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Background: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis., Methods: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others., Results: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths., Conclusion: In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Purpose: Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy., Methods: We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99m Tc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months., Results: Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P  = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P  = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge ( N  = 42) and BI-RADS 3 lesions ( N  = 113) MBI detected 7 of 8 occult malignancies., Conclusion: MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Pectoral fascia (PF) removal during mastectomy still seems to be the standard procedure. However, preservation of the PF might improve postoperative and cosmetic outcomes, without compromising oncological safety. Here, we report on a national survey among Dutch plastic surgeons and oncological breast surgeons to evaluate their techniques and opinions regarding the PF., Materials and Methods: A survey based study was performed in the Netherlands, in which both plastic surgeons and oncological breast surgeons were included, each receiving a different version of the survey. The surveys were distributed to 460 and 150 e-mail addresses, respectively., Results: A total of 68 responses were included from more than half of all Dutch medical centers. The results of this study indicate that circa one in five plastic surgeons and breast surgeons routinely preserve the PF during mastectomies and even more surgeons preserve the PF in specific cases. The surgical techniques and opinions regarding PF preservation widely differ between surgeons., Conclusions: Preservation of the PF does occur in a substantial part of the Dutch medical centers and techniques and opinions are contradictory. Future studies on this topic should clarify the effect of PF preservation on oncological safety, complication rates, postoperative pain, cosmetic outcomes, and patient satisfaction., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Radioactive seed localization (RSL) uses an iodine-125 ((125)I) seed as a marker for tumour location. The (125)I seed is implanted into the tumour and enables intraoperative localization with a conventional gamma probe. However, specimen margins in relation to the (125)I seed are estimated on the basis of gamma-probe readings only. A novel device, freehand SPECT, is capable of measuring the distance from the resection plane to the (125)I seed. The aim of this feasibility study was to establish the accuracy of this device in predicting resection margins in ex-vivo tumour specimens excised with RSL guidance., Patients and Methods: In this feasibility study 10 patients with nonpalpable breast cancer scheduled for wide local excision with RSL were included. After surgery, the specimens containing the breast tumour and the (125)I seed were scanned using freehand SPECT. Measurements from five directions were taken and compared with distances measured by means of an ex-vivo computed tomographic (CT) scan and related to the pathology report., Results: The difference between freehand SPECT and CT measurements was 2.9±2.7 mm (mean±SD). One patient had a positive margin based on freehand SPECT. This specimen contained a focal irradical resection ventral of the tumour based on the pathology report. The smallest distance to the (125)I seed was 4 mm for the freehand SPECT and 5 mm for the CT scan., Conclusion: Accurate ex-vivo measurements of the tumour resection margins using (125)I seeds and freehand SPECT are feasible in patients undergoing breast-conserving surgery. Incorporation of the freehand-SPECT device in RSL protocols may enable a real-time estimation of resection margins, which may be useful for surgeons to adjust resection planes.

Diffuse reflectance spectroscopy (DRS) is a promising new technique for breast cancer diagnosis. However, inter-patient variation due to breast tissue heterogeneity may interfere with the accuracy of this technique. To tackle this issue, we aim to determine the diagnostic accuracy of DRS in individual patients. With this approach, DRS measurements of normal breast tissue in every individual patient are directly compared with measurements of the suspected malignant tissue. Breast tissue from 47 female patients was analysed ex vivo by DRS. A total of 1,073 optical spectra were collected. These spectra were analyzed for each patient individually as well as for all patients collectively and results were compared to the pathology analyses. Collective patient data analysis for discrimination between normal and malignant breast tissue resulted in a sensitivity of 90 %, a specificity of 88 %, and an overall accuracy of 89 %. In the individual analyses all measurements per patient were categorized as either benign or malignant. The discriminative accuracy of these individual analyses was nearly 100 %. The diagnosis was classified as uncertain in only one patient. Based on the results presented in this study, we conclude that the analysis of optical characteristics of different tissue classes within the breast of a single patient is superior to an analysis using the results of a cohort data analysis. When integrated into a biopsy device, our results demonstrate that DRS may have the potential to improve the diagnostic workflow in breast cancer.

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

We report on the use of diffuse optical spectroscopy analysis of breast spectra acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A total of 102 ex vivo samples of five different breast tissue types, namely adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ from 52 patients were measured. A model deriving from the diffusion theory was applied to the measured spectra in order to extract clinically relevant parameters such as blood, water, lipid, and collagen volume fractions, β-carotene concentration, average vessels radius, reduced scattering amplitude, Mie slope, and Mie-to-total scattering fraction. Based on a classification and regression tree algorithm applied to the derived parameters, a sensitivity-specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic performance of 94%. Sensitivity-specificity values obtained for discriminating malignant from nonmalignant tissue were compared to existing reported studies by applying the different classification methods that were used in each of these studies. Furthermore, in these reported studies, either lipid or β-carotene was considered as adipose tissue precursors. We estimate both chromophore concentrations and demonstrate that lipid is a better discriminator for adipose tissue than β-carotene.

