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Intraoperative radiation therapy (IORT) has gained popularity for early stage breast cancer treatment. Few studies have examined the relationship between complications and both demographic and technical factors. The objective of the current study was to determine if applicator size or distances to the skin were significant risk factors for complications. Data was prospectively collected on patients who underwent lumpectomy followed by IORT from November 1, 2013 to August 31, 2018. Exclusion criteria included any prior radiation exposure or personal history of breast cancer. Comorbid conditions such as body mass index, diabetes, and smoking as well as technical specifications such as applicator size and distances to the skin were included for investigation. Student's t -test, Fisher's exact test, and odds ratios were utilized for statistical analysis. The study was comprised of 219 patients. None developed Clavien-Dindo grade 2 or above complications. Of 21.0% (n = 46) had minor complications. The most common complication was a palpable breast seroma (n = 37). Diabetes was the only comorbid condition with increased risk for complications (OR 3.2; 95% CI1.3-7.5; P = 0.008). The applicator sizes and average skin distances were similar between groups. Surprisingly, the closest skin distance was not a significant risk factor for post-operative complications (1.4 +/- 1.6 versus 1.4 +/- 1.9 cm; P = 1.0). Neither applicator size nor the closest skin distance were associated with increased complications. Traditionally described risk factors such as BMI and smoking were not predictive. This data provides support for potentially expanding the utilization for IORT without increasing complications. [ABSTRACT FROM AUTHOR]

Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan–Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51–11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms. [ABSTRACT FROM AUTHOR]

Non-invasive diagnosis of breast cancer is still challenging due to the low specificity of the imaging modalities that calls for unnecessary biopsies. The diagnostic accuracy can be improved by assessing the breast tissue mechanical properties associated with pathological changes. Harmonic motion imaging (HMI) is an elasticity imaging technique that uses acoustic radiation force to evaluate the localized mechanical properties of the underlying tissue. Herein, we studied the in vivo feasibility of a clinical HMI system to differentiate breast tumors based on their relative HMI displacements, in human subjects. We performed HMI scans in 10 female subjects with breast masses: five benign and five malignant masses. Results revealed that both benign and malignant masses were stiffer than the surrounding tissues. However, malignant tumors underwent lower mean HMI displacement (1.1 ± 0.5 µm) compared to benign tumors (3.6 ± 1.5 µm) and the adjacent non-cancerous tissue (6.4 ± 2.5 µm), which allowed to differentiate between tumor types. Additionally, the excised breast specimens of the same patients (n = 5) were imaged post-surgically, where there was an excellent agreement between the in vivo and ex vivo findings, confirmed with histology. Higher displacement contrast between cancerous and non-cancerous tissue was found ex vivo, potentially due to the lower nonlinearity in the elastic properties of ex vivo tissue. This preliminary study lays the foundation for the potential complementary application of HMI in clinical practice in conjunction with the B-mode to classify suspicious breast masses. [ABSTRACT FROM AUTHOR]

