Axillary nodal metastatic burden in patients with breast cancer with clinically positive axillary nodes.

BACKGROUND: The aim of this study was to determine preoperative factors and tumour characteristics related to a high nodal tumour burden in patients with clinically node-positive breast cancer. These findings were used to construct a predictive tool to evaluate the patient-specific risk of having more than two axillary lymph node metastases. METHODS: Altogether, 507 consecutive patients with breast cancer and axillary lymph node metastasis diagnosed by preoperative ultrasound-guided needle biopsy were reviewed. These patients underwent breast surgery and axillary lymph node dissection at Helsinki University Hospital between 2010 and 2014. Patients were grouped into those with one or two, and those with more than two lymph node metastases. RESULTS: There were 153 patients (30·2 per cent) with one or two lymph node metastases and 354 (69·8 per cent) with more than two metastases. Five-year disease-free survival was poorer for the latter group (P = 0·032). Five-year overall survival estimates for patients with one or two and those with more than two lymph node metastases were 87·0 and 81·4 per cent respectively (P = 0·215). In multivariable analysis, factors significantly associated with more than two lymph node metastases were: age, tumour size, lymphovascular invasion in the primary tumour, extracapsular extension of metastasis in lymph nodes, and morphology of lymph nodes. These factors were included in a multivariable predictive model, which had an area under the curve of 0·828 (95 per cent c.i. 0·787 to 0·869). CONCLUSION: The present study provides a patient-specific prediction model for evaluating nodal tumour burden in patients with clinically node-positive breast cancer.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Aesthetic and functional outcome after breast conserving surgery - Comparison between conventional and oncoplastic resection.

BACKGROUND: Recent studies implicate that oncoplastic breast cancer surgery provides better aesthetic outcome than conventional resection. Several factors have been associated with poor aesthetic outcome. This study aims to compare patient-reported aesthetic and functional outcome after conventional and oncoplastic resection and to evaluate prognostic factors for poor aesthetic outcome in a population-based setting. METHODS: 637 patients having breast conserving treatment (BCT) due to unilateral primary breast cancer at a single hospital district during 2010 were included. Aesthetic and functional outcome were evaluated using two questionnaires three years after surgery. RESULTS: Questionnaires were returned by 379 (59%) patients; 293 (77%) of these had conventional and 86 (23%) oncoplastic resection. Patients in oncoplastic resection group had larger tumour diameter (p < 0.001), larger resection specimens (p < 0.001), and more often multifocal tumours (p = 0.032), node positive cancer (p = 0.029) and lower quadrant tumour localization (p = 0.007). Aesthetic outcome according to BCTOS questionnaire was good in 284 (75%) patients; 52 (61%) patients in the oncoplastic group and 230 patients (81%) in the conventional resection group, p < 0.001. Larger tumour diameter (p = 0.033), multifocality (p = 0.022), weight of resection specimen (<0.001) and oncoplastic surgery (p < 0.001) were predicting poor aesthetic outcome, when all patients were included. Tumour multifocality (p = 0.013) remained predictor of poor aesthetic outcome in conventional resection group but not in oncoplastic resection group. CONCLUSIONS: Patient satisfaction to aesthetic outcome after BCT is high. Conventional resection provides good aesthetic outcome in appropriately selected patients. Oncoplastic resection enables BCT in patients with larger and multifocal tumours with favourable aesthetic outcome.

Feasibility of Day Surgery in Patients With Breast Conservation and Sentinel Node Biopsy: A Randomized Controlled Trial.

