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Background: Women recalled from breast cancer screening receive post-screening work-up in the hospital with conventional breast imaging. The RACER trial aimed to study whether contrast-enhanced mammography (CEM) as primary imaging instead of conventional imaging resulted in more accurate and efficient diagnostic work-up in recalled women. Methods: In this randomised, controlled trial (registered under NL6413/NTR6589) participants were allocated using deterministic minimisation to CEM or conventional imaging as a primary work-up tool in two general and two academic hospitals. Predefined patients' factors were reason for recall, BI-RADS score, and study centre. Primary outcomes were sensitivity and specificity. Secondary outcomes were the proportion of women needing supplemental examinations, and number of days until diagnosis. Findings: Between April, 2018, and September, 2021, 529 patients recalled from the Dutch screening program were randomised, 265 to conventional imaging and 264 to CEM. Three patients in the control arm had to be excluded from analysis due to a protocol breach. After the entire work-up, sensitivity was 98.0% (95% CI; 92.2-99.7%) in the intervention arm and 97.7% (91.8-99.6%) in the control arm (p = 1.0), and specificity was 75.6% (72.5-76.6%) and 75.4% (72.5-76.4%, p = 1.0), respectively. Based on only primary full-field digital mammography/digital breast tomosynthesis or CEM, final diagnosis was reached in 27.7% (73/264) in the intervention arm and 1.1% (3/262) in the control arm. The frequency of supplemental imaging was significantly higher in the control arm (p < 0.0001). Median time needed to reach final diagnosis was comparable: 1 day (control arm: IQR 0-4; intervention arm: IQR 0-3). Thirteen malignant occult lesions were detected using CEM, versus three using conventional imaging. No serious adverse events occurred. Interpretation: Diagnostic accuracy of CEM in the work-up of recalled women is comparable with conventional imaging. However, work-up with CEM as primary imaging is a more efficient pathway. Funding: ZonMw (grant number 843001801) and GE Healthcare.
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INTRODUCTION: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS. MATERIALS AND METHODS: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS. RESULTS: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293). CONCLUSION: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST.
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BACKGROUND: 5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient's prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts. METHODS: A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin. RESULTS: We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control. CONCLUSIONS: These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies.
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Colon , Fibras de la Dieta , Disbiosis , Fluorouracilo , Microbioma Gastrointestinal , Prebióticos , Fluorouracilo/farmacología , Disbiosis/microbiología , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Fibras de la Dieta/farmacología , Colon/microbiología , Colon/efectos de los fármacos , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Masculino , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/análisis , Femenino , Adulto , Pectinas/farmacologíaRESUMEN
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.
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Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Mama/patología , Mastectomía , Metástasis Linfática/patología , Escisión del Ganglio Linfático , Ganglio Linfático Centinela/patología , Mastectomía Segmentaria , Axila/patología , Sistema de Registros , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patologíaRESUMEN
BACKGROUND: In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure). METHODS: PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool. RESULTS: Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality. CONCLUSION: Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.
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Axila , Neoplasias de la Mama , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Escisión del Ganglio Linfático/métodos , Femenino , Metástasis Linfática , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
BACKGROUND: Stromal tumour infiltrating lymphocytes (sTILs) and presence of tertiary lymphoid structures have been proposed as indicators of tumour-related immune response in breast cancer. An increased number of germinal centres (GCs) in lymph nodes is considered a sign of humoral immune reactivity. AIMS: It is unclear whether a relationship exists between number and size of GCs within tumour positive sentinel lymph nodes (SLNpos), sTILs and tertiary lymphoid structures within matched primary breast cancer and breast cancer subtype. METHODS: Axillary SLNpos from 175 patients with breast cancer were manually contoured in digitized haematoxylin and eosin stained sections. Total SLN area, GC number and GC area were measured in SLNpos with the largest metastatic area. To correct for SLN size, GC number and GC area were divided by SLN area. sTILs and presence of tertiary lymphoid structures were assessed in the primary breast cancer. RESULTS: A higher GC number and larger GC area were found in patients with high sTILs (≥2%) (both P < 0.001) and in patients with presence of tertiary lymphoid structures (PGC number = 0.034 and PGC area = 0.016). Triple negative and HER2-positive (N = 45) breast cancer subtypes had a higher GC number and higher sTILs compared to hormone receptor positive, HER2-negative breast cancer (N = 130) (PGC number < 0.001 and PsTILs= 0.001). CONCLUSION: This study suggests GCs measured within SLNpos might be useful indicators of the humoral anti-tumour immune response in breast cancer. Future studies are needed investigating underlying biological mechanisms and prognostic value of GCs in SLNs.