Background: Radial scars/radial sclerosing lesions (RS) are benign breast lesions identified on core needle biopsy (CNB) which can upgrade to malignancy at excision. There is limited data on RS detection and upgrade rates with more sensitive imaging such as magnetic resonance imaging (MRI) and none during their detection for breast cancer workup and its implication on patient treatment decisions., Methods: A retrospective institutional study of RS diagnosed on CNB between January 2008 and December 2017 was conducted. Clinicopathologic and radiologic features of RS, patient treatment decisions, upgrade rates and long-term follow-up were examined., Results: We identified 133 patients with RS on CNB, of whom 106 opted for surgery for an upgrade rate to malignancy of 1.9%, 2 patients. Radial scar was diagnosed on mammogram in 60%, MRI in 25% and ultrasound in 15% of patients. In this cohort, 32 patients had their RS detected during breast cancer workup (coexistent group) and they were more likely to have their radial scar detected by MRI (60% vs. 14%, P < .001) and undergo more extensive surgery (94% vs. 75%, P = .02). Among the 27 patients electing observation of their RS, only one (3.7%) developed breast cancer., Conclusions: Our results show an extremely low upgrade rate to malignancy of RS, regardless if there is coexisting breast cancer elsewhere. Despite this, RS still prompted more extensive surgical excisions. The findings do not support excision of RS even among breast cancer patients when identified at a separate site from their cancer., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Axillary lymph node dissection (ALND) remains the leading cause of lymphedema nationally, and there is still no cure for the disease. The lymphatic microsurgical preventive healing approach (LYMPHA) is a promising option for lymphedema prophylaxis in patients undergoing ALND, but long-term outcomes of the LYMPHA are not well established., Methods: The authors conducted a retrospective review of patients undergoing ALND at their center from November of 2012 to November of 2016 and assembled two cohorts, those who received the LYMPHA and those who did not (non-LYMPHA). Patient data were collected to evaluate lymphedema risk and long-term lymphedema incidence of each group., Results: Forty-five women were included in both our LYMPHA and non-LYMPHA cohorts. Mean body mass index (27.7 kg/m2 versus 29.9 kg/m2; P = 0.15) and radiation therapy rates (60.0% versus 68.9%; P = 0.51) did not differ between groups. Non-LYMPHA patients underwent complete mastectomy more frequently than LYMPHA patients (97.8% versus 77.8%; P = 0.007), but had a similar number of nodes removed during ALND (14.4 versus 15.8; P = 0.32). Median follow-up time was greater than 4 years for both LYMPHA and non-LYMPHA groups (57.0 months versus 63.0 months; P = 0.07). Overall, lymphedema incidence was 31.1% in the LYMPHA group and 33.3% in the non-LYMPHA group (P > 0.99). No significant differences in lymphedema incidences were observed between the LYMPHA and non-LYMPHA groups for patients with obesity, patients who received radiation therapy, or patients with obesity who also received radiation therapy (P > 0.05 for all subgroups)., Conclusions: The LYMPHA may not prevent lymphedema long-term in patients who undergo ALND. More long-term studies are needed to determine the true potential of the procedure., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Mini-Abstract: The coronavirus disease 2019 (COVID-19) pandemic has had catastrophic repercussions across the world and here in the United States. The healthcare system in New York City, the epicenter, has faced significant disruptions due to the sheer volume of cases and critical care needs of severely ill patients. For surgical specialty services, the postponement of all elective surgeries, redeployment of faculty and staff, and cancellation of outpatient clinics became a rapid reality. These circumstances required a nimble restructuring of services and communications to facilitate continued support of academic and clinical missions. Throughout the course of the pandemic, significant adjustments were made in regards to duties, patient services, and communication. The frameworks and techniques utilized are described along with the relevant outcomes. Immediate restructuring of tumor boards, a focused multidisciplinary approach to management that incorporated the barriers presented by the pandemic, optimization of telehealth services, inclusive communication, and a service-oriented approach to redeployment were critical to sustaining the Division of Breast, Melanoma, and Soft Tissue surgery., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The purpose of this study was to develop a deep learning classification approach to distinguish cancerous from noncancerous regions within optical coherence tomography (OCT) images of breast tissue for potential use in an intraoperative setting for margin assessment., Methods: A custom ultrahigh-resolution OCT (UHR-OCT) system with an axial resolution of 2.7 μm and a lateral resolution of 5.5 μm was used in this study. The algorithm used an A-scan-based classification scheme and the convolutional neural network (CNN) was implemented using an 11-layer architecture consisting of serial 3 × 3 convolution kernels. Four tissue types were classified, including adipose, stroma, ductal carcinoma in situ, and invasive ductal carcinoma., Results: The binary classification of cancer versus noncancer with the proposed CNN achieved 94% accuracy, 96% sensitivity, and 92% specificity. The mean five-fold validation F1 score was highest for invasive ductal carcinoma (mean standard deviation, 0.89 ± 0.09) and adipose (0.79 ± 0.17), followed by stroma (0.74 ± 0.18), and ductal carcinoma in situ (0.65 ± 0.15)., Conclusion: It is feasible to use CNN based algorithm to accurately distinguish cancerous regions in OCT images. This fully automated method can overcome limitations of manual interpretation including interobserver variability and speed of interpretation and may enable real-time intraoperative margin assessment., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer-related lymphedema (BCRL) represents a major source of morbidity among breast cancer survivors. Increasing data support early detection of subclinical BCRL followed by early intervention. A randomized controlled trial is being conducted comparing lymphedema progression rates using volume measurements calculated from the circumference using a tape measure (TM) or bioimpedance spectroscopy (BIS)., Methods: Patients were enrolled and randomized to either TM or BIS surveillance. Patients requiring early intervention were prescribed a compression sleeve and gauntlet for 4 weeks and then re-evaluated. The primary endpoint of the trial was the rate of progression to clinical lymphedema requiring complex decongestive physiotherapy (CDP), with progression defined as a TM volume change in the at-risk arm ≥ 10% above the presurgical baseline. This prespecified interim analysis was performed when at least 500 trial participants had ≥ 12 months of follow-up., Results: A total of 508 patients were included in this analysis, with 109 (21.9%) patients triggering prethreshold interventions. Compared with TM, BIS had a lower rate of trigger (15.8% vs. 28.5%, p < 0.001) and longer times to trigger (9.5 vs. 2.8 months, p = 0.002). Twelve triggering patients progressed to CDP (10 in the TM group [14.7%] and 2 in the BIS group [4.9%]), representing a 67% relative reduction and a 9.8% absolute reduction (p = 0.130)., Conclusions: Interim results demonstrated that post-treatment surveillance with BIS reduced the absolute rates of progression of BCRL requiring CDP by approximately 10%, a clinically meaningful improvement. These results support the concept of post-treatment surveillance with BIS to detect subclinical BCRL and initiate early intervention.

