Identifying pathologic complete response of the breast after neoadjuvant systemic therapy with ultrasound guided biopsy to eventually omit surgery: Study design and feasibility of the MICRA trial (Minimally Invasive Complete Response Assessment).

PURPOSE: Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). The MICRA trial (NTR6120) aims at identifying pCR with post-NST biopsies. Here, we report the study design and feasibility. METHODS: The MICRA-trial is a multi-center prospective cohort study. Patients with a pre-NST placed marker and radiologic complete (rCR) or partial response on MRI after NST are eligible for inclusion. Ultrasound guided biopsy of the original tumor area is performed. Pathology results of the biopsies and surgery specimens are compared. The primary endpoint is false-negative rate of biopsies in identifying pCR. RESULTS: During the first year of the trial 58 patients with rCR were included. One patient was a screening failure and excluded for analysis. Twenty-one percent had hormone receptor (HR)+/HER2- tumors, 21% HR+/HER2+ tumors, 18% HR-/HER2+ tumors and 40% TN tumors. Overall pCR was 68%. In seven patients biopsies could not be obtained: in 6 patients, the marker could not be identified on ultrasound in the OR and in 1 patient there were technical difficulties. A median of eight biopsies was obtained (range 4-9). The median of histopathological representative biopsies was 4 (range 1-8). CONCLUSION: Ultrasound guided biopsy of the breast in patients with excellent response on MRI after NST is feasible. Accuracy results of the MICRA trial will be presented after inclusion of 525 patients to determine if ultrasound guided biopsy is an accurate alternative to surgical resection for assessment of pCR after NST.

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure.

BACKGROUND: Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy. METHODS: All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node. RESULTS: The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment. CONCLUSION: Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN + breast cancer patients.

Enrichment of high-grade tumors in breast cancer gene expression studies.

PURPOSE: Gene expression (GE) profiling for breast cancer classification and prognostication has become increasingly used in clinical diagnostics. GE profiling requires a reasonable tumor cell percentage and high-quality RNA. As a consequence, a certain amount of samples drop out. If tumor characteristics are different between samples included and excluded from GE profiling, this can lead to bias. Therefore, we assessed whether patient and tumor characteristics differ between tumors suitable or unsuitable for generating GE profiles in breast cancer. METHODS: In a consecutive cohort of 738 breast cancer patients who received neoadjuvant chemotherapy at the Netherlands Cancer Institute, GE profiling was performed. We compared tumor characteristics and treatment outcome between patients included and excluded from GE profiling. Results were validated in an independent cohort of 812 patients treated with primary surgery. RESULTS: GE analysis could be performed in 53% of the samples. Patients with tumor GE profiles more often had high-grade tumors [odds ratio 2.57 (95%CI 1.77-3.72), p < 0.001] and were more often lymph node positive [odds ratio 1.50 (95%CI 1.03-2.19), p = 0.035] compared to the group for which GE profiling was not possible. In the validation cohort, tumors suitable for gene expression analysis were more often high grade. CONCLUSIONS: In our gene expression studies, tumors suitable for GE profiling had more often an unfavorable prognostic profile. Due to selection of samples with a high tumor percentage, we automatically select for tumors with specific features, i.e., tumors with a higher grade and lymph node involvement. It is important to be aware of this phenomenon when performing gene expression analysis in a research or clinical context.

Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

BACKGROUND AND OBJECTIVES: Breast conserving surgery (BCS) can be challenging for large regions of ductal carcinoma in situ (DCIS), resulting in high rates of positive resection margins. Radioactive seed localization (RSL) using multiple radioactive iodine (125I) seeds can be used to bracket extensive DCIS (eDCIS). The goal of this study was to retrospectively compare the use of a single or multiple 125I seeds in RSL to enable BCS in patients with eDCIS. METHODS: All patients with eDCIS (area of ≥3.0 cm) who underwent either single or multiple-seed RSL between January 2008 and December 2016 were included. Patient, tumor and surgery characteristics were compared between both groups. Primary outcome measures were positive resection margin and re-operation rates. RESULTS: Respectively 48 and 58 patients with eDCIS underwent single- and multiple-seed RSL and subsequent BCS. The rate of positive resection margin (focal and more than focal) with single-seed RSL was 47.9%, compared to 29.3% with multiple-seed RSL (p = 0.06). The re-operation rate was 39.6% with single-seed RSL and 20.7% in the multiple-seed RSL group (p = 0.05). CONCLUSION: Multiple-seed RSL enables bracketing of large areas of DCIS, with the potential to decrease the high rate of positive resection margins in this patient group.

