DCIS knowledge of women choosing between active surveillance and surgery for low-risk DCIS.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. Therefore, we assessed women's DCIS knowledge in association with socio-demographic and clinical characteristics. METHODS: LORD-PPT participants (N = 376) completed a questionnaire assessing socio-demographic and clinical characteristics, risk perception, treatment choice and DCIS knowledge after being informed about their diagnosis and treatment options. RESULTS: 66 % of participants had poor knowledge (i.e., answered ≤3 out of 7 knowledge items correctly). Most incorrect answers involved overestimating the safety of AS and misunderstanding of DCIS prognostic risks. Overall, women with higher DCIS knowledge score perceived their risk of developing IBC as being somewhat higher than women with poorer knowledge (p = 0.049). Women with better DCIS knowledge more often chose surgery whilst most women with poorer knowledge chose active surveillance (p = 0.049). DISCUSSION: Our findings show that there is room for improvement of information provision to patients. Decision support tools for patients and clinicians could help to stimulate effective shared decision-making about DCIS management.

Estimating the aquatic risk from exposure to up to twenty-two pesticide active ingredients in waterways discharging to the Great Barrier Reef.

Pesticides decrease the quality of water reaching the Great Barrier Reef (GBR), Australia. Up to 86 pesticide active ingredients (PAIs) were monitored between July 2015 to end of June 2018 at 28 sites in waterways that discharge to the GBR. Twenty-two frequently detected PAIs were selected to calculate their combined risk when they co-occur in water samples. Species sensitivity distributions (SSDs) for the 22 PAIs to fresh and marine species were developed. The SSDs, the multi-substance potentially affected fraction (msPAF) method, Independent Action model of joint toxicity and a Multiple Imputation method were combined to convert measured PAI concentration data to estimates of the Total Pesticide Risk for the 22 PAIs (TPR22) expressed as the average percentage of species affected during the wet season (i.e., 182 days). The TPR22 and percent contribution of active ingredients of Photosystem II inhibiting herbicides, Other Herbicides, and Insecticides to the TPR22 were estimated. The TPR22 ranged from <1 % to 42 % of aquatic species being affected. Approximately 85 % of the TPR22 estimates were >1 % - meaning they did not meet the Reef 2050 Water Quality Improvement Plan's pesticide target for waters entering the GBR. There were marked spatial differences in TPR22 estimates - regions dominated by grazing had lower estimates while those with sugar cane tended to have higher estimates. On average, active ingredients of PSII herbicides contributed 39 % of the TPR22, the active ingredients of Other Herbicides contributed ~36 % and of Insecticides contributed ~24 %. Nine PAIs (diuron, imidacloprid, metolachlor, atrazine, MCPA, imazapic, metsulfuron, triclopyr and ametryn) were responsible for >97 % of TPR22 across all the monitored waterways.

The value of mammography in women with focal breast complaints in addition to initial targeted ultrasound.

PURPOSE: To determine the added value of mammography in women with focal breast complaints and the utility of initial targeted ultrasound in this setting. METHODS: Women with symptomatic breast disease who were evaluated by breast imaging (mammography/digital breast tomosynthesis and ultrasound) between January 2016 and December 2016 in the Radboud University Medical Centre were included. We retrospectively collected the following data: date of birth, indication of imaging, visibility on mammography/ultrasound, whether biopsy was taken, additional findings, BI-RADS-classification, pathology and follow-up results. RESULTS: A total of 494 women were included (mean age 46.5, range 30 to 93). In 49 women (9.9%), symptomatic breast cancer was diagnosed, all visible during targeted ultrasound. The negative predictive value of targeted ultrasound was very high (99.8%). Additional findings on mammography were significantly more often malignant when the symptomatic lesion was also malignant (3.8% vs 70%, P < 0.05). In only one patient with symptoms caused by a benign finding, an incidental malignancy was detected on mammography outside the area of complaint (detection rate 2.2/1000 examinations). CONCLUSIONS: The contribution of mammography for cancer detection in women with focal breast complaints is very low when targeted ultrasound is performed. Additional findings are most common in patients with symptomatic breast cancer. Our results suggest that initial targeted ultrasound is a more appropriate initial tool for the evaluation of focal breast complaints. Mammography could be performed on indication only.

Minimally invasive breast cancer excision using the breast lesion excision system under ultrasound guidance.

