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Background: The natural history and role of axillary staging in microinvasive breast cancer (DCISM) remains controversial. We report clinical characteristics and outcome in patients with DCISM, focusing on the role of sentinel lymph node (SLN) biopsy., Methods: From our prospective database we retrospectively identified 112 patients with DCISM who underwent SLN biopsy between 1996 and 2004 at our institution. Median follow-up was 6 years., Results: We found positive SLN in 12% of patients (14 of 112): macrometastasis in 2.7% (3 of 112) and micrometastases or isolated tumor cells (ITC) in 10% (11 of 112). We performed axillary dissection (ALND) in all patients with macrometastasis (3 of 3), finding additional positive nodes in 66% (2 of 3), and in 27% of those with micrometastases/ITCs (3 of 11), finding no additional positive nodes. Among 98 patients with negative SLN (38% of whom received systemic therapy), there were 5 locoregional recurrences (1 in the ipsilateral axilla, 4 in the ipsilateral breast, all DCIS) and 4 contralateral second primary cancers. Among 14 patients with positive SLN (82 % of whom received systemic adjuvant therapy), there were no locoregional or distant recurrences., Conclusions: Our results suggest that SLN biopsy may be justified for DCISM, but is clearly most beneficial to identify a very small subset of DCISM patients (2.7%, with SLN macrometastasis) who could benefit from systemic adjuvant therapy. The benefit of SLN biopsy for patients with SLN micrometastases/ITCs (pN0mi or pN0(i+)) is uncertain, and in these cases ALND does not appear to be warranted. We suggest a wider reappraisal of routine SLN biopsy for DCISM.

Background: Volume of disease in the sentinel lymph node (SLN) is a significant predictor of additional nodal metastasis. This study assesses incidence of residual non-SLN disease in a large cohort of women with minimal SLN metastases and compares three methods of SLN micrometastasis volume measurement to determine which best predicts residual disease on completion axillary lymph node dissection (cALND)., Methods: A total of 505 patients with invasive breast cancer and minimal SLN metastasis (pN1mi or pN0(i+)) underwent cALND and had complete data. All SLNs were evaluated by three measurement methods for volume of metastasis: (1) method of detection (frozen section, routine hematoxylin and eosin, serial hematoxylin and eosin, immunohistochemistry), (2) American Joint Committee on Cancer's AJCC Cancer Staging Manual, 7th edition, N category, and (3) number of metastatic cells (1-100, 101-999, ≥1000). Multivariable logistic regression models were used to predict the presence of additional non-SLN disease., Results: A total of 251 patients (50%) had pN0(i+) and 254 patients (50%) had pN1mi disease. Twelve percent of those with pN0(i+) and 20% with pN1mi had additional non-SLN disease. On multivariate analyses including eight variables, only lymphovascular invasion (odds ratio >2.2, P < 0.01) and volume of nodal metastasis as assessed by any method of measurement (method of detection, AJCC, and cell count) were significantly correlated with additional non-SLN disease (P = 0.04, 0.03, and 0.02, respectively). All three models had similar goodness of fit and discrimination (Akaike information criterion = 442, 442, 441; -2log likelihood = 416, 420, 417; concordance index = 0.680, 0.675, 0.676, respectively)., Conclusions: A significant proportion of women with minimal SLN metastases have additional non-SLN disease at cALND. Assessments of SLN volume of disease by three different methods of measurement are equivalent for prediction of additional non-SLN metastases.

Background: Completion axillary lymph node dissection (ALND) remains the standard of care for patients with disease-positive sentinel lymph nodes (SLN). However, approximately two-thirds will have no additional disease-positive nodes. To identify the patient's individual risk for non-SLN metastases, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram., Methods: The records of 182 breast cancer patients who underwent SLN and ALND were selected. Serial hematoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. For application of the nomogram, the detection method was assigned in two ways: for all metastases visible by serial HE, the method of detection was scored as "serial HE" (method 1), independent of the tumor size, and by a combination of size and staining method (method 2); so macrometastasis were scored as detected by routine HE, micrometastasis by serial HE, and isolated tumor cells by immunohistochemistry. A receiver operating characteristic curve (ROC) was drawn, and the area under the curve was calculated to assess the discriminative power of the nomogram., Results: The area under the ROC was .71 (range, .64-.79) according to method 1 and .75 (range, .67-.88) according to method 2., Conclusions: Because the variable "method of detection" in the MSKCC nomogram is a surrogate for SLN metastasis size, the size category of the SLN metastasis can be used in applying the nomogram to patients in whom the SLN histologic analysis is performed by a much different procedure than that used to develop the MSKCC nomogram. This results in an improved predictive accuracy.

