Implementation of a clinical breast exam and referral program in a rural district of Pakistan.

BACKGROUND: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan. METHODS: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up. RESULTS: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community's breast cancer knowledge at the follow-up visits using the standardized post-test. CONCLUSIONS: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatment.

Impact of Postoperative Antibiotic Prophylaxis on Surgical Site Infections Rates After Mastectomy with Drains but Without Immediate Reconstruction: A Multicenter, Double-Blinded, Randomized Control Superiority Trial.

BACKGROUND: There is no consensus on the use of postoperative antibiotic prophylaxis (PAP) after mastectomy with indwelling drains. We explored the utility of continued PAP in reducing surgical site infection (SSI) rates after mastectomy without immediate reconstruction and with indwelling drains. PATIENTS AND METHODS: A multicenter, two-armed, randomized control superiority trial was conducted in Pakistan. We enrolled all consenting adult patients undergoing mastectomy without immediate reconstruction. All patients received a single preoperative dose of cephalexin within 60 min of incision, and postoperatively were randomized to receive either continued PAP using cephalexin (intervention) or a placebo (control) for the duration of indwelling, closed-suction drains. The primary outcome was the development of SSI within 30 days and 90 days postoperatively. Secondary outcomes included study-drug-associated adverse events. Intention-to-treat analysis was performed using multivariable Cox regression. RESULTS: A total of 369 patients, 180 (48.8%) in the intervention group and 189 (51.2%) in the control group, were included in the final analysis. Overall cumulative SSI rates were 3.5% at 30 days and 4.6% at 90 days postoperatively. PAP was not associated with SSI reduction at 30 (hazard ratio, HR 1.666 [95% confidence interval CI 0.515-5.385]) or 90 (1.575 [0.558-4.448]) days postoperatively, or with study-drug-associated adverse effects (0.529 [0.196-1.428]). CONCLUSIONS: Continuing antibiotic prophylaxis for the duration of indwelling drains after mastectomy without immediate reconstruction offers no additional benefit in terms of SSI reduction. There is a need to update existing guidelines to provide clearer recommendations regarding use of postoperative antibiotic prophylaxis after mastectomy in the setting of indwelling drains.

Practice Patterns of Antibiotic Prophylaxis in Patients Undergoing Mastectomy: A Survey of Members of the American Society of Breast Surgeons.

BACKGROUND: Surgical site infections after breast surgery range from 1 to 16%. Both the American Society of Breast Surgeons (ASBrS) and the American Association of Plastic Surgeons guidelines lack clarity on postoperative antibiotic prophylaxis (AP) after mastectomy. We surveyed the ASBrS membership to understand their practice patterns of AP after mastectomy and familiarity with ASBrS guidelines. METHODS: A self-designed, 19-question survey was emailed to all 2934 ASBrS members. Information was obtained on the participants' training, familiarity with ASBrS guidelines, and practices of prescribing perioperative AP after mastectomy with/without reconstruction and with indwelling drains. RESULTS: In total, 556 (19%) responses were analyzed. Half were fellowship-trained breast surgeons/surgical oncologists (50.2%), with 55.6% having practiced for > 15 years and 66.9% in community/private practice. Only 53.6% reported familiarity with ASBrS guidelines for perioperative AP. Most (> 90%) surgeons reported "always" placing drains after mastectomy and "always" prescribing preoperative AP. Postoperatively, preference for continuing AP in cases with drains in place varied by procedure: 7.7% when no reconstruction, 29.1% when autologous-only, and 52.5% when implant reconstruction. Academic surgeons were less likely than surgeons in community/private practice to continue postoperative AP, whether for the duration of indwelling drains (5.1% versus 9.4%) or even till 7 days postoperatively (0.6% versus 3.2%) (p < 0.05). CONCLUSIONS: Surgeons uniformly adhere to ASBrS guidelines for preoperative AP. However, there is wide variation in AP postoperatively in patients with/without reconstruction and with indwelling drains. Our results highlight the need for high-quality evidence based on which guidelines must be updated, and the need to familiarize surgeons with current guidelines.

Challenges and opportunities in the establishment of a hereditary breast cancer clinic at an academic medical center in a low-middle income country.

