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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., Competing Interests: Authors Mantrala, Mitkari, Joshi, Prabhala, Ramachandra, Kini, and Koka are current employees of Onward Assist., (© 2022 College of American Pathologists.)

Approximately one-quarter of annual global cervical cancer deaths occur in India, possibly due to cultural norms promoting vaccine hesitancy. We sought to determine whether people of Indian ancestry (POIA) in the USA exhibit disproportionately lower human papilloma virus (HPV) vaccination rates than the rest of the US population. We utilised the 2018 National Health Interview Survey to compare HPV vaccine initiation and completion rates between POIA and the general US population and determined factors correlating with HPV vaccine uptake among POIA. Compared to other racial groups, POIA had a significantly lower rate of HPV vaccination (8.18% vs. 12.16%, 14.70%, 16.07% and 12.41%, in White, Black, Other Asian and those of other/mixed ancestry, respectively, P = 0.003), but no statistically significant difference in vaccine series completion among those who received at least one injection (3.17% vs. 4.27%, 3.51%, 4.31% and 5.04%, P = 0.465). Among POIA, younger individuals ( vs. older), single individuals ( vs. married), those with high English proficiency ( vs. low English proficiency), those with health insurance and those born in the USA ( vs. those born outside the USA) were more likely to obtain HPV vaccination ( P = 0.018, P = 0.006, P = 0.029, P = 0.020 and P = 0.019, respectively). Public health measures promoting HPV vaccination among POIA immigrants may substantially improve vaccination rates among this population.

Purpose: Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer., Experimental Design: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind-body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor and serum were collected at baseline and surgery., Results: Forty-nine women were randomized (27 exercise, 22 control). At baseline, mean age was 52.6, body mass index was 30.2 kg/m 2 , and exercise was 49 minutes/week. Exercise participants significantly increased exercise versus controls (203 vs. 23 minutes/week, P < 0.0001). There were no differences in changes of expression of Ki-67, insulin receptor, and cleaved caspase-3 in exercise participants versus controls. KEGG pathway analysis demonstrated significant upregulation of 18 unique pathways between the baseline biopsy and surgical excision in exercise participants and none in control participants ( q < 0.1). Top-ranked pathways included several implicated in immunity and inflammation. Exploratory analysis of tumor immune infiltrates demonstrated a trend toward a decrease in FOXP3 + cells in exercise versus control participants over the intervention period ( P = 0.08)., Conclusions: A window-of-opportunity exercise intervention did not impact proliferation but led to alterations in gene expression in breast tumors, suggesting that exercise may have a direct effect on breast cancer. See related commentary by Koelwyn and Jones, p. 5179 ., (©2019 American Association for Cancer Research.)

Purpose: The age at which women present with breast cancer varies widely among nations, and breast cancer may behave differently in younger women. Differences in clinicopathological characteristics based on age have not been well characterized in Pakistani patients with breast cancer., Methods: We conducted a retrospective review of patients with symptoms of breast cancer presenting to Aga Khan University Hospital (AKUH), a large tertiary care center in Pakistan, between 2001 and 2010; we compared young (≤ 40 years) versus older (> 40 years) patients in terms of their clinicopathological characteristics. We also compared this Pakistani cohort with the US population using data from the National Cancer Database (NCDB)., Results: A total of 1,334 patients with breast cancer presented to our center over the 10-year review period. The median age at diagnosis was 50 years, compared with 60 years for patients in the NCDB. In the AKUH cohort, younger patients were significantly more likely than their older counterparts to present with metastatic disease (13.1% v 10.8%; P < .01). They also were more likely to present with higher-grade tumors (grade 3: 40.1% v 28.3%; P < .001), have triple hormone receptor-negative phenotype (25.4% v 14.1%, P < .001), and have positive axillary lymph node involvement (70.9% v 57.5%; P < .001) compared with older women. Younger and older patients in the AKUH cohort tended to present with higher-stage disease ( P < .001) and were more likely to have triple hormone receptor-negative disease ( P < .001), compared with all patients in the NCDB and with those of Indo-Pakistani origin., Conclusion: Young Pakistani women, similar to their Western counterparts, present with more advanced disease and more aggressive tumor biology than their older counterparts.