Eigentumors for prediction of treatment failure in patients with early-stage breast cancer using dynamic contrast-enhanced MRI: a feasibility study.

We present a radiomics model to discriminate between patients at low risk and those at high risk of treatment failure at long-term follow-up based on eigentumors: principal components computed from volumes encompassing tumors in washin and washout images of pre-treatment dynamic contrast-enhanced (DCE-) MR images. Eigentumors were computed from the images of 563 patients from the MARGINS study. Subsequently, a least absolute shrinkage selection operator (LASSO) selected candidates from the components that contained 90% of the variance of the data. The model for prediction of survival after treatment (median follow-up time 86 months) was based on logistic regression. Receiver operating characteristic (ROC) analysis was applied and area-under-the-curve (AUC) values were computed as measures of training and cross-validated performances. The discriminating potential of the model was confirmed using Kaplan-Meier survival curves and log-rank tests. From the 322 principal components that explained 90% of the variance of the data, the LASSO selected 28 components. The ROC curves of the model yielded AUC values of 0.88, 0.77 and 0.73, for the training, leave-one-out cross-validated and bootstrapped performances, respectively. The bootstrapped Kaplan-Meier survival curves confirmed significant separation for all tumors (P < 0.0001). Survival analysis on immunohistochemical subgroups shows significant separation for the estrogen-receptor subtype tumors (P < 0.0001) and the triple-negative subtype tumors (P = 0.0039), but not for tumors of the HER2 subtype (P = 0.41). The results of this retrospective study show the potential of early-stage pre-treatment eigentumors for use in prediction of treatment failure of breast cancer.

Feasibility of magnetic marker localisation for non-palpable breast cancer.

OBJECTIVES: Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. MATERIALS AND METHODS: Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. RESULTS: Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. CONCLUSION: Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies.

A novel semi-robotized device for high-precision 18F-FDG-guided breast cancer biopsy.

PURPOSE: To assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high 18F-FDG uptake. MATERIALS AND METHODS: In the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm3 voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with 18F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of 18F-FDG uptake areas within the tumour. RESULTS: Needle positioning tests revealed an average accuracy of 0.5mm (range 0-1mm), 0.6mm (range 0-2mm), and 0.4mm (range 0-2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high 18F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application. CONCLUSIONS: Accuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.

Radioactive seed localization in breast cancer treatment.

BACKGROUND: Breast cancer screening, improved imaging and neoadjuvant systemic therapy (NST) have led to increased numbers of non-palpable tumours suitable for breast-conserving surgery (BCS). Accurate tumour localization is essential to achieve a complete resection in these patients. This study evaluated the role of radioactive seed localization (RSL) in improving breast- and axilla-conserving surgery in patients with breast cancer with or without NST. METHODS: Patients who underwent RSL between 2007 and 2014 were included. Learning curves were analysed by the rates of minimally involved (in situ/invasive tumour cells on a length of 0-4 mm on ink) and positive resection margins (over 4 mm on ink) after BCS, and the median resection volume over time. RESULTS: A total of 367 patients with in situ carcinomas and 199 with non-palpable invasive breast cancer underwent RSL before primary surgery. A further 697 patients had RSL before NST, of whom 206 also underwent RSL of a histologically verified axillary lymph node metastasis. BCS was performed in 93·2 and 87·9 per cent of patients undergoing primary surgery for in situ and invasive tumours respectively, and 57·5 per cent of those in the NST group. The rate of BCS with positive resection margins was low and stable over time in the three groups (9·1, 9·7 and 11·2 per cent respectively). The median resection volume decreased significantly with time in the invasive cancer and NST groups. CONCLUSION: In the present study of more than 1200 patients and 7 years of experience, RSL was shown to facilitate breast- and axilla-conserving surgery in a diverse patient population. There was a significant reduction in resection volume while maintaining low positive resection margin rates after BCS.

The prognostic value of the neoadjuvant response index in triple-negative breast cancer: validation and comparison with pathological complete response as outcome measure.

