Lumpectomy For Ductal Carcinoma In Situ Research Articles

Abstract P3-18-11: Meeting the challenge of successful one-stage lumpectomy for DCIS

Abstract Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p<0.001). Papillary-type DCIS was associated with an increased rate of re-excision surgery (Table 1). Prior to the introduction of the MarginProbe® for intraoperative margin assessment in 2014, approximately 42% of patients with DCIS underwent re-excisions. This decreased to 24.9% in the post-2013 time frame (p=0.02). In an unadjusted estimate for the odds ratio for association, patients who underwent lumpectomy with MarginProbe® were 81% less likely to require re-excision (OR = 0.19, 95% CI = 0.12, 0.31, p<0.0001). In a logistic regression model controlling for potential confounders with re-excision as the dependent variable and MarginProbe® as the primary explanatory variable, patients for whom the MarginProbe® was used were 66% less likely to require re-excision when controlling for age, tumor size, menopausal status, breast density, and pathology (OR = 0.34, 95% CI 0.16, 0.69). Of patients who required re-excision, 20% went on to mastectomies as their second procedure. After each unsuccessful re-excision, a larger proportion of patients converted to mastectomy. In total, 26% of patients who had unsuccessful primary surgery went on to mastectomies. Of patients who proceeded to mastectomy as their second procedures, 13% were found to carry BRCA1 or 2 mutations. Conclusions: In our study of patients diagnosed with pure DCIS and treated with primary breast conserving surgery, larger size of DCIS and papillary subtype were associated with an increased rate of re-excision procedures. A proportion of patients with unsuccessful primary lumpectomies required multiple procedures to complete their surgical treatment and 26% went on to mastectomy. Patients whose primary procedures included intraoperative margin assessment with the MarginProbe® were significantly less likely to require re-excision. Intraoperative margin assessment is an important tool that can support breast conserving surgery in the challenging population of patients with DCIS. Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)<0.001Breast Density (%)0.149N/A6 (1.9)2 (2.0)Entirely Fatty10 (3.2)3 (3.0)Extremely Dense19 (6.1)13 (13.0)Heterogeneously Dense165 (52.7)42 (42.0)Scattered Fibroglandular113 (36.1)40 (4.0)DCIS SubtypePapillary93 (29.7)48 (48.0)0.001Cribiform206 (65.8)69 (69.0)0.641Solid190 (60.7)60 (60.0)0.994Comedo54 (17.3)25 (25.0)0.117Surgical Margins (%)<0.001Close (>0 and <1mm)3 (1.0)60 (60.0)Negative (≥1 mm)310 (99.0)13 (13.0)Positive (≤0 mm)0 (0.0)27 (27.0) Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-11.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data.Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set.A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors.Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery.When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Management of Ductal Carcinoma In Situ (DCIS) of the Breast: Present Approaches and Future Directions.

Ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast is commonly found in an asymptomatic woman on routine screening mammography. The purpose of this review is to describe current approaches to the management of DCIS as well as areas for future investigation. Randomized trials have demonstrated that adding radiation treatment after breast conservation surgery (lumpectomy; surgical excision) reduces the rate of ipsilateral local recurrence by about half, and that adding hormonal therapy reduces the rate of all breast cancer events (ipsilateral plus contralateral). Early clinical studies attempted to stratify the risk of recurrence using conventional clinical and pathologic features. More recent clinical studies have attempted to define prospectively patients with lower risk DCIS for whom omission of radiation treatment after lumpectomy is a reasonable option. Molecular profiling is a newer approach to define risk stratification for DCIS. Combining molecular profiling with clinical and pathologic features appears to be more accurate in defining and stratifying the risk of recurrence after lumpectomy. After lumpectomy for DCIS, risk stratification using clinical and pathologic characteristics, and more recently molecular profiling, can help guide clinical decision-making for the use of radiation treatment and hormonal therapy. Ongoing studies are evaluating the possibility of de-escalating therapy, and in some studies, even using core biopsy alone, without surgical excision.

Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in-situ: A meta-analysis of randomized controlled trials.

