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Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are two often co-occurring neurodevelopmental conditions. Nevertheless, there is limited research about symptom differences between ASD and ASD + ADHD groups. This study examined differences in social interaction and communication between children and adolescents with ASD and with ASD + ADHD. A total of 112 participants were identified from two clinical trials. Fifty-six children and adolescents with ASD aged 8–17 years were matched for age, gender and general intelligence quotient with fifty-six children and adolescents with ASD + ADHD. Group differences in scores on the Autism Diagnostic Observation Schedule were analysed. Our results showed that participants with ASD and with ASD + ADHD had similar profiles of social communication interaction challenges and restricted behaviour. However, items assessing gestures: Conventional, Instrumental or Informational Gestures and Empathic or Emotional gestures showed significant differences between the groups suggesting that the ASD + ADHD group used descriptive gestures to communicate to a greater extent than the ASD group. These findings suggest that children and adolescents in both groups have similar difficulties in social communication and interaction with observed differences in the use of gestures. Possible reasons and implications for the differences in the use of gestures are discussed.

Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-12.

Our objective was to assess distress levels in female breast cancer patients as a function of race, ethnicity, and preferred language. We hypothesized minority patients and non-English screen-takers would report higher distress levels compared to English screen-takers and non-Hispanic whites. We conducted a retrospective observational study of female breast cancer patients at an NCI designated cancer center from 2009 to 2016 who were administered a validated biopsychosocial distress screening questionnaire. Self-reported data on race and ethnicity was collected. A total of 3,156 patients were included in the analysis; mean age of 56.3 (SD 12.25) years. The racial/ethnic cohort distribution included 54% non-Hispanic white (NHW), 19% Hispanic, 16% Asian, 7% Black/African American, and 4% other. On multivariable analysis only Hispanic patients were significantly more likely to report overall distress compared to NHW (OR [1.39; CI [1.03-1.87; p=0.03). Asians were significantly less likely to report distress in the functional domain (OR 0.71, CI [0.58-0.88]; p=0.002), while Black patients were significantly more likely to report highest distress levels in the physical (OR 1.53, CI [1.11-2.12]; p=0.01) domain. Hispanic Spanish screen-takers reported significantly more distress compared to Hispanic English screen-takers across all four domains of distress (p

In response to rising rates of bacterial sexually transmitted infections (STIs) in the United States, this evaluative study of the implementation of four evidence-based interventions was developed and implemented. In three STI and HIV high-incidence jurisdictions of the United States, nine federally funded Health Resources and Services Administration Ryan White HIV/AIDS Program clinical demonstration sites implemented (1) audio computer-assisted self-interview sexual history taking, (2) patient self-collection of urogenital and extragenital site chlamydia/gonorrhea nucleic acid amplification test specimens, (3) sexual and gender minority welcoming indicators, and (4) provider training, to make STI screening, testing, and treatment routine in their HIV primary care clinics. The priority populations of young adults, men who have sex with men, and sexual and gender minority patients were found to have risk behaviors identified in the self-interview sexual history, to prefer to self-collect urogenital and extragenital site specimens for STI testing, and to notice and like the sexual and gender minority welcoming indicators. Testing positive for a bacterial STI was significantly associated with using alcohol or recreational drugs before sex, being younger than 50 years, and having two or more sexual partners with other concurrent sexual partners. Of 255 cases of chlamydia, gonorrhea, and syphilis infections, only 13.73% of patients reported related symptoms when screened and tested.