The Neoadjuvant response index (NRI) has been proposed as a simple measure of downstaging by neoadjuvant treatment in breast cancer. It was previously found to predict recurrence-free survival (RFS) in triple-negative (TN) breast cancer. It was at least as accurate as the standard binary system, the absence or presence of a pathological complete remission (pCR), which is the commonly employed outcome measure. The NRI was evaluated in an independent consecutive series of patients to validate the previous findings. Univariable and multivariable analyses were done to assess the predictive value of clinical parameters and of the NRI for RFS. We combined the original and validation series of patients to build a multivariable predictive model for RFS after neoadjuvant chemotherapy in TN breast cancer. The validation set (N = 108) confirmed that patients with a higher-than-median NRI (>0.7) had excellent RFS (P = 0.002), similar to that of patients who had achieved a pCR. Multivariable analysis in 191 patients showed that the NRI was a strong independent predictor of RFS (P = 0.0002), with N-stage (P = 0.001) and T-stage (P = 0.014) ranking second and third, respectively. Importantly, among patients who did not achieve a pCR (NRI values below 1), higher NRI values were still associated with better RFS. The NRI is a simple method and a practical tool to predict RFS in TN breast cancer patients treated with neoadjuvant chemotherapy. It adds prognostic information to the presence or absence of pCR and could be useful to compare the efficacies of different chemotherapy regimens.

The use of radioactive iodine-125 seed localization in patients with non-palpable breast cancer: a comparison with the radioguided occult lesion localization with 99m technetium.

BACKGROUND: Radioactive Seed Localization with a radioactive iodine-125 seed (RSL) and Radioguided Occult Lesion Localization with 99mTechnetium colloid (ROLL) are both attractive alternatives to wire localization for guiding breast conserving surgery (BCS) of non-palpable breast cancer. The aim of this study was to evaluate and compare the efficacy of RSL and ROLL. METHODS: We retrospectively analyzed 387 patients with unifocal non-palpable ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCS at the Netherlands Cancer Institute. In total 403 non-palpable lesions were localized either by RSL (N = 128) or by ROLL (N = 275). Primary outcome measures were positive margins and re-excision rates; the secondary outcome measure was weight of the specimen. RESULTS: Pre-operative mammography or ultrasound showed similar sizes of DCIS and invasive tumours in both RSL and ROLL groups. In the RSL group, more lesions were DCIS (58%) than in the ROLL group, where 32% of the lesions were pure DCIS. The proportions of focally positive margins (11% vs. 10%) and more than focally positive margins (9% vs. 9%) were comparable between the RSL and the ROLL group, resulting in the same re-excision rate in both RSL and ROLL groups (9% vs. 10%). For DCIS lesions, the specimen weight was significantly lower in the RSL group than in the ROLL group after adjusting for tumour size on mammography (12 g; 95% CI 2.6-21). CONCLUSION: Margin status and re-excision rates were comparable for RSL and ROLL in patients with non-palpable breast lesions. Because of the significant lower weight of the resected specimen in DCIS, the feasibility of position verification of the I-125 seed and more convenient logistics, we favour RSL over ROLL to guide breast-conserving therapy.

Neoadjuvant chemotherapy adaptation and serial MRI response monitoring in ER-positive HER2-negative breast cancer.

BACKGROUND: Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with 'luminal'-type breast cancer in whom the second half of neoadjuvant chemotherapy was selected based on the response to the first half. METHODS: Patients with oestrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer received three courses of neoadjuvant dose-dense doxorubicin and cyclophosphamide (ddAC). Three further courses of ddAC were administered in case of a 'favourable response' on the interim magnetic resonance imaging (MRI) and a switch to docetaxel and capecitabine (DC) was made in case of an 'unfavourable response', using previously published response criteria. The efficacy of this approach was evaluated by tumour size reductions on serial contrast-enhanced MRI, pathologic response and relapse-free survival. RESULTS: Two hundred and forty-six patients received three courses of ddAC. One hundred and sixty-four patients (67%) had a favourable response at the interim MRI, with a mean tumour size reduction of 31% after the first three courses and 34% after the second three courses. Patients with unfavourable responsive tumours had a mean tumour size reduction of 12% after three courses and received three courses of DC rather than ddAC. This led to a mean shrinkage of 27%. CONCLUSION: The tumour size reduction of initially less responsive tumours after treatment adaptation adds further evidence that a response-adapted strategy may enhance the efficacy of neoadjuvant chemotherapy.

Fully automated deformable registration of breast DCE-MRI and PET/CT.