It is now standard of care to offer genetic testing to patients at risk of hereditary breast cancer and make management decisions based on these results. Although great strides have been made in ensuring access to genetic testing and genetic counseling by establishing hereditary breast cancer clinics in well-resourced countries, these are essentially non-existent in low-middle income countries like Pakistan. We established a hereditary breast cancer clinic involving a multidisciplinary team, including a medical geneticist and a genetic counselor. Our efforts were based on consensus guidelines and included educating medical providers about the importance of genetic testing in breast cancer care and the mandatory presence of a genetics team member at the weekly Breast Tumor Board meeting. This resulted in an increase in the number of referrals of breast cancer patients for genetic testing. In this report, we describe the challenges we faced in setting up such a system in Pakistan and the measures to overcome them. There is a need to establish such hereditary breast cancer clinics, which can also be replicated at other centers in low-resource settings, to improve standardized assessment and management of the patients with hereditary breast cancer according to consensus guidelines.

Histologic grading of breast carcinoma: a multi-institution study of interobserver variation using virtual microscopy.

Breast carcinoma grading is an important prognostic feature recently incorporated into the AJCC Cancer Staging Manual. There is increased interest in applying virtual microscopy (VM) using digital whole slide imaging (WSI) more broadly. Little is known regarding concordance in grading using VM and how such variability might affect AJCC prognostic staging (PS). We evaluated interobserver variability amongst a multi-institutional group of breast pathologists using digital WSI and how discrepancies in grading would affect PS. A digitally scanned slide from 143 invasive carcinomas was independently reviewed by 6 pathologists and assigned grades based on established criteria for tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). Statistical analysis was performed. Interobserver agreement for grade was moderate (κ = 0.497). Agreement was fair (κ = 0.375), moderate (κ = 0.491), and good (κ = 0.705) for grades 2, 3, and 1, respectively. Observer pair concordance ranged from fair to good (κ = 0.354-0.684) Perfect agreement was observed in 43 cases (30%). Interobserver agreement for the individual components was best for TF (κ = 0.503) and worst for MC (κ = 0.281). Seventeen of 86 (19.8%) discrepant cases would have resulted in changes in PS and discrepancies most frequently resulted in a PS change from IA to IB (n = 9). For two of these nine cases, Oncotype DX results would have led to a PS of 1A regardless of grade. Using VM, a multi-institutional cohort of pathologists showed moderate concordance for breast cancer grading, similar to studies using light microscopy. Agreement was the best at the extremes of grade and for evaluation of TF. Whether the higher variability noted for MC is a consequence of VM grading warrants further investigation. Discordance in grading infrequently leads to clinically meaningful changes in the prognostic stage.

Factors Affecting Women Surgeons' Careers in Low-Middle-Income Countries: An International Survey.

BACKGROUND: Despite increasing numbers of women surgeons globally, barriers to career advancement persist. While these barriers have been extensively discussed in high-income countries (HICs), the topic has received minimal attention in lower-middle-income countries (LMICs) like Pakistan. METHODS: The Association of Women Surgeons of Pakistan (AWSP)-an organization in Pakistan consisting of female surgeons and trainees-carried out this international cross-sectional study over July-Sept 2019. An anonymous online survey was disseminated via social media platforms and various institutions across Pakistan and internationally. RESULTS: A total of 218 female surgeons responded to the survey, with 146 (67%) from Pakistan and 72 (33%) from HICs. While HIC surgeons were more likely to report gender discrimination/bias (GD/bias) during residency (29.2% vs 11.6%; p = 0.001), more Pakistani surgeons reported that GD/bias negatively affected their job satisfaction (80.7% vs. 64.9%; p = 0.024). GD/bias manifested most commonly as differences in mentoring relationships (72%). A higher percentage Pakistani surgeons reported having experienced a family-related interruption in their career (24.7% vs. 11.1%; p = 0.019). The vast majority (95%) felt that surgery was perceived as a masculine field, and the majority (56.4%) of respondents reported having been told that they could not be a surgeon because of their gender. CONCLUSION: Our study highlights keys factors that must be addressed to provide equal career opportunities to women surgeons. It is the responsibility of surgical educators, policy makers, and healthcare organizations to facilitate women surgeons' career progression by developing systems that support equitable career growth for women surgeons.

Cultural Barriers for Women in Surgery: How Thick is the Glass Ceiling? An Analysis from a Low Middle-Income Country.

