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Trismus/reduced mouth opening (RMO) is a common side effect of radiotherapy (RT) for head and neck cancer (HNC). The objective was to measure RMO, identify risk factors for RMO, and determine its impact on quality of life (QOL). OraRad is an observational, prospective, multicenter cohort study of patients receiving curative intent RT for HNC. Interincisal mouth opening measurements (n = 565) and patient-reported outcomes were recorded before RT and every 6 months for 2 years. Linear mixed-effects models were used to evaluate change in mouth opening and assess the relationship between trismus history and change in QOL measures. Interincisal distance decreased from a mean (SE) of 45.1 (0.42) mm at baseline to 42.2 (0.44) at 6 months, with slight recovery at 18 months (43.3, 0.46 mm) but no additional improvement by 24 months. The odds of trismus (opening <35 mm) were significantly higher at 6 months (odds ratio [OR] = 2.21, 95% CI: 1.30 to 3.76) and 12 months (OR = 1.87, 95% CI: 1.08 to 3.25) compared with baseline. Females were more likely to experience trismus at baseline and during follow-up (P <.01). Patients with oral cavity cancer had the highest risk for trismus at baseline and post-RT (P <.01). RMO was associated with higher RT dose to the primary site and receiving concomitant chemotherapy (P <.01). Trismus was associated with self-reported difficulty opening the mouth and dry mouth (P <.01). A decrease in mouth opening is a common treatment-related toxicity after RT, with some recovery by 18 months. Trismus has a significant impact on survivor QOL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine effects of radiation therapy (RT) for head and neck cancer (HNC) on periodontal disease and relationships to caries.Study Design: A multicenter prospective observational cohort study (OraRad) was conducted in patients undergoing RT for HNC. Assessments were conducted by calibrated examiners at the pre-RT (baseline) visit (n = 533), the 12-month visit (n = 414), and the 24-month visit (n = 365).Results: The average whole mouth mean (standard error (SE)) distance from the cementoenamel junction to the gingival margin (CEJ-GM) decreased significantly from 0.43 (0.04) mm at baseline to 0.24 (0.04) mm at 12 months and 0.11 (0.04) mm at 24 months (P ≤ .001). Whole mouth mean (SE) percentage of sites with CEJ-GM distance of <0 mm increased significantly from 23.3% (1.0%) at baseline to 28.5% (1.0%) at 12 months and 30.5% (1.1%) at 24 months (P ≤ .02). Higher mean radiation dose to the mandible was associated with a greater increase in the percentage of mandibular sites with CEJ-GM distance of <0 mm (P = .003). Both mean CEJ-GM distance and the percentage of sites with a CEJ-GM distance <0 mm were strongly associated with whole mouth mean proportion of decayed, missing, and filled surfaces, as well as proportion of decayed or filled facial/buccal surfaces specifically, (P < .001), with greater gingival recession associated with increased caries.Conclusions: RT for HNC leads to mandibular gingival recession in a dose-dependent manner. This gingival recession may contribute to increased risk for cervical caries seen in these patients. [ABSTRACT FROM AUTHOR]

Tributaries provide spawning habitat for three of four major sub-stocks of Lake Erie walleye (Sander vitreus). Despite anthropogenic degradation and the extirpation of other potamodromous species, the Maumee River, Ohio, USA continues to support one of the largest fish migrations in the Laurentian Great Lakes. To determine if spawning habitat availability and quality could limit production of Maumee River walleye, two habitat suitability models were created for the lower 51 km of the Maumee River and the distribution and numbers of walleye eggs deposited in a 25 km stretch of river were assessed. Walleye eggs were collected using a diaphragm pump at 7 and 10 sites from March/April to May 2014 and 2015. The habitat suitability models showed that <3% of the river yielded 'good' walleye spawning habitat and 11–38% yielded 'moderate' walleye spawning habitat, depending on the model. However, a large set of rapids at river kilometer 28 and more than five river kilometers of less suitable habitat separated areas of 'good' habitat. The rapids may present a migratory barrier for many spawning walleye, as modeled water velocities exceed maximum estimated walleye swim speeds 71–100% of days during pre-spawn migration and spawning during the study period. In both study years, there was a sharp decline in mean egg numbers from spawning sites downstream of the rapids (439.7 eggs/2 min tow ± 990.6 SD) to upstream sites (5.9 eggs/2 min tow ± 19.4 SD). Physical barriers like rapids may reduce spawning habitat connectivity and could limit walleye production in the Maumee River. [ABSTRACT FROM AUTHOR]

