A Prospective Trial of Single-Fraction Radiation to the Tumor Bed with a Novel Breast-Specific Stereotactic Radiation Therapy Device: The GammaPod.

Purpose: Radiation therapy for early-stage breast cancer is typically delivered in a hypofractionated regimen to the whole breast followed by a tumor bed boost. This results in a treatment course of approximately 4 weeks. In this study, the tumor bed boost was delivered in a single fraction as part of a safety and feasibility study for FDA clearance of the device. Methods and Materials: Eligible women with early-stage breast cancer underwent lumpectomy followed by radiation therapy. Patients underwent breast immobilization using a system specific to the GammaPod followed by CT simulation, boost treatment planning, and boost treatment delivery all in a single treatment day. Patients then started whole-breast radiation therapy within 1 week of the boost treatment. Patients and treatments were assessed for safety and feasibility. Acute toxicities were recorded. Results: A single-fraction boost of 8 Gy was delivered to the tumor bed before a course of whole-breast radiation. The GammaPod treatment was successfully delivered to 14 of 17 enrolled patients. Acute toxicities from all radiation therapy, inclusive of the boost and whole-breast radiation, were limited to grade 1 events. Conclusions: The GammaPod device successfully delivered a single-fraction boost treatment to the tumor bed with no change in expected acute toxicities. The results of this study led to FDA clearance of the device through the Investigational Device Exemption process at the FDA. The GammaPod is in clinical use at 4e institutions nationally and internationally, with additional sites pending in 2023.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

PURPOSE: Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. METHODS: We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. RESULTS: 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. CONCLUSION: To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer (BCa) tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. SUMMARY BACKGROUND DATA: ND is associated with shorter BCa recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity (NF-kB, AP-1), sympathetic nervous system (SNS) activity (CREB), and protective cellular responses (IRF, STAT). To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB, AP-1, down-regulated IRF, STAT) and SNS activation (up-regulated CREB). Increasing subjective ND (e.g., threat to safety), was associated with up-regulated NF-kB and CREB and down-regulated IRF. These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Prevalence, clinical characteristics, and management of silicone lymphadenopathy: A systematic review of the literature.

INTRODUCTION: Implant-based breast augmentations and reconstructions are one of the most common surgical procedures performed by plastic surgeons in the United States, which has rapidly increased in popularity since the 2000s. Silicone lymphadenopathy (SL) is a complication of breast implants that involves migration of silicone to nearby soft tissue/lymph nodes. Data on its clinical features and management is scarce. METHODS: SL-related search terms were used to find articles in 3 databases. Of 598 articles, 101 studies met the inclusion criteria. Demographics, clinical presentation, workup, and management data were analyzed. RESULTS: Of 279 cases of SL and 107 with information on initial diagnosis, 35 (33%) were incidental. The most common symptom was painless lymphadenopathy, followed by painful lymphadenopathy. 251 (95%) and 13 (5%) patients had silicone and saline implants, respectively. 149 (68%) patients had implant rupture. Axillary lymphadenopathy was the most affected region (136 cases, 72%), followed by internal mammary (40 cases, 21%), cervical/supraclavicular (36 cases, 19%), and mediastinal (24 cases, 13%) regions. 25% of patients underwent fine-needle aspiration, 12% core needle biopsy, and 59% excisional biopsy. 32% of cases underwent explantation and/or implant exchange. The most common indication for surgery was implant rupture. Histology showed multinucleated giant cells, large histiocytes, and silicone accumulation. CONCLUSIONS: SL is a complication associated with breast implants. The majority of patients are asymptomatic, and most cases are managed conservatively. Minority need a biopsy and surgical interventions due to abnormal imaging, persistent symptoms, and/or implant rupture. Workup and management should be tailored to the patient.

Unmet Social Needs and Breast Cancer Screening Utilization and Stage at Presentation.