BACKGROUND: This study aimed to highlight cultural barriers faced by surgeons pursuing a surgical career faced by surgeons at a tertiary care hospital in Pakistan. As more females opt for a surgical career, barriers faced by female surgeons are becoming increasingly evident, many of which are rooted in cultural norms. In Pakistan, a predominantly Muslim-majority, low middle-income country, certain societal expectations add additionally complexity and challenges to existing cultural barriers. METHODS: A cross-sectional survey was administered via e-mail to the full-time faculty and trainees in the Department of Surgery at the Aga Khan University Hospital, Karachi, Pakistan, from July 2019 to November 2019. RESULTS: In total, 100 participants were included in this study, with the majority being residents (55.6%) and consultants (33.3%). 71.9% of female surgeons felt that cultural barriers towards a surgical career existed for their gender, as compared to 25.4% of male surgeons (p < 0.001). 40.6% of females reported having been discouraged by family/close friends from pursuing surgery, as compared to only 9.0% of males (p < 0.001). Moreover, a greater percentage of females surgeons were responsible for household cooking, cleaning and laundry, as compared to male surgeons (all p < 0.001). Lastly, 71.4% of female surgeons felt that having children had hindered their surgical career, as compared to 4.8% of males (p < 0001). CONCLUSION: Our study shows that significant cultural barriers exist for females pursuing a surgical career in our setting. Findings such as these emphasize the need for policy makers to work towards overcoming cultural barriers.

Management of Breast Intraductal Papilloma Diagnosed on Core Needle Biopsy: Excision or Follow-up?

Introduction Management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial. We report our experience of IDPs identified on CNB, our institutional rates of upgradation to atypia/malignancy as well as radiologic/pathologic features that may allow selection for surgery as well as those for safe observation. Methods The study is a retrospective review of patient records from 2012 to 2019, at a tertiary care hospital in Pakistan. Data was analyzed using Statistical Package for Social Sciences (SPSS), version 21.0 (IBM Corp., Armonk, NY). Associations between various patient factors were assessed using Pearson's chi-square test. Results This study included a total of 55 female patients with IDPs, with a mean age of 54.67 ± 15.57 years. On CNB, 69.1% (n = 38) of patients had IDP without atypia while 30.9% (n = 17) had IDP with atypia, with single IDPs being the most common lesions on excisional biopsy. Overall, of all CNB-diagnosed IDPs, only 4/55 (7.3%) demonstrated upgradation (3/4 to DCIS, 1/4 showed atypia) on excisional biopsy, and all these upgraded cases had failed to demonstrate atypia on initial CNB. Conclusion CNB-identified cases of IDPs are rarely upgraded on excision and thus routine excision in all cases may be unnecessary. Appropriate patient selection based on radiology-pathology findings should be done. Those with suspicious findings on imaging as well as those that demonstrate atypia on CNB must be excised.

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.

Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information. Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making. Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories. Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 (P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative. Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.

Comparing Ki-67 and Oncotype-Dx Tests for Predicting Early Breast Cancer Outcomes: A Comprehensive Review The study explored the correlation between the expensive Oncotype-Dx (ODx) test and the more affordable Ki-67 index in predicting outcomes for certain breast cancers. Results from 16 out of 18 studies indicated a significant link between the 2 tests, suggesting Ki-67 could be a cost-effective alternative, especially in low- to middle-income countries.

Breast development and disorders in children and adolescents.

Breast masses are infrequently encountered in pediatric and adolescent populations. Most breast masses in children are benign entities arising from embryological defects which can be managed once breast development is complete. Diagnostic and management dilemmas arise when fibroepithelial lesions of the breast are seen in clinical practice. Differentiation between a fibroadenoma and a phyllodes tumor is important to guide management. Breast cancer in children under 18 years of age is extremely rare and invasive diagnostic testing and aggressive management is only recommended when clinical suspicion of malignancy is very high. Patient and caregiver counseling plays an important role in the management of these diseases. While adult-onset breast diseases have been studied very closely, there is a dearth of literature on pediatric breast anomalies. This review aims to provide a scoping overview of the available literature on benign, fibroepithelial, and malignant lesions of the breast in pediatric and adolescent populations to help guide physicians and surgeons with decision-making regarding the diagnosis and management of pediatric breast diseases.

Ultrasound-Guided Percutaneous Aspiration for the Treatment of Breast Abscess at a Tertiary Care Center in the Developing World.