Accurate characterization of breast tumors is important for the appropriate selection of therapy and monitoring of the response. For this purpose breast imaging and tissue biopsy are important aspects. In this study, a fully automated method for deformable registration of DCE-MRI and PET/CT of the breast is presented. The registration is performed using the CT component of the PET/CT and the pre-contrast T1-weighted non-fat suppressed MRI. Comparable patient setup protocols were used during the MRI and PET examinations in order to avoid having to make assumptions of biomedical properties of the breast during and after the application of chemotherapy. The registration uses a multi-resolution approach to speed up the process and to minimize the probability of converging to local minima. The validation was performed on 140 breasts (70 patients). From a total number of registration cases, 94.2% of the breasts were aligned within 4.0 mm accuracy (1 PET voxel). Fused information may be beneficial to obtain representative biopsy samples, which in turn will benefit the treatment of the patient.

Radioguided occult lesion localisation (ROLL) in breast-conserving surgery after neoadjuvant chemotherapy.

BACKGROUND: An important benefit of neoadjuvant chemotherapy, as compared to adjuvant chemotherapy, in breast cancer patients is down staging of the primary tumour, which allows for more breast-conserving surgery. When a tumour becomes non-palpable after this down staging, precise localisation of the original tumour bed is crucial to be able to perform breast-conserving surgery. Radioguided Occult Lesion Localisation with (99m)Technetium (ROLL-(99m)Tc) is commonly used to perform breast-conserving surgery in patients with non-palpable breast tumours. We modified this technique to use it in the neoadjuvant setting. The present analysis was performed to assess its feasibility and analyse the number of patients in which a mastectomy was correctly withheld using this technique. METHODS: A retrospective analysis was performed for all patients who were treated with neoadjuvant chemotherapy between 2007 and 2010 in our institute and underwent breast-conserving surgery with the ROLL-(99m)Tc technique afterwards. The status of the margins and the weight of the resected specimen were assessed. RESULTS: The median weight of the resected specimen in these 83 patients was 53 g (range: 11-204 g). Eleven of the 58 patients with residual disease revealed positive margins at pathological examination. However, in only 5 of those 11 patients a secondary mastectomy was indicated. This means that in 94% of all included patients a mastectomy was correctly withheld. CONCLUSION: The ROLL-(99m)Tc technique is a feasible technique that can be used to perform breast-conserving surgery after neoadjuvant chemotherapy in a carefully selected group of patients.

Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET.

Positron emission tomography (PET), with or without integrated computed tomography (CT), using 18F-fluorodeoxyglucose (FDG) is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

PURPOSE: To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. METHODS: Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. RESULTS: Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. CONCLUSION: Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

Marking the axilla with radioactive iodine seeds (MARI procedure) may reduce the need for axillary dissection after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: An important benefit of neoadjuvant chemotherapy is the increased potential for breast-conserving surgery. At present the response of axillary lymph node metastases to chemotherapy is not easily assessed, rendering axilla-conserving treatment difficult. The aim was to assess a new surgical method for evaluating the axillary response to chemotherapy. METHODS: Before neoadjuvant chemotherapy, proven tumour-positive axillary lymph nodes were localized using ultrasound-guided insertion of iodine-125-labelled (I-125) seeds. After neoadjuvant chemotherapy, the marked lymph nodes were removed selectively with the use of a gamma probe. A complete axillary lymph node clearance was carried out to determine whether the pathological response in the marked node was indicative of that in the other lymph nodes. RESULTS: Tumour-positive axillary lymph nodes were localized successfully with I-125 seeds in 15 patients. The marked lymph node was detected and removed selectively after neoadjuvant chemotherapy in all patients. The pathological response to chemotherapy in the marked lymph node was indicative of the overall response in other removed lymph nodes. CONCLUSION: This study showed that marking and selectively removing metastatic lymph nodes after neoadjuvant chemotherapy was feasible. The tumour response in the marked lymph node may be used to tailor further axillary treatment, making axilla-conserving surgery a possibility.

The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy.

BACKGROUND: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy. METHOD: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed. RESULTS: The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34-0.49) and 20% (7 of 35, 95% CI 0.10-0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30-0.48), 24% (11 of 45, 95% CI 0.14-0.38), and 45% (20 of 44, 95% CI 0.32-0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004). CONCLUSION: In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumors.

The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast.

