Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma

Abstract:  The role of sentinel lymph node (SLN) biopsy in patients with initial diagnosis of ductal carcinoma in situ (DCIS) is still a dilemma. Different studies are trying to define predicting factors of invasive cancer in DCIS. The aim of this study was to confirm the value of SLN biopsy in DCIS because of the invasive upstaging risk on final histology. Patients with initial diagnosis of DCIS and with axillary SLN biopsy were selected. All diagnoses were confirmed by biopsy of mammographic lesions. Surgical treatment was lumpectomy or mastectomy associated with SLN biopsy. Imprint stains were performed, and then serial sections were stained with hematoxylin and eosin (H&E) and with immunohistochemistry (IHC). A complete axillary lymph node dissection (ALND) was performed during the same surgery when a node metastasis was found. Eighty patients were enrolled in the study. Of the 61 patients who were initially diagnosed with DCIS, 12 (20%) were upstaged to microinvasive or invasive carcinoma and 9 (15%) had a metastatic SLN. Patients upstaged to invasive carcinoma had macrometastatic SLN immediately fed by a complete ALND. SLN micrometastases and isolated cells were detected by IHC and secondary complete ALND found an additional metastatic lymph node in one patient. Tumor size larger than 30 mm and mastectomy were the only significative predicting factors of upstaged disease (p < 0.0001) in our study. In patients with initial diagnosis of large DCIS programmed for mastectomy, SLN biopsy should be discussed in order to detect underlying invasive disease and to spare patients a second operating time.     

Sentinel lymph node positivity in patients undergoing mastectomies for ductal carcinoma in situ (DCIS)

Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico‐pathologic variables were analyzed using Pearson's chi‐squared, Wilcoxon Rank‐Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P = .0289), palpability (P < .0001), extent of disease on imaging (P = .0121), mass on preoperative imaging (P = .0003), multifocality (P = .0231) and multicentricity (P = .0395). In multivariate analysis, palpability (P = .0080), extent of disease on imaging (P = .0074) and mass on preoperative imaging (P = .0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.     

Role of sentinel lymph node biopsy in patients with ductal carcinoma in situ and microinvasion

Aim: Ductal carcinoma in situ with microinvasion (DCISMI) is characterized by one or more areas of focal invasion, 1 mm or less in diameter. While pure ductal carcinoma in situ (DCIS) does not have the potential to metastasize to regional nodes, the presence of microinvasion makes lymph node metastasis possible, leading to current guidelines recommending staging of the axilla with sentinel lymph node biopsy (SLNB). However, there are few studies looking at the risk of lymphatic spread in patients with DCISMI, and indications for axillary staging in such cases is controversial. The aim of the present study was to assess the prevalence of nodal metastasis in patients with DCISMI in order to help ascertain whether SLNB can be safely avoided in DCISMI. Patients and Methods: A retrospective analysis was performed of patients undergoing surgery for DCIS over a 2‐year period (April 2006–08). Data were collected from the National Health Service Breast Screening Programme database and patient case notes. Patients having a SLNB had injection of radioisotope and blue dye. All SLNB were evaluated with serial sectioning and haematoxylin–eosin staining. Results: Over the 2‐year period, 399 screen‐detected breast cancers were treated, of which 310 (77 per cent) were invasive, 17 (4 per cent) had DCISMI and 72 (19 per cent) pure DCIS. The group with DCISMI was studied in more detail. Twelve out of the 17 patients had a wide local excision and five had a mastectomy. All 17 patients with DCISMI had a SLNB. No positive lymph nodes were found in this group. Conclusion: Our data suggest that the risk of nodal metastasis in DCISMI might be low, and question the role of SLNB in DCISMI. We highlight the lack of data on DCISMI and risk of nodal metastasis, and the need for further investigation.     

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

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

The current treatment of ductal carcinoma in situ

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

Infiltrating ductal carcinoma and ductal carcinoma in situ associated with mammary hamartoma

Mammary hamartoma is a rare nonmalignant lesion. Only 11 cases of carcinoma associated with hamartoma have been previously described in the literature. We describe a case of infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) associated with hamartoma in a 35-year-old woman. Mammography showed the features of a typical hamartoma with suspicious microcalcifications arising in it. The patient underwent a radical modified mastectomy. It is likely that hamartoma is a coincidental finding. The identification of suspicious microcalcifications in a typical mammographic image of a hamartoma should prompt continued examination to exclude an underlying tumor.     