PURPOSE: Percutaneous ultrasound (US)-guided aspiration is the first line of management for breast abscess. Our study aimed to look at the success of US-guided percutaneous drainage in managing breast abscesses at a tertiary care center and additionally to look for any correlation between US features and failure rate.  Methods: A retrospective review of the radiology database at a tertiary care hospital in Pakistan was done to identify 54 patients through non-probability convenience sampling who underwent a US-guided percutaneous aspiration with laboratory confirmation of abscess. A treatment course was observed for the development of complications or failure of treatment. A chi-square test was performed to correlate US features and patient characteristics with outcomes of treatment (p<0.05). Fisher's exact test was applied to evaluate the success of aspiration in small versus large abscesses, and in lactating versus non-lactating patients.  Results: 75% of all women were successfully able to avoid surgery. Specifically, 80.6% of all lactating women and 66.7 % of non-lactating women with breast abscesses were successfully managed with US-guided percutaneous aspiration. Across a variety of parameters measured, including pathological and etiological factors, as well as features on imaging, no significant association was established between the variables and the failure of the intervention. CONCLUSION: Low morbidity and high patient satisfaction rates make percutaneous aspiration preferable to surgical intervention as a first-line treatment of breast abscess. Early use of antibiotics is recommended as an adjunct to drainage.

Concordance in Breast Cancer Grading by Artificial Intelligence on Whole Slide Images Compares With a Multi-Institutional Cohort of Breast Pathologists.

CONTEXT.­: Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). The advent of digital pathology and artificial intelligence (AI) have increased interest in virtual microscopy using digital whole slide imaging (WSI) more broadly. OBJECTIVE.­: To compare concordance in breast carcinoma grading between AI and a multi-institutional group of breast pathologists using digital WSI. DESIGN.­: We have developed an automated NGS framework using deep learning. Six pathologists and AI independently reviewed a digitally scanned slide from 137 invasive carcinomas and assigned a grade based on scoring of the TF, NP, and MC. RESULTS.­: Interobserver agreement for the pathologists and AI for overall grade was moderate (κ = 0.471). Agreement was good (κ = 0.681), moderate (κ = 0.442), and fair (κ = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good (κ = 0.313-0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF (κ = 0.471 each) followed by NP (κ = 0.342) and was worst for MC (κ = 0.233). There were no observed differences in concordance amongst pathologists alone versus pathologists + AI. CONCLUSIONS.­: Ours is the first study comparing concordance in breast carcinoma grading between a multi-institutional group of pathologists using virtual microscopy to a newly developed WSI AI methodology. Using explainable methods, AI demonstrated similar concordance to pathologists alone.

The Novel Coronavirus (COVID-19) Pandemic and the Response in Low-to-Middle Income Countries.

Purpose of Review: The COVID-19 pandemic has posed an unprecedented challenge to healthcare, particularly in resource-constrained low and middle-income countries (LMICs). We aim to summarize the challenges faced by LMICs in providing breast cancer care during the pandemic and their response during this crisis. Recent Findings: Conversion of oncology centers into COVID-19 isolation centers and lack of LMIC applicable guidelines for breast cancer treatment worsened the challenge for providers. Few LMICs changed their management framework, taking steps like triaging patients, prioritizing care, therapeutic spacing, and a shift to telehealth. Summary: Modified protocols where available have served LMICs well for resource allocation; however, effectiveness of these cannot be determined due to lack of outcomes reporting. This pandemic has underscored the importance of flexibility, prompt intervention, good communication, and reassessment to address unexpected healthcare challenges and has been a learning lesson to help tailor guidelines early in the future.

Impact of duration of antibiotic prophylaxis on rates of surgical site infection (SSI) in patients undergoing mastectomy without immediate reconstruction, comparing a single prophylactic dose versus continued antibiotic prophylaxis postoperatively: a multicentre, double-blinded randomised control trial protocol.