BACKGROUND AND AIMS: The aim of this study was to analyze feasibility of day surgery in breast cancer patients with breast conserving surgery and sentinel node biopsy. MATERIAL AND METHODS: The study was a randomized controlled trial comparing day surgery with one night hospital stay in breast cancer patients with breast conserving surgery and sentinel node biopsy. A total of 40 patients with ⩽3-cm tumor and clinically N0 were randomized to one night stay group and 38 patients to day surgery group. Within discharge, patients and their relatives were given questionnaires in order to evaluate their experience regarding the duration of hospital stay. RESULTS: Randomized groups were similar regarding patient age and tumor stage. A total of 18 (47%) day surgery group patients were discharged the same day. The most common reason for overnight hospital stay was axillary clearance, 9 (24%). None of the patients in the day surgery group, but 2 patients in the overnight hospital stay group had re-operation due to complications. Perception and preference results were analyzed both according to randomization and actual treatment groups. Patients in both groups had rather similar experiences on the first postoperative day. Also, spouse's or relative's perception after discharge was similar in both groups. CONCLUSION: Day surgery was well received by the patients and their relatives. Day surgery appears as feasible in patients with breast conservation and sentinel node biopsy.

A predictive tool to estimate the risk of axillary metastases in breast cancer patients with negative axillary ultrasound.

BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from four other centers. All statistical tests were two-sided. RESULTS: A total of 426 of the 1,395 (30.5 %) patients in the original patient series had axillary lymph node metastases. Histological size (P < 0.001), multifocality (P < 0.001), lymphovascular invasion (P < 0.001), and palpability of the primary tumor (P < 0.001) were included in the predictive model. Internal validation of the model produced an area under the receiver operating characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79. CONCLUSIONS: We present a predictive model to assess the patient-specific probability of axillary lymph node metastases in patients with clinically node-negative breast cancer. The model performs well in internal and external validation. The model needs to be validated in each center before application to clinical use.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Outcome of patients with ductal carcinoma in situ and sentinel node biopsy.

BACKGROUND: In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB. METHODS: A total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki University Central Hospital. Patient, tumor, SNB procedure, and follow-up data were gathered. The median follow-up was 50 months (range 7-123 months). RESULTS: Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14 were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7 in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16 patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph node dissection (ALND). Only 1 of them, a patient with DCISM, had additional tumor positive finding in the ALND. During a median follow-up of 50 months (range 7-123 months) there were 5 local recurrences. One patient with pure DCIS and tumor-negative SNB developed overt axillary metastases and later also distant metastases. CONCLUSIONS: DCIS and DCISM patients do have tumor positive findings, but a majority of these are ITC or micrometastases. In light of this study, these findings do not affect the outcome of DCIS or DCISM patients.

Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer.

Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.

A simple nomogram to evaluate the risk of nonsentinel node metastases in breast cancer patients with minimal sentinel node involvement.

BACKGROUND: Tumor-positive sentinel node biopsy (SNB) suggests a risk of nonsentinel node metastases in breast cancer. This risk is lower after micrometastasis or isolated tumor cells (ITC) in the sentinel node (SN), and recent studies suggest that completion axillary lymph node dissection (ALND) might not improve outcome in these patients. We aim to validate existing predictive models and to develop a new model for micrometastatic and ITC patients. METHODS: A series of 484 patients with micrometastases or ITC in SN followed by ALND was used to evaluate factors affecting nonsentinel node involvement. Logistic regression analysis was performed to construct a predictive model, which was validated by a separate series of 51 patients. RESULTS: Only 7.2% of patients had additional metastases on completion ALND. Tumor diameter and multifocality associated with nonsentinel status on multivariate analysis. A predictive model was constructed showing good [area under the curve (AUC) 0.791] discrimination in the validation series. Previously published models performed poorly in our patient population. CONCLUSIONS: Nonsentinel node metastases are rare with micrometastasis or ITC in SN. Most published predictive models for nonsentinel node involvement perform poorly in the present patient population. We developed a new predictive model which seems to perform well in discriminating patients with more than 10% risk of additional metastases. However, the presented nomogram needs to be validated with an independent patient series to evaluate its accuracy, especially for high-risk patients.

Ipsilateral breast recurrence after breast conserving surgery in patients with small (≤ 2cm) breast cancer treated with modern adjuvant therapies.

