Neighborhood characteristics and breast tumor methylation: using epigenomics to explore cancer outcome disparities.

BACKGROUND: Social exposures may drive epigenetic alterations that affect racial disparities in breast cancer outcomes. This study examined the association between neighborhood-level factors and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. METHODS: Genome-wide DNA methylation was measured using the EPIC array in the tumor tissue of 96 women. Linear regression models were used to examine the association between nine neighborhood-level factors and methylation, regressing ß values for each cytosine-phosphate guanine dinucleotide (CpG) site on neighborhood-level factors while adjusting for covariates. Neighborhood data were obtained from the Opportunity Atlas. We used a false discovery rate (FDR) threshold < 0.05, and for CpGs below this threshold, we examined interactions with race. We employed multivariable Cox proportional-hazards models to estimate whether aberrant methylation was associated with all-cause mortality. RESULTS: 26 of the CpG sites were associated with job density or college education (FDR < 0.05). Further exploration of these 26 CpG sites revealed no interactions by race, but a single probe in TMEM204 was associated with all-cause mortality. CONCLUSION: We identified novel associations between neighborhood-level factors and the breast tumor DNA methylome. Our data are the first to show that dysregulation in neighborhood associated CpG sites may be associated with all-cause mortality. Neighborhood-level factors may contribute to differential tumor methylation in genes related to tumor progression and metastasis. This contributes to the increasing body of evidence that area-level factors (such as neighborhood characteristics) may play an important role in cancer disparities through modulation of the breast tumor epigenome.

Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality.

BACKGROUND: Black women are more likely to die of breast cancer than White women. This study evaluated the contribution of time to primary surgical management and surgical facility characteristics to racial disparities in breast cancer mortality among both Black and White women. METHODS: The study identified 2224 Black and 3787 White women with a diagnosis with stages I to III breast cancer (2010-2014). Outcomes included time to surgical treatment (> 30 days from diagnosis) and breast cancer mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) associating surgical facility characteristics with surgical delay were computed, and Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% CIs associating delay and facility characteristics with breast cancer mortality. RESULTS: Black women were two times more likely to have a surgical delay (OR, 2.15; 95% CI, 1.92-2.41) than White women. Racial disparity in surgical delay was least pronounced among women treated at a non-profit facility (OR, 1.95; 95% CI, 1.70-2.25). The estimated mortality rate for Black women was two times that for White women (HR, 2.00; 95% CI, 1.83-2.46). Racial disparities in breast cancer mortality were least pronounced among women who experienced no surgical delay (HR, 1.81; 95% CI, 1.28-2.56), received surgery at a government facility (HR, 1.31; 95% CI, 0.76-2.27), or underwent treatment at a Commission on Cancer-accredited facility (HR, 1.82; 95% CI, 1.38-2.40). CONCLUSIONS: Black women were more likely to experience a surgical delay and breast cancer death. Persistent racial disparities in breast cancer mortality were observed across facility characteristics except for government facilities.

Screening for Individuals at Risk for Hereditary Breast and Ovarian Cancer: A Statewide Initiative, Georgia, 2012-2020.

Georgia implemented a statewide family history screening program for hereditary breast and ovarian cancer. From November 2012 through December 2020, 29 090 individuals were screened, 16 679 of whom (57.3%) self-identified as a racial/ethnic minority. Of the 4% (1172/29 090) of individuals who screened as high risk, more than half underwent genetic consultation (793/1172; 67.7%) and testing (416/589; 70.6%). Compared with White women, Black and Hispanic women had higher uptake rates of genetic consultation. Public health settings serving racial minorities are well suited to address disparities in genetic service access. (Am J Public Health. 2022;112(9):1249-1252. https://doi.org/10.2105/AJPH.2022.306932).

Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?

PURPOSE: As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. METHODS: Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used-regressing methylation ß value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) < 0.05. In the top 20 CpG sites, we explored the interactions with race and estrogen receptor (ER) status. We used multivariable Cox-proportional hazard models to examine whether methylation in the top 20 sites was associated with all-cause mortality. RESULTS: While none of the CpG sites passed the FDR threshold for significance, among the top 20 CpG sites, we observed interactions with race (TOMM20) and ER status (PSMB1, QSOX1 and PHF1). The same CpG sites in TOMM20, PSMB1, and QSOX1 were associated with all-cause mortality. CONCLUSIONS: We identified novel interactions between obesity-associated methylation and both race and ER status in genes that have been associated with tumor regulation. Our data suggest that dysregulation in two sites may associate with all-cause mortality.