INTRODUCTION: In breast surgeries, prophylactic antibiotics given before the surgical incision as per Joint Commission Surgical Care Improvement Project guidelines have been shown to decrease the rate of postoperative infections. There is, however, no clear consensus on postoperative antibiotic prophylaxis in patients undergoing mastectomy with indwelling drains. This trial protocol proposes to study the difference in rates of surgical site infection (SSI) with or without continuation of postoperative antibiotics in patients undergoing mastectomy without immediate reconstruction and with indwelling drains. METHODS AND ANALYSIS: In this multicentre, double-blinded clinical trial, all patients undergoing mastectomy (without immediate reconstruction) will receive a single prophylactic dose of preoperative antibiotics at induction of anaesthesia and will then get randomised to either continue antibiotic prophylaxis or a placebo postoperatively, for the duration of indwelling drains. The primary and secondary outcomes will be development of an SSI and antibiotic-associated adverse effects, respectively. Data will be collected through a standard questionnaire by wound assessors. Intention-to-treat analysis will be carried out using STATA V.12. For categorical variables, frequencies and percentages will be assessed by χ2 test/Fisher's exact test as appropriate. The quantitative variables will be computed by their mean±SD or median (IQR) and will be assessed by independent t-test/Mann-Whitney test as appropriate. Unadjusted and adjusted relative risk with their 95% CI will be reported using Cox proportional regression. A p value of <0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from each site's Ethical Review Board. The study background and procedure will be explained to the study participants and informed consent will be obtained. Participation in the study is voluntary. All data will be deidentified and kept confidential. The study findings will be published in scientific media and authorship guidelines of International Committee of Medical Journal Editors will be followed. TRIAL REGISTRATION NUMBER: NCT04577846. (patient recruitment).

A multidisciplinary approach to triage patients with breast disease during the COVID-19 pandemic: Experience from a tertiary care center in the developing world.

BACKGROUND: The COVID-19 pandemic has created a need to prioritize care because of limitation of resources. Owing to the heterogeneity and high prevalence of breast cancers, the need to prioritize care in this vulnerable population is essential. While various medical societies have published recommendations to manage breast disease during the COVID-19 pandemic, most are focused on the Western world and do not necessarily address the challenges of a resource-limited setting. AIM: In this article, we describe our institutional approach for prioritizing care for patients presenting with breast disease. METHODS AND RESULTS: The breast disease management guidelines were developed and approved with the expertise of the Multidisciplinary Breast Program Leadership Committee (BPLC) of the Aga Khan University, Karachi, Pakistan. These guidelines were inspired, adapted, and modified keeping in view the needs of our resource-limited healthcare system. These recommendations are also congruent with the ethical guidelines developed by the Center of Biomedical Ethics and Culture (CBEC) at the Sindh Institute of Urology and Transplantation (SIUT), Karachi. Our institutional recommendations outline a framework to triage patients based on the urgency of care, scheduling conflicts, and tumor board recommendations, optimizing healthcare workers' schedules, operating room reallocation, and protocols. We also describe the "Virtual Blended Clinics", a resource-friendly means of conducting virtual clinics and a comprehensive plan for transitioning back into the post-COVID routine. CONCLUSION: Our institutional experience may be considered as a guide during the COVID-19 pandemic, particularly for triaging care in a resource-limited setting; however, these are not meant to be universally applicable, and individual cases must be tailored based on physicians' clinical judgment to provide the best quality care.

Clinicopathologic Features Predictive of Distant Metastasis in Patients Diagnosed With Invasive Breast Cancer.

PURPOSE: National Comprehensive Cancer Network and European Society for Medical Oncology guidelines suggest screening for distant metastasis (M1) in symptomatic patients or those with locally advanced breast cancer. These guidelines are based on studies that often used pathologic staging for analysis. Physician variability in screening for M1 has also resulted in overuse of diagnostic tests. We sought to identify clinicopathologic features at diagnosis that could guide testing for metastatic disease. METHODS: Patients diagnosed with invasive breast cancer between January 2014 and December 2015 were identified from our institutional database. Demographic and clinical variables were collected, including receptor profiles and clinical TNM staging. Rates of upstaging for each clinical stage and rates of concordance of pathologic and clinical staging were analyzed. Univariate analysis and multivariate regression analysis (P < .05) identified predictors of upstaging to stage IV disease. RESULTS: A total of 370 patients met the inclusion criteria. Seventy patients (18.9%) had metastatic disease at diagnosis. The rate of upstaging for stages I, IIA, IIB, and III were 0%, 5.6%, 18.8%, and 36.6%, respectively. Advancing clinical stage, tumor size, and nodal status resulted in a significantly higher rate (P < .001) of upstaging to M1 disease. Age and hormone receptor status were not associated with upstaging to stage IV disease. Clinical stages I-III were concordant with pathologic staging in 65(42.8%) of 152 patients (kappa's index, 0.197; P < .000). CONCLUSION: Advancing clinical stage, tumor size, and nodal status at diagnosis were predictive of upstaging to M1 disease in patients with breast cancer. Distant metastatic workup should be considered in patients with clinical stage IIB disease or higher.