Location and extent of positive resection margins and ductal carcinoma in situ in lumpectomy specimens of ductal breast carcinoma examined with a microscopic three-dimensional view

The location of positive margins in lumpectomy specimens for ductal carcinoma could be predicted due to the common pattern of the geographic relationship between the intraductal and invasive carcinomas. To test this hypothesis, 62 lumpectomy specimens for ductal carcinoma of the breast were submitted for this study. The specimens were microscopically examined by serially sectioning them into giant sections in a plane parallel to the chest wall (frontal plane). The margins were identified as proximal (closest to the nipple), distal (opposite to proximal), and peripheral (nonproximal or distal). We found that the location of positive or close margins was proximal in 6 cases, peripheral in 13 cases, and none were found to be distal. Ductal carcinoma in situ (DCIS) was found to be located in the area adjacent to the invasive carcinoma. The invasive carcinoma was located at the periphery of the intraductal carcinoma. All six specimens with invasive carcinoma without DCIS had free margins. Nine of 16 specimens (56%) with extensive intraductal carcinoma (EIC) component and 7 of 40 (18%) with DCIS but negative EIC contained positive or close margins involved by DCIS. One case with multifocal invasive carcinoma measuring 3.5 cm in diameter and with DCIS but EIC negative had margins involved by both DCIS and invasive carcinoma. In conclusion, in ductal carcinoma, invasive carcinoma arose at the peripheral areas of the DCIS. DCIS tends to spread toward the nipple and the peripheral margins of the resected specimens. Incomplete excision of the ductal carcinoma and the wide positive margins are most likely caused by the failure to estimate the extent and location of DCIS.     

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

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

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

Background: The optimal treatment of ductal carcinoma in situ (DCIS) is one of the most controversial issues in the management of breast cancer. Identification of factors that affect the risk of local recurrence is very important as the incidence of DCIS increases and the use of breast conservation becomes more widespread. Because the extent of resection may affect the relapse rate, we hypothesized that larger volumes of resection (VR) may account for the lower local recurrence rates we have previously found in elderly patients. Methods: Between 1978 and 1990, 173 cases of histologically confirmed DCIS were treated at MSKCC with breast conservation therapy. Of these, complete VR data were available for 126 cases. The VRs thus obtained were divided into two groups, <60 cm³ and 60 cm³, and were evaluated for correlating factors. The patients were divided into three groups by age at diagnosis: younger than 40 years, 40 to 69 years, and 70 years or older. Results: The eldest group had a significantly greater proportion of large VRs (30%) as compared to the middle group (11%) and the youngest group (9%) (P=.03, x²). Although not statistically significant, the large VR group had a lower 6-year actuarial local recurrence rate (5.6%) than did the small VR group (21.3%) (P=.16, log-rank test). This trend was observed even though adjuvant radiotherapy was used less often in patients who had large VRs. Conclusion: Breast conservation surgery for DCIS in elderly patients is more likely to employ a large VR. This may explain, at least in part, the observation that elderly patients have a lower local recurrence rate.Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Do not contemplate invasive surgery for ductal carcinoma in situ

BACKGROUND: Ductal carcinoma in-situ (DCIS), by definition, has no metastatic potential. The routine examination of axillary lymph nodes in these patients may expose them to unnecessary operative morbidity and is the subject of continuing controversy. This study evaluates the lymph node status of patients with DCIS. METHODS: A retrospective review of all tumor registry patients diagnosed with DCIS between January 1996 and December 2000 was performed. Data obtained included (1) patient demographics, (2) the surgical procedure performed, (3) the histologic grade of the tumor, and (4) the lymph node status, if obtained. All analysis was by hematoxylin and eosin (H&E) stain only. RESULTS: In all, 380 patients were diagnosed with DCIS. Surgical therapy for these patients varied from lumpectomy (with negative margins) to modified radical mastectomy. Ninety-seven (25.5%) had their axillary lymph nodes (average 9, range 1 to 33) analyzed by H&E stain and are the subject of this study. One patient (1%) was found to have a lymph node micrometastasis. CONCLUSIONS: This study demonstrates that axillary lymph node examination is a low-yield endeavor for patients diagnosed with DCIS, regardless of the histologic grade of the tumor. Routine sampling of lymph nodes in these patients is not warranted.     