PURPOSE: To assess the feasibility of completely excising small breast cancers using the automated, image-guided, single-pass radiofrequency-based breast lesion excision system (BLES) under ultrasound (US) guidance. METHODS: From February 2018 to July 2019, 22 patients diagnosed with invasive carcinomas ≤ 15 mm at US and mammography were enrolled in this prospective, multi-center, ethics board-approved study. Patients underwent breast MRI to verify lesion size. BLES-based excision and surgery were performed during the same procedure. Histopathology findings from the BLES procedure and surgery were compared, and total excision findings were assessed. RESULTS: Of the 22 patients, ten were excluded due to the lesion being > 15 mm and/or being multifocal at MRI, and one due to scheduling issues. The remaining 11 patients underwent BLES excision. Mean diameter of excised lesions at MRI was 11.8 mm (range 8.0-13.9 mm). BLES revealed ten (90.9%) invasive carcinomas of no special type, and one (9.1%) invasive lobular carcinoma. Histopathological results were identical for the needle biopsy, BLES, and surgical specimens for all lesions. None of the BLES excisions were adequate. Margins were usually compromised on both sides of the specimen, indicating that the excised volume was too small. Margin assessment was good for all BLES specimens. One technical complication occurred (retrieval of an empty BLES basket, specimen retrieved during subsequent surgery). CONCLUSIONS: BLES allows accurate diagnosis of small invasive breast carcinomas. However, BLES cannot be considered as a therapeutic device for small invasive breast carcinomas due to not achieving adequate excision.

Reliability of MRI tumor size measurements for minimal invasive treatment selection in small breast cancers.

INTRODUCTION: Due to the shift towards minimal invasive treatment, accurate tumor size estimation is essential for small breast cancers. The purpose of this study was to determine the reliability of MRI-based tumor size measurements with respect to clinical, histological and radiomics characteristics in small invasive or in situ carcinomas of the breast to select patients for minimal invasive therapy. MATERIALS AND METHODS: All consecutive cases of cT1 invasive breast carcinomas that underwent pre-operative MRI, treated in two hospitals between 2005 and 2016, were identified retrospectively from the Dutch cancer registry and cross-correlated with local databases. Concordance between MRI-based measurements and final pathological size was analyzed. The influence of clinical, histological and radiomics characteristics on the accuracy of MRI size measurements were analyzed. RESULTS: Analysis included 343 cT1 breast carcinomas in 336 patients (mean age, 55 years; range, 25-81 years). Overall correlation of MRI measurements with pathology was moderately strong (ρ = 0.530, P < 0.001), in 42 cases (12.2%) MRI underestimated the size with more than 5 mm. Underestimation occurs more often in grade 2 and grade 3 disease than in low grade invasive cancers. In DCIS the frequency of underestimation is higher than in invasive breast cancer. Unfortunately, none of the patient, imaging or biopsy characteristics appeared predictive for underestimation. CONCLUSION: Size measurements of small breast cancers on breast MRI are within 5 mm of pathological size in 88% of patients. Nevertheless, underestimation cannot be adequately predicted, particularly for grade 2 and grade 3 tumors, which may hinder patient selection for minimal invasive therapy.

Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.

The frequency of missed breast cancers in women participating in a high-risk MRI screening program.

PURPOSE: To evaluate the frequency of missed cancers on breast MRI in women participating in a high-risk screening program. METHODS: Patient files from women who participated in an increased risk mammography and MRI screening program (2003-2014) were coupled to the Dutch National Cancer Registry. For each cancer detected, we determined whether an MRI scan was available (0-24 months before cancer detection), which was reported to be negative. These negative MRI scans were in consensus re-evaluated by two dedicated breast radiologists, with knowledge of the cancer location. Cancers were scored as invisible, minimal sign, or visible. Additionally, BI-RADS scores, background parenchymal enhancement, and image quality (IQ; perfect, sufficient, bad) were determined. Results were stratified by detection mode (mammography, MRI, interval cancers, or cancers in prophylactic mastectomies) and patient characteristics (presence of BRCA mutation, age, menopausal state). RESULTS: Negative prior MRI scans were available for 131 breast cancers. Overall 31% of cancers were visible at the initially negative MRI scan and 34% of cancers showed a minimal sign. The presence of a BRCA mutation strongly reduced the likelihood of visible findings in the last negative MRI (19 vs. 46%, P < 0.001). Less than perfect IQ increased the likelihood of visible findings and minimal signs in the negative MRI (P = 0.021). CONCLUSION: This study shows that almost one-third of cancers detected in a high-risk screening program are already visible at the last negative MRI scan, and even more in women without BRCA mutations. Regular auditing and double reading for breast MRI screening is warranted.