Background: Fanconi Anemia (FA) proteins facilitate homologous recombination (HR)-mediated repair of DNA interstrand cross-links. Germline monoallelic, pathogenic/likely pathogenic (P/LP) variants in the highly-penetrant (HP) breast cancer (BC) FA genes, BRCA1 (FANCS), BRCA2 (FANCD1) and PALB2 (FANCN)), compromise HR and predispose to hereditary BC. The effects of monoallelic, pathogenic variants in other non-HP BC FA genes upon HR and BC predisposition remain less understood. In this investigation we report the germline mutational landscape of FA gene P/LP variants and somatic molecular consequences of patients with BC diagnoses from City of Hope’s (COH) INSPIRE (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation) study. Methods: COH-INSPIRE is a universal access study open to all patients at COH with a personal and/or family history of cancer. Patients undergo custom panel-based germline genetic testing to detect P/LP single nucleotide variants (SNVs), short insertions/deletions (indels) and exon-level deletions/duplications in 155 cancer-predisposition genes including the HP BC FA genes and 15 non-HP BC FA genes [FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCO (RAD51C), FANCP (SLX4), FANCQ (ERCC4) and FANCU (XRCC2)]. Patients’ tumor specimens undergo somatic tumor (>400X)-normal (>180X) whole exome and transcriptome sequencing (>50 million reads). Somatic sequencing identifies P/LP SNVs, indels, copy number events, and fusions. Secondary analyses assessed somatic homologous recombination deficiency (HRD) by examining tumor mutational signatures, as well as an ensemble HRD score derived by combining individual genomic loss of heterozygosity, telomeric allelic imbalance and large-scale molecular transition scores. Reference comparison of germline and somatic features to current FDA therapeutic guidelines and NIH clinical trials registrations determined eligibility for precision therapeutic intervention and clinical trial enrollment. Results: Of 7,584 patients enrolled in COH-INSPIRE, 1,651 (21.8%) patients had a BC diagnosis. Germline panel testing of BC patients identified 204 (12.4%) with germline P/LP variant in a FA gene. Greater than one third of FA gene-altered BC patients (37.7%) carried a P/LP variant in a non-HP BC FA gene. We observed that BC patients with a non-HP BC FA gene variant may demonstrate HR compromise as evidenced by presence of a Signature 3 mutational profile or an elevated combined HRD score (> 33 and/or > 42). (Table 1) Further, we identified ostensible segregation of triple negative BC in a family harboring a germline pathogenic variant in FANCG. With regard to precision clinical actionability (i.e. qualification for targeted therapeutic intervention [PARP inhibitor (PARPi)] and/or clinical trial) for patients with advanced stage BC: All patients with germline P/LP HP BC FA gene variant and 20.7% (N=16) of patients with a P/LP FA non-HPBC FA gene variant met criteria for treatment with on/off-label PARPi. 100% of patients with advanced BC with germline P/LP HP BC or non-HPBC FA gene variant qualified for a clinical trial. Conclusions: Patients with BC often carry a germline monoallelic, P/LP FA gene variant; in more than one third, the FA gene alteration occurs in a non-HP BC FA gene. BC patients harboring a monoallelic germline non-HP BC P/LP FA gene may exhibit somatic mutational signatures and HRD scoring consistent with compromise of HR. Somatic tumor evaluation of BC patients with germline P/LP non-HP BC FA gene variants expands opportunities for precision therapeutic intervention and clinical trial enrollment. Continued appraisal will clarify emerging questions of germline non-HP P/LP FA gene-associated autosomal dominant BC risk and management as well as facilitate optimization of precision BC care. Table 1 Summary Molecular Features of BC patients with P/LP Variants in FA gene from COH-INSPIRE Citation Format: Laura Kruper, Kevin McDonnell, Joseph Bonner, Kevin K. Tsang, Veronica Jones, Joanne Mortimer, Sidney S. Lindsey, Ilana Solomon, Heather Hampel, Wai Park, Gregory E. Idos, Stacy Gray, Stephen Gruber. PD14-03 Reappraising the Fanconi Anemia DNA repair pathway in breast cancer risk and precision intervention: Insights and opportunities from the City of Hope INSPIRE study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-03.

Introduction: Black/African American (BAA) women have 4x higher mortality from hormone receptor positive breast cancer (HR+BC) than White women. Despite this disparity, HR+BC across races is treated with relative uniformity: endocrine therapy. Previous studies have focused on the adjuvant setting. We examined use of neoadjuvant endocrine therapy (NET) in BAA and White women in the National Cancer Database (NCDB) and assessed treatment response by race. Methods: We queried the NCDB for women with clinical stage I-III HR+BC treated between the years 2004-2017 with NET. Patients receiving neoadjuvant chemotherapy and with unknown surgery or race were excluded. Time between initiation of NET and date of first operation was used to proxy duration of NET. Our primary objective was to compare in BAA and White women changes in tumor size and nodal status after NET, considering duration of treatment. Univariate and multivariable logistic regression was performed. Results: The final sample included 9,864 White and 1,090 BAA women. BAA women were disproportionately excluded for receipt of neoadjuvant chemotherapy (OR=1.8, 95%CI 1.6-1.9). Sociodemographic variables differed between the two groups with p24 weeks (OR=1.5, 95%CI 1.2-1.8). On multivariate analyses, compared to White women, BAA women were more likely to downstage to pT0/Tis. BAA women who downstaged to pT0/Tis had longer duration of NET than their White counterparts (median 241 vs 167.5 days, respectively); race was a significant predictor of downstaging on multivariate analysis adjusting for duration of NET and clinical stage (OR=2.85, p=0.016 for BAA). Compared to White women, BAA women were more likely to upstage to Stage IV on multivariate analysis despite being treated longer with NET and controlling for stage at presentation. Conclusion: This study offers important insight into the heterogeneity of HR+BC biology across races in response to NET. While longer duration of NET appears beneficial for BAA women presenting with lower stage clinical disease, it did not demonstrate benefit in BAA women with higher clinical stage. These findings suggest a dichotomous presentation of HR+BC biology in BAA women. Citation Format: Veronica Jones, Mary Schroeder, Mya Roberson, James De Andrade, Ingrid Lizarraga. Differential response to neoadjuvant endocrine therapy for Black and White women in NCDB [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B122.