Background: In approximately 40% of the breast cancer patients with sentinel lymph node (SLN) metastases, additional nodal metastases are detected in the completion axillary lymph node dissection (cALND). The MSKCC nomogram can help to quantify a patient's individual risk for non-SLN metastases with fairly accurate predicted probability. The aim of this study was to compare the predictions of surgical oncologists for non-SLN metastases with nomogram results and to clarify the impact of nomogram results on clinical decision-making., Methods: Questionnaires, containing patient scenarios, were sent to surgical oncologists involved in breast cancer care. The surgeon was asked to predict the probability for non-SLN metastases for the first five scenarios. For the remaining scenarios, the patient's actuarial likelihood, calculated by the nomogram, was supplied. The surgeon was asked whether or not (s)he would perform a cALND. The type of hospital and the surgeon's experience were registered., Results: The concordance-index amounted to 0.78, indicating moderate concurrence between the surgical predictions and nomogram results. The intersurgeon variation was important. About 25% of the surgeons was influenced by nomogram information and decided in one or more patients to abandon the cALND. Neither the type of hospital nor experience influenced predicting abilities or the clinical decision-making process., Conclusion: Individual predictions of surgical oncologists for non-SLN metastases do not correlate well with the MSKCC nomogram. The distribution between intersurgeon predictions for one scenario is important. Therefore, the nomogram is superior to clinical estimations for predicting the likelihood for non-SLN metastases.

Background: With increasing frequency, breast cancer patients and clinicians are questioning the need for completion axillary lymph node dissection (ALND) in the setting of a positive sentinel lymph node (SLN). We previously developed a nomogram to estimate the likelihood of residual disease in the axilla after a positive SLN biopsy result. In this study, we compared the predictions of clinical experts with those generated by the nomogram and evaluated the ability of the nomogram to change clinicians' behavior., Methods: Pathologic features of the primary tumor and SLN metastases of 33 patients who underwent completion ALND were presented to 17 breast cancer specialists. Their predictions for each patient were recorded and compared with results from our nomogram. Subsequently, clinicians were presented with clinical information for eight patients and asked whether they would perform a completion ALND before and after being presented with the nomogram prediction., Results: The predictive model achieved an area under the receiver operating characteristic curve of .72 when applied to the test data set of 33 patients. In comparison, the clinicians as a group were associated with an area under the receiver operating characteristic curve of .54 (P < .01 vs. nomogram). With regard to performing a completion ALND, providing nomogram results did not alter surgical planning., Conclusions: Our predictive model seemed to substantially outperform clinical experts. Despite this, clinicians were unlikely to change their surgical plan based on nomogram results. It seems that most clinicians can improve their predictive ability by using the nomogram to predict the likelihood of additional non-SLN metastases in a woman with a positive SLN biopsy result.

Background: The standard of care for breast cancer patients with sentinel lymph node (SLN) metastases includes complete axillary lymph node dissection (ALND). However, many question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the axilla could assist greatly in decision-making regarding further treatment., Methods: Pathological features of the primary tumor and SLN metastases of 702 patients who underwent complete ALND were assessed with multivariable logistic regression to predict the presence of additional disease in the non-SLNs of these patients. A nomogram was created using pathological size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. The model was subsequently applied prospectively to 373 patients., Results: The nomogram for the retrospective population was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the prospective group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77)., Conclusions: We have developed a user-friendly nomogram that uses information commonly available to the surgeon to easily and accurately calculate the likelihood of having additional, non-SLN metastases for an individual patient.

Axillary lymph node status is the most important prognostic marker in patients with breast cancer; the presence of axillary metastases impacts prognosis as well as subsequent systemic therapy. Axillary lymph node dissection (ALND) is associated with significant morbidity and psychological distress; the introduction of sentinel lymph node (SLN) biopsy with lymphatic mapping affords the ability to identify those patients most likely to benefit from ALND, sparing node-negative patients. The lymphatic drainage of the breast is poorly understood, and the situation is further complicated by the lack of standardization of the SLN biopsy technique among institutions. Multicentricity has generally been considered to be a contraindication to SLN biopsy due to concerns about potential inaccuracies. Here we report five cases of patients with multicentric breast cancers (two tumors in two distinct quadrants). In each case, injection of one site with technetium-labeled sulfur colloid and the second site with isosulfan blue dye resulted in successful identification of at least one node that was both hot and blue within the axilla. These observations suggest that the lymphatic drainage of the entire breast coincides with drainage of the tumor bed, regardless of the quadrant. However, further studies are needed to validate the accuracy of SLN biopsy in multicentric breast cancers.