Multi-region sequencing is used to detect intratumor genetic heterogeneity (ITGH) in tumors. To assess whether genuine ITGH can be distinguished from sequencing artifacts, we performed whole-exome sequencing (WES) on three anatomically distinct regions of the same tumor with technical replicates to estimate technical noise. Somatic variants were detected with three different WES pipelines and subsequently validated by high-depth amplicon sequencing. The cancer-only pipeline was unreliable, with about 69% of the identified somatic variants being false positive. Even with matched normal DNA for which 82% of the somatic variants were detected reliably, only 36%-78% were found consistently in technical replicate pairs. Overall, 34%-80% of the discordant somatic variants, which could be interpreted as ITGH, were found to constitute technical noise. Excluding mutations affecting low-mappability regions or occurring in certain mutational contexts was found to reduce artifacts, yet detection of subclonal mutations by WES in the absence of orthogonal validation remains unreliable., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue., Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012)., Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

The burden of cancer in low- to middle-income countries is growing and is expected to rise dramatically while resources to manage this disease remain inadequate. All authorities for the management of cancer recommend multidisciplinary care. Educational efforts by international organizations to assist local professionals in caring for their patients tend to have a lasting impact because they empower local professionals and enhance their skills. A multidisciplinary cancer management course was designed by American Society of Clinical Oncology staff and local experts to provide a roadmap for cross-specialty interaction and coordination of care in Zimbabwe. The outcome of the course was measured through feedback obtained from participants and impact on local workforce. The cancer management course was relevant to daily practice and fostered long-lasting partnerships and collaborations. Furthermore, it resulted in a more motivated local workforce and strengthened existing multidisciplinary practices. Cancer care is in a critical state in low- to middle-income countries. Educational efforts and collaborative partnerships may provide a cost-effective strategy with sustainable benefits. A multidisciplinary approach to optimize therapy is desirable. Evaluation of the course impact after a period of 6 months to 1 year is needed to determine the sustainability and impact of such efforts., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Sandra NdarukwaNo relationship to discloseAnna Mary NyakabauTravel, Accommodations, Expenses: Genentech, AstraZeneca, NovartisAnees B. ChagparNo relationship to discloseDavid RabenEmployment: AstraZeneca Consulting or Advisory Role: AstraZeneca Travel, Accommodations, Expenses: AstraZenecaNtokozo NdlovuNo relationship to discloseWebster KadzatsaNo relationship to discloseVanessa J. EatonNo relationship to disclosePaida MafundaNo relationship to discloseEvangelia RazisHonoraria: Roche, AstraZeneca, GlaxoSmithKline, Amgen, Novartis, Zeincro, Merck, Pfizer, Bristol-Myers Squibb Consulting or Advisory Role: Roche, Amgen, AstraZeneca, Janssen-Cilag, Astellas Pharma, Novartis, Bristol-Myers Squibb, Merck, Pfizer, Zeincro Research Funding: Sanofi, Genentech, Novartis, AstraZeneca, Demo Pharmaceutical, Celldex, PAREXEL International Travel, Accommodations, Expenses: Genesis Pharmaceuticals, LEO Pharma, Pfizer, Roche, GlaxoSmithKline, Sanofi, Amgen, Bristol-Myers Squibb, Genekor, Eisai, Merck, Pierre Fabre, Novartis

Purpose Indoor tanning is associated with an increased risk of non-melanoma skin cancers (NMSC), yet little is known about indoor tanning habits of individuals with a history of NMSC. Methods We examined self-reported history of NMSC and tanning bed use among non-Hispanic white respondents in the 2010 National Health Interview Survey (NHIS), a cross-sectional population-based survey designed to be representative of the civilian US population. We computed weighted population estimates and standard errors using the Taylor series linearization method. We then evaluated chi-square tests of independence and conducted weighted logistic regression analyses to evaluate if NMSC status was a predictor of indoor tanning. Results In our analytic sample of 14,400 non-Hispanic white participants, representing 145,287,995 in the population, 543 participants (weighted proportion = 3.45%) self-reported a history of NMSC or "skin cancer type not known." In multivariate analyses, non-melanoma skin cancer survivors were no less likely to use tanning beds in the last 12 months than skin cancer free controls (OR = 0.70, 95% CI: 0.34-1.43, p = 0.33). Conclusions Non-melanoma skin cancer survivors should be educated on their increased risk of recurrence and other skin cancers and in particular the role of indoor tanning in skin tumorigenesis.

The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases., Competing Interests: The authors have no conflicts of interest to declare.