An infrared 3D scanning device as a novel limb volume measurement tool in breast cancer patients.

BACKGROUND: Lymphedema is a common complication of breast cancer treatment that affects one in five breast cancer survivors, yet there is no reliable method to detect lymphedema in the subclinical range. The objective of this study was to determine the feasibility and reliability of using an infrared 3D scanning device (ISD) as a peri-operative limb volume measurement tool. METHODS: Fifteen patients were analyzed based on inclusion criteria. Peri-operative measurements were obtained using tape measure and an ISD. Volumes were calculated using a standard algorithm for tape measure and a custom algorithm for ISD measurements. Linear regression models were used to assess ISD and tape measurement volume and circumference correlation. One-way ANOVA was used to compare change in percent difference at set time points post-operatively (2-3 weeks, 4-6 weeks, and 7-12 weeks) for both ISD and tape measure. t tests for unequal variances with the Bonferroni correction were performed among these groups. RESULTS: There is a positive linear correlation (R2 = 0.8518) between absolute volume measurements by the ISD and tape measure. Analyses over 2-10 weeks post-operatively showed that the ISD was able to detect volume changes in both the unaffected and the affected arm. Furthermore, the affected arm tended to have a greater increase in volume in the majority of patients, indicating these patients could be at risk for lymphedema. CONCLUSIONS: Technology utilizing infrared 3D scanners can reliably measure limb volume pre- and post-treatment similarly to tape measure in a small sample of patients. Further research using 3D scanning technology with a longer follow up is warranted.

Georgia Primary Care Providers' Knowledge of Hereditary Breast and Ovarian Cancer Syndrome.

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited condition associated with mutations in the BRCA1 or BRCA2 (BRCA) genes. Identification of individuals with HBOC requires that primary care providers understand the genetic principles required to appropriately collect family history and refer individuals for genetic evaluation. A survey was developed and administered to primary care providers in Georgia to assess their existing knowledge of HBOC and direct targeted educational efforts.We found that Georgia providers demonstrate some knowledge of basic genetic principles but were unable to consistently identify individuals at risk for HBOC. Knowledge deficits included lack of understanding of inheritance patterns and failure to recognize the significance of ovarian cancer history. Strategies for improving identification of patients with HBOC include increasing provider knowledge and integrating HBOC risk assessment tools into practice. Identification of individuals at risk is the critical first step in the process of reducing incidence of breast and ovarian cancer associated with BRCA mutations.

Addressing disparities in cancer clinical trials: a roadmap to more equitable accrual.

The Georgia Center for Oncology Research and Education (Georgia CORE) and the Georgia Society of Clinical Oncology (GASCO) held a one-day summit exploring opportunities and evidence-based interventions to address disparities in cancer clinical trials. The purpose of the summit was to identify clear and concise recommendations aimed at decreasing clinical trial accrual disparities in Georgia for rural and minority populations. The summit included expert presentations, panel discussions with leaders from provider organizations throughout Georgia, and breakout sessions to allow participants to critically discuss the information presented. Over 120 participants attended the summit. Recognizing the need for evidence-based interventions to improve clinical trial accrual among rural Georgians and persons of color, summit participants identified four key areas of focus that included: improving clinical trial design, providing navigation for all, enhancing public education and awareness of cancer clinical trials, and identifying potential policy and other opportunities. A comprehensive list of takeaways and action plans was developed in the four key areas of focus with the expectation that implementation of the strategies that emerged from the summit will enhance cancer clinical trial accrual for all Georgians.

Evaluation of the Avon Foundation community education and outreach initiative Community Patient Navigation Program.

INTRODUCTION: Black women in the United States experience disproportionate breast cancer mortality. Culturally appropriate community education on the importance of breast health coupled with the availability of free or low-cost mammography screening services may help improve the use of mammography screening services among Black women. The Avon Foundation Community Patient Navigation Program seeks to fill this need. The current study presents a process and outcome evaluation of this program. METHOD: Trained and uniformed community patient navigators (PNs) host breast health education events where they recruit community members to complete a mammography interest form. Participants are referred to a nurse practitioner who determines eligibility for a free or low-cost mammogram. The community PN delivers telephone follow-up to encourage participants to make and keep their mammogram appointments. RESULTS: Over a 15-month period, 22 community PNs hosted 207 breast health events, which included 9,601 attendees. Three hundred and four participants completed a mammography interest form, and 21% of these individuals received mammograms at the collaborating health facility. Participants who reported breast symptoms were twice as likely to get a mammogram as those who did not report symptoms. DISCUSSION: Community patient navigation may be a useful resource for encouraging mammography screening among underserved women.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing ß values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality. Results: Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (ß=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock. Conclusion: We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.