G-protein–coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins. In the gastrointestinal tract, GPCRs expressed by epithelial cells sense contents of the lumen, and GPCRs expressed by epithelial cells, myocytes, neurons, and immune cells participate in communication among cells. GPCRs control digestion, mediate digestive diseases, and coordinate repair and growth. GPCRs are the target of more than one third of therapeutic drugs, including many drugs used to treat digestive diseases. Recent advances in structural, chemical, and cell biology research have shown that GPCRs are not static binary switches that operate from the plasma membrane to control a defined set of intracellular signals. Rather, GPCRs are dynamic signaling proteins that adopt distinct conformations and subcellular distributions when associated with different ligands and intracellular effectors. An understanding of the dynamic nature of GPCRs has provided insights into the mechanism of activation and signaling of GPCRs and has shown opportunities for drug discovery. We review the allosteric modulation, biased agonism, oligomerization, and compartmentalized signaling of GPCRs that control digestion and digestive diseases. We highlight the implications of these concepts for the development of selective and effective drugs to treat diseases of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that chronic cancer pain as well as high-dose opioid use lead to mu-opioid receptor downregulation. In this study we explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high-dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients. We then reverse-translate our clinical findings by creating a mouse cancer pain model; we create opioid tolerance in the mouse cancer model to mimic opioid tolerance in the cancer patients. Using this model we determine the functional significance of OPRM1 methylation on cancer pain and opioid tolerance. We focus on 2 main cells within the cancer microenvironment: the cancer cell and the neuron. We show that targeted re-expression of mu-opioid receptor on cancer cells inhibits mechanical and thermal hypersensitivity, and prevents opioid tolerance, in the mouse model. The resultant analgesia and protection against opioid tolerance are likely due to preservation of mu-opioid receptor expression on the cancer-associated neurons.Perspective: We demonstrate that epigenetic regulation of OPRM1 contributes to opioid tolerance in cancer patients, and that targeted gene therapy could treat cancer-induced nociception and opioid tolerance in a mouse cancer model. [ABSTRACT FROM AUTHOR]

The problem of classifying traffic flows in networks has become more and more important in recent times, and much research has been dedicated to it. In recent years, there has been a lot of interest in classifying traffic flows by application, based on the statistical features of each flow. Information about the applications that are being used on a network is very useful in network design, accounting, management, and security. In our previous work we proposed a classification algorithm for Internet traffic flow classification based on Artificial Immune Systems (AIS). We also applied the algorithm on an available data set, and found that the algorithm performed as well as other algorithms, and was insensitive to input parameters, which makes it valuable for embedded systems. It is also very simple to implement, and generalizes well from small training data sets. In this research, we expanded on the previous research by introducing several optimizations in the training and classification phases of the algorithm. We improved the design of the original algorithm in order to make it more predictable. We also give the asymptotic complexity of the optimized algorithm as well as draw a bound on the generalization error of the algorithm. Lastly, we also experimented with several different distance formulas to improve the classification performance. In this paper we have shown how the changes and optimizations applied to the original algorithm do not functionally change the original algorithm, while making its execution 50–60% faster. We also show that the classification accuracy of the Euclidian distance is superseded by the Manhattan distance for this application, giving 1–2% higher accuracy, making the accuracy of the algorithm comparable to that of a Naïve Bayes classifier in previous research that uses the same data set. [ABSTRACT FROM AUTHOR]

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes.Perspective: The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer-related pain syndromes. [ABSTRACT FROM AUTHOR]