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

Background: Prior work has shown that the competitiveness of the market in which hospitals operate is associated with use of surgical procedures. This study examined the association between regional market competition and use of breast reconstruction for women with breast cancer and ductal carcinoma in situ undergoing mastectomy., Methods: Women who underwent mastectomy from 2010 to 2011 recorded in the National Inpatient Sample were selected. The competitive market environment for each hospital in which patients were treated was estimated using the Herfindahl-Hirschman Index. Multivariable models were developed to examine the association between regional market competition and breast reconstruction, with adjustment for other clinical, demographic, and structural variables., Results: Immediate breast reconstruction was performed for 9902 (45%) of 22,011 women. The rate of immediate breast reconstruction was 34.5% at hospitals in non-competitive markets, 49% at hospitals in moderately competitive markets, and 56.4% at hospitals in highly competitive markets (P < 0.0001). In a multivariable model, women in moderately competitive markets were 24% (risk ratio [RR] 1.24; 95% confidence interval [CI] 1.10-1.41) more likely to undergo immediate breast reconstruction than women in noncompetitive markets, whereas those in competitive markets were 25% (RR 1.25; 95% CI 1.11-1.41) more likely to have reconstruction. Later year of treatment, higher census tract income level, and residence in an urban area were associated with an increased likelihood of reconstruction (P < 0.05 for all). In contrast, older age, non-white race, and non-commercial insurance were associated with a lower likelihood of reconstruction (P < 0.05 for all)., Conclusion: Patients who undergo mastectomy at hospitals in competitive markets are more likely to undergo immediate breast reconstruction.