BACKGROUND: Modern multimodality treatment greatly influences the rate and the predictive factors for ipsilateral cancer recurrence (IBR) after breast conserving surgery. MATERIAL AND METHODS: The study is based on 1297 patients with pT1 breast cancer and treated with breast conserving surgery in February 2001-August 2005. The median duration of follow-up was 57 months. RESULTS: IBR occurred in 27 (2.1%) patients. It was located in the quadrant of prior breast resection in 17 (63%) cases. The median time to an IBR was 41 months (range, 6-78) regardless of whether the recurrence was located in the same or in another quadrant. Omission of radiotherapy was associated with a higher IBR incidence, HR 10,344 (95% CI 1904-56,184; p=0.007). The IBRs occurred particularly often, in 27% of the 11 patients who refused radiotherapy. Patients diagnosed with ER+ cancer had a lower risk of IBR when compared with those with ER-/HER2+ cancer, HR 0.215 (95% CI 0.049-0.935; p=0.040). CONCLUSIONS: The risk of IBR was low during the first 5 years after breast resection among patients with pT1 breast cancer and treated with modern surgical and adjuvant therapies. The majority IBRs still occur at or close to the prior resection site underlining the importance of local therapies. Omission of radiotherapy was the most significant risk factor for IBR.

Local recurrence of stage 1 and 2 breast cancer after skin-sparing mastectomy and immediate breast reconstruction in a 15-year series.

AIMS: Since the introduction of skin-sparing mastectomy (SSM) in 1991 concerns on local control and recurrence rates have been discussed in the literature. The aim of this study is to examine in particular incidence of local recurrence in a 15-year consecutive series of breast cancer patients having undergone SSM and immediate breast reconstruction (IBR) at a single population-based institution. METHODS: One hundred and forty-six consecutive patients with either stage 1 or 2 breast cancer who underwent SSM followed by IBR from 1992 to 2006 were included in this study. A retrospective review of patient records was conducted. RESULTS: During a mean follow-up time of 51 months, four local recurrences of the native breast skin were accounted for. In addition, three regional lymph node recurrences and four systemic recurrences took place. All of the local and regional recurrences were handled by salvage surgery followed by adjuvant oncological therapies. During a mean follow-up of 35 months after the detection and treatment of the locoregional recurrences none of the patients developed new recurrences. CONCLUSIONS: Our present study concludes that SSM followed by IBR seems oncologically sound procedure for stage 1 and 2 breast cancer patients. In addition, local recurrences and regional lymph node recurrences are not always associated with systemic relapse.

Sentinel node biopsy with intraoperative diagnosis in patients undergoing skin-sparing mastectomy and immediate breast reconstruction.

AIMS: False negative cases in the intraoperative assessment of sentinel node (SN) metastases in breast cancer prompt for a secondary axillary lymph node dissection (ALND). Such ALND is technically demanding and prone to complications in patients with immediate breast reconstruction (IBR) if there is a microvascular anastomosis or the thoracodorsal pedicle of a latissimus dorsi flap in the axilla. This study aims to evaluate the feasibility of the intraoperative diagnosis of sentinel node biopsy (SNB) in breast cancer patients undergoing IBR. METHODS: Sixty-two consecutive breast cancer patients undergoing SNB with the intraoperative diagnosis of SN metastases simultaneously with mastectomy and IBR between 2004 and 2006 were included in this study. Results of the SNB and especially the false negative cases in the intraoperative diagnosis were evaluated. RESULTS: Eleven patients had tumor positive SN. Nine of these cases were detected intraoperatively. The two false negative cases in the intraoperative diagnosis constituted of isolated tumor cells only. CONCLUSIONS: Our present study suggests that SNB with intraoperative diagnosis of SN metastases is feasible in patients undergoing IBR if the risk of nodal metastasis is low and the sensitivity of intraoperative SNB diagnosis is high.

A second radioisotope injection enhances intraoperative sentinel node identification in breast cancer patients without visualized nodes on preoperative lymphoscintigraphy.