Chemically intensive crop production depletes wildlife food resources, hinders animal development, health, survival, and reproduction, and it suppresses wildlife immune systems, facilitating emergence of infectious diseases with excessive mortality rates. Gut microbiota is crucial for wildlife's response to environmental stressors. Its composition and functionality are sensitive to diet changes and environmental pollution associated with modern crop production. In this study we use shotgun metagenomics (median 8,326,092 sequences/sample) to demonstrate that exposure to modern crop production detrimentally affects cecal microbiota of sharp-tailed grouse (Tympanuchus phasianellus : 9 exposed, 18 unexposed and greater prairie chickens (T. cupido ; 11, 11). Exposure to crop production had greater effect on microbiota richness (t = 6.675, P < 0.001) and composition (PERMANOVA r 2 = 0.212, P = 0.001) than did the host species (t = 4.762, P < 0.001; r 2 = 0.070, P = 0.001) or their interaction (t = 3.449; r 2 = 0.072, both P = 0.001), whereas sex and age had no effect. Although microbiota richness was greater in exposed (T. cupido chao1 = 152.8 ± 20.5; T. phasianellus 115.3 ± 17.1) than in unexposed (102.9 ± 15.1 and 101.1 ± 17.2, respectively) birds, some beneficial bacteria dropped out of exposed birds' microbiota or declined and were replaced by potential pathogens. Exposed birds also had higher richness and load of virulome (mean ± standard deviation; T. cupido 24.8 ± 10.0 and 10.1 ± 5.5, respectively; T. phasianellus 13.4 ± 6.8/4.9 ± 2.8) and resistome (T. cupido 46.8 ± 11.7/28.9 ± 10.2, T. phasianellus 38.3 ± 16.7/18.9 ± 14.2) than unexposed birds (T. cupido virulome: 14.2 ± 13.5, 4.5 ± 4.2; T. cupido resistome: 31.6 ± 20.2 and 13.1 ± 12.0; T. phasianellus virulome: 5.2 ± 4.7 and 1.4 ± 1.5; T. phasianellus resistome: 13.7 ± 16.1 and 4.0 ± 6.4). [Display omitted] • Cropland grouse exhibit dysbiosis and elevated virulence and antibiotic resistance. • Crop production similarly affects microbiota in both study species. • Crop production affects microbiota to a greater extent than host species. • Naturally distinct microbiotas of study species converge in croplands. • Sex or age of grouse do not affect cecal microbiota, virulome, or resistome. [ABSTRACT FROM AUTHOR]

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Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction. Perspective Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up. [ABSTRACT FROM AUTHOR]

Background: Understanding normal volume asymmetry is essential for accurate assessment of limb volume changes following breast cancer (BC) treatment in which lymphatic function is disrupted. The purposes of this study were to evaluate for differences in dominant and nondominant limb volumes and to evaluate for interactions between the effects of dominance and side of cancer on limb volume. Methods and Results: This study evaluated preoperative limb volumes of 397 women enrolled in a prospective, longitudinal study of neuropathic pain and lymphedema. Volume was calculated from circumference. Limb resistance was measured with bioimpedance. Women were dichotomized into two groups: those whose cancer was on their dominant side and those whose cancer was on their nondominant side. Analyses of variance were used to evaluate for differences. In 47%, BC occurred on the side of the dominant limb. Except for the 30 to 40 centimeter (cm) limb volume segment, a main effect of dominance was found for all measures. The volume of the dominant limb was significantly greater than that of the nondominant limb. No main effects were found for side of cancer. A statistically significant interaction was found only at the 0 to 10 cm limb volume segment. Conclusions: Prior to BC treatment, the dominant limb demonstrated lower bioimpedance resistance (−2.09%) and greater total limb volume (1.12%) than the nondominant limb. Segmental volume differences were greatest at the proximal forearm segment (2.31%) and least at the proximal arm segment (0.21%). This study provides evidence that preoperative volume assessment is important due to normal variability associated with limb dominance. [ABSTRACT FROM AUTHOR]

