The aim was to investigate whether pathologic complete response (pCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with ...neoadjuvant systemic therapy (NST) for different breast cancer subtypes.
Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast pCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.
Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pathologic response of the primary tumor with associated pathologic axillary outcome. Multivariable analysis was performed to determine clinicopathological variables correlated with ypN0.
A total of 4084 patients were included for analyses, of whom 986 (24.1%) achieved breast pCR. In clinically node negative patients (cN0), 97.7% (432/442) with breast pCR had ypN0 compared with 71.6% (882/1232) without breast pCR (P < 0.001). In clinically node positive patients (cN1), 45.0% (245/544) with breast pCR had ypN0 compared with 9.4% (176/1866) without breast pCR (P < 0.001). The odds of ypN0 was decreased in case of clinical T3 stage (OR 0.59, 95% CI 0.40-0.87), cN1 (OR 0.03, 95% CI 0.02-0.04) and ER+HER2- subtype (OR 0.30, 95% CI 0.20-0.44), and increased in case of breast pCR (OR 4.53, 95% CI 3.27-6.28).
Breast pCR achieved after NST is strongly correlated with ypN0 in cN0 patients, especially in ER+HER2+, ER-HER2+, and triple negative subtypes. These results provide data to proceed with future clinical trials to investigate if axillary surgery can be safely omitted in these selected patients when image-guided tissue sampling identifies a breast pCR.
Clinical interest in the human intestinal microbiota has increased considerably. However, an overview of clinical studies investigating the link between the human intestinal microbiota and systemic ...cancer therapy is lacking. This systematic review summarizes all clinical studies describing the association between baseline intestinal microbiota and systemic cancer therapy outcome as well as therapy-related changes in intestinal microbiota composition. A systematic literature search was performed and provided 23 articles. There were strong indications for a close association between the intestinal microbiota and outcome of immunotherapy. Furthermore, the development of chemotherapy-induced infectious complications seemed to be associated with the baseline microbiota profile. Both chemotherapy and immunotherapy induced drastic changes in gut microbiota composition with possible consequences for treatment efficacy. Evidence in the field of hormonal therapy was very limited. Large heterogeneity concerning study design, study population, and methods used for analysis limited comparability and generalization of results. For the future, longitudinal studies investigating the predictive ability of baseline intestinal microbiota concerning treatment outcome and complications as well as the potential use of microbiota-modulating strategies in cancer patients are required. More knowledge in this field is likely to be of clinical benefit since modulation of the microbiota might support cancer therapy in the future.
The aim of this study was to perform a systematic review and meta-analysis to assess the accuracy of different surgical axillary staging procedures compared with ALND.
Optimal axillary staging after ...neoadjuvant systemic therapy (NST) in node-positive breast cancer is an area of controversy. Several less invasive procedures, such as sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and targeted axillary dissection (a combination of SLNB and a MARI-like procedure), have been proposed to replace the conventional axillary lymph node dissection (ALND) with its concomitant morbidity.
PubMed and Embase were searched for studies comparing less invasive surgical axillary staging procedures to ALND to identify axillary burden after NST in patients with pathologically confirmed node-positive breast cancer (cN+). A meta-analysis was performed to compare identification rate (IFR), false-negative rate (FNR), and negative predictive value (NPV).
Of 1132 records, 20 unique studies with 2217 patients were included in quantitative analysis: 17 studies on SLNB, 1 study on MARI, and 2 studies on a combination procedure. Overall axillary pathologic complete response rate was 37%. For SLNB, pooled rates of IFR and FNR were 89% and 17%. NPV ranged from 57% to 86%. For MARI, IFR was 97%, FNR 7%, and NPV 83%. For the combination procedure, IFR was 100%, FNR ranged from 2% to 4%, and NPV from 92% to 97%.
Axillary staging by a combination procedure consisting of SLNB with excision of a pre-NST marked positive lymph node appears to be most accurate for axillary staging after NST. More evidence from prospective multicenter trials is needed to confirm this.
An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is ...lacking.
To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease.
The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies.
Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy).
Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype.
The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease.
This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy.
The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.
Background
Cancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on ...prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short‐chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia.
Methods
Faecal samples were prospectively collected in patients (N = 107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N = 76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6 months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme‐linked immunosorbent assay. Serum C‐reactive protein and leucocyte counts were retrieved from medical records.