The role of adjuvant radiotherapy (RT) following lumpectomy for ductal carcinoma in-situ (DCIS) was addressed in four major randomized controlled trials (RCTs) which were conducted two to three decades ago. Initial results of these trials suggested the protective role of RT in reducing the ipsilateral breast recurrences. Long-term results of all these four trials, based on more than 10-years follow-up data, have recently been published. A meta-analysis of four published RCTs which have addressed the role of adjuvant RT following lumpectomy for DCIS was conducted. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Evaluated events were ipsilateral breast recurrences (both DCIS and invasive), regional recurrences, contralateral breast events, distant recurrences, and overall mortality. The events were entered as dichotomous variable. The present meta-analysis included four RCTs and a total of 3680 patients - 1710 received adjuvant RT following lumpectomy while 1970 patients did not receive any adjuvant treatment. Patients who received RT had almost half of risk of ipsilateral breast recurrence (RR=0.53, 95% CI=0.45-0.62) and regional recurrence (RR=0.54, 95% CI=0.32-0.91) compared to those who did not receive adjuvant treatment - there was absolute risk reduction in 15% (95% CI=12%-17%) for ipsilateral breast recurrences in adjuvant RT treated patients. There was no significant difference in distant recurrence (RR=1.06, 95% CI=0.74-1.53), contralateral breast events (RR=1.22, 95% CI=0.98-1.52) and overall mortality (RR=0.93, 95% CI=0.79-1.09). Though addition of postoperative RT to lumpectomy does not reduce overall mortality, the present meta-analysis confirms that it decreases the ipsilateral breast and regional recurrence by almost half.

Abstract ES8-3: Endocrine management of premalignant lesions and DCIS

Abstract It has been recognized for many years that there exist pathological entities associated with an increased risk of invasive breast cancer. The most frequently encountered are atypical hyperplasia (AH), lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), although other diagnoses have also been identified. Often these lesions are discovered incidentally, and when diagnosed are found to confer a wide range of elevated breast cancer risk. Clinical management of these conditions has largely consisted of surveillance, sometimes with the addition of endocrine therapy. The selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, have been the mainstay of endocrine therapy in this setting. A prospective randomized trial, NSABP P-1 randomized over 13,000 high risk women, defined by a Gail score >1.66, to either 5 years of tamoxifen or placebo.1 Tamoxifen reduced the risk of invasive breast cancer by 49% (p<.00001), with the greatest risk reduction seen in women with ADH or LCIS. The IBIS I study also compared to tamoxifen to placebo and confirmed a risk reduction with tamoxifen, although lower than that reported initially in the P-1 trial (hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001).2 Most recently, the role of aromatase inhibitors as chemoprevention in this setting has been studied; the results of IBIS II trial, which randomized 3864 high risk postmenopausal women to anastrozole or placebo, found a substantial risk reduction in the AI group (hazard ratio 0.47, 95% CI 0.32-0.68, p<0.0001).3 Endocrine therapy in the adjuvant setting has been reported for DCIS in two prospective clinical studies, the NSABP-B24 and UK/ANZ trials. A meta-analysis of these two trials demonstrated that tamoxifen after lumpectomy for DCIS reduced recurrence of both ipsilateral (HR 0.75; 95% CI 0.61 to 0.92) and contralateral (RR 0.50; 95% CI 0.28 to 0.87) DCIS.4 There was a trend towards decreased ipsilateral invasive cancer (HR 0.79; 95% CI 0.62 to 1.01) and reduced contralateral invasive cancer (RR 0.57; 95% CI 0.39 to 0.83). In addition, the findings of NSABP B-35 randomizing postmenopausal women with ER-positive DCIS reported that 10-year point estimates for DFS were 77.9% for tamoxifen and 82.7% for anastrozole.5 Future challenges for this field will include more precise patient selection for these treatments, as all confer risk of side effects. These have resulted in poor uptake of chemoprevention despite the definitive benefit demonstrated in the large randomized studies. In addition, the utility of endocrine therapy as primary treatment for low risk DCIS or in the neoadjuvant setting are important questions which are currently under investigation. More precise quantification and communication of the risks and benefits of the endocrine therapies will be increasingly needed in order to maximize the benefits of endocrine intervention in this setting. 1Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371-88, 1998 2Cuzick J, Sestak I, Cawthorn S, et al: Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 16:67-75, 2015 3Cuzick J, Sestak I, Forbes JF, et al: Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383:1041-8, 2014 4Staley H, McCallum I, Bruce J: Postoperative tamoxifen for ductal carcinoma in situ. Cochrane Database Syst Rev 10:CD007847, 2012 5Margolese RG: Primary Results of NRG Oncology/NSABP B-35: A Clinical Trial of Anastrozole vs Tamoxifen in Postmenopausal Patients with DCIS. J Clin Oncol 33, 2015 (suppl; abstr LBA500), 2015. Citation Format: Hwang ES. Endocrine management of premalignant lesions and DCIS. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES8-3.