Background: Lymphedema (LE) is a frequent complication following breast cancer treatment. While progress is being made in the identification of phenotypic risk factors for the development of LE, little information is available on the molecular characterization of LE. The purpose of this study was to determine if variations in pro- and anti-inflammatory cytokine genes were associated with LE following breast cancer treatment. Methods and Results: Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with ( n=155) and without LE ( n=387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease, and a higher number of lymph nodes removed. Genetic associations were identified for three genes (i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory responses. Conclusions: These genetic associations suggest a role for a number of pro- and anti-inflammatory genes in the development of LE following breast cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Plexiform schwannoma is a soft tissue tumor that rarely presents in the lower extremity. We have reported on 2 cases of plexiform schwannomas that occurred in the foot and ankle. Owing to the relative obscurity of this condition in the lower extremity, we have also provided an overview of plexiform schwannomas and discussed the differences between this and other suspicious nodular soft tissue masses. The first patient was a 38-year-old female, who had a soft tissue mass located on the lateral aspect of her right foot that became symptomatic. The second patient was an 11-year-old male, who had a symptomatic soft tissue mass on the plantar aspect of his right foot. Both patients underwent surgical excision of the tumor. [Copyright &y& Elsevier]

Abstract: Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. Perspective: This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain. [Copyright &y& Elsevier]

Purpose: Surgical resection of midface neoplasms and subsequent reconstruction have been shown to have significant negative effects on quality of life (QOL). The purpose of this pilot study was to assess individuals' health-related QOL after maxillectomy and reconstruction with a prosthetic obturator. Materials and Methods: The QOL of 25 of 43 patients who underwent maxillectomy and prosthetic obturator reconstruction at the University of California–San Francisco was assessed using 3 questionnaires: University of Washington Quality of Life version 4 (UWQOL), Obturator Functioning Scale (OFS), and Mental Health Inventory (MHI). Results: The response rate to the QOL questionnaires was 92% (23 of 25 patients). Time elapsed from maxillectomy and prosthetic obturator reconstruction to the QOL survey response ranged from 0.3 to 6.6 years (mean, 2.7 years; standard deviation [SD], 1.9 years). The post-treatment mean QOL scores were 77.3 (SD, 13.6) for UWQOL, 72.0 (SD, 12.6) for OFS, and 4.5 (SD, 0.9) for Mental Health Inventory. Individuals who received adjuvant radiation scored lower for speech and appearance (OFS, P = .05, P = .03, respectively) as well as for saliva and overall QOL (UWQOL, P = .02, P = .08, respectively). There was a strong correlation between QOL scores in OFS and UWQOL questionnaires (r = 0.78, P < .001). Conclusion: The results of this pilot study suggest that postoperative radiation therapy was the strongest variable affecting QOL in patients with maxillectomy and prosthetic obturator reconstruction. There is further need for a multicenter trial with a larger sample to identify how factors affecting QOL of patients after maxillectomy might influence the choice of reconstruction. [Copyright &y& Elsevier]

Abstract: Study purposes were to determine the prevalence of persistent pain in the breast; characterize distinct persistent pain classes using growth mixture modeling; and evaluate for differences among these pain classes in demographic, preoperative, intraoperative, and postoperative characteristics. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the pain classes, were evaluated. Patients (n = 398) were recruited prior to surgery and followed for 6 months. Using growth mixture modeling, patients were classified into no (31.7%), mild (43.4%), moderate (13.3%), and severe (11.6%) pain groups based on ratings of worst breast pain. Differences in a number of demographic, preoperative, intraoperative, and postoperative characteristics differentiated among the pain classes. In addition, patients in the moderate and severe pain classes reported higher preoperative levels of depression, anxiety, and sleep disturbance than the no pain class. Findings suggest that approximately 25% of women experience significant and persistent levels of breast pain in the first 6 months following breast cancer surgery. Perspective: Persistent pain is a significant problem for 25% of women following surgery for breast cancer. Severe breast pain is associated with clinically meaningful decrements in functional status and quality of life. [Copyright &y& Elsevier]

