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.     

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.     

Subclinical ductal carcinoma in situ of the breast. Treatment by local excision and surveillance alone.

BACKGROUND. Mammography has led to earlier detection of subclinical ductal carcinoma in situ (DCIS) of the breast either as nonpalpable calcifications or as an incidental finding in a biopsy performed for another reason. Many women in whom DCIS was detected early may not be destined to have an invasive carcinoma. How should subclinical DCIS be treated if that is the case? What is the role of excision and surveillance only as an alternative to mastectomy or irradiation? METHODS. All patients with DCIS detected as nonpalpable calcifications or as an incidental finding were eligible for this study. Diagnosis was confirmed, and the histologic subtype was determined. Results of postbiopsy mammography confirmed excision of calcifications; wide local reexcision and assessment of margins was also performed in most patients. The maximum diameter of calcifications considered suitable for this treatment was 25 mm. RESULTS. Between 1978 and 1990, 70 women (72 breasts) were entered into this study (mean follow-up time, 49 months; median follow-up time, 47 months). Of this group, 66% were detected as calcifications and 33% were detected as incidental findings. The recurrence rate was 15.3%. All but one of the patients who experienced a recurrence had the comedo type of DCIS as the initial lesion. Each of the recurrences was of the comedo type. All but one recurrence was at the same site as the primary lesion. None of the patients with DCIS as an incidental finding experienced a recurrence. CONCLUSIONS. Excision and surveillance is a reasonable alternative to mastectomy or irradiation for selected women with DCIS that presents as nonpalpable calcifications or as an incidental finding.     

Recurrence of Breast Cancer following local excision alone for ductal carcinoma in situ

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.     

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.     

Margin width and local recurrence after breast conserving surgery for ductal carcinoma in situ

Introduction

Ductal Carcinoma in situ (DCIS) represents 5% of symptomatic and 20–30% of screen detected cancers. Breast conserving surgery (BCS) ± radiotherapy is performed in over 70% of women with DCIS. What constitutes an adequate margin for BCS remains unclear.

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

AimsDetermination of the risk of recurrence after local excision of ductal carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on immunohistochemical staining to oestrogen receptor (ER), progesterone receptor (PR) and HER2neu improved risk prediction in invasive breast cancer, but few studies have evaluated if molecular classification of DCIS predicts local recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to determine if molecular classification predicts local recurrence after breast-conserving therapy for DCIS.Materials and methodsWe reviewed the records of patients with DCIS treated between 1987 and 2000, carried out a pathology review and immunohistochemical staining for ER, PR and HER2neu and categorised cases into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu–), luminal B (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER–, PR–, HER2neu+), triple negative (ER–, PR–, HER2neu–)]. We evaluated the association between the molecular subtype and the development of local recurrence.ResultsIn total, 180 cases of DCIS were included in the study (luminal A, n = 113; luminal B, n = 25; HER2neu type, n = 29; triple negative, n = 13). The median follow-up time was 8.7 years. We observed higher rates of local recurrence among luminal B (40%) and HER2neu type (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On multivariable analysis, HER2neu overexpression was associated with an increased risk of local recurrence (hazard ratio = 1.98; 95% confidence interval: 1.11, 3.53, P = 0.02).ConclusionHER2neu expression in DCIS is a significant predictor of local recurrence, whereas luminal A and triple negative phenotypes are associated with relatively low risks of local recurrence.     

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.     

Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast

The development of an invasive recurrence following treatment for ductal carcinoma in situ (DCIS) converts a non-fatal disease to one associated with mortality. To date, no pathological or molecular features have been found to predict for the type of recurrence. Previous studies have suggested that in DCIS angiogenesis may be an important factor in determining the transformation from in situ to invasive carcinoma. We looked at 355 cases of DCIS and found that 32 had subsequently developed recurrent disease. In these 32 cases and in matched controls, periductal vascular density was determined using morphometry and anti-endothelial antibodies, von Willebrand factor (vWF) and CD34. Vascular density was related to the risk of both invasive and in situ recurrence. Normal lobules at least 2 mm away were used as controls. Differences in the phenotype of individual blood vessels was detected by performing dual staining immunofluorescence on selected cases. The microvessel density (MVD), as detected with the CD34 antibody, was higher around foci of DCIS than around normal breast lobules (P=0.001). Furthermore, it was significantly higher in cases of DCIS that recurred (P<0.0001). The findings with the vWF antibody were less clear cut and suggested a trend in decreasing MVD with increasingly aggressive disease. Dual immunofluorescence staining shows that the increase in MVD seen around DCIS is due to an increase in CD34+/vWF-blood vessels. An increase in CD34+/vWF-of blood vessels may be able to predict cases of DCIS that are at a high risk of developing a recurrence.     

