Comparison of vacuum-assisted excision (VAE) and breast lesion excision system (BLES) in the treatment of intraductal papillomas.

PURPOSE: This study aims to compare the feasibility of VAE and BLES in the treatment of intraductal papillomas. MATERIAL AND METHODS: Patients with a suspected intraductal papilloma who underwent a BLES or a VAE procedure were included in this retrospective study. The BLES procedures were performed between November 2011 and June 2016 and the VAE procedures between May 2018 and September 2020 at the Department of Radiology of Helsinki University Hospital (HUH). The procedures were performed with an intent of complete removal of the lesions. RESULTS: In total, 72 patients underwent 78 BLES procedures and 95 patients underwent 99 VAE procedures. Altogether 52 (60%) papillomas with or without atypia were completely removed with VAE, whereas 24 (46%) were completely removed with BLES, p = 0.115. The median radiological size of the high-risk lesions completely removed with BLES was 6 mm (4-12 mm), whereas with VAE it was 8 mm (3-22 mm), p = 0.016. Surgery was omitted in 90 (94.7%) non-malignant breast lesions treated with VAE and in 66 (90.4%) treated with BLES, p = 0.368. CONCLUSION: Both VAE and BLES were feasible in the treatment of intraductal papillomas. In most non-malignant lesions surgery was avoided, but VAE was feasible in larger lesions than BLES. However, follow-up ultrasound was needed more often after VAE. The histopathologic assessment is more reliable after BLES, as the lesion is removed as a single sample.

Resection margins and local recurrences of impalpable breast cancer: Comparison between radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL).

OBJECTIVES: The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). MATERIALS AND METHODS: We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. RESULTS: 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p < 0.001), extensive intraductal component (p < 0.001), larger tumour size (p = 0.011), and smaller specimen weight (p = 0.014). The median follow-up time in the ROLL group was 81 (8-94) months and 64 (3-73) months in the RSL group. The five-year local recurrence-free survival (LRFS) estimates for ROLL and RSL groups were 98.0% and 99.4%, respectively (log-rank test, p = 0.323). CONCLUSION: Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS.

Resection margins and local recurrences in breast cancer: Comparison between conventional and oncoplastic breast conserving surgery.

BACKGROUND: This retrospective cohort study aims to compare surgical margins, reoperations and local recurrences after conventional or oncoplastic breast conservation surgery (BCS). Furthermore, we aim to investigate differences between various oncoplastic techniques. MATERIAL AND METHODS: We reviewed 1800 consecutive patients with primary invasive breast cancer (N = 1707) or ductal carcinoma in situ (N = 93) who underwent BCS at Helsinki University Hospital between 2010 and 2012. RESULTS: Conventional BCS was performed in 1189 (66.1%) patients, oncoplastic BCS in 611 (33.9%). Various oncoplastic techniques were used. Patients with oncoplastic BCS had more often multifocal (p < 0.001), larger (p < 0.001), palpable tumours (p < 0.001) with larger resection specimens (p < 0.001). The amount of resected tissue varied substantially depending on the oncoplastic technique. Patients treated with oncoplastic BCS were younger (p < 0.001) and their tumours were more aggressive according to histological grade (p < 0.001), T-stage (p < 0.001), Ki-67 (p < 0.001) and lymph node status (p < 0.001). There was no difference, however, in surgical margins (p = 0.578) or reoperation rates (p = 0.430) between the groups. A total of 152 (8.4%) patients were reoperated because of insufficient margins, 96 (8.1%) in the conventional, 56 (9.2%) in the oncoplastic BCS group. The median follow-up time was 75 (2-94) months. There was no difference in local recurrence-free survival between the conventional and oncoplastic BCS groups (log-rank test, p = 0.172). CONCLUSIONS: Oncoplastic BCS was used for larger, multifocal and more aggressive tumours. Nevertheless, no difference in reoperation rate or local recurrences were found. Oncoplastic BCS is as safe as conventional BCS enabling breast conserving for patients who otherwise were candidates for mastectomy.

Surgical treatment and prognosis of breast cancer in elderly - A population-based study.