Importance: Unmet social needs in local populations may hinder the development of targeted cancer control interventions aimed at improving screening utilization and early-stage breast cancer diagnosis to ultimately improve breast cancer survival disparities. Objective: To evaluate if (1) city-funded screening mammography is associated with utilization of screening mammography, (2) unmet social needs are associated with utilization of screening mammography, and (3) unmet social needs are associated with later-stage disease at diagnosis. Design, Setting, and Participants: This cohort study included patients with stages I-IV invasive ductal or lobular carcinoma treated at an academic medical center (including both an underserved safety-net hospital [SNH] and a National Cancer Institute-designated academic cancer center [ACC]) from 2020 to 2023. Eligible patients were aged 18 years or older and able to consent. Data were analyzed between July 2023 and September 2023. Exposure: The Health Leads Social Needs Screening Toolkit, a screening tool that gathers information on the most common social need domains affecting patient health. Main Outcomes and Measures: Univariable and multivariable logistic regression was utilized to evaluate the following primary outcomes: (1) routine screening mammography and (2) American Joint Committee on Cancer 8th edition clinical stage at presentation. Results: Of the 322 women who completed the Health Leads Social Needs Screening Toolkit, 201 (62%) self-identified as Hispanic, 63 (19%) as non-Hispanic Black, and 63 (19%) as non-Hispanic White. Two hundred fifty-five (76%) patients with access to city-funded screening mammography completed a screening mammogram. Patients who presented to the SNH were more likely to present with late-stage disease compared with early-stage disease (15 of 48 [31%] vs 50 of 274 [18%]; P = .04). On multivariable logistic regression, not completing a screening mammography was associated with having an increasing number of unmet social needs (OR, 0.74; 95% CI, 0.55-0.99; P = .047) and an increasing age at diagnosis (OR, 0.92; 95% CI, 0.89-0.96; P < .001). Moreover, increasing unmet social needs was significantly associated with late-stage diagnosis above and beyond screening mammography (OR, 1.38; 95% CI, 1.01-1.89; P = .04). Conclusions and Relevance: In this cohort study, access to screening mammography did not translate to utilization of screening mammography, increasing unmet social needs were significantly associated with lower rates of screening mammography, and those with increasing unmet social needs were more likely to present with late-stage disease. This association transcended recruitment site (SNH vs ACC), indicating that patients in either hospital setting may benefit from unmet social needs screening to overcome access to care barriers associated with late-stage disease at diagnosis.

A Multi-institutional Analysis of Factors Influencing the Rate of Positive MRI Biopsy Among Women with Early-Stage Breast Cancer.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for early-stage breast cancer (ESBC) is increasing, but its utility in detecting additional malignancy is unclear and delays surgical management (Jatoi and Benson in Future Oncol 9:347-353, 2013. https://doi.org/10.2217/fon.12.186 , Bleicher et al. J Am Coll Surg 209:180-187, 2009. https://doi.org/10.1016/j.jamcollsurg.2009.04.010 , Borowsky et al. J Surg Res 280:114-122, 2022. https://doi.org/10.1016/j.jss.2022.06.066 ). The present study sought to identify ESBC patients most likely to benefit from preoperative MRI by assessing the positive predictive values (PPVs) of ipsilateral and contralateral biopsies. METHODS: A retrospective cohort study included patients with cTis-T2N0-N1 breast cancer from two institutions during 2016-2021. A "positive" biopsy result was defined as additional cancer (PositiveCancer) or cancer with histology often excised (PositiveSurg). The PPV of MRI biopsies was calculated with respect to age, family history, breast density, and histology. Uni- and multivariate logistic regression determined whether combinations of age younger than 50 years, dense breasts, family history, and pure ductal carcinoma in situ (DCIS) histology led to higher biopsy yield. RESULTS: Of the included patients, 447 received preoperative MRI and 131 underwent 149 MRI-guided biopsies (96 ipsilateral, 53 contralateral [18 bilateral]). PositiveCancer for ipsilateral biopsy was 54.2%, and PositiveCancer for contralateral biopsy was 17.0%. PositiveSurg for ipsilateral biopsy was 62.5%, and PositiveSurg for contralateral biopsy was 24.5%. Among the contralateral MRI biopsies, patients younger than 50 years were less likely to have PositiveSurg (odds ratio, 0.02; 95% confidence interval, 0.00-0.84; p = 0.041). The combinations of age, density, family history, and histology did not lead to a higher biopsy yield. CONCLUSION: Historically accepted factors for recommending preoperative MRI did not appear to confer a higher MRI biopsy yield. To prevent delays to surgical management, MRI should be carefully selected for individual patients most likely to benefit from additional imaging.

Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population.

BACKGROUND: Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS: Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS: Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION: We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.

Post-Mastectomy Implant Complications in the Hispanic Breast Cancer Patient Population.