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Neoplasias de la Mama , Ganglio Linfático Centinela , Estructuras Linfoides Terciarias , Humanos , Femenino , Neoplasias de la Mama/patología , Ganglio Linfático Centinela/patología , Linfocitos Infiltrantes de Tumor/patología , Estructuras Linfoides Terciarias/patología , Ganglios Linfáticos/patología , Centro Germinal/patología , Axila/patologíaRESUMEN
PURPOSE: In breast cancer, neoadjuvant chemotherapy (NAC) can downstage the nodal status, and can even result in a pathological complete response, which is associated with improved prognosis. This study aimed to determine the prognostic effect of nodal status before and after NAC. METHODS: Women with breast cancer treated with NAC were selected from the Netherlands Cancer Registry if diagnosed between 2005 and 2019, and classified based on nodal status before NAC: node-negative (cN0), or node-positive based on fine needle aspiration cytology or core needle biopsy (cN+). Subgroups were based on nodal status after NAC: absence (ypN0) or presence (ypN+) of nodal disease. Five-year overall survival (OS) was assessed with Kaplan-Meier survival analyses, also per breast cancer molecular subtype. To adjust for potential confounders, multivariable analyses were performed. RESULTS: A total of 6,580 patients were included in the cN0 group, and 11,878 in the cN+ group. The 5-year OS of the cN0ypN0-subgroup was statistically significant better than that of the cN+ypN0-subgroup (94.4% versus 90.1%, p < 0.0001). In cN0 as well as cN+ disease, ypN+ had a statistically significant worse 5-year OS compared to ypN0. For hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-, HR+ HER2+, HR-HER2+, and triple negative disease, respectively, 5-year OS in the cN0ypN+-subgroup was 89.7%, 90.4%, 73.7%, and 53.6%, and in the cN+ypN+-subgroup 84.7%, 83.2%, 61.4%, and 48.8%. In multivariable analyses, cN+ and ypN+ disease were both associated with worse OS. CONCLUSION: This study suggests that both cN-status and ypN-status, and molecular subtype should be considered to further improve prognostication.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Ganglios Linfáticos/patología , Terapia Neoadyuvante , Estimación de Kaplan-Meier , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Introduction: Sentinel lymph node (SLN) metastasis is an important predictor of prognosis in breast cancer (BC) patients, guiding treatment decisions. However, patients with the same BC subtype and tumor negative SLN (SLNneg) can have different survival outcomes. We hypothesized that the host anti-tumor immune reaction in SLNneg is important and results in morphometrically measurable changes in SLN size or shape which are related to patient prognosis. Methods: Surface area, circumference, long axis and short axis were histologically measured in 694 SLNneg from 356 cases of invasive BC and 67 ductal carcinoma in situ cases. The area occupied by fat was categorized as less or more than 50%. The long to short axis (L/S) ratio was calculated. The relationship between SLNneg morphometries and clinicopathological variables like tumor-infiltrating lymphocytes (TILs) within the primary tumor, as well as prognosis at 10 years follow up were analyzed. Results: The mean SLNneg surface area was 78.7mm2, circumference 40.3mm, long axis 13.1mm, short axis 8.2mm and L/S ratio 1.7. Larger surface area, long axis and short axis, including age >55 years were associated with higher body mass index (BMI) and SLN fat over 50% (p<0.003). In invasive BC, a high SLNneg L/S ratio (≥1.9) was related to poorer disease-free (HR=1.805, 95%CI 1.182-2.755, p=0.006) and overall (HR=2.389, 95%CI 1.481-3.851, p<0.001) survival. A low SLNneg L/S ratio (<1.9) was associated with high TILs in the primary BC (≥10%) (p=0.005). However a high TIL count was not of prognostic relevance. Conclusions: This is the first study to suggest that morphometric characteristics of axillary SLNneg, like L/S ratio, could be used to predict prognosis in patients with SLNneg invasive BC of all subtypes. The association between low L/S ratio and high TILs suggest that SLN shape is related to immunological functioning of the SLN and could be used in addition to TIL evaluation. Regarding the dubious role of TILs in hormone receptor positive breast cancer, SLNneg morphometry to gain information about host immune status could especially be of benefit in this subtype. Further studies are warranted to better understand the underlying biological mechanisms.