BACKGROUND: The aim of this study was to investigate outcome of treatment in patients over 80 years of age with early breast cancer at the time of the diagnosis with special interest in surgical treatment. MATERIALS AND METHODS: Breast cancer patients older than 80 years of age, treated at the Breast Surgery Unit of Helsinki University Hospital in 2005-2010 were identified from electronic patient records. Patients were followed-up until the end of 2014. Patient and tumour characteristics, recurrences, co-morbidities and reasons for omission of surgery were collected from electronic patient records. Survival data was obtained from Finnish Cancer Registry. RESULTS: 446 patients were eligible for the study: 401 (90%) received surgery. The median follow-up time was 52 months. In the entire study population, local and regional recurrences/disease progression were diagnosed in 16 (3.6%) and 6 (1.3%) patients, respectively. The five-year overall survival was 50.6% in the surgical treatment and only 15.2% in non-surgical treatment group, p < 0.001. Also, the five-year breast cancer specific survival was significantly better in the patients with surgery, 82.0%, but 56.0% in the patients without surgery, p < 0.001. There was no mortality related to the surgery, but 122 (30%) patients died within three years from surgery. CONCLUSION: Surgical treatment rate was high. OS and BCSS were better in surgically treated elderly patients. Local and regional disease control was excellent, probably due to high rate of surgical treatment. Surgical treatment also seemed safe in this elderly patient population. However, surgical overtreatment was obvious in some patients.

Breast Lesion Excision System in the diagnosis and treatment of intraductal papillomas - A feasibility study.

OBJECTIVES: This study aims to evaluate the feasibility of Breast Lesion Excision System (BLES) in the treatment of intraductal papillomas. MATERIAL AND METHODS: All patients with a needle biopsy -based suspicion of an intraductal papilloma who consequently underwent a BLES procedure at Helsinki University Hospital between 2011 and 2016 were included in this retrospective study. The purpose of the BLES procedure was either to excise the entire lesion or in few cases to achieve better sampling. RESULTS: In total, 74 patients underwent 80 BLES procedures. Pathological diagnosis after the BLES biopsy confirmed an intraductal papilloma without atypia in 43 lesions, whereas 10 lesions were upgraded to high-risk lesions (HRL) with either atypical ductal hyperplasia or lobular carcinoma in situ. Five cases were upgraded to malignancy, two were invasive ductal carcinomas and three were ductal carcinoma in situ. Additionally, 18 lesions were diagnosed as other benign lesions. Four procedures failed. Complete excision with BLES was achieved in 19 out of 43 intraductal papillomas, 6 out of 10 HRL and two out of five malignant lesions. No major complications occurred. The BLES procedure was adequate in the management of the 71 breast lesions. CONCLUSION: The BLES procedure is an acceptable method for the management of small benign and high-risk breast lesions such as intraductal papillomas in selected patients. Thus, a great amount of diagnostic surgical biopsies can be avoided.

The quality of preoperative diagnostics and surgery and their impact on delays in breast cancer treatment - A population based study.

BACKGROUND AND OBJECTIVES: This study aims to clarify quality of breast cancer surgery in population-based setting. We aim to elucidate factors influencing waiting periods, and to evaluate the effect of hospital volume on surgical treatment policies. Special interest was given to diagnostic and surgical processes and their impact on waiting times. METHODS: All 1307 patients having primary breast cancer surgery at the Helsinki and Uusimaa Hospital District during 2010 were included in this retrospective study. RESULTS: Median waiting time for primary surgery was 24 days and significantly affected by additional imaging and diagnostic biopsies as well as hospital volume. Final rate of breast conserving surgery was surprisingly low, 51%, not affected by hospital volume, p = 0.781. Oncoplastic resection and immediate breast reconstruction (IBR) were performed more often in high volume units, p < 0.001. Quality of axillary surgery varied with unit size. Multiple operations, IBR and high volume unit were factors prolonging initiation of adjuvant treatment. CONCLUSION: Quality of preoperative diagnostics play a crucial role in minimizing the need of repeated imaging and biopsies as well as multiple operations. Positive impact of high-volume hospitals becomes evident when analyzing procedures requiring advanced surgical techniques. High-volume hospitals achieved better quality in axillary surgery.

Effect of delayed autologous breast reconstruction on breast cancer recurrence and survival.

BACKGROUND: The goal of the present study was to evaluate the impact of delayed autologous breast reconstruction on disease relapse in breast cancer patients treated with mastectomy. MATERIAL AND METHODS: The study was based on 503 consecutive patients younger than 70 years of age who underwent mastectomy between January 2000 and December 2003. Overall, 391 (78 %) received mastectomy alone and 112 (22 %) underwent a delayed breast reconstruction. The median time from mastectomy to delayed breast reconstruction was 34 months. The median duration of follow-up was 102 months. RESULTS: There were no locoregional recurrences (LRR) in patients who underwent delayed reconstruction (0.0 %); 21 LRR developed in patients treated with mastectomy only (5.4 %), P = 0.011. Distant metastases occurred less frequently in the reconstruction group (12.5 %) than in the patients who underwent mastectomy alone (21.5 %); P = 0.0343. The 8-year breast cancer specific survival in the reconstruction group was 98.2 and 85.7 % for the mastectomy only group, P = 0.000. CONCLUSIONS: Delayed autologous breast reconstruction does not appear to adversely influence disease progression when compared to patients treated with mastectomy only.