BACKGROUND/AIM: The purpose was to analyze the impact of post-mastectomy radiation therapy (PMRT) on implant-based breast reconstruction (IBR) in self-identified Hispanic patients compared to non-Hispanic counterparts. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent IBR between January 1, 2017 and December 31, 2019 at a single hospital system. Patients were cisgender women, assigned female at birth, 18 years or older, and underwent mastectomy with immediate IBR +/- PMRT. We compared characteristics between Hispanic and non-Hispanic patients, assessing capsular contracture and implant loss rates. Multivariable analysis was performed to identify factors associated with complications. RESULTS: A total of 317 patients underwent mastectomy and reconstruction. Of these patients, 302 underwent a total of 467 mastectomies with IBR, and these 467 procedures were included in the analysis of complications. Complications occurred in 175 breasts (37.5%), regardless of PMRT. Seventy-two of the 302 patients (24%) received PMRT to one breast. The overall rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively). Following PMRT the rate of any complication was 71% in Hispanic women and 53% in non-Hispanic women. CONCLUSION: Our study illuminates a trend towards higher complication rates after PMRT in Hispanic versus non-Hispanic patients. Further studies are needed to understand why Hispanic patients may have more side effects from radiation therapy.

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

Omission of Completion Lymph Node Dissection in Sentinel Node Biopsy Positive Head and Neck Cutaneous Melanoma Patients.

BACKGROUND: Recent studies evaluating patients with a positive sentinel lymph node biopsy (SLNB+) show no melanoma-specific survival difference between patients undergoing lymph node basin surveillance and completion lymph node dissection (CLND). This has been broadly applied, despite underrepresentation of head and neck (HN) cutaneous melanoma patients. We evaluated whether this was upheld in the HN melanoma cohort. METHODS: Patients with HN melanoma with a SLNB+ were selected from the National Cancer Database (NCDB) from 2012 to 2019. Overall survival (OS) of patients who underwent SLNB only versus SLNB + CLND were compared. Subgroup analyses were performed based on pathologic N (pN) and receipt of immunotherapy. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated. RESULTS: Analysis of 634 patients with multivariable Cox regression showed no difference in OS in SLNB only versus SLNB + CLND cohorts (hazard ratio [HR] 1.13; 95% confidence interval [CI] 0.71-1.81; p = 0.610). Charlson-Deyo score (CDS) 1 versus 0 (HR 1.70; 95% CI 1.10-2.63; p = 0.016), pN2+ versus pN1 (HR 1.74; 95% CI 1.23-2.45; p = 0.002), and lymphovascular invasion (LVI) versus no (HR 2.07; 95% CI 1.34-3.19; p = 0.001) were associated with worse prognosis. Subgroup analysis by pN showed no OS benefit for CLND in either pN1 (HR 1.04; 95% CI 0.51-2.10; p = 0.922) or pN2+ (HR 1.31; 95% CI 0.67-2.57; p = 0.427) patients or in patients who received immunotherapy (HR 1.32; 95% CI 0.54-3.22; p = 0.549). CONCLUSIONS: This study of SLNB + HN melanoma patients showed no OS difference in SLNB only versus SLNB + CLND. Further studies need to be performed to better define the role of CLND.

Predictors of initial engagement with an asynchronous cognitive behavioral stress management website among older women with nonmetastatic breast cancer.

PURPOSE: Digital interventions, like websites, offer greater access to psychosocial treatments; however, engagement is often suboptimal. Initial use may be a target to "hook" participants. Few studies examine engagement with cognitive behavioral stress management (CBSM). We tested predictors of engagement in the first week of using a CBSM website among women with breast cancer (BC). METHODS: Older women (≥ 50 years) with nonmetastatic BC enrolled in an on-going trial (8/2016-4/2022, #NCT03955991) and were randomized to receive 10 synchronous, virtual CBSM group sessions immediately (n = 41) or after a 6-month waitlist (n = 34). All received simultaneous access to an asynchronous website, where supplemental videos and resources were released weekly. Engagement was tracked via breadth (features used) and depth (clicks within content). Multilevel modeling tested predictors of engagement (i.e., time, condition, age, daily stress, depression, race, ethnicity, disease stage). RESULTS: Breadth decreased over the first week of CBSM (b = -0.93, p < .01), and women with more advanced stage disease engaged with more breadth (b = 0.52, p < .01) and depth (b = 14.06, p < .01) than women with earlier stage disease. Non-Hispanic (b = -0.59, p = .03) and White (b = -0.97, p < .01) women engaged with more features. Cancer stage and intervention timing interacted. Women with more advanced cancer stage who received CBSM later engaged with the most depth (b = -11.73, p = .04). All other characteristics did not predict engagement. CONCLUSIONS: Disease stage, race, ethnicity, and intervention timing predicted engagement with a CBSM website in older BC patients. IMPLICATIONS FOR CANCER SURVIVORS: Delivering CBSM later in cancer treatment may mitigate competing demands. Fostering greater engagement in racial/ethnic minorities is needed.