The importance of early detection of calcifications associated with breast cancer in screening.

PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer. METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined. RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n = 177) of cancer-related calcifications that could have been detected earlier were associated with invasive cancer when diagnosed. CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.

Advances in breast intervention: where are we now and where should we be?

In the past four decades, a variety of methods for minimal or non-invasive diagnosis and treatment of breast cancer have been introduced. Although breast imaging has become more and more specific for diagnosis, specimen biopsy with histopathological confirmation is still necessary. Core-needle biopsy under ultrasound guidance is the appropriate first choice for the diagnosis of most lesions. Fine-needle aspiration is of interest for identification of the presence of metastatic disease in abnormal lymph nodes. For microcalcifications, vacuum-assisted biopsy is recommended, especially with stereotactic guidance. In recent years different therapeutic techniques have been developed for the treatment of solid lesions, including breast cancer. Certainly, with the improvement of technology and medical scientific progress, it is becoming more common to use minimal- or non-invasive therapies. The proposed minimally invasive techniques may offer complete treatment of breast cancer, with better cosmetic results, less psychological stress, and shorter hospital stays. In this article, the strengths and weaknesses of the different diagnostic and therapeutic techniques are presented, and promising techniques for the future are discussed.

Online self-test identifies women at high familial breast cancer risk in population-based breast cancer screening without inducing anxiety or distress.

INTRODUCTION: Identifying high familial breast cancer (FBC) risk improves detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both highly likely and potentially preventable. We assessed whether a new online self-test could identify women at high FBC risk in population-based BC screening without inducing anxiety or distress. METHODS: After their visit for screening mammography, women were invited by email to take an online self-test for identifying highly increased FBC risk-based on Dutch guidelines. Exclusion criteria were previously diagnosed as increased FBC risk or a personal history of BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital Anxiety Depression Scale) and BC risk perception were assessed using questionnaires, which were completed immediately before and after taking the online self-test and 2 weeks later. RESULTS: Of the 562 women invited by email, 406 (72%) completed the online self-test while 304 also completed questionnaires (response rate 54%). After exclusion criteria, 287 (51%) were included for data analysis. Median age was 56 years (range 50-74). A high or moderate FBC risk was identified in 12 (4%) and three (1%) women, respectively. After completion of the online self-test, anxiety and BC risk perception were decreased while distress scores remained unchanged. Levels were below clinical relevance. Most women (85%) would recommend the self-test; few (3%) would not. CONCLUSION: The online self-test identified previously unknown women at high FBC risk (4%), who may carry a BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend offering this self-test to women who attend population-based screening mammography for the first time.

Improved cancer detection in automated breast ultrasound by radiologists using Computer Aided Detection.

OBJECTIVE: To investigate the effect of dedicated Computer Aided Detection (CAD) software for automated breast ultrasound (ABUS) on the performance of radiologists screening for breast cancer. METHODS: 90 ABUS views of 90 patients were randomly selected from a multi-institutional archive of cases collected between 2010 and 2013. This dataset included normal cases (n=40) with >1year of follow up, benign (n=30) lesions that were either biopsied or remained stable, and malignant lesions (n=20). Six readers evaluated all cases with and without CAD in two sessions. CAD-software included conventional CAD-marks and an intelligent minimum intensity projection of the breast tissue. Readers reported using a likelihood-of-malignancy scale from 0 to 100. Alternative free-response ROC analysis was used to measure the performance. RESULTS: Without CAD, the average area-under-the-curve (AUC) of the readers was 0.77 and significantly improved with CAD to 0.84 (p=0.001). Sensitivity of all readers improved (range 5.2-10.6%) by using CAD but specificity decreased in four out of six readers (range 1.4-5.7%). No significant difference was observed in the AUC between experienced radiologists and residents both with and without CAD. CONCLUSIONS: Dedicated CAD-software for ABUS has the potential to improve the cancer detection rates of radiologists screening for breast cancer.

3D quantitative breast ultrasound analysis for differentiating fibroadenomas and carcinomas smaller than 1cm.