Predictors of invasion and axillary lymph node metastasis in patients with a core biopsy diagnosis of ductal carcinoma in situ: an analysis of 255 cases

The diagnosis of ductal carcinoma in situ (DCIS) using core biopsy does not ensure the absence of invasion on final excision. We performed a retrospective analysis of 255 patients with DCIS who had subsequent excision. Clinical, radiologic, and pathologic findings were correlated with risk of invasion and sentinel lymph node (SLN) metastasis. Of 255 patients with DCIS, 199 had definitive surgery and 52 (26%) had invasive ductal carcinoma (IDC) on final excision. Extent of abnormal microcalcification on mammography, and presence of a radiologic/palpable mass and solid type of DCIS were significantly associated with invasion on final excision. Sentinel lymph node biopsy was performed in 131 (65.8%) patients of whom 18 (13.4%) had metastasis. Size of IDC and extent of DCIS on final pathology were significantly associated with positive SLN. Micrometastasis and isolated tumor cells comprised majority (71.4%) of the metastases in DCIS. SLN biopsy should be considered in those with high risk DCIS.     

Role of primary tumor characteristics in predicting positive sentinel lymph nodes in patients with ductal carcinoma in situ or microinvasive breast cancer

BACKGROUND: We determined the incidence of positive sentinel lymph nodes (SLNs) in patients with ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC) and the predictive factors of SLN metastasis in these patients. METHODS: Of 4,503 patients who underwent SLN dissection between March 1994 and March 2006 at our institution, we identified those with a preoperative diagnosis or final diagnosis of DCIS or MIC. Clinicopathologic factors were examined by logistic regression analysis. RESULTS: Of the 624 patients with a preoperative diagnosis of DCIS or MIC, 40 had positive SLNs (6.4%). Of the 475 patients with a final diagnosis of DCIS or MIC, 9 had positive SLNs (1.9%). Clinical DCIS size >5 cm was the only independent predictor of positive SLN for patients with a preoperative diagnosis and patients with a final diagnosis of DCIS or MIC. Core biopsy as the method of preoperative diagnosis and DCIS size >5 cm were independent predictors for a final diagnosis of invasive carcinoma in the 149 patients who had a preoperative diagnosis of DCIS or MIC. CONCLUSIONS: SLN dissection for patients with a diagnosis of DCIS should be limited to patients who are planned for mastectomy or who have DCIS size >5 cm. Patients who have a core-needle biopsy diagnosis of DCIS have a higher risk of invasive breast cancer on final pathologic assessment of the primary tumor. This information can be used in preoperative counseling of patients with DCIS regarding the timing of SLN biopsy.     

p53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast

BACKGROUND: Several biological markers have been related to prognosis in mammary ductal carcinoma. The aim of the study was to determine biological markers that could predict local recurrence following treatment for all stages of primary operable ductal carcinoma of the breast. MATERIALS AND METHODS: A consecutive series of patients treated for pure ductal carcinoma in situ (DCIS, n = 110) and invasive ductal carcinoma (IDC, n = 243) was studied. Twenty-three patients with DCIS were excluded because of lack of original paraffin embedded tissue. All patients had been treated between July 1996 and December 2001. Median follow-up was 49.8 mo. From the original paraffin embedded tumors, tissue microarrays (TMAs) were constructed. On these TMAs, immunohistochemistry was performed for estrogen-receptor (ER), progesterone-receptor (PR), Her2/neu, p53, and cyclin D1. Main outcome was the event of LR. All analyses were stratified for diagnosis (DCIS or IDC) and pathological grade. RESULTS: In univariate analyses, Her2/neu overexpression (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.1-8.7, P = 0.032) and p53 overexpression (HR 3.5, 95% CI 1.3-9.3, P = 0.014) were associated with LR in patients treated for both DCIS and IDC. In multivariate analysis, p53 overexpression (HR 3.0, 95% CI 1.1-8.2, P = 0.036 and HR 4.4, 95% CI 1.5-12.9, P = 0.008) and adjuvant radiotherapy (HR 0.2, 95% CI 0.1-0.8, P = 0.026) were independent common predictors of LR in patients who had received treatment for both DCIS and IDC. CONCLUSIONS: p53 overexpression is a common predictor of LR following treatment for all stages of primary operable ductal carcinoma of the breast. This marker may help in planning optimal treatment and follow-up.     

Predictors of residual invasive disease after core needle biopsy diagnosis of ductal carcinoma in situ

Core needle biopsy (CNB) is used to sample both mammographically and ultrasound detected breast lesions. A diagnosis of ductal carcinoma in situ (DCIS) by CNB does not ensure the absence of invasive cancer upon surgical excision and as a result an upstaged patient may need to undergo additional surgery for axillary nodal evaluation. This study evaluates the accuracy of CNB in excluding invasive disease and the preoperative features that predict upstaging of DCIS to invasive breast cancer. Two hundred fifty-four patients over an 8-year period from 1994 to 2002 with a diagnosis of DCIS alone by CNB were retrospectively reviewed. Underestimation of invasive cancer by CNB was determined. Radiographic, pathologic, and surgical features of the cohort were compared using univariate and multivariate analysis. The mean age was 55 years (range 27-84) and mean follow-up was 25 months with one patient unavailable for follow-up. There were a total of six patient deaths, all of which were not disease-specific. A total of 21 out of 254 patients (8%) with DCIS by CNB were upstaged to invasive cancer following surgical excision. There was a significant inverse relationship between the number of core biopsies and the incidence of upstaging (p < 0.006) in that patients with fewer core samples were more likely to be upstaged at surgical pathology. No relationship was noted between the size of the core samples and the likelihood of upstaging (p > 0.4). Of 21 patients with invasion, all but two had comedonecrosis by CNB. Comedonecrosis by CNB significantly increased the likelihood of upstaging (p < 0.001). Of the 21 patients who were upstaged, 12 required subsequent surgery for nodal evaluation while nine had sentinel node biopsy at initial operation. Finally, upstaged patients were significantly more likely to have a positive margin (p < 0.008). Ductal carcinoma in situ with comedonecrosis on CNB can help to predict the possibility of invasion. Increasing the number of core biopsies reduced the likelihood of sampling error.     

BI-RADS MRI enhancement characteristics of ductal carcinoma in situ

To identify the Breast Imaging Reporting and Data System magnetic resonance imaging (MRI) enhancement characteristics of ductal carcinoma in situ (DCIS). A retrospective review of consecutive patients who underwent breast MRI for newly diagnosed breast carcinoma prior to surgery was conducted. This yielded 381 lesions in 361 patients with pathologic confirmation of either DCIS alone, invasive carcinoma alone, or mixed invasive and in-situ disease. Presence or absence of a MRI lesion at the site of the documented carcinoma was recorded, and for all identified MRI lesions the Breast Imaging Reporting and Data System morphology patterns were recorded. MRI features of the different malignancy types were compared utilizing Fisher's exact tests; 64/381 (16.8%) lesions had DCIS, 101/381 (26.5%) had invasive carcinoma, and 216/381 (56.7%) had mixed invasive/in situ carcinoma. A MRI lesion corresponding to the known cancer was identified in 55/64 (85.9%) cases of DCIS, 98/101 (97.0%) cases of invasive carcinoma, and 212/216 (98.1%) cases of mixed invasive and in-situ carcinoma. For pure DCIS lesions, 38/64 (59.4%) exhibited nonmass-like enhancement (NMLE), 9/64 (14.1%) were masses, and 8/64 (12.5%) were a focus. For pure invasive carcinomas 79/101(78.2%) were masses, 16/101 (15.8%) were NMLE, and 3/101 (3.0%) were a focus. For mixed lesions 163/216 (75.5%) were masses, 44/216 (20.4%) demonstrated NMLE, and 5/216 (2.3%) were a focus. The most common NMLE patterns of pure DCIS were segmental distribution and clumped internal enhancement. Although there is overlap in the MRI morphology and enhancement pattern of in situ and invasive breast carcinoma, DCIS more frequently manifests as NMLE than does invasive carcinoma.     

Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is poorly defined. However, up to 20% of patients with DCIS will have invasive carcinoma; these patients require staging for axillary metastasis. The aim of this study was to identify patients with a core biopsy diagnosis of DCIS who may benefit from SLNB. METHODS: In a prospective study, we performed SLNB on patients with a preoperative diagnosis of >2.5 cm of high-grade DCIS or DCIS when mastectomy was indicated. RESULTS: Sixty-two patients underwent surgery for high-grade DCIS, and 35 of these patients underwent SLNB. Postsurgical excision histology revealed invasive disease in 20 patients, 19 of whom had undergone SLNB. Before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second surgery axillary staging (P < .01, chi-square test). CONCLUSIONS: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. However, selective lymphadenectomy may be a useful clinical adjuvant in selected high-risk DCIS patients.     

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