Purpose: Intraoperative radiation therapy (IORT) as a form of accelerated partial breast irradiation (APBI) is controversial given the limited evidence to support its efficacy. However, it remains an attractive option for low-risk patients with ductal carcinoma in situ (DCIS), who derive a small absolute benefit in local control with standard whole breast irradiation (WBI). We examine how the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines (CG) may be applied to the preoperative selection of patients with DCIS for IORT and determine treatment outcomes by CG group., Methods and Materials: We identified patients with biopsy-proven pure DCIS enrolled in an institutional prospective registry IORT database using the Zeiss Intrabeam ® device between September 2013 and February 2017. Based on available preoperative clinicopathologic information, patients were deemed suitable, cautionary, or unsuitable for IORT according to the ASTRO CG. Change in CG group based on final pathologic diagnosis was determined, and additional therapy was recommended for unsuitable patients. Outcome in terms of ipsilateral breast tumor recurrence was determined., Results: A total of 61 DCIS lesions in 60 patients were treated with IORT. Preoperatively, 21 patients (35%) were suitable and 36 (59%) were cautionary. Four (6%) were unsuitable because of lesion size but declined WBI. Final pathologic diagnosis changed the CG grouping of 10 patients (16%) because of either occult high-grade disease in 2 (3%) or close/positive margins in 8 (13%). Ultimately 12 patients total were considered unsuitable, of whom 8 (66%) accepted additional WBI after IORT. At a median follow-up of 2.2 years, ipsilateral breast tumor recurrence was identified among 2 suitable, 1 cautionary, and no unsuitable patients., Conclusion: Further investigation is necessary to refine selection of patients with DCIS who may be optimally treated with IORT alone. High acceptance of additional therapy among unsuitable patients resulted in excellent outcomes. The use of biomarkers in addition to traditional clinical and pathologic factors may help to better select patients for IORT.

Background: Recently there are efforts to use sentinel lymph node biopsy (SLNB) techniques after neoadjuvant chemotherapy (NAC) to minimize axillary surgery. However, studies have shown higher false negative rates in this scenario, which might result in inaccurate assessment of treatment response and patient prognosis as well as leaving residual disease behind. In this study, we describe the use of reflector-guided excision of the percutaneously biopsied node (PBN) as an aid to conventional SLNB and its predictor of the axillary status after NAC., Patients and Methods: This was a single-institution analysis of patients who underwent axillary fiducial-reflector placement and subsequent SLNB compared with conventional SLNB., Results: Nineteen patients in the reflector group were matched with 19 patients who underwent conventional SLNB (conventional group). The PBN was identified in the SLNB in 19 patients (100%) in the reflector group and in 9 patients (47.3%) in the conventional group (P = .002). In the remaining 10 patients in the conventional group, the PBN was identified in the axillary lymph node dissection specimen in 4 patients (21%) and not identified in 6 patients (31.7%). Among the 38 patients, traditional mapping failed to identify the PBN in 13 patients (34.2%). The PBN was negative in 10 patients (36%) and positive in 18 patients (64%); no additional positive nodes were identified among patients with a negative PBN, correctly reflecting the status of the axilla in 100% of cases., Conclusion: Mapping failure after NAC might compromise SLNB. Reflector-guided excision of the PBN is not only facile and feasible, but more accurately reflects the status of the axilla after NAC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: In the postneoadjuvant chemotherapy (NAC) setting, conventional radiographic complete response (rCR) is a poor predictor of pathologic complete response (pCR) of the axilla. We developed a convolutional neural network (CNN) algorithm to better predict post-NAC axillary response using a breast MRI dataset., Methods: An institutional review board-approved retrospective study from January 2009 to June 2016 identified 127 breast cancer patients who: (1) underwent breast MRI before the initiation of NAC; (2) successfully completed Adriamycin/Taxane-based NAC; and (3) underwent surgery, including sentinel lymph node evaluation/axillary lymph node dissection with final surgical pathology data. Patients were classified into pathologic complete response (pCR) of the axilla group and non-pCR group based on surgical pathology. Breast MRI performed before NAC was used. Tumor was identified on first T1 postcontrast images underwent 3D segmentation. A total of 2811 volumetric slices of 127 tumors were evaluated. CNN consisted of 10 convolutional layers, 4 max-pooling layers. Dropout, augmentation and L2 regularization were implemented to prevent overfitting of data., Results: On final surgical pathology, 38.6% (49/127) of the patients achieved pCR of the axilla (group 1), and 61.4% (78/127) of the patients did not with residual metastasis detected (group 2). For predicting axillary pCR, our CNN algorithm achieved an overall accuracy of 83% (95% confidence interval [CI] ± 5) with sensitivity of 93% (95% CI ± 6) and specificity of 77% (95% CI ± 4). Area under the ROC curve (0.93, 95% CI ± 0.04)., Conclusions: It is feasible to use CNN architecture to predict post NAC axillary pCR. Larger data set will likely improve our prediction model.