Introduction: The majority of estrogen receptor positive (ER+) breast cancer carry a good prognosis; however, there is a subset, luminal B breast cancer (LBC), that is highly aggressive. LBC is more common in Black/African American (BAA) women who have a four-times higher death rate from ER+ breast cancer compared to other races. There is evidence that LBC shares biologic similarities with triple negative breast cancer (TNBC); common differentially expressed genes have been identified in TNBC and LBC, particularly among BAA women. Specifically, ubiquitin-conjugating enzyme 2C (UBE2C) expression is elevated in both. UBE2C is a driver of the cell cycle and involved in Wnt/β-catenin signaling, epithelial to mesenchymal transition (EMT), invasion and metastasis. Here we interrogate the association of UBE2C mRNAseq expression with survival in BAA women with ER+ breast cancer in The Cancer Genome Atlas (TCGA). Methods: TCGA Breast (BRCA) cohorts were queried to investigate the differential UBE2C mRNA seq expression in normal vs tumor patient samples in the general breast cancer population and specifically in the ER+ patients. Expression was also compared across races (BAA vs. White). Kaplan-Meier (KM) curves were generated to determine overall survival by gene expression using median as threshold. Results: In TCGA, compared to normal (n=112), UBE2C mRNAseq expression was statistically significantly higher in tumor in all breast cancer patients (n=1092) as well as specifically in the ER+ cohort (n=805). UBE2C mRNAseq expression was higher in the ER- (n=237) compared to the ER+ breast cancer patients (n=805) (p=3.7e-45). Expression was also significantly higher in the progesterone receptor (PR) negative (n=342) compared to the PR positive patients (n=697) (p=1.89e-40). Higher UBE2C mRNAseq expression was associated with poorer disease-free survival in all breast cancer patients as well as specifically in the ER+ patients. When examining the BAA population compared to White, UBE2C mRNA seq expression was significantly higher among BAA (n=183) compared to White (n=753) patients (FC=1.9; p=6.02e-15). Genes involved in cell cycle pathways were significantly correlated with UBE2C mRNAseq expression among BAA ER+ patients (n=110) including CDCA5 (p=1.42e-26, r=0.81), CDK2 (p=1.13e-05, r=0.41), and CDK4 (p=4.67e-06, r=0.42). The proliferation gene MKI67 was also significantly correlated with UBE2C mRNA seq expression (p=6.24e-18, r=0.71). UBE2C mRNAseq high expression was significantly associated with poor progression-free survival for BAA patients with breast cancer (n=179, p= 0.0353). UBE2C mRNAseq high expression was positively associated with African ancestry and negatively associated with European ancestry. Conclusion: UBE2C is a poor prognostic marker in BAA women with ER+ breast cancer using the TCGA dataset. UBE2C plays an integral role in the cell cycle. Given the prevalence of resistance to cell cycle targets, such as CDK 4/6 inhibitors, UBE2C demonstrates a potential drug target to improve outcomes in LBC and mitigate disparities. Citation Format: Veronica Jones, Yate-Ching Yuan, Melissa Davis, Victoria Seewaldt, Rick Kittles. UBE2C a poor prognostic biomarker in Black women with estrogen receptor positive (ER+) breast cancer in TCGA [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C047.