Results
Cachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial α‐diversity was not significantly different between cachectic cancer patients (N = 33), non‐cachectic cancer patients (N = 74), or healthy controls (N = 76) (species richness P = 0.31; Shannon effective index P = 0.46). Community structure (β‐diversity) tended to differ between these groups (P = 0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P < 0.001), an unknown genus from the Enterobacteriaceae family (P < 0.01), and Veillonella (P < 0.001) were more abundant among cachectic cancer patients. Megamonas (P < 0.05) and Peptococcus (P < 0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P < 0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters.
Conclusions
This clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target.
Background
Pathological complete response (pCR) is the ultimate response in breast cancer patients treated with neoadjuvant chemotherapy (NCT). It might be a surrogate outcome for disease-free ...survival (DFS) and overall survival (OS). We studied the effect of clinical tumor stage (cT-stage) on tumor pCR and the effect of pCR per cT-stage on 5-year OS and DFS.
Methods
Using the Netherlands Cancer Registry, all primary invasive breast cancer patients treated with NCT from 2005 until 2008 were identified. Univariable logistic regression analysis was performed to evaluate the effect of cT-stage on pCR, stepwise logistic regression analysis to correct for potential confounders and Kaplan–Meier survival analyses to calculate OS and DFS after five years.
Results
In 2366 patients, overall pCR rate was 21%. For cT1, cT2, cT3, and cT4, pCR rates were 31, 22, 18, and 17%, respectively. Lower cT-stage (cT1-2 vs cT3-4) was a significant independent predictor of higher pCR rate (
p
< 0.001, OR 3.15). Furthermore, positive HER2 status (
p
< 0.001, OR 2.30), negative estrogen receptor status (
p
= 0.062, OR 1.69), and negative progesterone receptor status (
p
= 0.008, OR 2.27) were independent predictors of pCR. OS and DFS were up to 20% higher in patients with cT2-4 tumors with pCR versus patients without pCR. DFS was also higher for cT1 tumors with pCR.
Conclusions
The most important predictor of pCR in breast cancer patients is cT-stage: lower cT-stages have significantly higher pCR rates than higher cT-stages. Patients with cT2-4 tumors achieving pCR have higher OS and DFS compared to patients not achieving pCR.
Gut microbiota and metabolic aspects of cancer cachexia Ziemons, Janine; Smidt, Marjolein L.; Damink, Steven Olde ...
Baillière's best practice and research in clinical endocrinology and metabolism/Baillière's best practice & research. Clinical endocrinology & metabolism,
05/2021, Letnik:
35, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Cancer cachexia is a metabolic syndrome characterized by unintended weight loss and muscle wasting. It has a strong negative impact on survival. Its underlying mechanisms involve systemic ...inflammation and insulin resistance, which are known to be influenced by the gut microbiota. Preclinical studies support a role for the gut microbiota in cancer cachexia by demonstrating that cachectic mice display: 1) various gut microbiota composition changes; 2) increased gut permeability and translocation of pro-inflammatory microbial compounds; 3) muscle atrophy-related processes linked to gut microbiota properties; 4) positive effects of microbiota-modulating interventions. Data on the relationships between gut microbiota, insulin resistance, and hepatic/adipose tissue metabolism in cachexia models are lacking. Nevertheless, the available data and existing evidence for the impact of gut microbiota on metabolic aberrations in human obesity urge for exploration of its role in human cancer cachexia. We provide practical recommendations and discuss the challenges for such future clinical studies.
Here we report for the first time the relation between breast cancer subtypes and 10‐year recurrence rates and mortality in the Netherlands. All operated women diagnosed with invasive non‐metastatic ...breast cancer in 2005 in the Netherlands were included. Patients were classified into breast cancer subtypes according to ER, PR, HER2 status and grade: luminal A, luminal B, HER2 positive and triple negative. Percentages and hazards of recurrence were compared among subtypes. Adjusted 10‐year overall (OS) and recurrence‐free survival (RFS) were calculated using multivariable Cox regression. Of 8,062 patients, 4,482 (56%) were luminal A, 2,090 (26%) luminal B, 504 (6%) HER2 positive and 986 (12%) triple negative. Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively). Regional recurrences were most often diagnosed in triple negative disease (5.2%), and the least often in luminal A (1.7%). HER2 positive and triple negative subtypes had the highest recurrence rates in the second year, while luminal A and B showed a more continuous pattern over time, with lobular tumours recurring more often. After adjustment for differences in baseline characteristics, triple negative disease showed worse 10‐year OS and triple negative and HER2 positive disease had the lowest 10‐year RFS. In the Netherlands, breast cancer subtypes are important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes, in combination with other prognostic factors, can support patient‐tailored treatment and individualised follow‐up.