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.     

Factors associated with local recurrence of mammographically detected ductal carcinoma in situ in patients given breast-conserving therapy

BACKGROUND: The authors reviewed their institution's experience treating patients with mammographically detected ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine 10-year rates of local control and survival and to identify factors associated with local recurrence. METHODS: From January 1980 to December 1993, 132 breasts in 130 patients were treated with BCT for mammographically detected DCIS at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent an excisional biopsy, and 64% were reexcised. All patients received postoperative whole-breast irradiation to a median dose of 45.0 Gray (Gy) (range: 43.1-56.0 Gy). One hundred twenty-four cases (94%) received a boost to the tumor bed for a median total dose of 60.4 Gy (range: 45.0-71.8 Gy). All cases underwent complete pathologic review by one pathologist. The median follow-up was 7.0 years. RESULTS: Of the entire study group, 13 patients developed recurrence within the ipsilateral breast, for 5- and 10-year actuarial rates of 8.9% and 10.3%, respectively. Nine of the 13 recurrences (69%) occurred within or immediately adjacent to the lumpectomy cavity and were designated as true recurrences or marginal misses (TR/MM). Four patients (31%) had recurrence elsewhere in the breast. Ten of the 13 recurrences (77%) were invasive, whereas 3 (23%) were pure DCIS. Only 1 patient died of disease, corresponding to 5- and 10-year actuarial cause specific survival rates of 100% and 99.0%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with ipsilateral breast failure or TR/MM. In multivariate analysis, only the absence of pathologic calcifications was significantly associated with ipsilateral breast failure. When specifically analyzed for TR/MM, younger age at diagnosis, number of slides with DCIS, number of DCIS and cancerization of lobules (COL) foci within 5 mm of the margin, and the absence of pathologic calcifications demonstrated a statistically significant association. Close or positive margin status did not significantly predict for either TR/MM (P = 0.14) or ipsilateral breast failure (P = 0.19). CONCLUSIONS: In patients with mammographically detected DCIS treated with BCT, adequate excision of all DCIS prior to RT can result in improved rates of local control. However, margin status may not adequately predict complete tumor extirpation. The volume of DCIS within 5 mm of the margin appears to be a more reliable surrogate for the adequacy of excision. In addition, young patient age and the absence of pathologic calcifications are independent risk factors for the development of local recurrence.     

Tumor characteristics as predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis

While ductal carcinoma in situ (DCIS) is seldom life threatening, the management of DCIS remains a dilemma for patients and their physicians. Aggressive treatment reduces the risk of ipsilateral breast tumor recurrence (IBTR), but has never been proven to improve survival. There is interest in identifying the prognostic factors for determining low-risk DCIS patients, but a comprehensive review of high-quality evidence on tumor characteristics in predicting local recurrence has never been carried out. We examined the following tumor characteristics: biomarkers, comedonecrosis, focality, surgical margin, method of detection, tumor grade, and tumor size. For this systematic review we restricted the analyses to the results of subgroup analyses from randomized controlled trials (RCTs) and multivariate analyses from RCTs and observational studies. We identified 44 eligible articles. The pooled random-effects risk estimates for IBTR are comedonecrosis 1.71(95% CI, 1.36–2.16), focality 1.95(95% CI, 1.59–2.40), margin 2.25(95% CI, 1.77–2.86), method of detection 1.35(95% CI, 1.12–1.62), tumor grade 1.81(95% CI, 1.53–2.13), and tumor size 1.63(95% CI, 1.30–2.06). Limited evidence indicated that women whose DCIS is ER-negative, PR-negative, or HER2/neu receptor positive have an IBTR higher than those whose DCIS is ER-positive, PR-positive, and HER2/neu receptor negative. A variety of tumor characteristics are significant predictors for IBTR. These results are important for both clinicians and patients to interpret the risk of local recurrence and to decide on a course of treatment.     

Wide local excision and radiotherapy for the treatment of ductal carcinoma in situ of the breast: the Hong Kong experience

AimsBreast conservation treatment for ductal carcinoma in situ (DCIS) was unpopular in the Chinese population and the outcome was seldom reported. We conducted a single-centre retrospective study to examine the clinical outcome of women in Hong Kong.Materials and methodsSeventy-five Chinese women were treated with wide local excision and radiotherapy for DCIS of the breast between 1994 and 2003. Only 26 (34.7%) women had non-palpable DCIS detected by screening mammograms. All women were treated with whole breast irradiation of 50 Gy in 2 Gy daily fractions, with 50 (66.7%) women receiving an additional electron boost of 10–16 Gy.ResultsThe median follow-up was 5.1 years (range 2.0–10.7). At the last assessment, four women developed local recurrences, but all remained disease-free after salvage mastectomy. The 5-year actuarial local failure-free rate and cause-specific survival rate were 92.9% (95% confidence interval 89.4–96.4) and 100.0%, respectively. Cosmetic results were rated as good to excellent in all women. On univariate analysis of prognostic factors for local failure, only a close (≤2 mm) final resection margin approached statistical significance (hazard ratio 9.108; 95% confidence interval 0.946–87.655; P = 0.056). The 5-year actuarial local failure-free rates for women with a close (≤2 mm) final resection margin and women with wider margins were 77.0 and 98.2%, respectively.ConclusionsDespite geographical and demographic differences, the clinical outcome after wide local excision and radiotherapy for DCIS of the breast in Chinese women is comparable with that in Western series. Efforts are needed to achieve cosmetically acceptable tumour-free margins greater than 2 mm.     

Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast.

The type 1 tyrosine kinase receptor HER2 (c-erbB2/neu) is associated with resistance to hormone therapy and poor survival in invasive breast cancer, whereas HER4 expression is associated with endocrine responsiveness. Patterns of tyrosine kinase receptor coexpression may aid prediction of recurrence risk after surgery for ductal carcinoma in situ (DCIS). Women who had undergone surgery for pure DCIS were studied. Out of 129 primary tumors, 39 had recurred and 90 had not recurred after 5 years of follow-up. Primary tumors were compared for HER2, HER3, and HER4, estrogen receptor, and Ki67 by immunohistochemistry. HER2 was expressed in 58%, HER3 in 49%, and HER4 in 63% of nonrecurrent DCIS, compared with HER2 expression in 82% (P = 0.008), HER3 expression in 71% (P = 0.04), and HER4 expression in 36% (P = 0.004) in DCIS that subsequently recurred. Dually expressing HER2/4 DCIS was more likely to be estrogen receptor positive than HER2-only-expressing DCIS (73% versus 53%; P = 0.05). HER2 expression was associated with a higher percentage and HER4 expression a significantly lower percentage of proliferating DCIS cells (median, 13.8% versus 8.4%; P = 0.001). Coexpression of HER2 with HER4 was associated with reduced recurrence compared with HER2-only positive DCIS (P = 0.003). This association remained significant when analyzing only high nuclear-grade DCIS (P = 0.015). Low nuclear grade, low proliferation rate and presence of HER4 expression were independent predictors of nonrecurrence. Potentially, HER4 expression may identify women who could avoid radiotherapy after breast-conserving surgery for DCIS.     

Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast

The optimal management of ductal carcinoma in situ (DCIS) is controversial, due in part to our poor understanding of its natural history. We undertook to identify subgroups of DCIS based on the expression of biomarkers, which were related to the likelihood of clinical recurrence. Biomarker expression of a total of 95 DCIS lesions in a nested case-control study within a population-based cohort with up to 135 months follow-up data (median 101 months) was analysed using immunohistochemistry. ERBB2-positivity and bcl-2-, oestrogen receptor (ER)- and progesterone receptor (PR)-negativity were individually associated with the risk of clinical recurrence. The predictive value of these biomarkers was independent of cytonuclear grade. ERBB2, bcl-2, ER and PR expression were conserved in the recurrent lesions, including subsequent invasive cancers. p21-positive DCIS was also associated with clinical recurrence, independently of the associations with ERBB2/bcl-2/ER/PR expression. These data identify clinically and biologically relevant subcategories of DCIS lesions, an essential basis for improving management.     

Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component

Background Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.Methods Consecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.Results A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.Conclusions IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.Subject terms: Genetics research, Surgical oncology, Breast cancer, Breast cancer     

Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases

PurposeDuctal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival.Patients and methodsThis study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS + RT), presenting local recurrences, with a 156-month median follow-up.ResultsEighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P = 0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P < 0.0007).ConclusionInvasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.