Background: Tumor-infiltrating lymphocyte (TIL) count in breast cancer carries prognostic information and represents a potential predictive marker for emerging immunotherapies. However, the distribution of the lymphocyte subpopulations is not well defined. The goals of this study were to examine intratumor heterogeneity in TIL subpopulation counts in different fields of view (FOV) within each section, in different sections from the same biopsy, and between biopsies from different regions of the same cancer using quantitative immunofluorescence (QIF)., Methods: We used multiplexed QIF to quantify cytokeratin-positive epithelial cells, and CD3-positive, CD8-positive and CD20-positive lymphocytes in tissue sections from multiple biopsies obtained from different areas of 31 surgically resected primary breast carcinomas (93 samples total). Log2-transformed QIF scores or concordance and variance component analyses with linear mixed-effects models were used. Cohen's kappa index [k] of high versus low scores, defined as above and below the median, was used to measure sample similarity between areas., Results: We found a strong positive correlation between CD3 and CD8 levels across all patients (Pearson correlation coefficient [CC] = 0.827). CD3 and CD8 showed a weaker but significant association with CD20 (CC = 0.446 and 0.363, respectively). For each marker, the variation between different FOVs in the same section was higher than the variation between sections or between biopsies of the same cancer. The intraclass correlation coefficients (ICC) were 0.411 for CD3, 0.324 for CD8, and 0.252 for CD20. In component analysis, 66-69 % of the variance was attributable to differences between FOVs in the same section and 30-33 % was due to differences between biopsies from different areas of the same cancer. Section to section differences were negligible. Concordance for low versus high marker status assignment in single biopsies compared to all three biopsies combined yielded k = 0.705 for CD3, k = 0.655 for CD8, and k = 0.603 for CD20., Conclusions: T and B lymphocytes show more heterogeneity across the dimensions of a single section than between different sections or regions of a given breast tumor. This observation suggests that the average lymphocyte score from a single biopsy of a tumor is reasonably representative of the whole cancer.

Introduction: Breast cancer is frequently diagnosed, yet variation remains in terms of practice patterns in presurgical workup. We sought to determine factors associated with this variation., Methods: An anonymous web-based survey was distributed to surgeons regarding their practices. Statistical analyses were conducted using SPSS., Results: A total of 253 surgeons responded to the survey. 17.0% were in academic practice, 37.5% were hospital employed, and 41.5% were in private practice. 53.3% claimed that >50% of their practice was breast related. Surgeons were asked how often they would use various tests in the workup of an otherwise healthy asymptomatic patients, presenting with a non-palpable mammographic abnormality and a core needle biopsy showing invasive breast cancer. 23.5% stated that they always would obtain a breast ultrasound, 17.2% stated that they never would. 12.8% stated that they never order a breast MRI; 4.1% always would. Workup of patients did not vary significantly based on number of years in practice nor practice setting. However, those whose practice was >50% breast were more likely to state that they would always order a breast ultrasound (32.5 vs. 12.9%, p < 0.001), and less likely to state that they would never order a breast MRI (3.4 vs. 25.8%, p < 0.001). However, the proportions of surgeons who would always order a breast MRI were similar in the two groups (3.4 and 3.2%, respectively)., Conclusion: These data highlight the lack of uniformity in the workup of asymptomatic patients presenting with non-palpable breast cancers, pointing to potential areas for improving value by minimizing variability.

Purpose: Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose of this study was to assess the relationship between increased pCR rate and trial-level survival benefit in triple-negative breast cancer (TNBC)., Experimental Design: We used bootstrap resampling from a neoadjuvant trial to simulate trials with different pCR rates. We used estimates from Adjuvant!Online to simulate trial populations with different baseline prognosis and estimated survival improvements associated with changes in pCR rate., Results: Assuming that survival is similar for patients with pCR regardless of treatment arm, a linear relationship exists between increasing pCR rate and increasing recurrence-free survival (RFS). The slope is equal to the difference in survival between those with pCR and residual disease, which in turn is influenced by (i) the baseline prognosis of the trial population, (ii) interactions between prognostic variables and pCR, and (iii) the efficacy of the postneoadjuvant therapies. For example, if the pCR rates are 30% and 60% (OR = 3.5) and the 10-year RFS of the control arm is 0.74, the trial would require 3,550 patients per arm, whereas if the RFS is 0.54, the trial would require only 425 patients per arm to detect significant survival benefit., Conclusions: We provide a framework for understanding the relationship between pCR and overall survival benefit that can help inform the design of neoadjuvant trials aiming to demonstrate improved survival from a regimen that results in higher pCR rate., (©2015 American Association for Cancer Research.)