Posterior tongue defects present a unique reconstructive challenge. The various reconstructive options available for treating the defect created by a posterior hemiglossectomy frequently result in a distorted tongue and functional impairment. This paper describes a novel sliding anterior hemitongue flap to allow reconstruction of moderate resection defects (i.e. for T1-T2 tongue squamous cell carcinomas) of the posterior tongue. By mobilizing the anterior tongue, near normal mobility and tongue length are maintained. This surgical technique may be performed alone intraorally or in combination with a neck dissection. [ABSTRACT FROM AUTHOR]

Purpose: To compare vascularity and angiogenic activity in aggressive and nonaggressive giant cell lesions (GCLs) of the jaws. Materials and Methods: This is a retrospective study of 14 GCLs treated at the University of California, San Francisco. Immunohistochemistry was used to determine of the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), CD34, and CD31. VEGF and bFGF expression in giant cells (GCs) and surrounding mononuclear stroma was classified into 1) high immunoreactivity (>50% staining) and 2) low immunoreactivity (<50% staining). CD31- and CD34-stained vessels were counted at 200× magnification. Clinical and radiographic records were reviewed to classify lesions as aggressive or nonaggressive. Results: Of the lesions, 8 were aggressive and 6 were nonaggressive. High VEGF expression was found within the GCs in 4 of 8 aggressive lesions compared with 1 of 6 nonaggressive lesions. The stroma in both groups had low staining. High staining of the GCs for bFGF was found in 6 of 8 aggressive lesions compared with 3 of 6 nonaggressive lesions. The stroma of all aggressive cases showed high expression of bFGF compared with 3 of 6 nonaggressive cases. The aggressive group had a mean of 20.1 ± 5.4 vessels/high-powered field (hpf) stained for CD31 compared with 11.5 ± 5.6 vessels/hpf in the nonaggressive group. The aggressive group had 24.6 ± 7.0 vessels/hpf stained with CD34 compared with 18.5 ± 4.0 vessels/hpf in the nonaggressive group. Conclusions: The vascularity and level of angiogenesis within aggressive GCLs are higher than those in nonaggressive lesions. [Copyright &y& Elsevier]

Abstract: Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that μ and δ opioid receptors are separately expressed on IB4 (−) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (−) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor agonist and a P2X3 antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective δ-opioid receptor agonist or P2X3 antagonist, might be useful in treating oral cancer pain. Perspective: To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (−) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief. [Copyright &y& Elsevier]

Abstract: The purposes of this study were to determine the occurrence rate for preoperative breast pain; describe the characteristics of this pain; evaluate for differences in demographic and clinical characteristics; and evaluate for variations in pro- and anti-inflammatory cytokine genes between women who did and did not report pain. Patients (n = 398) were recruited prior to surgery and completed self-report questionnaires on a number of pain characteristics. Genotyping was done using a custom genotyping array. Women (28.2%) who reported breast pain were significantly younger (P < .001); more likely to be nonwhite (P = .032); reported significantly lower Karnofsky Performance Status scores (P = .008); were less likely to be postmenopausal (P = .012); and had undergone significantly more biopsies (P = .006). Carriers of the minor allele for a single nucleotide polymorphism in interleukin (IL)1-receptor 1 (IL1R1) (rs2110726) were less likely to report breast pain prior to surgery (P = .007). Carriers of the minor allele for a single nucleotide polymorphism in IL13 (rs1295686) were more likely to report breast pain prior to surgery (P = .019). Findings suggest that breast pain occurs in over a quarter of women who are about to undergo breast cancer surgery. Based on phenotypic and genotypic characteristics found, inflammatory mechanisms contribute to preoperative breast pain. Perspective: In women with breast cancer, preoperative pain may be associated with increases in inflammatory responses associated with an increased number of biopsies. In addition, differences in cytokine genes may contribute to this preoperative breast pain. [Copyright &y& Elsevier]