PURPOSE: To evaluate the influence of a second radioisotope injection on the intraoperative success rate in patients with non-visualized axillary sentinel nodes (SN). MATERIAL AND METHODS: Altogether, 534 consecutive breast cancer patients with lymphoscintigraphy (LS) and SN biopsy and were included. An intratumoral injection of 99mTc-labeled human albumin colloid with a median dose of 93 MBq was applied. Forty-two of the 80 patients without axillary hot spots on LS received a second tracer injection with a median dose of 70 MBq. RESULTS: The visualization rate of axillary SN was 454/534 (85%). The intraoperative SN identification rate was 97% in patients with and 69% in patients without visualized SN in the axilla (P<0.00005), but the success rate was higher (88%) with a second radioisotope injection than without it (47%; P<0.0002). CONCLUSION: The failure rate in intraoperative SN identification was minimized using a second radioisotope injection in patients without axillary SN on LS.

Adjusting the radioisotope tracer dose according to the body mass index does not enhance the visualization of axillary sentinel lymph nodes.

PURPOSE: To investigate whether the visualization of axillary sentinel nodes (SN) in the lymphoscintigraphy (LS) can be enhanced by adjusting the amount of radioactivity in accordance with the patient's body mass index (BMI). MATERIAL AND METHODS: Group I consisted of 356 consecutive breast cancer patients who underwent LS and SN biopsy after a single, intratumoral radioactive tracer injection with a median dose of 92 MBq. In group II (178 consecutive patients), the dose of the tracer was adjusted according to BMI; 80, 100, or 140 MBq. RESULTS: The visualization rate of axillary SN was 86% in group I and 83% in group II (P = 0.303). In patients with BMI >30 with visualized axillary SN, the median number of SN was 1 (1-4) in group I and 3 (1-7) in group II (P = 0.002). CONCLUSION: Adjusting the tracer dose in accordance with patient BMI did not enhance the visualization rate of axillary SN in LS.

Sentinel node biopsy is not sensible in breast cancer patients with large primary tumours.

AIMS: We aimed to evaluate the outcome of sentinel node biopsy (SNB) in breast cancer patients with large primary tumours. METHODS: Nine hundred and eighty-four patients with invasive breast cancer and SNB were studied. The histological tumour size was larger than 3 cm in 70 patients. The advantages of SNB like avoiding axillary clearance (AC) or more accurate staging by detecting micrometastases or parasternal sentinel node metastases were evaluated in relation to the tumour size. RESULTS: Axillary metastases were detected in 351/914 patients with a tumour size of 3 cm or smaller and in 50/70 patients with larger tumours (p<<0.0001). Micrometastases or isolated tumour cells only, were observed in 134/351 node positive patients with tumours not larger than 3 cm and in 10/50 cases with larger tumours (p=0.022). Parasternal sentinel node metastases were detected in 17/914 patients with a tumour size of 3 cm or smaller and 2/70 patients with larger tumours (p=ns). AC was omitted because of tumour negative sentinel node findings 168 of the 232 patients with stage T1 a-b tumours and 281 of those 489 with T1c tumours. Twenty of the 70 patients with tumours larger than 3 cm avoided AC. CONCLUSIONS: SNB is not sensible in breast cancer patients with tumours larger than 3 cm, because of the small proportion avoiding AC after SNB.

The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases.

AIMS: The aim of the study was to estimate the prevalence of and risk factors for non-sentinel node (NSN) involvement in breast cancer patients with sentinel node (SN) micrometastases. METHODS: Eighty-four patients with SN micrometastases were included. Both the SN and NSN were examined using serial sectioning and immunohistohemistry. Various indices were evaluated as possible risk factors for NSN involvement. RESULTS: NSN involvement was found in 22/84 patients. The median size of the NSN metastases was 1.25 mm (0.01-12 mm). The NSN metastases were larger than 2 mm in 8 patients and smaller than 0.2 mm in 6 patients. NSN involvement was observed in 14/35 patients with metastatic findings in all removed SN. Three of the 23 patients with 2 or 3 tumour negative SN had NSN metastases. None of the 12 patients with 4 or more uninvolved SN had NSN metastases. NSN involvement could not excluded by other patient, tumour or sentinel node related factors. CONCLUSIONS: Every fourth patient will have residual disease in the axilla, 10% even large metastases, if axillary clearance is omitted in patients with SN micrometastases. The risk of NSN involvement seems negligible in patients with a single SN micrometastasis and four or more healthy SN harvested.