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Neoplasias de la Mama , Neoplasias Mamarias Animales , Ganglio Linfático Centinela , Humanos , Animales , Persona de Mediana Edad , Femenino , Pronóstico , Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/métodos , Metástasis Linfática , Neoplasias Mamarias Animales/patologíaRESUMEN
BACKGROUND: Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients. METHODS: Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided. RESULTS: This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24). CONCLUSION: In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.
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Neoplasias de la Mama , Humanos , Femenino , Anastrozol/uso terapéutico , Índice de Masa Corporal , Pronóstico , Sobrepeso/complicaciones , Obesidad/complicacionesRESUMEN
PURPOSE: Ductal carcinoma in situ (DCIS) is present in more than half of HER2-positive invasive breast cancer (IBC). Recent studies show that DCIS accompanying HER2-positive IBC can be completely eradicated by neoadjuvant systemic therapy (NST). Our aim was to determine the percentage of pathologic complete response of the DCIS component in a nationwide cohort and to assess associated clinicopathologic variables. Furthermore, the impact on surgical treatment after NST was investigated. METHODS: Women diagnosed with HER2-positive IBC, treated with NST and surgery, between 2010 and 2020, were selected from the Netherlands Cancer Registry. Pre-NST biopsy and postoperative pathology reports were obtained from the Dutch Nationwide Pathology Databank and assessed for the presence of DCIS. Clinicopathologic factors associated with DCIS response were assessed using logistic regression analyses. RESULTS: A DCIS component was present in the pre-NST biopsy in 1403 (25.1%) of 5598 included patients. Pathologic complete response of the DCIS component was achieved in 730 patients (52.0%). Complete response of DCIS occurred more frequently in case of complete response of IBC (63.4% versus 33.8%, p < 0.001). ER-negative IBC (OR 1.79; 95%CI 1.33-2.42) and more recent years of diagnosis (2014-2016 OR 1.60; 95%CI 1.17-2.19, 2017-2019 OR 1.76; 95%CI 1.34-2.34) were associated with DCIS response. Mastectomy rates were higher in IBC+DCIS compared to IBC (53.6% versus 41.0%, p < 0.001). CONCLUSION: Pathologic complete response of DCIS occurred in 52.0% of HER2-positive IBC patients and was associated with ER-negative IBC and more recent years of diagnosis. Future studies should investigate imaging evaluation of DCIS response to improve surgical decision making.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Terapia Neoadyuvante , Mastectomía , Biopsia , Carcinoma Ductal de Mama/patologíaRESUMEN
Deep learning (DL) applied to breast tissue segmentation in magnetic resonance imaging (MRI) has received increased attention in the last decade, however, the domain shift which arises from different vendors, acquisition protocols, and biological heterogeneity, remains an important but challenging obstacle on the path towards clinical implementation. In this paper, we propose a novel Multi-level Semantic-guided Contrastive Domain Adaptation (MSCDA) framework to address this issue in an unsupervised manner. Our approach incorporates self-training with contrastive learning to align feature representations between domains. In particular, we extend the contrastive loss by incorporating pixel-to-pixel, pixel-to-centroid, and centroid-to-centroid contrasts to better exploit the underlying semantic information of the image at different levels. To resolve the data imbalance problem, we utilize a category-wise cross-domain sampling strategy to sample anchors from target images and build a hybrid memory bank to store samples from source images. We have validated MSCDA with a challenging task of cross-domain breast MRI segmentation between datasets of healthy volunteers and invasive breast cancer patients. Extensive experiments show that MSCDA effectively improves the model's feature alignment capabilities between domains, outperforming state-of-the-art methods. Furthermore, the framework is shown to be label-efficient, achieving good performance with a smaller source dataset. The code is publicly available at https://github.com/ShengKuangCN/MSCDA.