Introduction: Young age at the time of diagnosis of breast cancer is an independent factor of poor prognosis. In many treatment guidelines, the recommendation is to treat young patients with adjuvant chemotherapy regardless of tumor characteristics. However, limited data on prognostic factors are available for young breast cancer patients. The purpose of this study was to determine the prognostic value of established clinical and pathological prognostic factors in young breast cancer patients., Methods: Data from four European Organisation for Research and Treatment of Cancer (EORTC) clinical trials were pooled, resulting in a dataset consisting of 9,938 early breast cancer patients with a median follow-up of 11 years. For 549 patients aged less than 40 years at the time of diagnosis, including 341 node negative patients who did not receive chemotherapy, paraffin tumor blocks were processed for immunohistochemistry using a tissue microarray. Cox proportional hazard analysis was applied to assess the association of clinical and pathological factors with overall and distant metastasis free survival., Results: For young patients, tumor size (P = 0.01), nodal status (P = 0.006) and molecular subtype (P = 0.02) were independent prognostic factors for overall survival. In the node negative subgroup, only molecular subtype was a prognostic factor for overall survival (P = 0.02). Young node negative patients bearing luminal A tumors had an overall survival rate of 94% at 10 years' follow-up compared to 72% for patients with basal-type tumors., Conclusions: Molecular subtype is a strong independent prognostic factor in breast cancer patients younger than 40 years of age. These data support the use of established prognostic factors as a diagnostic tool to assess disease outcome and to plan systemic treatment strategies in young breast cancer patients.

Introduction: Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status., Methods: Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years., Results: Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status., Conclusion: Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors.

The aim of this retrospective study was to identify markers capable of predicting pathological complete (pCR) and overall clinical tumour response to preoperative anthracycline-based chemotherapy and clinical outcome in women with operable breast cancer. Therefore, we used the pre-treatment core biopsies from 107 patients who were enrolled in the EORTC trial 10902 to analyse tumour characteristics and the oncogenic markers Bcl-2, p53, ER, PgR, HER2, and p21. Median follow-up was 7 years (95% confidence interval [CI], 6.89-7.45). pCR was seen in seven patients (6.5%) and was associated with improved overall survival (hazards ratio, 0.39; 95% CI, 0.05-2.56; P = 0.30). In multivariate logistic regression analysis, pCR was independently predicted by p53 overexpression estimated by immunohistochemistry (odds ratio [OR], 16.83; 95% CI, 1.78-159.33; P = 0.01). Fifty-eight patients showed clinical tumour response (>50% decrease in tumour size), however responders experienced no benefit in clinical outcome. Clinical tumour response was independently predicted by p53 overexpression (OR, 5.57; 95% CI, 1.58-19.65; P = 0.008) and small clinical tumour size (OR, 10.26; 95% CI, 2.01-52.48; P = 0.005). In multivariate Cox regression analysis, negative pathological lymph node status, low tumour grade and use of tamoxifen showed improved overall survival. In conclusion, our data suggest p53 expression is of predictive significance in anthracycline-containing chemotherapeutic regimens.

Background: Large phase III clinical trials convey a lot of important information besides the main analysis of the treatment effect. For example, the use of multicenter clinical trial data to identify prognostic indices is now common. In addition, the study of heterogeneity in patient outcome between centers has received considerable attention in recent years. In this paper, we explain and illustrate a method used to investigate such heterogeneity with data from an early breast cancer clinical trial., Methods: The inclusion of a random effect for center in a Cox proportional hazards model allows us to study the heterogeneity in time-to-event outcomes between centers. Such a model has the major advantage that it provides a measure of the spread of outcomes over centers. This technique is illustrated using data from EORTC trial 10854, a randomized phase III trial comparing perioperative chemotherapy with no perioperative chemotherapy for early breast cancer; 2793 patients were entered by 14 centers., Results: Substantial heterogeneity between centers was detected for disease-free survival. This can be explained by the geographical area in which the center is located, with better outcomes achieved in France as compared with southern Europe and South Africa. None of the prognostic factors considered could explain this heterogeneity., Conclusion: Although clinical trials are run with the objective of removing as much heterogeneity as possible, some heterogeneity in the outcome of patients between centers may remain, as was the case in our study. The use of a random effect for center within a Cox PH model is an excellent method to investigate this heterogeneity. Such types of analyses, although exploratory, provide further insight into possible factors which may have an impact on the patient's outcome.