Background: Newer approaches to mammography, including digital image acquisition and computer-aided detection (CAD), and adjunct imaging (e.g., magnetic resonance imaging [MRI]) have diffused into clinical practice. The impact of these technologies on screening-related cost and outcomes remains undefined, particularly among older women., Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we constructed two cohorts of women without a history of breast cancer and followed each cohort for 2 years. We compared the use and cost of screening mammography including digital mammography and CAD, adjunct procedures including breast ultrasound, MRI, and biopsy between the period of 2001 and 2002 and the period of 2008 and 2009 using χ(2) and t test. We also assessed the change in breast cancer stage and incidence rates using χ(2) and Poisson regression. All statistical tests were two-sided., Results: There were 137150 women (mean age = 76.0 years) in the early cohort (2001-2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008-2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P < .001). CAD use increased from 3.2% to 33.1% (P < .001). Average screening-related cost per capita increased from $76 to $112 (P < .001), with annual national fee-for-service Medicare spending increasing from $666 million to $962 million. There was no statistically significant change in detection rates of early-stage tumors (2.45 vs 2.57 per 1000 person-years; P = .41)., Conclusions: Although breast cancer screening-related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about the cost-effectiveness of external beam radiation therapy (EBRT) or newer radiation therapy (RT) modalities such as intensity modulated radiation (IMRT) or brachytherapy among older women with favorable-risk breast cancer., Methods: Using a Markov model, we estimated the cost-effectiveness of no RT, EBRT, and IMRT over 10 years. We estimated the incremental cost-effectiveness ratio (ICER) of IMRT compared with EBRT under different scenarios to determine the necessary improvement in effectiveness for newer modalities to be cost-effective. We estimated model inputs using women in the Surveillance, Epidemiology, and End Results-Medicare database fulfilling the Cancer and Leukemia Group B C9343 trial criteria., Results: The incremental cost of EBRT compared with no RT was $9500 with an ICER of $44600 per quality-adjusted life year (QALY) gained. The ICERs increased with age, ranging from $38300 (age 70-74 years) to $55800 (age 80 to 94 years) per QALY. The ICERs increased to more than $63800 per QALY for women aged 70 to 74 years with an expected 10-year survival of 25%. Reduction in local recurrence by IMRT compared with EBRT did not have a substantial impact on the ICER of IMRT. IMRT would have to increase the utility of baseline state by 20% to be cost-effective (<$100000 per QALY)., Conclusions: EBRT is cost-effective for older women with favorable risk breast cancer, but substantially less cost-effective for women with shorter expected survival. Newer RT modalities would have to be substantially more effective than existing therapies in improving quality of life to be cost-effective.

Background. Prior studies have shown earlier recurrence and decreased survival in patients with head and neck cancer who smoked while undergoing radiation therapy. The purpose of the current study was to determine whether smoking status at the time of partial mastectomy and radiation therapy for breast cancer affected recurrence or survival. Method. A single institution retrospective chart review was performed to correlate smoking status with patient demographics, tumor characteristics, and outcomes for patients undergoing partial mastectomy and radiation therapy. Results. There were 624 patients who underwent breast conservation surgery between 2002 and 2010 for whom smoking history and follow-up data were available. Smoking status was associated with race, patient age, and tumor stage, but not with grade, histology, or receptor status. African American women were more likely to be current smokers (22% versus 7%, P < 0.001). With a mean follow-up of 45 months, recurrence was significantly higher in current smokers compared to former or never smokers (P = 0.039). In a multivariate model adjusted for race and tumor stage, recurrence among current smokers was 6.7 times that of never smokers (CI 2.0-22.4). Conclusions. Although the numbers are small, this study suggests that smoking may negatively influence recurrence rates after partial mastectomy and radiation therapy. A larger study is needed to confirm these observations.

Objective: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma., Summary Background Data: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood., Methods: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)., Results: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001)., Conclusions: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Objective: To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy., Background: Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting., Methods: We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic., Results: Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of +/-1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24-0.35) indicated poor agreement between clinical and pathologic measurements., Conclusion: Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy.