Characterization of a novel silencer element in the human aromatase gene PII promoter

The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p=0.001), with reduction of distance to margins (p=0.05), with histologic grade (p=0.02), with percentage of positive blocks (p=0.0003) and with VNPI score (p=0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p=0.0001).Conclusion: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.     

Prognostic Significance of Clinicopathologic Features in Patients With Breast Ductal Carcinoma-in-Situ Who Received Breast-Conserving Surgery

Purpose

To identify whether a certain group of breast ductal carcinoma-in-situ (DCIS) patients can be treated with breast-conserving surgery (BCS) alone; to analyze the clinicopathologic features of DCIS and tamoxifen administration in patients treated with BCS who developed ipsilateral breast tumor recurrence (IBTR).

Choosing treatment for patients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index

The University of Southern California/Van Nuys Prognostic Index is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (tumor size, margin width, nuclear grade, age, and comedonecrosis). With three times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥ 3 mm. Excision plus RT achieves the less than 20% local recurrence requirement at 12 years for patients who score 7 and have margins < 3 mm, patients who score 8 and have margins ≥ 3 mm, and for patients who score 9 and have margins ≥ 5 mm. Mastectomy is required for patients who score 8 and have margins < 3 mm, who score 9 and have margins < 5 mm, and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. These recommendations in this article represent substantial changes from those previously published.     

An argument against routine use of radiotherapy for ductal carcinoma in situ

Three prospective randomized trials have shown that postexcisional radiation therapy can reduce the relative risk of local recurrence by about 50% in conservatively treated patients with ductal carcinoma in situ (DCIS). In an era of evidence-based medicine, how then can one possibly take a stand against the routine use of radiation therapy after local excision? Surprisingly, the rationale is straightforward. In some low-risk DCIS patients, the costs may far outweigh the potential benefits. In spite of a relative 50% reduction in the probability of local recurrence, the absolute reduction may only be a few percentage points. In addition, the prospective trials focus on local recurrence as their primary end point because it is, by far, the most common untoward event following conservative treatment. Local recurrence is clearly important, but breast cancer-specific survival is, in fact, an even more important end point, and no trial in patients with DCIS has ever shown a survival benefit with the use of radiation. Moreover, radiation therapy is not without financial and physical cost. So, if there is no difference in breast cancer-specific survival regardless of the treatment and in some subgroups the absolute benefit from radiation therapy is extremely small, it seems reasonable to attempt to develop a system to select patients with DCIS who could be safely treated in the least aggressive way. The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) uses five independent predictors of local recurrence to do exactly that. The combination of tumor size, margin width, nuclear grade, age, and the presence or absence of comedonecrosis can be used to identify subgroups of patients with an extremely low probability of developing a local recurrence after excision alone. When accurate measurements of tumor size cannot be made, margin width can be used as a surrogate parameter for the USC/VNPI. New oncoplastic techniques that allow more extensive excisions can be used to achieve both acceptable cosmesis and widely clear margins, helping to alleviate the need for radiation therapy in many cases.     

Is expert breast pathology assessment necessary for the management of ductal carcinoma in situ?

Background.Current guidelines include a recommendation that a pathologist with expertise in breast disease review all ductal carcinoma in situ (DCIS) specimens due to the presence of significant variability in pathologic reporting of DCIS. The objective of this study was to evaluate the completeness and accuracy of pathologic reporting of DCIS over the past decade and to determine the current impact of expert breast pathology assessment on the management of DCIS. Methods.All patients with a diagnosis of DCIS referred to a single regional cancer centre between 1982 and 2000 have been reviewed. Inter-observer variability between initial and secondary reports has been evaluated using kappa statistics. For each case, the Van Nuys Prognostic Index (VNPI) using pathologic data obtained from the initial and reviewed pathology reports were compared. The impact of expert breast pathology on risk assessment and treatment was determined. Results.481 individuals with DCIS were referred and pathology review was performed on 350 patients (73%). Inter-observer agreement was high for the main pathologic features of DCIS. From 1996 to 2000, secondary pathology assessments lead to a change in the assessment of local recurrence risk in 100 cases (29%) and contributed to a change in treatment recommendation in 93 (43%) cases. ConclusionExpert breast pathology assessments continue to be necessary in the management of DCIS     

Outcomes and factors impacting local recurrence of ductal carcinoma in situ

BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.     