Objective: The purpose of this article is to report on a study conducted to determine whether the lesions in patients with what is deemed to be low-risk ductal carcinoma in situ (DCIS) selected for two large clinical trials are in fact low-risk lesions., Conclusion: A retrospective review was conducted to determine whether the eligibility criteria of the two trials are predictive that DCIS is low risk. More than 20% of lesions are upgraded to invasive carcinoma in patients with low-risk DCIS as defined in two large clinical trials. More accurate methods are needed to determine whether patients with a diagnosis of low-grade DCIS can be treated less aggressively.

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., Competing Interests: The authors declare no competing interests.

Background: In this study we aimed to review the outcomes of nipple-sparing mastectomy (NSM) in the setting of expanded criteria: previous breast surgery/irradiation, neoadjuvant chemotherapy (NAC), post-NSM irradiation, and to assess conversion to acceptable criteria after NAC., Patients and Methods: In this single-institution institutional review board-approved retrospective review, we identified patients who underwent NSM after previous breast intervention or NAC from January 2010 to February 2017. Clinicopathologic features, previous breast surgeries, response rate, complications, and recurrences were recorded., Results: Sixty-three patients underwent 106 NSMs. Among 63 patients, 39 (61.9%) received NAC, 30 (47.6%) previous lumpectomy, 4 (6.3%) with cosmetic implants, 4 (6.3%) with mastopexy, 5 (7.9%) with previous radiation therapy, and 21 (33%) underwent post-NSM radiation therapy. Transient epidermolysis occurred in 24 patients (38.1%), with 16 patients (66.6%) having complete flap recovery and nipple loss in 8 patients (12.6%). All 10 patients with central disease on pre-NAC imaging converted to acceptable criteria, with 9 having successful NSM. At mean 67.2-month follow-up, 56 patients (88.9%) were disease-free, 5 (7.9%) experienced a systemic recurrence, and 2 (3.2%) a local recurrence., Conclusion: NSM is oncologically acceptable in this patient cohort. Patients with large central tumors who undergo NAC should be reconsidered after completion of chemotherapy because many might convert to successful nipple-areolar preservation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: No established standard of care exists for aggressive cutaneous squamous cell carcinoma (CSCC)., Objective: We sought to establish an aggressive CSCC management protocol by reviewing high-risk CSCC (HCSCC) and very high-risk CSCC (VCSCC) cases at our institution., Methods: This was a retrospective review of all CSCC cases treated at our institution., Results: A total of 27 patients were identified of 1591 cases treated between 2000 and 2011. Four patients with HCSCC received surgery alone and 1 received surgery and radiation. All remain disease free (median follow-up 5 years). Among patients with VCSCC, 4 received surgery alone: 1 (25%) showing a complete response and 3 (75%) showing disease progression. Eleven received surgery and radiation: 4 (36.4%) with complete response (median follow-up 3 years) and 7 (63.6%) with disease progression (median time to recurrence 6 months). Six received surgery and cetuximab: 3 (50%) had a complete response (median follow-up 3 years), 2 (33%) had disease progression, and 1 (14%) could not be assessed because of inability to tolerate infusions. One patient received surgery, cetuximab, and radiation, and remains disease-free after 4 years., Limitations: Lack of randomization, blinding, a true control arm, or standardization of treatment protocols are limitations., Conclusions: Patients with very HCSCC may have improved outcomes with surgery and adjuvant cetuximab., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Circulating nucleic acids have been detected in plasma/serum from cancer patients with a variety of tumor types. Polymerase chain reaction techniques provide a ubiquitous and facile approach for the identification of these tumor-associated genetic alterations from a minimal amount of tissue and body fluids. Increased levels of free DNA and RNA during malignancy, as well as in various medical conditions and infectious states, offers potential clinical utility for disease screening, diagnosis, prognosis, assessing occult disease progression, identifying potential therapeutic targets and monitoring treatment response. Additionally, elevated fetal DNA and RNA circulate in maternal blood and may serve as a diagnostic aide for assessing chromosomal abnormalities, fetal sexing and monitoring complications associated with pregnancy. Issues persist regarding the characteristics, etiology and potential pathological consequences of circulating cell-free DNA and RNA. Regardless, disease surveillance using nucleic acid-based assays for the evaluation of plasma/serum and body fluids provides a non-invasive and highly practical method for assessing patients.