Re-excision rates after breast conserving surgery(BCS) of invasive lobular carcinoma (ILC) are high.Preoperative breast MRI has the potential to reduce re-excision rates, but may lead to an increased rate of mastectomies. Hence, we assessed the influence of preoperative breast MRI on the re-excision rate and the rate of mastectomies. We performed a retrospective cohort study of a consecutive series of patients with ILC who presented in one of two dedicated tertiary cancer centers between 1993 and 2005. We assessed the initial type of surgery(BCS or mastectomy), the re-excision rate and the final type of surgery. Patients were stratified into two groups:those who received preoperative MRI (MR? group) and those who did not (MR- group). In the MR- group, 27%of the patients underwent a re-excision after initial BCS. In the MR? group, this rate was significantly lower at 9%.The odds ratio was 3.64 (95% CI: 1.30-10.20, P = 0.010).There was a trend towards a lower final mastectomy rate in the MR? group compared to the MR- group (48 vs. 59%,P = 0.098). In conclusion, preoperative MRI in patients with ILC can reduce re-excision rates without increasing the rate of mastectomies.

The impact of preoperative MRI on breast-conserving surgery of invasive cancer: a comparative cohort study.

AIM: To assess whether preoperative contrast-enhanced magnetic resonance imaging (MRI) of the breast influences the rate of incomplete tumor excision. METHODS: In a cohort of 349 women with invasive breast cancer, patients eligible for breast-conserving therapy (BCT) on the basis of conventional imaging and palpation only (N = 176) were compared to those who had an additional preoperative MRI (N = 173). Multivariate analysis was applied to explore associations with incomplete tumor excision. RESULTS: MRI detected larger extent of breast cancer in 19 women (11.0%), leading to treatment change: mastectomy (8.7%) or wider excision (2.3%). Tumor excision was incomplete in 22/159 (13.8%) wide local excisions in the MRI group and in 35/180 (19.4%) in the non-MRI group (P = 0.17). Stratified to tumor type, incompletely excised infiltrating ductal carcinoma (IDC) was significantly associated with absence of MRI: 11/136 (8.1%) versus 2/126 (1.6%) (MRI present) (P = 0.02). No significant factors explained incomplete excision of other tumor types. CONCLUSION: Preoperative MRI did not significantly affect the overall rate of incomplete tumor excision, but it yielded significantly lower rate of incompletely excised IDC. The reduction of incomplete excisions after MRI was smaller than the rate of a prior treatment change incurred by MRI.

[Neoadjuvant systemic therapy in patients with operable primary breast cancer: more benefits than breast-conserving therapy]. / Neoadjuvante systemische therapie bij het primair operabel mammacarcinoom: meer voordelen dan alleen borstsparende behandeling.

OBJECTIVE: To analyse the extent to which primary systemic therapy (PST) achieves the main goals in patients with operable primary breast cancer, these goals being breast-conserving therapy and pathological complete remission (pCR), and to evaluate the response. DESIGN: Retrospective. METHOD: In a retrospective analysis of 254 patients treated with PST in 2000-2007 in the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, patients with inoperable disease (T4 and/or N3) were excluded. The response was mostly evaluated using contrast-enhanced MRI, whereby the chemotherapy regimen was switched if the reduction in the largest diameter of contrast washout was less than 25%. pCR was defined as no evidence of invasive cancer in the breast and axilla in the resection specimen. RESULTS: In patients with ductal carcinoma and lobular carcinoma an increase in breast-conserving therapy was seen in 32% and 17% of patients respectively. The pCR rate was 12% and 2% respectively. Secondary mastectomy because of irradical resection was required in 3% and 50% respectively. Multivariate analysis indicated that molecular type, defined on the basis of the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), i.e. luminal (oestrogen receptor-positive), basal (hormone receptor-negative and HER2-negative) and HER2-positive tumours treated with trastuzumab was the only independent predictor of pCR; 2%, 28% and 35% respectively (p=0.004). In 43 patients the chemotherapy regimen was adjusted because the tumour did not respond sufficiently. A favourable clinical response was observed in 72% (31/43) of these patients. CONCLUSION: The observed increase in the number of breast-conserving therapies after PST was clinically relevant. PST may be more effective when contrast-enhanced MRI is used for interim evaluation, based on which the treatment may be switched. There was a clear difference in histological and molecular types of tumour and therefore the choice of treatment may be adjusted accordingly.