PURPOSE: In (3D) ultrasound, accurate discrimination of small solid masses is difficult, resulting in a high frequency of biopsies for benign lesions. In this study, we investigate whether 3D quantitative breast ultrasound (3DQBUS) analysis can be used for improving non-invasive discrimination between benign and malignant lesions. METHODS AND MATERIALS: 3D US studies of 112 biopsied solid breast lesions (size <1cm), were included (34 fibroadenomas and 78 invasive ductal carcinomas). The lesions were manually delineated and, based on sonographic criteria used by radiologists, 3 regions of interest were defined in 3D for analysis: ROI (ellipsoid covering the inside of the lesion), PER (peritumoural surrounding: 0.5mm around the lesion), and POS (posterior-tumoural acoustic phenomena: region below the lesion with the same size as delineated for the lesion). After automatic gain correction (AGC), the mean and standard deviation of the echo level within the regions were calculated. For the ROI and POS also the residual attenuation coefficient was estimated in decibel per cm [dB/cm]. The resulting eight features were used for classification of the lesions by a logistic regression analysis. The classification accuracy was evaluated by leave-one-out cross-validation. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the classification. All lesions were delineated by two readers and results were compared to assess the effect of the manual delineation. RESULTS: The area under the ROC curve was 0.86 for both readers. At 100% sensitivity, a specificity of 26% and 50% was achieved for reader 1 and 2, respectively. Inter-reader variability in lesion delineation was marginal and did not affect the accuracy of the technique. The area under the ROC curve of 0.86 was reached for the second reader when the results of the first reader were used as training set yielding a sensitivity of 100% and a specificity of 40%. Consequently, 3DQBUS would have achieved a 40% reduction in biopsies for benign lesions for reader 2, without a decrease in sensitivity. CONCLUSION: This study shows that 3DQBUS is a promising technique to classify suspicious breast lesions as benign, potentially preventing unnecessary biopsies.

3-T breast magnetic resonance imaging in patients with suspicious microcalcifications on mammography.

OBJECTIVE: To investigate the diagnostic value of 3-Tesla (T) breast MRI in patients presenting with microcalcifications on mammography. METHODS: Between January 2006 and May 2009, 123 patients with mammographically detected BI-RADS 3­5 microcalcifications underwent 3-T breast MRI before undergoing breast biopsy. All MRIs of the histopathologically confirmed index lesions were reviewed by two breast radiologists. The detection rate of invasive carcinoma and ductal carcinoma in situ (DCIS) was evaluated, as well as the added diagnostic value of MRI over mammography and breast ultrasound. RESULTS: At pathology, 40/123 (33%) lesions proved malignant; 28 (70%) DCIS and 12 (30%) invasive carcinoma. Both observers detected all invasive malignancies at MRI, as well as 79% (observer 1) and 86% (observer 2) of in situ lesions. MRI in addition to conventional imaging led to a significant increase in area under the receiver operating characteristic (ROC) curve from 0.67 (95% CI 0.56­0.79) to 0.79 (95% CI 0.70­0.88, observer 1) and to 0.80 (95% CI 0.71­0.89, observer 2), respectively. CONCLUSIONS: 3-T breast MRI was shown to add significant value to conventional imaging in patients presenting with suspicious microcalcifications on mammography. KEY POINTS: • 3-T MRI is increasingly used for breast imaging in clinical practice. • On 3-T breast MRI up to 86% of DCIS lesions are detected. • 3-T MRI increases the diagnostic value in patients with mammographically detected microcalcifications.

Breast cancer size estimation with MRI in BRCA mutation carriers and other high risk patients.

OBJECTIVE: To assess the value of breast MRI in size assessment of breast cancers in high risk patients, including those with a BRCA 1 or 2 mutation. Guidelines recommend invariably breast MRI screening for these patients and therapy is thus based on these findings. However, the accuracy of breast MRI for staging purposes is only tested in sporadic cancers. METHODS: We assessed concordance of radiologic staging using MRI with histopathology in 49 tumors in 46 high risk patients (23 BRCA1, 12 BRCA2 and 11 Non-BRCA patients). The size of the total tumor area (TTA) was compared to pathology. In invasive carcinomas (n=45) the size of the largest focus (LF) was also addressed. RESULTS: Correlation of MRI measurements with pathology was 0.862 for TTA and 0.793 for LF. TTA was underestimated in 8(16%), overestimated in 5(10%), and correctly measured in 36(73%) cases. LF was underestimated in 4(9%), overestimated in 5(11%), and correctly measured in 36(80%) cases. Impact of BRCA 1 or 2 mutations on the quality of size estimation was not observed. CONCLUSIONS: Tumor size estimation using breast MRI in high risk patients is comparable to its performance in sporadic cancers. Therefore, breast MRI can safely be used for treatment planning.