Cutaneous melanoma is a highly aggressive tumor that is relatively resistant to chemotherapy and radiotherapy. This resistance may be in part due to inhibition of apoptosis. Apoptotic protease activating factor-1(APAF-1), a candidate tumor suppressor gene, mediates p53-induced apoptosis, and its loss promotes oncogenic transformation. To determine whether loss of the APAF-1 locus influences tumor progression, we assessed loss of heterozygosity microsatellites on the APAF-1 locus (12q22-23) in 62 primary and 112 metastatic melanomas. We discovered that frequency of allelic imbalance was significantly higher in metastatic tumors (n = 36 of 98; 37%) than in primary melanomas (n = 10 of 54; 19%; P = 0.02). In metastatic melanomas, APAF-1 loss significantly correlated with a worse prognosis (P < 0.05) in the patients, and its loss during melanoma tumor progression suggests that APAF-1 is a tumor suppressor gene. Furthermore, loss of heterozygosity was frequent in the 12q22-23 chromosome region centromeric to the APAF-1 locus suggesting that other tumor-related genes may be present in the 12q22-23 region. In summary, the study demonstrates that allelic imbalance in the 12q22-23 region is a genomic surrogate of poor disease outcome for cutaneous melanoma patients.

Detection of genetic markers associated with early breast cancer may prove clinically relevant for identifying patients at increased risk for relapse. Loss of heterozygosity (LOH), a specific genetic aberration, commonly occurs during breast cancer initiation and metastasis. Early detection of tumor metastasis to bone marrow (BM) using conventional histochemical techniques has been limited because of suboptimal efficiency and sensitivity. Because bone is such a common site of breast cancer recurrence, we sought to determine whether microsatellite markers associated with breast cancer could be detected in BM aspirates from patients with early-stage breast cancer. Cell-free plasma from BM aspirates in 48 patients was assessed for LOH using a panel of eight polymorphic microsatellite markers. LOH was detected in 11 (23%) of 48 patients' BM aspirates. Advancing American Joint Committee on Cancer (AJCC) stage was associated with an increased incidence of LOH. Concordance was present between LOH identified in BM aspirates and matched-pair primary tumors. No samples contained detectable tumor cells on routine histology. In 24 patients, paired peripheral blood serum samples were available for analysis. In these cases, BM detection of LOH was more frequent than serum. This study demonstrates the novel finding of tumor-related genetic markers in BM aspirate plasma of early-stage breast cancer patients and provides a unique approach for assessing subclinical systemic disease progression and the monitoring of breast cancer patients.