Local recurrence of breast cancer after mastectomy and modern multidisciplinary treatment.

BACKGROUND: To study the incidence of local recurrence (LR) of early breast cancer in the ipsilateral thoracic wall after mastectomy and outcome of patients with LR. MATERIAL AND METHODS: A retrospective cohort study based on 2220 consecutive breast cancer patients treated at the Helsinki University Central Hospital, Finland, in 2000 to 2003. A subset of 755 (34.0%) patients had mastectomy which was usually followed by postoperative radiotherapy (51.2%) and/or systemic adjuvant therapy (79.2%). RESULTS: During a median follow-up of 89 months, 22 (2.9%) patients treated with mastectomy had LR. The median time to LR was 27 months. None of the 12 patient- or tumour-related standard risk factors studied were independently associated with LR-free survival in a multivariate model. Six (27.3%) of the 22 patients with LR had distant metastases diagnosed either prior to or simultaneously with LR. The subset of 16 patients who were diagnosed with LR without concomitant distant recurrence had five-year breast cancer-specific survival of 77.5% as calculated from the date of LR detection, and overall survival of 59.2%. CONCLUSIONS: LR after mastectomy has become a rare event. Most women with isolated LR survive for five years after LR.

Multi-institutional comparison of non-sentinel lymph node predictive tools in breast cancer patients with high predicted risk of further axillary metastasis.

Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.

International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer.

BACKGROUND: Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS: Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS: Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS: We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.

Axillary and supraclavicular recurrences are rare after axillary lymph node dissection in breast cancer.

BACKGROUND: This study was designed to evaluate the incidence of and risk factors for axillary recurrence (AR) and supraclavicular recurrence (SR) in breast cancer patients with axillary lymph node dissection. METHODS: The study was based on 1,180 patients with unilateral invasive breast cancer operated between January 2000 and December 2003. The median duration of follow-up was 78 months. RESULTS: The 7-year AR incidence was 0.7% and SR incidence was 1.3%. Twelve of the 14 SR patients and 4 of the 8 AR patients had concomitant distant recurrences. No risk factors for AR were identified. Histological tumor grade III as well as estrogen and progesterone negativity were risk factors for SR. SR, but not AR, was an independent risk factor for poor breast cancer-specific survival [hazard ratio, 10.116; P < 0.0001]. Among N1 patients, the extent of radiotherapy (RT) had no influence on regional recurrences. Among N2-N3 patients, the 7-year regional recurrence rates were 34.3% in patients without RT, 0% in patients with local RT, and 1.2% in patients with locoregional RT (P < 0.0001). CONCLUSIONS: AR and SR are rare events that often are detected concomitantly with distant metastases. SRs are associated with aggressive disease and poor survival. Our results also suggest that regional RT reduces regional recurrences in N2-N3 patients but not in N1 patients, but the retrospective, nonrandomized study setting renders this conclusion as uncertain.

Influence of isolated tumor cells in sentinel nodes on outcome in small, node-negative (pT1N0M0) breast cancer.

PURPOSE: To evaluate the prognostic significance of isolated tumor cells found on sentinel node biopsy. METHODS: The study is based on a prospectively followed up cohort of 1,865 consecutive patients diagnosed with pT1 (tumor size

Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer.

BACKGROUND: There is evidence that the immune systems of patients with breast cancer are dysfunctional. Regulatory T cells (Tregs), and IDO, an immunosuppressive enzyme, are associated with more advanced disease in some cancers and may promote immunologic tolerance to tumors. Our aim was to assess whether expression of Foxp3, a marker of Tregs, and IDO were linked with nodal metastasis in breast cancer patients. Inhibitors of IDO are available and could potentially demonstrate utility in breast cancer if IDO drives progression of disease. METHODS: Sentinel lymph nodes (SLN) of 47 breast cancer patients with varying degrees of nodal disease and 10 controls were evaluated for expression of Foxp3 and IDO using immunohistochemistry. Positively stained cells were quantified and their distribution within the SLN noted. RESULTS: The proportion of Foxp3+ cells was higher in SLN of cancer patients than controls (19% v. 10%, p < 0.001). Specifically, there were more Foxp3+ cells in SLN with metastasis than tumor-free SLN (20% v. 14%, p = 0.02). The proportion IDO+ cell in SLN of cancer patients was not statistically different than controls (4.0% v. 1.6%, p = 0.08). In order to demonstrate the combined immunosuppressive effect of Foxp3 and IDO, we categorized each SLN as positive or negative for Foxp3 and IDO. The Foxp3+/IDO+ group almost exclusively consisted of cancer patients with node positive disease. CONCLUSION: In conclusion, our study shows that Foxp3+ cells are associated with more advanced disease in breast cancer, a finding that is proving to be true in many other cancers. As IDO has been found to promote differentiation of Tregs, IDO may become a suitable target to abrogate the development of T-cell tolerance and to promote an effective immune response to breast cancer. Our results about the combined expression of IDO and Foxp3 in metastastic SLN support this assumption.