New Treatment Paradigms for Patients with Ductal Carcinoma In Situ

One of the most poorly understood clinical diagnoses in breast cancer is ductal carcinoma in situ (DCIS), which now accounts for almost one third of all mammographically detected malignancies. Detection and diagnosis of DCIS have improved, and mature data from randomized controlled trials of lumpectomy for DCIS have provided some measure of the magnitude of benefit to be derived from adjuvant treatments. The past 5 years have seen the emergence of molecular prognostic tools, which together with clinical factors have the potential to allow better selection of individualized therapies for these heterogeneous lesions. Ongoing and future research to identify which patients with DCIS can be safely managed with active surveillance are underway and will create opportunities to better understand the biology of this disease, thereby informing treatment strategies that are more closely aligned with the invasive potential of specific DCIS subtypes.

Ductal carcinoma in situ of the breast and gene expression markers for prediction of invasive recurrence

550 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive cancers with varying propensity for recurrence. There are no validated markers that identify patients at risk for invasive recurrence following lumpectomy. HOXB13/IL17BR (H/I) is expressed in both DCIS and invasive cancer (Ma Cancer Cell. 2004) and associated with recurrence in stage I cancer. A 5-gene molecular grade index (MGI) distinguishes outcome in grade II disease (Ma Clin Cancer Res. 2008). We sought to determine whether H/I or MGI was associated with invasive recurrence in resected DCIS. Methods: We identified patients at Mayo Rochester who underwent lumpectomy ± radiation for DCIS between 1988 and 2001 and performed a nested case/control study. Cases were patients with ipsilateral invasive recurrence, matched to controls based on age, surgery date, length of follow-up, and adjuvant radiation. DCIS was macrodissected from paraffin sections and RNA extracted to obtain H/I and MGI RT-PCR profiles. The association of H/I and MGI with case-control status was assessed with conditional logistic regression; results reported are odds ratios (OR) with 95% confidence intervals (CI). The association of H/I and MGI as continuous variables with nuclear grade (low, intermediate, high) was estimated with Spearman's rank correlation. Results: 427 patients underwent lumpectomy for DCIS, and 33 were identified as possible cases. Histologic review excluded 8 (non-sufficient tissue or DCIS recurrence without invasion). 25 cases were matched to 48 controls (2 controls for 23 cases, 1 control for 2 cases). Both H/I (r = 0.43, p = 0.0001) and MGI (r = 0.41, p = 0.0004) were significantly correlated with nuclear grade. Positive H/I was associated with trend towards higher recurrence (OR 1.9; p = 0.22) that was most pronounced in cases/controls (15/28) treated with lumpectomy alone (OR 3.3; CI: 0.8–13.2, p = 0.09). Similarly, positive MGI was associated with a trend towards higher recurrence risk in patients treated with surgery alone (OR 2.0; CI: 0.6–6.4, p = 0.27). Conclusions: These data suggest that both HOXB13/IL17BR and MGI can identify a subset of patients with surgically resected DCIS who are at risk for invasive recurrence. Further studies in larger cohorts are needed to confirm these findings. [Table: see text]

Association between Breast Density and Subsequent Breast Cancer Following Treatment for Ductal Carcinoma In situ

Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DCIS. A prospective cohort study of 3,274 women ages 30 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DCIS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis. Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2) breast density. During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events. High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease.