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Neoplasias de la Mama , Semántica , Humanos , Femenino , Imagen por Resonancia Magnética , Neoplasias de la Mama/diagnóstico por imagen , Voluntarios Sanos , Procesamiento de Imagen Asistido por ComputadorRESUMEN
OBJECTIVES: In approximately 45% of invasive breast cancer (IBC) patients treated with neoadjuvant systemic therapy (NST), ductal carcinoma in situ (DCIS) is present. Recent studies suggest response of DCIS to NST. The aim of this systematic review and meta-analysis was to summarise and examine the current literature on imaging findings for different imaging modalities evaluating DCIS response to NST. More specifically, imaging findings of DCIS pre- and post-NST, and the effect of different pathological complete response (pCR) definitions, will be evaluated on mammography, breast MRI, and contrast-enhanced mammography (CEM). METHODS: PubMed and Embase databases were searched for studies investigating NST response of IBC, including information on DCIS. Imaging findings and response evaluation of DCIS were assessed for mammography, breast MRI, and CEM. A meta-analysis was conducted per imaging modality to calculate pooled sensitivity and specificity for detecting residual disease between pCR definition no residual invasive disease (ypT0/is) and no residual invasive or in situ disease (ypT0). RESULTS: Thirty-one studies were included. Calcifications on mammography are related to DCIS, but can persist despite complete response of DCIS. In 20 breast MRI studies, an average of 57% of residual DCIS showed enhancement. A meta-analysis of 17 breast MRI studies confirmed higher pooled sensitivity (0.86 versus 0.82) and lower pooled specificity (0.61 versus 0.68) for detection of residual disease when DCIS is considered pCR (ypT0/is). Three CEM studies suggest the potential benefit of simultaneous evaluation of calcifications and enhancement. CONCLUSIONS AND CLINICAL RELEVANCE: Calcifications on mammography can remain despite complete response of DCIS, and residual DCIS does not always show enhancement on breast MRI and CEM. Moreover, pCR definition effects diagnostic performance of breast MRI. Given the lack of evidence on imaging findings of response of the DCIS component to NST, further research is demanded. KEY POINTS: ⢠Ductal carcinoma in situ has shown to be responsive to neoadjuvant systemic therapy, but imaging studies mainly focus on response of the invasive tumour. ⢠The 31 included studies demonstrate that after neoadjuvant systemic therapy, calcifications on mammography can remain despite complete response of DCIS and residual DCIS does not always show enhancement on MRI and contrast-enhanced mammography. ⢠The definition of pCR has impact on the diagnostic performance of MRI in detecting residual disease, and when DCIS is considered pCR, pooled sensitivity was slightly higher and pooled specificity slightly lower.
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Neoplasias de la Mama , Calcinosis , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/tratamiento farmacológico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Mama/patología , Mamografía/métodos , Calcinosis/patología , Imagen por Resonancia Magnética/métodos , Carcinoma Ductal de Mama/patologíaRESUMEN
BACKGROUND: Gut bacteria-derived short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) are considered to have beneficial metabolic, anti-inflammatory as well as anti-carcinogenic effects. Previous preclinical studies indicated bidirectional interactions between gut bacteria and the chemotherapeutic capecitabine or its metabolite 5-FU. This study investigated the effect of three cycles of capecitabine on fecal SCFA and BCFA levels and their associations with tumor response, nutritional status, physical performance, chemotherapy-induced toxicity, systemic inflammation and bacterial abundances in patients with colorectal cancer (CRC). METHODS: Forty-four patients with metastatic or unresectable CRC, scheduled for treatment with capecitabine (± bevacizumab), were prospectively enrolled. Patients collected a fecal sample and completed a questionnaire before (T1), during (T2) and after (T3) three cycles of capecitabine. Tumor response (CT/MRI scans), nutritional status (MUST score), physical performance (Karnofsky Performance Score) and chemotherapy-induced toxicity (CTCAE) were recorded. Additional data on clinical characteristics, treatment regimen, medical history and blood inflammatory parameters were collected. Fecal SCFA and BCFA concentrations were determined by gas chromatography-mass spectrometry (GC-MS). Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. RESULTS: Fecal levels of the SCFA valerate and caproate decreased significantly during three cycles of capecitabine. Furthermore, baseline levels of the BCFA iso-butyrate were associated with tumor response. Nutritional status, physical performance and chemotherapy-induced toxicity were not significantly associated with SCFA or BCFA. Baseline SCFA correlated positively with blood neutrophil counts. At all time points, we identified associations between SCFA and BCFA and the relative abundance of bacterial taxa on family level. CONCLUSIONS: The present study provided first indications for a potential role of SCFA and BCFA during capecitabine treatment as well as implications for further research. TRIAL REGISTRATION: The current study was registered in the Dutch Trial Register (NTR6957) on 17/01/2018 and can be consulted via the International Clinical Trial Registry Platform (ICTRP).
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Antineoplásicos , Neoplasias Colorrectales , Humanos , Capecitabina/efectos adversos , ARN Ribosómico 16S/genética , Ácidos Grasos Volátiles/química , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/farmacología , Ácidos Grasos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Bacterias/genética , Bacterias/metabolismo , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: The aim of this study was to investigate whether sequential hybrid [18F]FDG PET/MRI can predict the final pathologic response to neoadjuvant chemo(targeted) therapy (NCT) in breast cancer. METHODS: Sequential [18F]FDG PET/MRI was performed before, halfway through and after NCT, followed by surgery. Qualitative response evaluation was assessed after NCT. Quantitatively, the SUVmax obtained by [18F]FDG PET and signal enhancement ratio (SER) obtained by MRI were determined sequentially on the primary tumour. For the response of axillary lymph node metastases (ALNMs), SUVmax was determined sequentially on the most [18F]FDG-avid ALN. ROC curves were generated to determine the optimal cut-off values for the absolute and percentage change in quantitative variables in predicting response. Diagnostic performance in predicting primary tumour response was assessed with AUC. Similar analyses were performed in clinically node-positive (cN+) patients for ALNM response. RESULTS: Forty-one breast cancer patients with forty-two primary tumours and twenty-six cases of pathologically proven cN+ disease were prospectively included. Pathologic complete response (pCR) of the primary tumour occurred in 16 patients and pCR of the ALNMs in 14 cN+ patients. The AUC of the qualitative evaluation after NCT was 0.71 for primary tumours and 0.54 for ALNM responses. For primary tumour response, combining the percentage decrease in SUVmax and SER halfway through NCT achieved an AUC of 0.78. The AUC for ALNM response prediction increased to 0.92 by combining the absolute and the percentage decrease in SUVmax halfway through NCT. CONCLUSIONS: Qualitative PET/MRI after NCT can predict the final pathologic primary tumour response, but not the ALNM response. Combining quantitative variables halfway through NCT can improve the diagnostic accuracy for final pathologic ALNM response prediction.
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BACKGROUND: To quantify the relationship between [18F]FDG uptake of the primary tumour measured by PET-imaging with immunohistochemical (IHC) expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers in breast cancer patients. METHODS: PubMed and Embase were searched for studies that compared SUVmax between breast cancer patients negative and positive for IHC expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers. Two reviewers independently screened the studies and extracted the data. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were estimated by using DerSimonian-Laird random-effects models. P values less than or equal to 5% indicated statistically significant results. RESULTS: Fifty studies were included in the final analysis. SUVmax is significantly higher in ER-negative (31 studies, SMD 0.66, 0.56-0.77, P < 0.0001), PR-negative (30 studies, SMD 0.56; 0.40-0.71, P < 0.0001), HER2-positive (32 studies, SMD - 0.29, - 0.49 to - 0.10, P = 0.0043) or Ki-67-positive (19 studies, SMD - 0.77; - 0.93 to - 0.61, P < 0.0001) primary tumours compared to their counterparts. The majority of clinical subtypes were either luminal A (LA), luminal B (LB), HER2-positive or triple negative breast cancer (TNBC). LA is associated with significantly lower SUVmax compared to LB (11 studies, SMD - 0.49, - 0.68 to - 0.31, P = 0.0001), HER2-positive (15 studies, SMD - 0.91, - 1.21 to - 0.61, P < 0.0001) and TNBC (17 studies, SMD - 1.21, - 1.57 to - 0.85, P < 0.0001); and LB showed significantly lower uptake compared to TNBC (10 studies, SMD - 0.77, - 1.05 to - 0.49, P = 0.0002). Differences in SUVmax between LB and HER2-positive (9 studies, SMD - 0.32, - 0.88 to 0.24, P = 0.2244), and HER2-positive and TNBC (17 studies, SMD - 0.29, - 0.61 to 0.02, P = 0.0667) are not significant. CONCLUSION: Primary tumour SUVmax is significantly higher in ER-negative, PR-negative, HER2-positive and Ki-67-positive breast cancer patients. Luminal tumours have the lowest and TNBC tumours the highest SUVmax. HER2 overexpression has an intermediate effect.
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Background: To provide a systematic review and meta-analysis that evaluates the diagnostic accuracy of contrast-enhanced mammography (CEM) compared to standard contrast-enhanced breast magnetic resonance imaging (breast MRI). Like breast MRI, CEM enables tumour visualization by contrast accumulation. CEM seems to be a viable substitute for breast MRI. Methods: This systematic search assessed the diagnostic accuracy of these techniques in women with suspicious breast lesions on prior imaging or physical examination, who have undergone both breast MRI and CEM. CEM had to be performed on a commercially available system. The MRI sequence parameters had to be described sufficiently to ensure that standard breast MRI sequence protocols were used. Pooled values of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR), were estimated using bivariate mixed-effects logistic regression modeling. Hierarchical summary receiver operating characteristic curves for CEM and breast MRI were also constructed. Results: Six studies (607 patients with 775 lesions) met the predefined inclusion criteria. Pooled sensitivity was 96% for CEM and 97% for breast MRI. Pooled specificity was 77% for both modalities. DOR was 79.5 for CEM and 122.9 for breast MRI. Between-study heterogeneity expressed as the I2 -index was substantial with values over 80%. Conclusion: Pooled sensitivity was high for both CEM and breast MRI, with moderate specificity. The pooled DOR estimates, however, indicate higher overall diagnostic performance of breast MRI compared to CEM. Nonetheless, current scientific evidence is too limited to prematurely discard CEM as an alternative for breast MRI.
