with or without adjuvant radiotherapy, reduced the risk of recurrent DCIS, it did not reduce the risk of all-cause mortality.     

Margin width as the sole determinant of local recurrence after breast conservation in patients with ductal carcinoma in situ of the breast

BACKGROUND: A previous study showed a 3% local recurrence risk at 8 years in ductal carcinoma in situ (DCIS) patients treated with excision alone with surgical margins of 10 mm or greater. This study updates those data. METHODS: A total of 272 DCIS patients treated conservatively with 10 mm or greater margins were reviewed in a prospective database. RESULTS: Among 212 excision-alone patients, there were 9 DCIS and 3 invasive recurrences. The 12-year probability of any local recurrence was 13.9%; of invasive recurrence it was 3.4%. Among 60 excision plus radiation patients, there was 1 local (invasive) recurrence (P = .06). The 12-year probability of local recurrence was 2.5%. CONCLUSIONS: Local recurrence in DCIS patients treated with excision alone with margins of 10 mm or greater compares favorably with local recurrence in DCIS patients with nontransected margins and treated with postoperative radiation. The risk of invasive recurrence among widely excised DCIS patients is extremely low.     

Breast conservative surgery for well-differentiated ductal intraepithelial neoplasia: Risk factors for ipsilateral breast tumor recurrence

RationalWe retrospectively analyzed 232 patients affected by well differentiated ductal intraepithelial neoplasia (DIN1c or DCIS G1) treated with conservative surgery without adjuvant radiotherapy.Results25 invasive and 18 non-invasive local recurrences were observed (median follow-up 80 months; 5-year cumulative incidence: 12.2%). Seven of the 15 young patients (<40 y) developed local recurrence (2 in situ, 5 invasive). Age <50 (HR 1.89, 95% C.I. 1.01–3.45), multifocality (HR 3.21, 95% C.I. 1.46–7.06), Ki-67 > 7% (HR 2.33, 95% C.I. 1.20–4.55) and surgical margins <10 mm (HR 2.00, 95% C.I. 1.06–3.76) were significantly associated with an increased risk of local recurrence.ConclusionsYoung age, multifocality and small margins appeared as clear risk factors of local recurrence in DIN1c (DCIS G1) population. The presence of multiple poor prognostic features warrant a thorough discussion regarding local treatment.     

A review of the management of ductal carcinoma in situ following breast conserving surgery

Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 10–20% of all new breast tumours. Evidence shows a statistically significant local control benefit for adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for all patients. The baseline recurrence risk of individual patients varies according to clinical-pathological criteria and in selected patients, omission of RT may be considered, following a discussion with the patient. The role of adjuvant endocrine therapy remains uncertain. Ongoing studies are attempting to define subgroups of patients who are at sufficiently low risk of recurrence that RT may be safely omitted; investigating RT techniques and dose fractionation schedules; and defining the role of endocrine therapy. Future directions in the management of patients with DCIS will include investigation of prognostic and predictive biomarkers to inform individualised therapy tailored to the risk of recurrence.     

Invasive local recurrence increased after radiation therapy for ductal carcinoma in situ

BACKGROUND: It is thought that equal numbers of invasive and noninvasive recurrences develop after conservative treatment for ductal carcinoma in situ. We analyzed our data to see if this was true. METHODS: A prospective database of 878 conservatively treated patients with ductal carcinoma in situ was analyzed. RESULTS: Among 551 excision patients, there were 88 recurrences. Thirty-five percent were invasive. Among 327 excision plus radiotherapy patients, there were 59 recurrences. Fifty-three percent were invasive. In an attempt to predict which patients develop invasive recurrences, prolonged time to recurrence was the only statistically significant factor. CONCLUSIONS: The median time to local recurrence for irradiated patients was more than twice as long when compared with nonirradiated patients, during which there is more time for local recurrence to progress to invasion. Irradiated patients had more breast scarring, making diagnosis by palpation and mammography harder. Irradiated patients develop invasive recurrences at a statistically higher rate than nonirradiated patients. Follow-up evaluation with magnetic resonance imaging should be considered.     

Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer

PURPOSE: The purpose of this study was to determine the rates of sentinel lymph node (SLN) positivity in patients with a final diagnosis of ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC). METHODS: One hundred thirty patients underwent SLN mapping from 1998 to 2003 for DCIS or MIC. RESULTS: One hundred nine patients with DCIS and 21 with MIC underwent SLN mapping. One patient with bilateral DCIS underwent 2 SLN procedures; therefore, the results of 131 SLN procedures are included. On hematoxylin and eosin (H&E) staining, 4 of 110 patients (3.6%) with DCIS had positive SLNs. Four additional patients had positive SLNs by IHC staining only (3.6%). Two of 8 patients underwent completion axillary dissection, and neither had additional involved nodes on completion axillary dissection. One of the 21 patients with MIC had positive SLNs by hematoxylin and eosin (H&E) (4.8%), and another had an involved SLN by IHC staining (4.8%). The patient with the positive SLN by H&E had 1 additional node on completion axillary dissection. CONCLUSION: Rates of SLN positivity for patients with DCIS are modest, even in a high-risk population, and there is continuing uncertainty about its clinical importance.     

Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study

PurposeTurkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study.Patients and methodsTotally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control.ResultsThe median follow-up time was 59 (21–220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control.ConclusionIn our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.     

乳腺导管原位癌的超声特征

目的探讨乳腺导管原位癌(DCIS)的超声表现特征。方法回顾性分析经病理证实的54例乳腺DCIS的超声表现,包括病灶形态、大小、边缘、边界、内部回声、后方回声、微钙化、导管改变及血供,并与病理结果进行对比。结果54例均经术后病理证实为乳腺DCIS,其中高级别34例,中级别13例,低级别7例;5例伴微浸润灶,均未见腋窝淋巴结转移。声像图表现为片状低回声型20例(20/51,39.22%)、结节状肿块型17例(17/51,33.33%)、导管扩张型8例(8/51,15.69%)、单纯微钙化型6例(6/51,11.76%),3例假阴性,检出率94.44%(51/54)。超声正确诊断44例,准确率81.48%(44/54)。结论乳腺DCIS超声表现具有一定特征性;正确认识其超声征象能有效提高诊断符合率。     

Severe fatigue after treatment of ductal carcinoma in situ: A comparison with age-matched breast cancer survivors and healthy controls

PurposeSevere fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients.Methods89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength.Results23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue.ConclusionsThe prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients.     

Breast-conserving therapy for ductal carcinoma in situ: a 20-year experience with excision plus radiation therapy

BACKGROUND: Breast conservation therapy is a practical alternative to mastectomy for the treatment of ductal carcinoma in situ (DCIS). The role of radiation therapy after excision for DCIS has been debated, however, its value in reducing recurrence has been proven by multiple prospective randomized trials and is well accepted. METHODS: We examined a prospective database of 260 patients treated for DCIS with excision and radiation from 1979 to 2002. Two different treatment regimens were examined for local recurrence-free survival. Patients treated with radiation therapy 4 days per week were compared with patients treated 5 days per week. The total doses were similar for both groups; boost types differed. Local recurrence as a function of other factors, including nuclear grade, comedonecrosis, and margin width was evaluated. RESULTS: The median time to local recurrence was 61 months for patients treated 4 days per week compared with 52 months for patients treated 5 days per week (P = not significant). There was no statistical difference in the Kaplan-Meier detailing the probability of local recurrence-free survival for patients treated 4 days per week versus patients treated 5 days per week. Overall, cosmetic results between the two groups were equivalent. CONCLUSIONS: The comparison of two different radiation treatment regimens shows no difference in local disease-free survival or cosmetic result.     

The current treatment of ductal carcinoma in situ

A consensus conference was held in April, 1999, to help sift through the maze of controversy surrounding the treatment of mammographically detected ductal carcinoma in situ (DCIS). Members of the panel included approximately 30 DCIS experts, who addressed issues relating diagnosis, treatment, treatment of breast (and axilla), adjuvant theraphy, among others. The panel agreed that the goal of treatment for DCIS is breast conservation and attempted to divide the population of patients with DCIS into subsets who are appropriately treated by mastectomy, radiation theraphy, or by excision alone. Major criteria for breast conservation include small size of area of DCIS, clear surgical margins, and favorable biology. Neither axilliary dissection nor sentinel node biopsy is appropriate for DCIS treated by breast conservation. The role of tamoxifen is currently under study, and although approved by the FDA for "risk reduction," its use in patients with DCIS is uncertain.     

Factors associated with decision to pursue mastectomy and breast reconstruction for treatment of ductal carcinoma in situ of the breast

Background

Factors influencing the treatment of ductal carcinoma in situ with mastectomy and reconstruction are poorly understood.