Radiation after lumpectomy for DCIS to reduce the risk of invasive breast cancer: A population-based study

516 Background: Although randomized trials have demonstrated the efficacy of radiation (RT) in reducing the risk of breast cancer after lumpectomy for Ductal Carcinoma in Situ (DCIS), the use of RT in the population remains relatively low. This study was designed to determine the effectiveness of RT after lumpectomy for DCIS in a population-based fashion using SEER data. Methods: We identified women with DCIS treated with lumpectomy in SEER registry data from 1987 through 1996. We evaluated the effect of RT on development of subsequent invasive breast cancer: the overall rate, the rate of ipsilateral invasive cancer, and the rate of contralateral invasive cancer. Using a proportional hazards model, we evaluated the effect of RT on development of invasive breast cancer over time adjusting for potential confounders. Results: A total of 10,034 women underwent lumpectomy for DCIS in this time period; 5063 underwent lumpectomy only and 4971 underwent RT after lumpectomy. Invasive breast cancer developed in 854...

Histological margin assessment for breast ductal carcinoma in situ: precision and implications

Local recurrence after lumpectomy for ductal carcinoma in situ (DCIS) is a major concern and is related to residual disease in the breast. We studied the predictive value of lumpectomy margins for residual DCIS and compared our results and pathological processing techniques with those published in the literature. Margin status was determined for 89 patients with screen-detected DCIS who had lumpectomy and re-excision, for the presence and extent of residual disease. Margin width was defined as the narrowest distance between tumor and any inked margin or, where margins were positive, classified into focal involvement (<1 mm of the inked surface involved), minimal (≥1<15 mm) and extensive (≥15 mm). The amount of residual tumor was quantified according to the number of ducts involved with tumor: small (fewer than 10 ducts) or large (10 or more ducts) residuum. The initial margin status was a significant predictor for the presence of residual tumor in re-excision specimens (P=0.006). There was residual tumor in 44 and 45% of close non-involved (>1 and ≤1 mm width) margins, 67% of focally, 71% of moderately and 94% of extensively positive margins. The pathologic tumor size was also a predictor for the presence of residual tumor with 27, 68 and 74% of lesions measuring ≤10, 11–25, >25 mm,respectively, showing residual disease. The presence of residual tumor was not significantly related to age, mammographic appearance, nuclear grade or intraductal necrosis. The initial margin status was found to predict for the amount of residual tumor. With careful margin assessment, margin status after lumpectomy for DCIS can be used to predict for the presence and amount of residual tumor in the breast and is a guide to further management decisions. A standard for margin status reporting and pathological processing of screen-detected DCIS in situ lesions will help in the interpretation of data from different institutions.

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of protocol B-17

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of protocol B-17

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight‐year update of protocol B‐17

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight‐year update of protocol B‐17

Tamoxifen added to lumpectomy and radiation therapy reduced breast cancer events in ductal carcinoma in situ

(1999) Lancet 353, 1993. Fisher B, Dignam J, Wolmark N, et al. . Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled...

Cytologic evaluation of lumpectomy margins in patients with ductal carcinoma in situ: clinical outcome.

Breast conservation therapy is controversial for ductal carcinoma in situ (DCIS) due to recently reported high recurrence rates. We believe that cytologic evaluation of lumpectomy margins improves efficiency and leads to a lower recurrence rate following lumpectomy for DCIS. A prospectively accrued database of 1255 breast cancer patients at the H. Lee Moffitt Cancer Center and Research Institute was found to have 218 patients with DCIS (17.4%). Of those 218 cases, 114 were treated with lumpectomy, axillary dissection, and radiation therapy; the remaining 104 patients were treated with mastectomy with or without reconstruction. Imprint cytology was used to evaluate all lumpectomy margins. Permanent sections and imprint cytology were reviewed by the same pathologist. All lumpectomy specimens (116 tumors in 114 patients) were evaluated. The median follow up was 57.5 months (range 2-110 months). One hundred and three patients with 104 tumors were selected on the basis of pure DCIS (with or without microinvasion), and treated with lumpectomy, axillary dissection and radiation therapy. Of the 104 tumors utilizing attempted breast conservation therapy, 7 (6.6%) required mastectomy. There were 6 recurrences (6.1%) with a median time for recurrence of 47.5 months (range 27-85 months); four recurrences were comedo and two were noncomedo at original diagnosis. The determination of lumpectomy margins in DCIS patients using imprint cytology leads to an overall recurrence rate of 6.1% with reduction in operative time, and re-excision rate. Significant recurrence rates were associated with microinvasion and multifocal tumors (28%) versus simple DCIS at 5 years. Breast conservation therapy and surgical margin determination with imprint cytology for DCIS is a cost-effective and reliable method of treatment for simple DCIS.