Sentinel node biopsy in breast cancer.

In breast cancer, sentinel node biopsy (SNB) has replaced diagnostic axillary clearance (AC) in nodal staging in numerous breast surgery units all over the world. However, there is no international standard in imaging, harvesting, and histological examination of the sentinel nodes. SNB has been validated in nodal staging of small, unifocal, clinically axillary-node-negative tumors, with a false-negative rate of approximately 5%, of all axillary-node-positive cases. Despite the false-negative results, the method is assumed to provide accurate nodal staging, revealing metastases that remain undetected in AC. Furthermore, clinically overt axillary metastases have been rare when omitting AC relying on tumor-negative sentinel node findings, at least during a short follow-up. SNB is associated with faster recovery and less long-term morbidity than AC. Although the results of the large randomized trials have still to come, SNB has become the standard of care in early breast cancer.

Towards reasonable workload in diagnosis of sentinel lymph nodes: comparison of two frozen section methods.

AIMS: To compare two methods of histological assessment with intraoperative diagnosis of sentinel node metastases in breast cancer. METHODS AND RESULTS: A total of 204 consecutive breast cancer cases with lymphatic mapping, sentinel node biopsy and intraoperative diagnosis were included. The sentinel nodes in the first 102 cases (method A) were bisected and serially sectioned. In the other 102 cases (method B) the nodes were sliced thinly with a razor blade. All 1-1.5 mm thick slices were mounted on prechilled mounting medium on frozen section buttons. Cytological imprints were also made of the attached tissue slices. Postoperative diagnosis of sentinel lymph node metatases was taken as gold standard. Sentinel node metastases were found in 28 (27%) cases in group A and in 42 (40%) cases in group B (P = 0.05). The median size of the sentinel node metastases was 4.3 mm in group A and 3.3 mm in group B (P < 0.05). CONCLUSION: Method B finds more and smaller metastases and takes less time and effort in the laboratory. When using method A, many small metastases are not detected at all.

The role of Tc99m-sestamibi scintimammography in combination with the triple assessment of primary breast cancer.

AIM: The aim of this study was to evaluate if Tc99m-sestamibi scintimammography in addition to the triple assessment consisting of clinical examination, mammography, breast ultrasonography and fine needle aspiration cytology (FNA) enhances the diagnosis of breast cancer and helps in avoiding unnecessary operative biopsies. METHODS: Pre-operational scintimammography was performed within 2 weeks of operation to 46 consecutive patients with abnormal findings in clinical breast examination, mammography or ultrasonography. Three patients had abnormalities in both breasts. Histological diagnosis was obtained in all 49 cases. RESULTS: The histological diagnosis was benign in 18 (37%) cases and malignant in 31 (63%) cases. The overall sensitivity of scintimammography was 77% and the specificity was 61%. The sensitivity of scintimammography was 95% in invasive ductal carcinoma, 50% in invasive lobular carcinoma and 25% in ductal carcinoma in situ. Scintimammography showed 100% sensitivity in cases with invasive carcinoma, with highly suspicious findings for malignancy in the other examinations. The sensitivity was 63% in cases with indeterminate or contradictory findings in mammography, ultrasonography and FNA. CONCLUSIONS: Adding scintimammography to the triple assessment does not seem to be helpful in the diagnosis of breast abnormalities because of low sensitivity in malignant cases with a challenging diagnosis by mammography, ultrasonography and FNA, and because of low overall specificity.