Neighborhood Disadvantage and Breast Cancer-Specific Survival.

Importance: Neighborhood-level disadvantage is an important factor in the creation and persistence of underresourced neighborhoods with an undue burden of disparate breast cancer-specific survival outcomes. Although studies have evaluated neighborhood-level disadvantage and breast cancer-specific survival after accounting for individual-level socioeconomic status (SES) in large national cancer databases, these studies are limited by age, socioeconomic, and racial and ethnic diversity. Objective: To investigate neighborhood SES (using a validated comprehensive composite measure) and breast cancer-specific survival in a majority-minority population. Design, Setting, and Participants: This retrospective multi-institutional cohort study included patients with stage I to IV breast cancer treated at a National Cancer Institute-designated cancer center and sister safety-net hospital from January 10, 2007, to September 9, 2016. Mean (SD) follow-up time was 60.3 (41.4) months. Data analysis was performed from March 2022 to March 2023. Exposures: Neighborhood SES was measured using the Area Deprivation Index (tertiles), a validated comprehensive composite measure of neighborhood SES. Main Outcomes and Measures: The primary outcome was breast cancer-specific survival. Random effects frailty models for breast cancer-specific survival were performed controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics. The Area Deprivation Index was calculated for each patient at the census block group level and categorized into tertiles (T1-T3). Results: A total of 5027 women with breast cancer were included: 55.8% were Hispanic, 17.5% were non-Hispanic Black, and 27.0% were non-Hispanic White. Mean (SD) age was 55.5 (11.7) years. Women living in the most disadvantaged neighborhoods (T3) had shorter breast cancer-specific survival compared with those living in the most advantaged neighborhoods (T1) after controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics (T3 vs T1: hazard ratio, 1.29; 95% CI, 1.01-1.65; P < .04). Conclusions and Relevance: In this cohort study, a shorter breast cancer-specific survival in women from disadvantaged neighborhoods compared with advantaged neighborhoods was identified, even after controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics. The findings suggest potential unaccounted mechanisms, including unmeasured social determinants of health and access to care measures. This study also lays the foundation for future research to evaluate whether social adversity from living in a disadvantaged neighborhood is associated with more aggressive tumor biologic factors, and ultimately shorter breast cancer-specific survival, through social genomic and/or epigenomic alterations.

Immature natural killer cells promote progression of triple-negative breast cancer.

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b-CD27- immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell-mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti-programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.

Endocrine resistance and breast cancer plasticity are controlled by CoREST.

Resistance to cancer treatment remains a major clinical hurdle. Here, we demonstrate that the CoREST complex is a key determinant of endocrine resistance and ER+ breast cancer plasticity. In endocrine-sensitive cells, CoREST is recruited to regulatory regions co-bound to ERα and FOXA1 to regulate the estrogen pathway. In contrast, during temporal reprogramming towards a resistant state, CoREST is recruited to AP-1 sites. In reprogrammed cells, CoREST favors chromatin opening, cJUN binding to chromatin, and gene activation by controlling SWI/SNF recruitment independently of the demethylase activity of the CoREST subunit LSD1. Genetic and pharmacological CoREST inhibition reduces tumorigenesis and metastasis of endocrine-sensitive and endocrine-resistant xenograft models. Consistently, CoREST controls a gene signature involved in invasiveness in clinical breast tumors resistant to endocrine therapies. Our studies reveal CoREST functions that are co-opted to drive cellular plasticity and resistance to endocrine therapies and tumorigenesis, thus establishing CoREST as a potential therapeutic target for the treatment of advanced breast cancer.

The Association of Preoperative Magnetic Resonance Imaging (MRI) With Surgical Management in Patients With Early-Stage Breast Cancer.