High expression of maspin is associated with early tumor relapse in breast cancer.

Maspin is a serine protease inhibitor with tumor suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Maspin also modulates apoptosis of tumor cells, possibly by modulating the expression of the B-cell lymphoma-2 family member. p53 regulates the expression of the tumor suppressor gene maspin. Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. This study was conducted to clarify the role of maspin and B-cell lymphoma-2 in early and late recurring breast cancer. The expression of maspin, B-cell lymphoma-2, p53, and estrogen receptor was studied by immunohistochemistry in 73 primary breast cancers and in their metastatic relapses detected within 2 years, or 5 or 10 years after primary surgery. The cytoplasmic expression of maspin was significantly higher in the primary tumors of the early metastasizing breast cancers (first tumor relapse within 2 years) and also in their metastases compared to late metastasizing cancers. An opposite activity was observed in the expression of B-cell lymphoma-2. The level of B-cell lymphoma-2 staining was lower in the early relapsing cancers and significantly lower in their metastases, compared to tumors which metastasized 5 or 10 years after primary surgery. High cytoplasmic expression of maspin and low expression of B-cell lymphoma-2 in primary breast cancer predict early tumor relapse.

The outcome of sentinel node biopsy in breast cancer patients with preoperative surgical biopsy.

BACKGROUND: The aim of the study was to evaluate the outcome of sentinel node biopsy (SNB), especially the medium term axillary recurrence rate after negative SNB in patients with preoperative surgical biopsy (SB). PATIENTS AND METHODS: The study included 1,641 patients with a histological stage T1 tumours and SNB. In 77 patients, the diagnosis was obtained with SB, while 1,564 patients had underwent needle biopsy (NB) only. Axillary clearance was omitted in 56 SB patients and 921 NB patients after negative SNB. The median duration of follow-up in these patients was 54 months. RESULTS: None of the SB patients had axillary recurrences during the follow-up. Six NB patients had isolated axillary recurrences while three patients had concomitant local and axillary recurrences. There were no differences in local or distant recurrences or breast cancer deaths between the SB and the NB patients. CONCLUSIONS: SNB seems a feasible axillary staging method in patients with histological stage T1 tumour also after preoperative SB. The risk of axillary recurrence after negative SNB is negligible in these patients.

Rapid immunohistochemistry enhances the intraoperative diagnosis of sentinel lymph node metastases in invasive lobular breast carcinoma.

BACKGROUND: The sensitivity of the intraoperative diagnosis of sentinel lymph node (SLN) micrometastases and the metastases of invasive lobular carcinoma (ILC) is low. The goal of the current study was to assess whether the use of intraoperative, rapid immunohistochistochemistry (IHC) enhances the intraoperative detection of micrometastases and metastases of ILC. METHODS: The sensitivity of the intraoperative diagnosis of SLN metastasis was evaluated in 438 patients when using rapid IHC with a cytokeratin biomarker. The results were compared with those obtained for 557 patients without rapid IHC but with conventional staining. RESULTS: For patients with ILC, the sensitivity of the intraoperative diagnosis was 87% (45 of 52) in the IHC group and 66% (39 of 59) in the non-IHC group (P = 0.02). The sensitivity of the intraoperative diagnosis was similar for patients with other types of invasive cancer regardless of the use of rapid IHC. However, rapid IHC enhanced marginally the intraoperative diagnosis of the smallest micrometastases, isolated tumor cells (P = 0.06). CONCLUSIONS: Rapid IHC with cytokeratin labeling enhanced the intraoperative diagnosis of SLN metastases in patients with ILC. It may also improve the intraoperative diagnosis of micrometastases.

Breast lymphedema after breast conserving treatment.

The authors aimed to evaluate breast lymphedema after breast conserving therapy (BCT) and sentinel node biopsy (SNB) or axillary clearance (AC). Fifty-seven breast cancer patients with BCT underwent SNB only and 103 underwent AC (57 with tumor negative and 46 with positive axillary nodes). Clinical examination and breast ultrasonography (US) were performed one year after surgery. Clinical examination revealed breast edema in 48% of patients in the AC node positive group, in 35% in the AC node negative group, and in 23% in the SNB group (p<0.05 between SNB and AC node positive). US revealed subcutaneous edema in the operated breast in 69-70% of the patients in the AC groups and in 28% in the SNB group (p=0.001-0.0001 between the SNB and the AC groups). Breast lymphedema was less common one year after BCT in patients with SNB only than in those with more extensive axillary treatment.