21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. METHODS: Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role.

Metropolitan area racial residential segregation, neighborhood racial composition, and breast cancer mortality.

PURPOSE: There are significant relationships between racial residential segregation (RRS) and a range of health outcomes, including cancer-related outcomes. This study explores the contribution of metropolitan area RRS, census tract racial composition and breast cancer and all-cause mortality among black and white breast cancer patients. METHODS: This study has three units of analysis: women diagnosed with breast cancer (n = 22,088), census tracts where they lived at diagnosis (n = 1,373), and the metropolitan statistical area (MSA)/micropolitan statistical area (MiSA) where they lived at diagnosis (n = 37). Neighborhood racial composition was measured as the percent of black residents in the census tract. Metropolitan area RRS was measured using the Information Theory Index. Multilevel Cox proportional hazards models examined the association of metropolitan area RRS and census tract racial composition with breast cancer and all-cause mortality. Survival analysis explored and compared the risk of death in women exposed to environments where a higher and lower proportion of residents were black. RESULTS: Breast cancer mortality disparities were largest in racially mixed tracts located in high MSA/MiSA segregation areas (RR = 2.06, 95 % CI 1.70, 2.50). For black but not white women, as MSA/MiSA RRS increased, there was an increased risk for breast cancer mortality (HR = 2.20, 95 % CI 1.09, 4.45). For all-cause mortality, MSA/MiSA segregation was not a significant predictor, but increasing tract percent black was associated with increased risk for white but not black women (HR 1.29, 95 % CI 1.05, 1.58). CONCLUSIONS: Racial residential segregation may influence health for blacks and whites differently. Pathways through which RRS patterns impact health should be further explored.

Locoregional recurrence after mastectomy with immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction.

BACKGROUND: The locoregional recurrence (LRR) rate after mastectomy is reported to be similar with immediate reconstruction. We aimed to identify characteristics of LRR after transverse rectus abdominis myocutaneous (TRAM) reconstruction. METHODS: We retrospectively reviewed patients undergoing immediate TRAM reconstruction for breast cancer who were diagnosed with LRR. RESULTS: We identified 18 LRR (4.6 %) in 18 of 390 patients who underwent immediate TRAM reconstructions for breast cancer from 1998 to 2008. The median follow-up was 69.2 months. The mean age at time of mastectomy was 49.5 years. All LRR were detected by physical examination. The LRR occurred in the TRAM subcutaneous tissue (n = 9), five in the ipsilateral axillary lymph node and four in the supraclavicular lymph node. Of the 18 patients who developed LRR, 14 (77.7 %) presented with stage 0-1-2 and 4 (22.2 %) with stage 3 disease at the time of the original mastectomy. The average time for a LRR to present was 35.8 months after initial mastectomy and reconstruction. For patients who initially presented with stage 3 disease, the average time to LRR was shorter (22.9 months). Nine patients (50.0 %) were found to have metastatic disease at the time of the LRR, and 6 (33.3 %) died of disease. CONCLUSIONS: All TRAM LRR were detected by routine physical examination by the patient or the surgeon. Our findings suggest that routine history and clinical breast examination of the breast reconstructed with a TRAM flap along with patient self-awareness are reliable in the diagnosis of LRR.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a series of 24 patients.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases had been reported since its initial description in 1986 by Vuitch et al. Our 24 cases represent one of the largest series to be reported from a single institution. We retrospectively reviewed data from 2004 to 2010 of patients diagnosed with PASH by surgical excision or image-guided biopsy. All pathological specimens were reviewed by a single pathologist. The samples were stained for estrogen and progesterone receptors (ER and PR), CD34, and the lymphatic marker D2-40. All but one of 24 (96%) patients presented with breast masses either on imaging or clinically. Fourteen of the 24 patients (58%) were diagnosed on surgical excision, 10 (42%) diagnosed with core needle biopsy, and five (20%) were diagnosed using both techniques. The tumors ranged in size from 0.3 cm to 7.0 cm. All women except two were premenopausal or perimenopausal at diagnosis. Nineteen samples were available for hormonal receptor staining and of these 18 of 19 (95%) were ER or PR positive. PASH was diagnosed in two men, a transgender male on hormones and the other with gynecomastia. The patients' ages ranged from 18 to 86 years old. In addition to PASH other benign histopathological findings include stromal fibrosis and atypical ductal or lobular hyperplasia. Imaging revealed no distinguishing feature for PASH with benign histology. One patient had synchronous ductal carcinoma in-situ (DCIS). Patients were treated with local excision or observation. This study suggests that PASH is primarily a diagnosis of premenopausal and perimenopausal women. Our series supports a hormonal basis for its development due to the positive staining for hormonal receptors. Management is conservative surgery for larger masses with careful observation being an option in patients not at high risk for breast cancer.