INTRODUCTION: The rate of mastectomy in lumpectomy-eligible patients with unilateral breast cancer is increasing. We sought to investigate the association between magnetic resonance imaging (MRI) and surgical management of patients with early-stage breast cancer by comparing the rate of mastectomy as first surgery in patients with and without preoperative MRI. METHODS: A bi-institutional retrospective study included patients diagnosed between 2016 and 2020. Lumpectomy-eligible patients with in situ and invasive cancer were included. Those receiving preoperative therapy, MRI before diagnosis, or with known bilateral cancer were excluded. The risk factors for bilateral and multicentric disease were accounted for. Fisher's exact and chi-square tests compared categorical variables, Wilcoxon two-sample test analyzed continuous variables, and multivariate analyses were performed with Poisson regression. RESULTS: Four hundred twenty-eight participants met inclusion criteria. Patients who received MRI were younger (58 versus 67 y; P < 0.001) and had denser breasts (group 3 or 4; 61% versus 25%; P < 0.001). Mastectomy rate was twice as high in patients undergoing MRI (32% versus 15%, rate ratio 2.16; P < 0.001), which remained significant in multivariate analysis (rate ratio 2.0; P < 0.001). Contralateral mastectomy (12% versus 4%; P = 0.466) and reexcision (13% versus 12%; P = 0.519) rates were similar. Time to surgery was greater in those receiving MRI alone and MRI biopsy (34 [no MRI] versus 45 [MRI] versus 62 [MRI biopsy]; P < 0.001 for both). CONCLUSIONS: MRI receipt is associated with a doubled rate of mastectomy in lumpectomy-eligible patients. Future work is needed to standardize patient selection for MRI to those with the highest likelihood of having additional undiagnosed disease.

Stalled at the intersection: insurance status and disparities in post-mastectomy breast reconstruction.

PURPOSE: Post-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety-net hospital and a private academic center. METHODS: Data were collected on all patients who underwent mastectomy for breast cancer from 2011 to 2019 in a private academic center and an adjacent public safety-net hospital served by the same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors. RESULTS: Of 1554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR, of which 592 (79.9%) were privately insured, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured. Multivariable logistic regression showed a significantly higher likelihood of not undergoing PMBR for uninsured (OR 6.0, 95% CI 3.7-9.8; p < 0.0001), Medicare (OR 1.9, (95% CI 1.2-3.0; p = 0.006), and Medicaid (OR 1.5, 95% CI 1.0-2.3; p = 0.04) patients compared with privately insured patients. Age, stage, race and ethnicity, and hospital type confounded this relationship. CONCLUSION: Patients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.

Translational Epidemiology: An Integrative Approach to Determine the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer.

OBJECTIVE: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. BACKGROUND: Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown. METHODS: Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease. RESULTS: Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC. CONCLUSIONS: In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

Impact of genomic assays on treatment and outcomes in locally advanced breast cancer.

PURPOSE: Genomic profiling in early-stage breast cancer provides prognostic and predictive information. Genomic profiling assays have not been validated in locally advanced breast cancer (LABC). We examined a large cancer registry to evaluate genomic profiling in LABC and its effect on treatment decisions and survival. METHODS: Females with ER+/HER2- LABC who did not receive neoadjuvant therapy were selected from the National Cancer Database 2004-2017. We compared characteristics between patients with and without genomic profiling and with low genomic risk, 21-gene recurrence score ≤ 25 or low-risk 70-gene signature, treated with endocrine therapy ± chemotherapy. Propensity score methods were utilized to account for covariates that may have predicted treatment. Univariable and multivariable survival analyses were performed. RESULTS: Of 18,437 patients with LABC, 1258 (7%) had genomic profiling and 1022 (81%) had low genomic risk results. 562 patients (55%) with low genomic risk received chemotherapy and endocrine therapy (chemoendocrine). Patients who received chemoendocrine therapy were younger, had fewer comorbidities, presented with higher stage disease, had higher grade tumors, more frequently had partial mastectomy, and more often received radiation than those who received endocrine therapy alone. On multivariable analysis, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy (HR 1.77, 95% CI 1.13-2.78, p = 0.013). CONCLUSION: In women with LABC and low genomic risk, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy. This suggests that genomic profiling is not predictive in LABC. Accordingly, genomic profiling should not be routinely utilized to make adjuvant treatment decisions in LABC in the absence of further data which shows a benefit.