What's new?
While breast cancer subtypes are known independent predictors of survival and recurrence risk, data on long‐term recurrences in daily practice remain scarce. In this population‐based study reporting on 10‐year recurrences, HER2 positive and triple negative subtypes showed the highest recurrence rates, which occurred most often in the second year, while luminal A and B recurred later on during the follow‐up. Lobular tumours recurred more often than ductal tumours. In the Netherlands, breast cancer subtypes are thus important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes can help support patient‐tailored treatment and individualised follow‐up.
The main purpose was to investigate the correlation between magnetic resonance imaging (MRI)-based response patterns halfway through neoadjuvant chemotherapy and immunotherapy (NAC) and pathological ...tumor response in patients with breast cancer. Secondary purposes were to compare the predictive value of MRI-based response patterns measured halfway through NAC and after NAC and to measure interobserver variability.
All consecutive patients treated with NAC for primary invasive breast cancer from 2012 to 2015 and who underwent breast MRI before, halfway through (and after) NAC were included. All breast tumors were reassessed on MRI by two experienced breast radiologists and classified into six patterns: type 0 (complete radiologic response); type 1 (concentric shrinkage); type 2 (crumbling); type 3 (diffuse enhancement); type 4 (stable disease); type 5 (progressive disease). Percentages of tumors showing pathological complete response (pCR), > 50% tumor reduction and > 50% tumor diameter reduction per MRI-based response pattern were calculated. Correlation between MRI-based response patterns and pathological tumor reduction was studied with Pearson's correlation coefficient, and interobserver agreement was tested with Cohen's Kappa.
Patients (n = 76; mean age 53, range 29-72 years) with 80 tumors (4 bilateral) were included. There was significant correlation between these MRI-based response patterns halfway through NAC and tumor reduction on pathology assessment (reader 1 r = 0.33; p = 0.003 and reader 2 r = 0.45; p < 0.001). Type-0, type-1 or type-2 patterns halfway through NAC showed highest tumor reduction rates on pathology assessment, with > 50% tumor reduction in 90%, 78% and 65% of cases, respectively. In 83% of tumors with type 0 halfway through NAC, pathology assessment showed pCR. There was no significant correlation between MRI-based response patterns after NAC and tumor reduction rates on pathology assessment (reader 1 r = - 0.17; p = 0.145 and reader 2 r = - 0.17; p = 0.146). In 41% of tumors with type 0 after NAC, pathology assessment showed pCR.
MRI-based response patterns halfway through NAC can predict pathologic response more accurately than MRI-based response patterns after NAC. Complete radiological response halfway NAC is associated with 83% pCR, while complete radiological response after NAC seems to be correct in only 41% of cases.
The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response ...after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients.
NST can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management.
PubMed and Embase were searched for studies that compared noninvasive imaging after NST with axillary surgery outcome to identify axillary response in patients with initial pathologically proven axillary lymph node metastasis. Two reviewers independently screened the studies and extracted the data. A meta-analysis was performed by computing the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Thirteen studies describing 2380 patients were included for final analysis. Of these patients, 1322 had undergone axillary ultrasound, 849 breast MRI, and 209 whole-body 18F-FDG PET-CT. The overall axillary pathologic complete response rate was 39.5% (941/2380). For axillary ultrasound, the pooled sensitivity, specificity, PPV, and NPV were 65%, 69%, 77%, 50%, respectively. For breast MRI, the pooled sensitivity, specificity, PPV, and NPV were 60%, 76%, 78%, 58%, respectively. For whole-body 18F-FDG PET-CT, the pooled sensitivity, specificity, PPV, and NPV were 38%, 86%, 78%, 49%, respectively.
The diagnostic performance of current noninvasive imaging modalities is limited to accurately assess axillary response after NST in clinically node-positive breast cancer patients.
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