Racial Disparities in Breast Cancer Outcomes in the Metropolitan Atlanta Area: New Insights and Approaches for Health Equity.

BACKGROUND: Racial disparities in breast cancer (BC) outcomes persist where non-Hispanic black (NHB) women are more likely to die from BC than non-Hispanic white (NHW) women, and the extent of this disparity varies geographically. We evaluated tumor, treatment, and patient characteristics that contribute to racial differences in BC mortality in Atlanta, Georgia, where the disparity was previously characterized as especially large. METHODS: We identified 4943 NHW and 3580 NHB women in the Georgia Cancer Registry with stage I-IV BC diagnoses in Atlanta (2010-2014). We used Cox proportional hazard regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing NHB vs NHW BC mortality by tumor, treatment, and patient characteristics on the additive and multiplicative scales. We additionally estimated the mediating effects of these characteristics on the association between race and BC mortality. RESULTS: At diagnosis, NHB women were younger-with higher stage, node-positive, and triple-negative tumors relative to NHW women. In age-adjusted models, NHB women with luminal A disease had a 2.43 times higher rate of BC mortality compared to their NHW counterparts (95% CI = 1.99 to 2.97). High socioeconomic status (SES) NHB women had more than twice the mortality rates than their white counterparts (HR = 2.67, 95% CI = 1.65 to 4.33). Racial disparities among women without insurance, in the lowest SES index, or diagnosed with triple-negative BC were less pronounced. CONCLUSIONS: In Atlanta, the largest racial disparities are observed in luminal tumors and most pronounced among women of high SES. More research is needed to understand drivers of disparities within these treatable features.

Phyllodes tumors in African American women.

BACKGROUND: Phyllodes is a rare tumor accounting for less than 1% of all breast neoplasms. Studies defining clinical predictors of malignant phyllodes (MP) are rare and inconsistent. Furthermore, MP occurrence in African American (AA) women has never been analyzed. This study will delineate clinical and pathologic features in AA patients that may reasonably predict the probability of malignancy. METHODS: A retrospective study of clinical records was carried out for 50 AA patients diagnosed with phyllodes tumors (PT) and treated between 1982 and 2012. Patients' charts were analyzed regarding demographics, pathology findings, and treatment. RESULTS: The diagnosis of benign disease was made in 40 (78%), borderline in 3 (6%), and malignancy in 7 (14%) patients; however, 1 patient (2%) had mixed phyllodes with ductal carcinoma in situ. The mean age was significantly different for patients with benign disease (33 years) compared with those with malignancy (54 years; P < .001). The average tumor size was twice as large (11.8 vs 4.1 cm; P = .029) and mitoses were higher with 50% of MPs having greater than 5 per 10 high power fields. Although rare, nodal metastasis, ulceration, and multicentric disease occurred only in MP. CONCLUSIONS: Among AA patients with phyllodes tumors, those with malignant tumors were older and had larger tumors and higher mitotic indices than those with benign disease. AA patients also displayed some of the more rare features of advanced disease and presented with malignancy near the highest reported frequency.

Screening Mammography in a Public Hospital Serving Predominantly African-American Women: A Stage-Survival-Cost Model.