Internal mammary lymph-node (IMN) metastases in breast carcinomas have a major influence on survival, comparable with the influence of axillary lymph-node metastases (ALNM). Prospective, randomized trials have demonstrated that complete IMN dissection as part of extended radical mastectomy does not improve overall or disease-free survival. In the subset of patients with tumours 1cm or less in size and no ALNM, information on IMN status would provide important information. In these cases, the presence of IMN metastases would change the staging from stage I to stage IIIB, according to the current tumour, node and metastasis classification. More importantly, it would influence these patients' adjuvant treatment. Lymphatic mapping for sentinel lymph-node (SLN) biopsy has demonstrated extra-axillary drainage in up to 35% of patients. Recent reports have demonstrated the feasibility of internal mammary sentinel lymph-node (IM-SLN) biopsy. Here we review the general prognostic and clinical significance of tumor location and lymph-node metastases in breast cancer and discuss the specific factors associated with IMN identification, metastases and treatment in the pre-SLN and SLN eras. Based on our review, we propose an algorithm for a selective approach to IM-SLN in breast cancer.

Aims: The purpose was to identify the independent predictive factors of axillary lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to create a prospective, validated statistical model to predict the likelihood of ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and enhanced histopathology., Methods: Univariate and multivariate analyses of 13 clinicopathological variables (including tumour location) were performed to determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic regression model was developed and then prospectively validated on a second population of 187 subsequent consecutive procedures., Results: Age, pathological tumour size, palpability, lymphovascular invasion (LVI), histological grade, nuclear grade, ductal histological subtype, tumour location (quadrant) and multifocality were associated with ALNM in univariate analyses (P < 0.001). Of these, only palpability and histological grade were not statistically associated with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper-inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other quadrants (P<0.0005). There was no statistical difference between UIQ and other-quadrant tumours in any clinicopathological variables analysed. The logistic regression model, developed based on the population of 1659, had the same accuracy, sensitivity, specificity, positive predictive value and negative predictive value when applied prospectively to the second population., Conclusion: Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and location in the breast were independent predictive factors for ALNM in IFDC. ALNM is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively validated predictive model could be valuable in pre-operative patient discussions, although staging of the axilla in the individual patient remains necessary.

Background: The combined approach of radioactive tracer and blue-dye mapping of sentinel lymph nodes (SLN) has evolved into a safe and effective alternative to routine axillary node dissection in specific patient populations with breast carcinoma. The optimal route of injection for the isotope has not been clearly defined. To assess the intradermal route of isotope injection, we prospectively evaluated 100 patients with biopsy-proven invasive breast carcinoma with SLN biopsy followed by planned axillary node dissection., Methods: All patients were given an intradermal injection of Tc-99m sulfur colloid and an intraparenchymal injection of blue dye. All patients underwent a complete axillary node dissection. Each sentinel node was serially sectioned and examined by immunohistochemistry., Results: Sentinel nodes were successfully identified in 99% of cases. Forty-six patients had axillary metastases; of these, four had falsely negative sentinel nodes (false-negative rate, 9%). The false-negative rate was 0 of 24 (0%) for T1 tumors, 2 of 18 (11%) for T2 tumors, and 2 of 4 (50%) for T3 tumors. Three of four patients with false negatives had palpable, clinically suspicious axillary nodes found intraoperatively. If these cases are excluded, the accuracy of the procedure was 100% for T1 and T2 tumors. Of the 42 positive axillae identified by SLNB (true positives), 40 were localized using the intradermal injection of radioisotope; in 13 of these cases, this was the only method that identified the true-positive node., Conclusion: These data demonstrate that intradermal injection of radioactive tracer is an effective method of localizing the SLN in cases involving small breast cancers. Further investigation is warranted before this technique is adopted for use in larger breast cancers. Intraoperative examination and biopsy of any suspicious nonsentinel nodes are critical.

Background: Management of patients with breast cancers < or = 1 cm remains controversial. Reports of infrequent nodal metastases in tumors < or = 5 mm has led to suggestions that axillary dissection should be selective, and that tumor characteristics should guide adjuvant therapy., Methods: A retrospective review of 290 patients with breast cancer 1 cm in size or smaller from 1989 to 1991 was done. Distant disease-free survival (DDFS) was the primary outcome measure., Results: There were 95 T1a (< or = 5 mm) and 196 T1b (6-10 mm) cancers. Nodal metastases were found in 8 T1a and 26 T1b tumors. Larger size, poorer differentiation, and lymphovascular invasion (LVI) were associated with more nodal metastases, but none of these trends reached statistical significance. The 6-year DDFS was 93% for node-negative and 87% for node-positive patients (P = .02). Overall, breast cancers with poorer differentiation and LVI trended toward a poorer outcome. For patients with node-negative tumors, LVI was associated with a poorer outcome (P = .03). The size of the primary tumor was not predictive of outcome. There were no nodal metastases or recurrences in the 18 patients with microinvasive breast cancer., Conclusions: Lymph node status is the major determinant of outcome in breast cancers 1 cm in size or smaller. Accurate axillary assessment remains crucial in management of small breast cancer.