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PURPOSE: We aimed to compare (1) treatments and time intervals between treatments of breast cancer patients diagnosed during and before the COVID-19 pandemic, and (2) the number of treatments started during and before the pandemic. METHODS: Women were selected from the Netherlands Cancer Registry. For aim one, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the treatment of women diagnosed within four periods of 2020: pre-COVID (weeks 1-8), transition (weeks 9-12), lockdown (weeks 13-17), and care restart (weeks 18-26), with data from 2018/2019 as reference. Wilcoxon rank-sums test was used to compare treatment intervals, using a two-sided p-value < 0.05. For aim two, number of treatments started per week in 2020 was compared with 2018/2019. RESULTS: We selected 34,097 women for aim one. Compared to 2018/2019, neo-adjuvant chemotherapy was less likely for stage I (OR 0.24, 95%CI 0.11-0.53), stage II (OR 0.63, 95%CI 0.47-0.86), and hormone receptor+/HER2- tumors (OR 0.55, 95%CI 0.41-0.75) diagnosed during transition. Time between diagnosis and first treatment decreased for patients diagnosed during lockdown with a stage I (p < 0.01), II (p < 0.01) or III tumor (p = 0.01). We selected 30,002 women for aim two. The number of neo-adjuvant endocrine therapies and surgeries starting in week 14, 2020, increased by 339% and 18%, respectively. The number of adjuvant chemotherapies decreased by 42% in week 15 and increased by 44% in week 22. CONCLUSION: The pandemic and subsequently altered treatment recommendations affected multiple aspects of the breast cancer treatment strategy and the number of treatments started per week.
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Neoplasias de la Mama , COVID-19 , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Pandemias , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Sistema de RegistrosRESUMEN
Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND. Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure. Design, Setting, and Participants: This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021. Intervention: Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND. Main Outcomes and Measures: The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure. Results: A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03). Conclusions and Relevance: Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.
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Neoplasias de la Mama , Yodo , Ganglio Linfático Centinela , Neoplasias de la Tiroides , Humanos , Persona de Mediana Edad , Femenino , Biopsia del Ganglio Linfático Centinela/métodos , Axila , Terapia Neoadyuvante , Neoplasias de la Mama/patología , Radioisótopos de Yodo/uso terapéutico , Estudios Prospectivos , Yodo/uso terapéutico , Metástasis Linfática/patología , Neoplasias de la Tiroides/cirugía , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Ganglio Linfático Centinela/patologíaRESUMEN
This clinical study explored the associations between the intestinal microbiota, chemotherapy toxicity, and treatment response in postmenopausal oestrogen receptor positive breast cancer patients.Oestrogen receptor positive postmenopausal breast cancer patients were prospectively enroled in a multicentre cohort study and treated with 4 cycles of (neo)adjuvant adriamycin, cyclophosphamide (AC) followed by 4 cycles of docetaxel (D). Patients collected a faecal sample and completed a questionnaire before treatment, during AC, during D, and after completing AC-D. Chemotherapy toxicity and tumour response were determined. Intestinal microbiota was analysed by amplicon sequencing of the 16 S rRNA V4 gene-region. In total, 44 patients, including 18 neoadjuvant patients, were included, and 153 faecal samples were collected before AC-D (n = 44), during AC (n = 43), during D (n = 29), and after AC-D treatment (n = 37), 28 participants provided all four samples. In the whole group, observed species richness reduced during treatment (p = 0.042). The abundance of Proteobacteria, unclassified Enterobacterales, Lactobacillus, Ruminococcaceae NK4A214 group, Marvinbryantia, Christensenellaceae R7 group, and Ruminococcaceae UCG-005 changed significantly over time. Patients with any grade diarrhoea during docetaxel treatment had a significantly lower observed species richness compared to patients without diarrhoea. In the small group neoadjuvant treated patients, pathologic response was unrelated to baseline intestinal microbiota richness, diversity and composition. While the baseline microbiota was not predictive for pathologic response in a rather small group of neoadjuvant treated patients in our study, subsequent shifts in microbial richness, as well as the abundance of specific bacterial taxa, were observed during AC-D treatment in the whole group and the neoadjuvant group.