Flow cytometric assessment of Cd genotoxicity in three plants with different metal accumulation and detoxification capacities.

Cadmium (Cd) is a widespread environmental contaminant, strongly mutagenic and known to cause DNA damage in plants. In this work, flow cytometry (FCM) was applied to determine if in vivo exposure to Cd would induce genotoxic effects at the genome level. The hyper-accumulator Thlaspi caerulescens (J. & C. Presl), the related non-accumulator Thlaspi arvense L. and the accumulator crop species Lactuca sativa L. were germinated in distilled water and grown in modified Hoagland's medium with increasing concentrations of Cd(NO3)2 (0, 1, 10 and 100 microM). After 28 days of exposure, shoot and root growth was recorded and the tissues were harvested for Cd and FCM analysis. In general, roots from treated plants contained higher content of Cd than leaves and growth inhibition was observed in the treated plants. Nuclear DNA content was estimated and the G0/G1 full peak coefficient of variation (FPCV), as an indicator of clastogenic damage, was recorded. In T. arvense and T. caerulescens no significant differences were detected between control and exposed plants. Leaves of L. sativa exposed to 10 microM Cd presented a statistically significant increase in FPCV values in comparison with the control group. Furthermore, roots exposed to 100 microM Cd presented a reduction in nuclear DNA content and an increase in FPCV when compared to the control. FCM data indicates that no major DNA damage was induced on both Cd-exposed Thlaspi species and L. sativa leaves. On the contrary, results obtained with L. sativa roots suggests clastogenic damage in these organs exposed to 100 microM of Cd.

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 additional value of three time point color coding in dynamic contrast-enhanced MRI of the breast for inexperienced and experienced readers.

PURPOSE: To evaluate the additional value of the color coding of dynamic data using the 3TP method in the evaluation of contrast-enhanced breast MRI for readers with different levels of experience. MATERIALS AND METHODS: A total of 52 lesions were included in this study, 25 malignant and 27 benign. All lesions were evaluated by four readers on two different workstations for the evaluation of dynamic breast MRI; one displaying the subtracted images and relative enhancement versus time curves and one displaying the subtracted images together with the 3TP color coding projected onto pre-contrast T1 images. Readers with different levels of experience were used. The diagnostic performance of both workstations was evaluated using ROC curve analyses. Interobserver variations were evaluated using kappa statistics. RESULTS: All lesions were detected by all four readers on both workstations. The diagnostic performance found in the inexperienced readers improved significantly when using the 3TP evaluations (p=0.04 and p=0.03). No significant difference was found for the more experienced readers (p=0.94 and p=0.54). The level of agreement between the readers improved significantly when using the 3TP evaluation method (p=0.01). CONCLUSION: Even though the 3TP color coding did not improve the diagnostic performance of the more experienced readers, this study clearly shows its value for inexperienced readers. The use of 3TP color coding is therefore recommended for inexperienced readers.

Assessment of biomarkers of cadmium stress in lettuce.

Laboratory and field studies have provided encouraging insights into the capacity of plants to act as biomonitors of environmental quality through the use of biomarkers. However, a better understanding of the overall process of Cd-induced senescence, describing the cascade of Cd effects in plants is needed for a selection of relevant biomarkers of Cd stress. In order to approach this, 5-week old Lactuca sativa L. were exposed for 14 days to 100muM Cd(NO(3))(2) and harvested at days 0, 1, 3, 7 and 14. The parameters measured included classical endpoints (shoot and root growth) and biochemical endpoints related to photosynthesis, nutrients content, and oxidative stress. Cadmium-exposed plants displayed nutrient imbalances in leaves and roots. Photosynthetic efficiency was significantly decreased and lipid peroxidation was enhanced. Antioxidant enzymes were significantly altered during exposure-catalase was inhibited by the end of exposure and peroxidase was induced at day 1 in young leaves. These alterations culminated in a decrease in shoot growth after 14-days exposure to Cd. Biochemical alterations could be used in integrative approaches with classical endpoints in ecotoxicological tests for Cd and after further testing in real scenarios conditions, they could form the basis of a plant biomarkers battery for monitoring and predicting early effects of exposure to Cd.