Breast conservation for ductal carcinoma in situ: Results at an Australian institution with evidence to recommend prospective assessment of the utility of a lumpectomy boost

Aim: We reviewed outcomes for ductal carcinoma in situ (DCIS) of the breast at our institution to assess risk factors for ipsilateral breast tumour recurrence (IBTR) after breast conservation (BCT). Methods: Records were reviewed of all patients who presented with biopsy‐confirmed DCIS of the breast prior to 1 January 2004. Variables analyzed included patient age, tumour size, grade, resection margins, comedonecrosis, surgery, tamoxifen, whole breast radiotherapy dose and addition of a boost. We also attempted to validate the University of Southern California/Van Nuys prognostic index (USC/VNPI). Results: One hundred and thirty patients had DCIS: four were excluded from analysis and another 10 had mastectomies. A total of 116 patients had BCT and this group comprised the study population. Median follow‐up was 7.7 years (1.6–12.4) and median age was 58 years. Five‐ and 10‐year overall survivals were 98% (93.5–99.6 95% CI) and 89% (74–95 95% CI). Five‐ and 10‐year breast failure‐free survivals were 96% (90–98 95% CI) and 93% (85–97 95% CI). Young age was the only significant factor associated with IBTR (P = 0.018). Patients with a high USC/VNPI score were also significant for increased IBTR (P = 0.04), but this effect disappeared when age was omitted from the index. There was a trend towards an increased risk of IBTR with a lower whole breast dose of less than 50 Gy (P = 0.18). A boost was not associated with reduced IBTR. The 10‐year IBTR for patients under 55 who received adjuvant radiotherapy to a whole breast dose of <50 Gy but no tamoxifen was 25%. Conclusion: Overall BCT local control and survival outcomes are excellent. There is a suggestion that younger patients should be treated with a whole breast dose equivalent to 50 Gy in 25 daily fractions regardless of a boost. However, this requires confirmation in a randomized phase III trial and therefore the currently active Trans‐Tasman Radiation Oncology Group randomized controlled trial 07.01 should be supported by the breast cancer treating community.     

The Role of Radiotherapy in the Conservative Treatment of Ductal Carcinoma in Situ of the Breast

Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard of care for the treatment of early-stage (St. I-II) invasive breast carcinoma. However, controversy exists regarding the value of RT in the conservative treatment of ductal carcinoma in situ (DCIS). In this article we review the role of RT in the management of DCIS. Retrospective and prospective trials and meta-analyses published between 1975 and 2007 in the MEDLINE database, and recent issues of relevant journals/handbooks relating to DCIS, BCS and RT were searched for. In retrospective series (10,194 patients) the 10-year rate of local recurrence (LR) with and without RT was reported in the range of 9-28% and 22-54%, respectively. In four large randomised controlled trials (NSABP-B-17, EORTC-10853, UKCCCR, SweDCIS; 4,568 patients) 50 Gy whole-breast RT significantly decreased the 5-year LR rate from 16-22% (annual LR rate: 2.6-5.0%) to 7-10% (annual LR rate: 1.3-1.9%). In a recent meta-analysis of randomised trials the addition of RT to BCS resulted in a 60% risk reduction of both invasive and in situ recurrences. In a multicentre retrospective study, an additional dose of 10 Gy to the tumour bed yielded a further 55% risk reduction compared to RT without boost. To date, no subgroups have been reliably identified that do not benefit from RT after BCS. In the NSABP-B-24 trial, the addition of tamoxifen (TAM) to RT reduced ipsilateral (11.1% vs. 7.7%) and contralateral (4.9% vs. 2.3%) breast events significantly. In contrast, in the UKCCCR study, TAM produced no significant reduction in all breast events. Based on available evidence obtained from retrospective and prospective trials, all patients with DCIS have potential benefit from RT after BCS. Further prospective studies are warranted to identify subgroups of low-risk patients with DCIS for whom RT can be safely omitted. Until long-term results of ongoing studies on outcomes of patients treated with BCS alone (with or without TAM or aromatase inhibitors) are available, RT should be routinely recommended after BCS for all patients except those with contraindication.     