BACKGROUND: Ethnic and socioeconomic disparities pervade breast cancer patterns and outcomes. Mammography guidelines reflect the difficulty in optimizing mortality reduction and cost-effectiveness, with controversy still surrounding the 2009 U.S. Preventive Services Task Force (USPSTF) recommendations. This study simulates USPSTF and American Cancer Society (ACS) guidelines' effects on stage, survival, and cost of treatment in an urban public hospital. METHODS: Charts of 274 women diagnosed with stage I, II, or III breast cancer (2008-2010) were reviewed. Published tumor doubling times were used to predict size at diagnosis under simulated screening guidelines. Stage distributions under ACS and USPSTF guidelines were compared with those observed. Cohort survival for observed and hypothetical scenarios was estimated using national statistics. Treatment costs by stage, calculated from Georgia Medicaid claims data, were similarly applied. RESULTS: Mean age at diagnosis was 56 years. African Americans predominated (82.5%), with 96% publically insured or uninsured. Simulated stages at diagnosis significantly favored ACS guidelines (43.1% stage 1/38.3% stage 2/9.9% stage 3 vs. USPSTF 23.0%/53.3 %/15.0%), as did 5-year survival and cost of treatment relative to both observed and USPSTF-predicted schema (p<.0001). Following USPSTF guidelines predicted lower survival and additional costs. CONCLUSIONS: Following ACS guidelines seems to lead to earlier diagnosis for low-income African-American women and increase 5-year survival with lower overall and breast-specific costs. The data suggest that adjusting screening practices for lower socioeconomic status, ethnic minority women may prove essential in addressing cancer disparities.

Treatment patterns among medicaid-eligible women with breast cancer in georgia: are patterns different under the breast and cervical cancer prevention and treatment act?

PURPOSE: To investigate breast cancer treatment of patients enrolled under traditional Medicaid categories versus those in the Breast and Cervical Cancer Prevention and Treatment Act (BCCPTA) in Georgia. METHODS: Georgia Comprehensive Cancer Registry linked to Medicaid enrollment files were used to identify 2,048 enrollees with a primary cancer of the breast, of whom 1,046 were enrolled in BCCPTA, 674 were disabled, and 328 were in other Medicaid eligibility groups. Logistic regressions were used to estimate factors associated with the odds of receiving lumpectomy, mastectomy, or other surgery in addition to any drug regimen (hormonal or chemotherapy) and radiation. RESULTS: Women in BCCPTA were more likely to receive any treatment (odds ratio [OR] = 4.71; 95% CI, 2.48 to 8.96), any drug regimen (OR = 3.58; 95% CI, 2.32 to 5.51), any radiation (OR = 1.61; 95% CI, 1.15to 2.24), and any definitive surgery (OR = 2.52; 95% CI, 1.74 to 3.66) than the "other" eligibility group after controlling for covariates. There were no significant differences by eligibility group in the receipt of a lumpectomy versus a mastectomy. However, women in BCCPTA were more likely to receive more adjuvant follow-up after a mastectomy. CONCLUSION: The BCCPTA program in Georgia appears to create a quicker pathway for low-income, previously uninsured women with breast cancer to access services and, in turn, receive more treatment than women enrolled in the other, more traditional Medicaid eligibility groups. Yet the overall rate of adjuvant therapy, whether radiation, hormonal, or chemotherapy, appears to fall short of national criteria. This deserves attention in Georgia and, most likely, Medicaid programs in other states as well.

Breath analysis by mass spectrometry: a new tool for breast cancer detection?

Breath analysis has received attention as a noninvasive diagnostic tool with increasing research into its potential usefulness. We are investigating the utility of the analysis of breath volatile organic compounds (VOCs) as an effective modality for breast cancer (BC) detection and monitoring by collecting breath samples with a simple portable device to determine whether BC patients have breath VOCs distinct from those in healthy volunteers. We prospectively enrolled 20 healthy volunteers and 20 newly diagnosed stage II-IV BC patients. The study subjects deeply exhaled into a commercially available Teflon/valved breath sampler equipped with a rapid passive diffusive sampler five times at 5-minute intervals trapping alveolar breath VOCs. The exhaled breath samples were analyzed by thermal desorption/gas chromatography/mass spectrometry monitoring 383 VOCs in the breath of both populations. Our results indicate that aggregate low-dimensional summaries and compound quantities result in specific patterns that can confirm BC. We found a definite clustering of the presence of BC from cancer-free points. Overall sensitivity was 72 per cent and specificity was 64 per cent resulting in a correct classification rate of approximately 77 per cent. Our data show promising evidence that BC patients can be differentiated from healthy volunteers through distinct breath VOCs.