CaeNDR, the Caenorhabditis Natural Diversity Resource.

Studies of model organisms have provided important insights into how natural genetic differences shape trait variation. These discoveries are driven by the growing availability of genomes and the expansive experimental toolkits afforded to researchers using these species. For example, Caenorhabditis elegans is increasingly being used to identify and measure the effects of natural genetic variants on traits using quantitative genetics. Since 2016, the C. elegans Natural Diversity Resource (CeNDR) has facilitated many of these studies by providing an archive of wild strains, genome-wide sequence and variant data for each strain, and a genome-wide association (GWA) mapping portal for the C. elegans community. Here, we present an updated platform, the Caenorhabditis Natural Diversity Resource (CaeNDR), that enables quantitative genetics and genomics studies across the three Caenorhabditis species: C. elegans, C. briggsae and C. tropicalis. The CaeNDR platform hosts several databases that are continually updated by the addition of new strains, whole-genome sequence data and annotated variants. Additionally, CaeNDR provides new interactive tools to explore natural variation and enable GWA mappings. All CaeNDR data and tools are accessible through a freely available web portal located at caendr.org.

Nutrient limitation of phytoplankton in three tributaries of Chesapeake Bay: Detecting responses following nutrient reductions.

Many coastal ecosystems suffer from eutrophication, algal blooms, and dead zones due to excessive anthropogenic inputs of nitrogen (N) and phosphorus (P). This has led to regional restoration efforts that focus on managing watershed loads of N and P. In Chesapeake Bay, the largest estuary in the United States, dual nutrient reductions of N and P have been pursued since the 1980s. However, it remains unclear whether nutrient limitation - an indicator of restriction of algal growth by supplies of N and P - has changed in the tributaries of Chesapeake Bay following decades of reduction efforts. Toward that end, we analyzed historical data from nutrient-addition bioassay experiments and data from the Chesapeake Bay long-term water-quality monitoring program for six stations in three tidal tributaries (i.e., Patuxent, Potomac, and Choptank Rivers). Classification and regression tree (CART) models were developed using concurrent collections of water-quality parameters for each bioassay monitoring location during 1990-2003, which satisfactorily predicted the bioassay-based measures of nutrient limitation (classification accuracy = 96%). Predictions from the CART models using water-quality monitoring data showed enhanced nutrient limitation over the period of 1985-2020 at four of the six stations, including the downstream station in each of these three tributaries. These results indicate detectable, long-term water-quality improvements in the tidal tributaries. Overall, this research provides a new analytical tool for detecting signs of ecosystem recovery following nutrient reductions. More broadly, the approach can be adapted to other waterbodies with long-term bioassays and water-quality data sets to detect ecosystem recovery.

Explainable machine learning improves interpretability in the predictive modeling of biological stream conditions in the Chesapeake Bay Watershed, USA.

Anthropogenic alterations have resulted in widespread degradation of stream conditions. To aid in stream restoration and management, baseline estimates of conditions and improved explanation of factors driving their degradation are needed. We used random forests to model biological conditions using a benthic macroinvertebrate index of biotic integrity for small, non-tidal streams (upstream area ≤200 km2) in the Chesapeake Bay watershed (CBW) of the mid-Atlantic coast of North America. We utilized several global and local model interpretation tools to improve average and site-specific model inferences, respectively. The model was used to predict condition for 95,867 individual catchments for eight periods (2001, 2004, 2006, 2008, 2011, 2013, 2016, 2019). Predicted conditions were classified as Poor, FairGood, or Uncertain to align with management needs and individual reach lengths and catchment areas were summed by condition class for the CBW for each period. Global permutation and local Shapley importance values indicated percent of forest, development, and agriculture in upstream catchments had strong impacts on predictions. Development and agriculture negatively influenced stream condition for model average (partial dependence [PD] and accumulated local effect [ALE] plots) and local (individual condition expectation and Shapley value plots) levels. Friedman's H-statistic indicated large overall interactions for these three land covers, and bivariate global plots (PD and ALE) supported interactions among agriculture and development. Total stream length and catchment area predicted in FairGood conditions decreased then increased over the 19-years (length/area: 66.6/65.4% in 2001, 66.3/65.2% in 2011, and 66.6/65.4% in 2019). Examination of individual catchment predictions between 2001 and 2019 showed those predicted to have the largest decreases in condition had large increases in development; whereas catchments predicted to exhibit the largest increases in condition showed moderate increases in forest cover. Use of global and local interpretative methods together with watershed-wide and individual catchment predictions support conservation practitioners that need to identify widespread and localized patterns, especially acknowledging that management actions typically take place at individual-reach scales.

A Highly Scalable Approach to Perform Ecological Surveys of Selfing Caenorhabditis Nematodes.

Caenorhabditis elegans is one of the major model organisms in biology, but only recently have researchers focused on its natural ecology. The relative sparsity of information about C. elegans in its natural context comes from the challenges involved in the identification of the small nematode in nature. Despite these challenges, an increasing focus on the ecology of C. elegans has caused a wealth of new information regarding its life outside of the laboratory. The intensified search for C. elegans in nature has contributed to the discovery of many new Caenorhabditis species and revealed that congeneric nematodes frequently cohabitate in the wild, where they feed on microbial blooms associated with rotting plant material. The identification of new species has also revealed that the androdioecious mating system of males and self-fertilizing hermaphrodites has evolved three times independently within Caenorhabditis. The other two selfing species, C. briggsae and C. tropicalis, share the experimental advantages of C. elegans and have enabled comparative studies into the mechanistic basis of important traits, including self-fertilization. Despite these advances, much remains to be learned about the ecology and natural diversity of these important species. For example, we still lack functional information for many of their genes, which might only be attained through an understanding of their natural ecology. To facilitate ecological research of selfing Caenorhabditis nematodes, we developed a highly scalable method to collect nematodes from the wild. Our method makes use of mobile data collection platforms, cloud-based databases, and the R software environment to enhance researchers' ability to collect nematodes from the wild, record associated ecological data, and identify wild nematodes using molecular barcodes.

Local adaptation and spatiotemporal patterns of genetic diversity revealed by repeated sampling of Caenorhabditis elegans across the Hawaiian Islands.

The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little is known about its natural ecology. Genetic diversity is low across much of the globe but high in the Hawaiian Islands and across the Pacific Rim. To characterize the niche and genetic diversity of C. elegans on the Hawaiian Islands and to explore how genetic diversity might be influenced by local adaptation, we repeatedly sampled nematodes over a three-year period, measured various environmental parameters at each sampling site, and whole-genome sequenced the C. elegans isolates that we identified. We found that the typical Hawaiian C. elegans niche comprises moderately moist native forests at high elevations (500-1,500 m) where ambient air temperatures are cool (15-20°C). Compared to other Caenorhabditis species found on the Hawaiian Islands (e.g., Caenorhabditis briggsae and Caenorhabditis tropicalis), we found that C. elegans were enriched in native habitats. We measured levels of genetic diversity and differentiation among Hawaiian C. elegans and found evidence of seven genetically distinct groups distributed across the islands. Then, we scanned these genomes for signatures of local adaptation and identified 18 distinct regions that overlap with hyper-divergent regions, which may be maintained by balancing selection and are enriched for genes related to environmental sensing, xenobiotic detoxification, and pathogen resistance. These results provide strong evidence of local adaptation among Hawaiian C. elegans and contribute to our understanding of the forces that shape genetic diversity on the most remote volcanic archipelago in the world.

Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles.

Infections by parasitic nematodes cause large health and economic burdens worldwide. We use anthelmintic drugs to reduce these infections. However, resistance to anthelmintic drugs is extremely common and increasing worldwide. It is essential to understand the mechanisms of resistance to slow its spread. Recently, four new parasitic nematode beta-tubulin alleles have been identified in benzimidazole (BZ) resistant parasite populations: E198I, E198K, E198T, and E198stop. These alleles have not been tested for the ability to confer resistance or for any effects that they might have on organismal fitness. We introduced these four new alleles into the sensitive C. elegans laboratory-adapted N2 strain and exposed these genome-edited strains to both albendazole and fenbendazole. We found that all four alleles conferred resistance to both BZ drugs. Additionally, we tested for fitness consequences in both control and albendazole conditions over seven generations in competitive fitness assays. We found that none of the edited alleles had deleterious effects on fitness in control conditions and that all four alleles conferred strong and equivalent fitness benefits in BZ drug conditions. Because it is unknown if previously validated alleles confer a dominant or recessive BZ resistance phenotype, we tested the phenotypes caused by five of these alleles and found that none of them conferred a dominant BZ resistance phenotype. Accurate measurements of resistance, fitness effects, and dominance caused by the resistance alleles allow for the generation of better models of population dynamics and facilitate control practices that maximize the efficacy of this critical anthelmintic drug class.

C-amidation of substitutedß3oligoamides yields novel supramolecular assembly motif.

N-acylated substitutedß3oligoamides are known to form unique supramolecular nanorods based on a 3-point hydrogen bond self-assembly motif. This motif is an intermolecular extension of the hydrogen bonding network that stabilizes the 14-helix secondary structure unique toß3oligoamides. Acetylation of the N-terminus of the molecule provides the necessary third hydrogen bond pair of the motif. Here, the possibility of introducing the third hydrogen bond pair via amidation of the C terminus is investigated. While similar in purpose, this modification introduces a chemically distinct new self-assembly motif, also removing the bulky carboxyl group that does not fold into the 14 helix positioning instead as a side chain. Three substitutedß3oligoamide variants with the base sequence LIA (where the letters denoteß3residues with side chains analogous to α amino acids) were compared: N-acylated Ac-ß3[LIA] as a reference, C-amidatedß3[LIA]-CONH2, andß3[LIA] with free unmodified N and C termini as a negative control. The three variants were dissolved in water to promote self-assembly. The self-assembly was characterised using mid- and far-infrared spectroscopy, small angle x-ray scattering (SAXS) and atomic force microscopy (AFM). IR measurements confirmed that all three samples were in a similar conformation, consistent with pseudo 14-helical secondary structures. Far-infrared spectroscopy measurements ofß3[LIA]-CONH2showed distinct peaks consistent with highly organised skeletal modes, i.e. regular supramolecular assembly, that was largely absent from the other two oligoamides. Modelling of SAXS data is consistent with elliptical cylinder structures resulting from nanorod bundling for bothß3[LIA]-CONH2and Ac-ß3[LIA], but not in the unmodified sample. Consistently, AFM imaging showed large nanorod bundling structures inß3[LIA]-CONH2, varied bundling structures in Ac-ß3[LIA], and only aggregation inß3[LIA]. Amidation showed much more organised and robust assembly compared to acetylation, providing a new, easy to synthesize self-assembly motif for helical nanorod assembly that is similar but distinct to N-acylation.

Linking Altered Flow Regimes to Biological Condition: an Example Using Benthic Macroinvertebrates in Small Streams of the Chesapeake Bay Watershed.

Regionally scaled assessments of hydrologic alteration for small streams and its effects on freshwater taxa are often inhibited by a low number of stream gages. To overcome this limitation, we paired modeled estimates of hydrologic alteration to a benthic macroinvertebrate index of biotic integrity data for 4522 stream reaches across the Chesapeake Bay watershed. Using separate random-forest models, we predicted flow status (inflated, diminished, or indeterminant) for 12 published hydrologic metrics (HMs) that characterize the main components of flow regimes. We used these models to predict each HM status for each stream reach in the watershed, and linked predictions to macroinvertebrate condition samples collected from streams with drainage areas less than 200 km2. Flow alteration was calculated as the number of HMs with inflated or diminished status and ranged from 0 (no HM inflated or diminished) to 12 (all 12 HMs inflated or diminished). When focused solely on the stream condition and flow-alteration relationship, degraded macroinvertebrate condition was, depending on the number of HMs used, 3.8-4.7 times more likely in a flow-altered site; this likelihood was over twofold higher in the urban-focused dataset (8.7-10.8), and was never significant in the agriculture-focused dataset. Logistic regression analysis using the entire dataset showed for every unit increase in flow-alteration intensity, the odds of a degraded condition increased 3.7%. Our results provide an indication of whether altered streamflow is a possible driver of degraded biological conditions, information that could help managers prioritize management actions and lead to more effective restoration efforts.

Nutrient limitation of phytoplankton in Chesapeake Bay: Development of an empirical approach for water-quality management.

Understanding the temporal and spatial roles of nutrient limitation on phytoplankton growth is necessary for developing successful management strategies. Chesapeake Bay has well-documented seasonal and spatial variations in nutrient limitation, but it remains unknown whether these patterns of nutrient limitation have changed in response to nutrient management efforts. We analyzed historical data from nutrient bioassay experiments (1992-2002) and data from long-term, fixed-site water-quality monitoring program (1990-2017) to develop empirical approaches for predicting nutrient limitation in the surface waters of the mainstem Bay. Results from classification and regression trees (CART) matched the seasonal and spatial patterns of bioassay-based nutrient limitation in the 1992-2002 period much better than two simpler, non-statistical approaches. An ensemble approach of three selected CART models satisfactorily reproduced the bioassay-based results (classification rate = 99%). This empirical approach can be used to characterize nutrient limitation from long-term water-quality monitoring data on much broader geographic and temporal scales than would be feasible using bioassays, providing a new tool for informing water-quality management. Results from our application of the approach to 21 tidal monitoring stations for the period of 2007-2017 showed modest changes in nutrient limitation patterns, with expanded areas of nitrogen-limitation and contracted areas of nutrient saturation (i.e., not limited by nitrogen or phosphorus). These changes imply that long-term reductions in nitrogen load have led to expanded areas with nutrient-limited phytoplankton growth in the Bay, reflecting long-term water-quality improvements in the context of nutrient enrichment. However, nutrient limitation patterns remain unchanged in the majority of the mainstem, suggesting that nutrient loads should be further reduced to achieve a less nutrient-saturated ecosystem.

Disentangling the potential effects of land-use and climate change on stream conditions.

Land-use and climate change are significantly affecting stream ecosystems, yet understanding of their long-term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land-use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin-wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land-use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project - Phase 5 (CMIP5) and a watershed-wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land-use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed-wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land-use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed-wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%-26.2% of stream kilometers, dependent on land-use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land-use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions.

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.

Revisiting the Chesapeake Bay phytoplankton index of biotic integrity.

In 2006, a phytoplankton index of biotic integrity (PIBI) was published for Chesapeake Bay Lacouture et al. (Estuaries 29(4):598-616, 2006). The PIBI was developed from data collected during the first 18 years (1985-2002) of the Chesapeake Bay Program long-term phytoplankton and water quality monitoring programs. Combinations of up to nine phytoplankton metrics were selected to characterize bay habitat health according to plankton community condition in spring and summer seasons across four salinity zones. The independent data available at the time for index validation was not sufficient to test the PIBI because they lacked critical index parameters (pheophytin and dissolved organic carbon) and reference samples for some seasons and salinity zones. An additional 8 years of monitoring data (2003-2010) are now available to validate the original index, reassess index performance and re-examine long-term trends in PIBI conditions in the Bay. The PIBI remains sensitive to changes in nutrient and light conditions. Evaluation of the PIBI results over the entire 1985-2010 time period shows no discernible trends in the overall health of Bay habitat based on phytoplankton community conditions. This lack of overall PIBI trend appears to be a combined response to declines in water clarity and improvements in dissolved inorganic nitrogen and dissolved phosphorus conditions in the bay.

An ignition key for atomic-scale engines.

A current-carrying resonant nanoscale device, simulated by non-adiabatic molecular dynamics, exhibits sharp activation of non-conservative current-induced forces with bias. The result, above the critical bias, is generalized rotational atomic motion with a large gain in kinetic energy. The activation exploits sharp features in the electronic structure, and constitutes, in effect, an ignition key for atomic-scale motors. A controlling factor for the effect is the non-equilibrium dynamical response matrix for small-amplitude atomic motion under current. This matrix can be found from the steady-state electronic structure by a simpler static calculation, providing a way to detect the likely appearance, or otherwise, of non-conservative dynamics, in advance of real-time modelling.

Accelerated Partial Breast Irradiation: Using the CyberKnife as the Radiation Delivery Platform in the Treatment of Early Breast Cancer.

We evaluate the CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) for non-invasive delivery of accelerated partial breast irradiation (APBI) in early breast cancer patients. Between 6/2009 and 5/2011, nine patients were treated with CyberKnife APBI. Normal tissue constraints were imposed as outlined in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 (NSABP/RTOG) Protocol (Vicini and White, 2007). Patients received a total dose of 30 Gy in five fractions (group 1, n = 2) or 34 Gy in 10 fractions (group 2, n = 7) delivered to the planning treatment volume (PTV) defined as the clinical target volume (CTV) +2 mm. The CTV was defined as either the lumpectomy cavity plus 10 mm (n = 2) or 15 mm (n = 7). The cavity was defined by a T2-weighted non-contrast breast MRI fused to a planning non-contrast thoracic CT. The CyberKnife Synchrony system tracked gold fiducials sutured into the cavity wall during lumpectomy. Treatments started 4-5 weeks after lumpectomy. The mean PTV was 100 cm(3) (range, 92-108 cm(3)) and 105 cm(3) (range, 49-241 cm(3)) and the mean PTV isodose prescription line was 70% for groups 1 and 2, respectively. The mean percent of whole breast reference volume receiving 100 and 50% of the dose (V(100) and V(50)) for group 1 was 11% (range, 8-13%) and 23% (range, 16-30%) and for group 2 was 11% (range, 7-14%) and 26% (range, 21-35.0%), respectively. At a median 7 months follow-up (range, 4-26 months), no acute toxicities were seen. Acute cosmetic outcomes were excellent or good in all patients; for those patients with more than 12 months follow-up the late cosmesis outcomes were excellent or good. In conclusion, the lack of observable acute side effects and current excellent/good cosmetic outcomes is promising. We believe this suggests the CyberKnife is a suitable non-invasive radiation platform for delivering APBI with achievable normal tissue constraints.

Development and evaluation of a spatially-explicit index of Chesapeake Bay health.

In an effort to better portray changing health conditions in Chesapeake Bay and support restoration efforts, a Bay Health Index (BHI) was developed to assess the ecological effects of nutrient and sediment loading on 15 regions of the estuary. Three water quality and three biological measures were combined to formulate the BHI. Water quality measures of chlorophyll-a, dissolved oxygen, and Secchi depth were averaged to create the Water Quality Index (WQI), and biological measures of the phytoplankton and benthic indices of biotic integrity (P-IBI and B-IBI, respectively) and the area of submerged aquatic vegetation (SAV) were averaged to create the Biotic Index (BI). The WQI and BI were subsequently averaged to give a BHI value representing ecological conditions over the growing season (i.e., March-October). Lower chlorophyll-a concentrations, higher dissolved oxygen concentrations, deeper Secchi depths, higher phytoplankton and benthic indices relative to ecological health-based thresholds, and more extensive SAV area relative to restoration goal areas, characterized the least-impaired regions. The WQI, P-IBI and BHI were significantly correlated with (1) regional river flow (r=-0.64, -0.57 and -0.49, respectively; p<0.01), (2) nitrogen (N), phosphorus (P) and sediment loads (all positively correlated with flow), and (3) the sum of developed and agricultural land use (highest annual r(2)=0.86, 0.71 and 0.68, respectively) in most reporting regions, indicating that the BHI is strongly regulated by nutrient and sediment loads from these land uses. The BHI uses ecological health-based thresholds that give an accurate representation of the health conditions in Chesapeake Bay and was the basis for an annual, publicly released environmental report card that debuted in 2007.

Is pleomorphic lobular carcinoma really a distinct clinical entity?

BACKGROUND: Attempts to define the clinical behavior of pleomorphic lobular carcinoma (PLC) have been limited to small series, and clinical management strategies have yet to be established. We describe our experience with PLC as compared to classic ILC and invasive ductal carcinoma (IDC). METHODS: From 9/1996 to 5/2003, clinical and histopathologic data for 5,635 patients undergoing primary surgical treatment and sentinel lymph node biopsy for breast cancer were collected. Four hundred eighty one (8.5%) patients were diagnosed with ILC; 3,978 (70.6%) with IDC. Of those with ILC, 356 (74%) patients had material available for pathologic re-review and comprise our study population: 52 were classified as PLC; 298 were classified as classic ILC; and 6 cases were reclassified as IDC. We compared clinical, pathologic, and treatment factors for patients with PLC, ILC, and IDC using the Wilcoxon rank sum and Fisher's exact tests. RESULTS: PLC were larger than ILC and IDC (20 vs. 15 vs. 13, P < 0.001), had more positive nodes (median 1 vs. 0 vs. 0, P < 0.05) and more frequently required mastectomy (63.5% vs. 38.7% vs. 28.8%, P < 0.001). In addition, more patients with PLC had developed metastatic disease compared to patients with ILC (11.5% vs. 3.7%, P < 0.05). CONCLUSIONS: These findings suggest that PLC is a distinct clinical entity that presents at a more advanced stage and may require more aggressive surgical and adjuvant treatment.

Breast cancer recurrence following prosthetic, postmastectomy reconstruction: incidence, detection, and treatment.

BACKGROUND: The purpose of this study was to evaluate the influence of prosthetic reconstruction on the incidence, detection, and management of locoregional recurrence following mastectomy for invasive breast cancer. METHODS: A matched retrospective cohort study was performed. Only patients with invasive breast cancer who had 2 years or more of follow-up and/or patients who had recurrence within 2 years of their primary cancer were included. RESULTS: In total, 618 patients who underwent mastectomy for invasive breast cancer from 1995 until 1999 were evaluated. Three hundred nine patients who had immediate, tissue expander/implant reconstruction were matched to 309 women who underwent mastectomy alone on the basis of age (+/-5 years) and breast cancer stage (I, II, or III). The incidence of locoregional recurrence following mastectomy was 6.8 percent in patients who had reconstruction and 8.1 percent in patients who had mastectomy alone (log rank p = 0.6015). Median time to detection of a locoregional recurrence was 2.3 years (range, 0.1 to 7.2 years) in the reconstructed cohort and 1.9 years (range, 0.1 to 8.8 years) in the nonreconstructed cohort (p = 0.733). Permanent implants were removed following infection in one patient and patient request in two. CONCLUSIONS: These results suggest that there is no difference in the incidence of locoregional recurrence in breast cancer patients who undergo immediate, tissue expander/implant reconstruction compared with those patients who do not have reconstruction. Prosthetic breast reconstruction does not appear to hinder detection of locoregional cancer recurrence. In the majority of patients, management of locoregional recurrence does not necessitate removal of a permanent prosthesis.