Methods

A retrospective cohort study of 196 patients presenting to one institution was performed.

Results

Forty-seven patients (24.0%) were treated with mastectomy, while 149 (76.0%) underwent breast-conserving surgery. Of the mastectomy patients, 28 (59.6%) elected for reconstruction. On bivariate analysis, patients who opted for mastectomy were younger than those treated with breast-conserving surgery (median age, 51.8 vs 56.5 years; P = .017) and had higher grade tumors (50.0% vs 34.6% grade 3, P = .009). Among patients treated with mastectomy, those who opted for reconstruction were younger than those forgoing reconstruction (49.4 vs 56.9 years, P = .024). Race, ductal carcinoma in situ tumor size, and histologic subtype were not associated with the decision to pursue mastectomy or reconstruction (P > .05 for all).

Conclusions

In patients with ductal carcinoma in situ, the decision to pursue mastectomy and reconstruction appears to be driven by younger patient age and higher tumor grade.     

The oncologic safety of breast-conserving surgery for breast ductal carcinoma in situ

Objective To evaluate the safety of breast-conserving surgery for ductal carcinoma in situ( DCIS) . Methods One hundred and nineteen patients with pathologically confirmed DCIS were analyzed retrospectively.     

Intraoperative margin assessment reduces reexcision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery

BACKGROUND: Reported rates of reexcision for margin control after breast-conserving surgery for ductal carcinoma in situ (DCIS) range from 48% to 59%. The optimal technique for intraoperative margin assessment in patients with DCIS has yet to be defined. We sought to determine whether intraoperative multidisciplinary evaluation using gross tissue assessment and sectioned-specimen radiography reduces the need for reoperation for margin control in DCIS. METHODS: A prospectively compiled database was used to identify patients who had DCIS diagnosed by core needle biopsy and were treated with breast-conserving surgery at our institution between July 1999 and July 2002. All patients had intraoperative gross margin assessment and specimen radiography of both the whole and sliced specimen for calcifications. RESULTS: Four hundred two patients with DCIS were evaluated at our institution during the study period. Of these, 160 had excisional biopsy for diagnosis prior to referral, 92 had mastectomy as their initial procedure, 40 were seen for a second opinion only, and 1 patient refused surgery. The remaining 109 patients formed the study population. The median age was 55 years (range 34 to 81). The median pathologic size of DCIS was 1.2 cm (range 0.2 to 8.0 cm). Fifty-nine patients had positive (less than 1 mm) or close (less than 5 mm) margins on intraoperative assessment. Final pathology agreed with intraoperative assessment of a positive or close margin in 43 of the 59 patients (P = 0.00005). Seventy-five percent of those thought to have a positive or close margin at the time of surgery (n = 44) underwent intraoperative reexcision. Of the total 109 patients, 31 (34%) had an intraoperative reexcision that resulted in a change in margin status from positive on intraoperative evaluation to negative on final pathologic evaluation (P < 0.00001). A second procedure for margin control was necessary in only 24 patients (22%). The decision to excise additional tissue at the first surgery on the basis of intraoperative assessment resulted in significantly fewer second procedures for margin control (P = 0.029). CONCLUSIONS: In patients with DCIS, intraoperative margin assessment by gross pathological examination and sliced specimen radiography significantly affects intraoperative decision making, and excision of further tissue on the basis of intraoperative assessment results in a substantial decrease in second procedures for margin control.     

Outcome after invasive recurrence in patients with ductal carcinoma in situ of the breast

BACKGROUND: Local recurrence is used as a marker of treatment failure for patients with ductal carcinoma in situ (DCIS). As follow-up lengthens, distant recurrence, breast cancer-specific survival (BCSS), and overall survival must be monitored. METHODS: A prospective database was used to analyze 1031 patients with DCIS. Patients having invasive recurrence after DCIS treatment were compared with patients having infiltrating ductal carcinoma (IDC). End points included distant recurrence, BCSS, and overall survival. RESULTS: Overall, patients with DCIS had a BCSS of 99%. BCSS was 85% for patients with invasive recurrences. DDFS in this group was 80%. Stage I IDC patients had a BCSS of 91%, whereas it was 38% in those with stage I IDC and invasive recurrences. CONCLUSIONS: Most patients with DCIS that recur can be salvaged. For the small subgroup of patients who recur with invasive breast cancer, survival is similar to that of patients with stage IIA IDC.