Predictors of local recurrence following excision alone for ductal carcinoma in situ

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) remains controversial, particularly in regard to the selection of patients who may be appropriately treated with wide excision alone. To help identify such patients, the authors assessed prognostic factors for local recurrence in patients with DCIS treated with excision alone. METHODS: The study population consisted of 59 patients diagnosed with DCIS between 1985 and 1990. All had been treated with excision alone, had their histologic slides available for re-review by a study pathologist, and had negative margins of excision on review. The median age at diagnosis was 54 years, and the median follow-up time was 95.5 months. Ninety-six percent presented with mammographic findings only; all patients had a reexcision. The size of the DCIS was assessed by the total number of low-power fields (LPF) in which DCIS was present (median LPF = 5). RESULTS: Ten patients experienced a local recurrence (LR) at 5-132 months (median, 37 months) after excision. The actuarial 5-year LR rate was 10%. Four of the recurrences were invasive carcinomas, and 6 were DCIS. No patients have developed metastatic disease or have died of disease. Lesion size >5 LPF was the only significant prognostic factor for local recurrence on univariate analysis (3% vs. 17% for < or = 5 vs. > or = 5 LPF, P = 0.02) and in proportional hazards models. Although patients with nuclear Grade 3 lesions had a higher LR rate than those with nuclear Grade 1 and 2 lesions (18% vs. 6% and 5%, respectively) and patients with close margins (< or = 1 mm) had a higher LR rate than patients with negative margins (>1 mm) (25% vs. 8%), these differences did not reach statistical significance. Among the 19 cases with margins negative by more than 1 mm, lesion size < or = 5 LPF, and nuclear Grade 1 or 2, there were no LRs; by contrast, the remaining 40 patients had a 5-year actuarial LR rate of 15% (P = 0.08). CONCLUSIONS: Lesion size was the only statistically significant prognostic factor for local recurrence in this series of patients with DCIS treated with excision alone. Other factors, such as margin status and nuclear grade, may also be useful in the identification of patients with DCIS who can be managed with excision alone. However, the most reliable and reproducible method of assessing these factors and the best way to combine them have not been determined.     

Ductal carcinoma in situ: a challenging disease

Ductal carcinoma in situ (DCIS) represents a heterogenous group of lesions with variable malignant potential. Although it is clearly pre-invasive, not all lesions progress to an invasive malignant disease. The significant increase in the frequency of diagnosis is the result of both widespread use of screening mammography and better recognition among pathologists. Treatment is controversial, but for several decades total mastectomy has been considered as the appropriate treatment. The tendency to be less aggressive in terms of surgery has followed the pattern of events observed in the treatment of invasive breast carcinomas. More recently, it has become clear that breast-conserving procedures could be applied and selected on the basis of diagnostics and risk factors. When all patients with DCIS are considered, the overall mortality is extremely low, only about 1–2%. On the other hand, breast-conserving surgery is only curative in 75–85%; 50% of the local recurrences have proven to be invasive with a mortality rate of 12–15%. There is no place for axillary node dissection, adjuvant hormonal treatment or chemotherapy in the treatment. Important factors in predicting local recurrence are age, family history, nuclear grade, comedo-type necrosis, tumor size and margin width. With the addition of radiation therapy to excisional surgery, there is a 50% reduction in the overall local recurrence rate. The Van Nuys Prognostic Index (VNPI), recently updated, is a tool that quantifies measurable prognostic factors that can be used in the decision-making process of treatment. Recent data from large cohort studies and randomized trials have emerged to guide treatment. DCIS is now understood to have diverse malignant potential and it is unlikely that there will be a single treatment for this wide range of lesions. Advances in molecular biology and gene expression profiling of human breast tumors have been providing important insights into the relationship between DCIS and invasive breast cancer.     

Predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis

BACKGROUND: Management of patients with ductal carcinoma in situ (DCIS) is a dilemma, as mastectomy provides nearly a 100% cure rate but at the expense of physical and psychologic morbidity. It would be helpful if we could predict which patients with DCIS are at sufficiently high risk of local recurrence after conservative surgery (CS) alone to warrant postoperative radiotherapy (RT) and which patients are at sufficient risk of local recurrence after CS + RT to warrant mastectomy. The authors reviewed the published studies and identified the factors that may be predictive of local recurrence after management by mastectomy, CS alone, or CS + RT. METHODS: The authors examined patient, tumor, and treatment factors as potential predictors for local recurrence and estimated the risks of recurrence based on a review of published studies. They examined the effects of patient factors (age at diagnosis and family history), tumor factors (sub-type of DCIS, grade, tumor size, necrosis, and margins), and treatment (mastectomy, CS alone, and CS + RT). The 95% confidence intervals (CI) of the recurrence rates for each of the studies were calculated for subtype, grade, and necrosis, using the exact binomial; the summary recurrence rate and 95% CI for each treatment category were calculated by quantitative meta-analysis using the fixed and random effects models applied to proportions. RESULTS: Meta-analysis yielded a summary recurrence rate of 22.5% (95% CI = 16.9-28.2) for studies employing CS alone, 8.9% (95% CI = 6.8-11.0) for CS + RT, and 1.4% (95% CI = 0.7-2.1) for studies involving mastectomy alone. These summary figures indicate a clear and statistically significant separation, and therefore outcome, between the recurrence rates of each treatment category, despite the likelihood that the patients who underwent CS alone were likely to have had smaller, possibly low grade lesions with clear margins. The patients with risk factors of presence of necrosis, high grade cytologic features, or comedo subtype were found to derive the greatest improvement in local control with the addition of RT to CS. Local recurrence among patients treated by CS alone is approximately 20%, and one-half of the recurrences are invasive cancers. For most patients, RT reduces the risk of recurrence after CS alone by at least 50%. The differences in local recurrence between CS alone and CS + RT are most apparent for those patients with high grade tumors or DCIS with necrosis, or of the "comedo" subtype, or DCIS with close or positive surgical margins. CONCLUSIONS: The authors recommend that radiation be added to CS if patients with DCIS who also have the risk factors for local recurrence choose breast conservation over mastectomy. The patients who may be suitable for CS alone outside of a clinical trial may be those who have low grade lesions with little or no necrosis, and with clear surgical margins. Use of the summary statistics when discussing outcomes with patients may help the patient make treatment decisions.     

The impact of tumor size and histology on local control after breast-conserving therapy

To investigate possible contraindications for breast-conserving therapy (BCT) a retrospective clinicopathological study was carried out in 585 patients treated conservatively in The Netherlands Cancer Institute from 1979 to 1984. The local recurrence rate in the breast was 2% at 6 years and was similar in stages I and II breast cancer. Invasive cancer with extensive ductal carcinoma in situ (DCIS) component appeared to be the only main prognostic factor when local failure in the breast was considered. A multivariate analysis revealed that tumor size, microscopically incomplete excision of the primary tumor and age did not have a significant influence on local control alone, when this was corrected for extensive DCIS. When breast and axillary recurrences were taken together, age and extensive DCIS component appeared to be two independent prognostic factors according to a multivariate analysis. Especially patients younger than 40 years with an extensive DCIS component had a higher locoregional recurrence rate.     

Ductal carcinoma in situ of the breast results of conservative and radical treatments in 716 patients

Until now, less than 5% of the patients with breast ductal carcinoma in situ (DCIS) have been enrolled in clinical trials. Consequently, we have analysed the results of ‘current practice’ among 716 women treated in eight French Cancer Centres from 1985 to 1992: 441 cases (61.6%) corresponded to impalpable lesions, 92 had a clinical size of less than or equal to 2 cm and 70 from 2 to 5 cm; in 113 cases, the size was unspecified. Median age was 53.2 years (range: 21–87 years). 145 patients underwent mastectomy (RS) and 571 conservative surgery (CS) without (136) or with (435) radiotherapy (CS+RT). The mean histological tumour sizes in these three groups were 25.6, 8.2, 14.8 mm, respectively (P<0.0001). After a 91-month median follow-up, local recurrence (LR) rates were 2.1, 30.1 and 13.8% in the RS, CS and CS +RT groups, respectively (P=0.001); LR were invasive in 59 and 60% in the CS and CS+RT groups, respectively. In these groups, the 8-year LR rates were 31.3 and 13.9%, respectively (P=0.0001). Nodal recurrence occurred in 3.7 and 1.8% in the CS and CS+RT groups. Metastases rates were 1.4, 4.4 and 1.4% in the RS, CS and CS+RT groups. Among the 60 cases of invasive LR, in CS and CS+RT groups 19% developed metastases. After multivariate analysis, we did not identify any significant LR risk factor in the CS group, whereas young age (<40years) and incomplete excision were significant in the CS+RT group (P=0.012 and P=0.02, respectively).     

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.     

Margins in breast cancer: How much is enough?

The appropriate negative margin width for women undergoing breast‐conserving surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is controversial. This review examines the available data on the margin status for invasive breast cancer and DCIS, and highlights the similarities and differences in tumor biology and standard treatments that affect the local recurrence (LR) risk and, therefore, the optimal surgical margin. Consensus guidelines support a negative margin, defined as no ink on tumor, for invasive carcinoma treated with breast‐conserving therapy. Because of differences in the growth pattern and utilization of systemic therapy, a margin of 2 mm has been found to minimize the LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT). Wider negative margins do not improve local control for DCIS or invasive carcinoma when they are treated with lumpectomy and RT. Re‐excision for negative margins should be individualized, and the routine practice of performing additional surgery to obtain a wider negative margin is not supported by the literature. Cancer 2018;124:1335‐41 . © 2018 American Cancer Society.     

Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: A meta-analysis of 2 randomized trials

Background

Surgical excision with adequate margins is the treatment of choice for ductal, in situ carcinoma of the breast (DCIS). The addition of radiotherapy (RT) halved local in situ and invasive recurrence. The purpose of our meta-analysis is to evaluate the reduction in recurrence (in situ or invasive) with the addition of tamoxifen (T), in particular in patients with DCIS treated with surgery + RT.

Patients and methods

The eligible studies (NSABP-B24 and UK ANZ DCIS trials) included prospective, randomized, controlled trials in which the addition of T had been compared with surgery + RT without T in women with DCIS of the breast. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for both in situ and invasive recurrence (local and controlateral).

Results

Tamoxifen does not reduce breast cancer-specific or overall mortality when added to loco-regional therapy for DCIS of the breast (surgery plus or minus RT). Tamoxifen reduces overall breast cancer recurrence by 29% in all patients and by 33% in those treated with both surgery and RT. Only ipsilateral invasive (RR 0.61 [95% CI 0.41, 0.92]; p = 0.02) and controlateral in situ relapses (RR 0.40 [95% CI 0.16, 0.96]; p = 0.04) are significantly lowered when T is added to RT. Tamoxifen seems to exert a local synergistic effect with RT. Both young and older women (< and >50 years) achieve some benefit from the addition of T (RR 0.6 and 0.74, respectively).

Conclusion

The addition of T to surgery and RT for DCIS of the breast reduces the risk of local invasive and controlateral in situ relapses, but not the survival. The benefit is independent of age. In conclusion, surgery associated with RT and T is the treatment of choice for patients with (estrogen-receptor positive) DCIS of the breast.     

Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ

We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990–2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among 2,995 patients, 325 had a LR [10.9 %; median follow-up 4.8 years (range 0.5–15.7)]. After adjusting for health plan and treatment, risk of LR was increased among women <45 years (RR = 2.1, 95 % CI 1.5–2.8), African-Americans (RR = 1.6; 95 % CI 1.1–2.1) and those with DCIS detected because of signs/symptoms (RR = 1.6; 95 % CI 1.2–2.0). After also adjusting for age and diagnosis year, pathologic features associated with increased LR were larger lesion size (RR = 2.9 for ≥20 low power fields of DCIS; 95 % CI 1.6–5.6) and involved (RR = 2.9; 95 % CI 1.6–5.2), or close margins (RR = 2.4; 95 % CI 1.6–3.8). Presentation with symptoms/signs was associated with increased risk of invasive recurrence; while African-American race, larger tumor size, and involved/close tumor margins were more strongly associated with increased risk of DCIS recurrence. Our findings suggest some risk factors differ for non-invasive and invasive LRs and that most factors are only moderately associated with increased LR risk. Future research efforts should focus on non-clinicopathologic factors to identify more powerful risk factors for LR.     

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696-13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126-28.926; HR=2.778, 95% CI 0.982-6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272-5.776 for time period 1992-1995 and HR=1.976, 95% CI 0.526-7.421 for time period 1996-1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.     

Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.

METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.     

Age as a predictor of outcome for women with DCIS treated with breast-conserving surgery and radiation: The University of Texas M. D. Anderson Cancer Center experience

PURPOSE: To analyze the long-term outcome of breast conservation therapy in patients with ductal carcinoma in situ (DCIS) in a single institution and to analyze the prognostic importance, if any, of young patient age. METHODS AND MATERIALS: The hospital records of 150 patients with DCIS treated with surgical excision and radiotherapy at our institution between 1980 and 1997 were retrospectively reviewed. For most of the patients, intraoperative specimen radiographs or postoperative mammograms were available for use in assessing that an adequate surgical resection had been performed. The median patient age was 53 years (range 32-81), with 13% of patients or=40 years, p = 0.39). In all cases of local recurrence, patients underwent surgery with or without chemotherapy, and disease control was achieved. CONCLUSION: The results of this study demonstrate high rates of long-term overall survival, disease-specific survival, and local control in patients with DCIS of the breast treated conservatively with segmental mastectomy and radiotherapy. On the basis of the excellent long-term local control and 100% disease-specific survival rates, we found that patient age does not affect the outcome if the margins are clear. Continued studies in young patients treated with breast conservative therapy for DCIS are needed.