BACKGROUND: Twenty-nine years since the National Institutes of Health (NIH) Revitalization Act was passed to encourage minority participation in clinical trials (CTs), and yet there remains a deficit of minorities recruited into CT. This induces the idea that Women-of-Color (WoC) (Blacks, Latinas, Native Americans, Asians) are less likely to participate than their Northern/European White (NE/W) counterparts. Using a mixed methods study that included quantitative surveys and qualitative interviews, we dive into understanding how a diverse group of women understand and perceive CT, along with concerns and attitudes towards clinical research. METHOD: The interview script was designed to capture patients’ understanding and concerns of clinical research, reasons for agreeing or declining participation, and facilitators or barriers to participation. The CRAs were trained in establishing rapport with the patient, clearly communicating the questions, and probing for more elaboration of responses. Interviewees and interviewers were matched based on gender and race. A total of four CRAs conducted the interviews – two Asian CRAs interviewed the Asian participants, one Latina CRA interviewed Latinas and White, non-Hispanics, and one African American CRA who interviewed the African American participants. Structured individual interviews were conducted by trained CRAs. The audio-recordings of all interviews were transcribed word for word and reviewed for accuracy. Two independent coders then read and coded each transcript and extracted a set of quotes (phrases or sentences) that reflected the themes. RESULTS: A total of 44 women were accrued between August 2019 and February 2020. The racial/ethnic makeup include the following: 20 Latinas ([White/Hispanic] - one Salvadorian, one half Mexican/half Armenian, and 18 Mexican), 8 Asian (one half Chinese/half Japanese, one Indian, three Chinese, two Vietnamese, one Thai), 8 African American/non-Hispanic, and 8 White/non-Hispanic (two Iranian and 6 European). Age range of women were 27 to 71 years of age. Seventeen women declined participation. CONCLUSION: The in-person interviews highlighted feelings of cultural mistrust among the WoC participants and not in the NE/W participating in the study. The results highlight the influence of cultural mistrust as a barrier and the importance of diversity of the clinical research team in overcoming this barrier, particularly among WoC clinical trial participants. Of course, there is undeniable heterogeneity within the WoC population; each community is influenced by its own historical and present contexts that influence its relationship with the medical system. Approaches to overcome this barrier must address the specific needs of each community. Diversity of the clinical research team and the ability of the team to address culturally relevant beliefs can increase trial diversity. The generalizability, quality, and effectiveness of healthcare treatment requires diverse representation in all clinical trials. Citation Format: Veronica Jones, Noe Chavez, Vanessa M. Robles, Laura Kruper, Lily Lai, Amy Polverini, Lusine Tumyan, Lesley Taylor, James Waisman, Angelica Sanchez, Christine Thai, Tanya Chavez, Nikita Wright. A qualitative exploration of women’s understanding of clinical research and decisions to participate: Improving diversity in clinical research [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B076.

BackgroundIn this phase II clinical trial, we evaluated the efficacy of the nonanthracycline combination of carboplatin and nab-paclitaxel in early stage triple-negative breast cancer (TNBC).Patients and MethodsPatients with newly diagnosed stage II–III TNBC (n = 69) were treated with neoadjuvant carboplatin (area under the curve 6) every 28 days for four cycles plus nab-paclitaxel (100 mg/m2) weekly for 16 weeks. Pathological complete response (pCR) and residual cancer burden (RCB) were analyzed with germline mutation status, tumor-infiltrating lymphocytes (TILs), TNBC molecular subtype, and GeparSixto immune signature (GSIS).ResultsSixty-seven patients were evaluable for safety and response. Fifty-three (79%) patients experienced grade 3/4 adverse events, including grade 3 anemia (43%), neutropenia (39%), leukopenia (15%), thrombocytopenia (12%), fatigue (7%), peripheral neuropathy (7%), neutropenia (16%), and leukopenia (1%). Twenty-four patients (35%) had at least one dose delay, and 50 patients (72%) required dose reduction. Sixty-three (94%) patients completed scheduled treatment. The responses were as follows: 32 of 67 patients (48%) had pCR (RCB 0), 10 of 67 (15%) had RCB I, 19 of 67 (28%) had RCB II, 5 of 67 (7%) had RCB III, and 1 of 67 (2%) progressed and had no surgery. Univariate analysis showed that immune-hot GSIS and DNA repair defect (DRD) were associated with higher pCR with odds ratios of 4.62 (p = .005) and 4.76 (p = .03), respectively, and with RCB 0/I versus RCB II/III with odds ratio 4.80 (p = .01). Immune-hot GSIS was highly correlated with DRD status (p = .03), TIL level (p < .001), and TNBC molecular subtype (p < .001). After adjusting for age, race, stage, and grade, GSIS remained associated with higher pCR and RCB class 0/I versus II/III with odds ratios 7.19 (95% confidence interval [CI], 2.01–25.68; p = .002) and 8.95 (95% CI, 2.09–38.23; p = .003), respectively.ConclusionThe combination of carboplatin and nab-paclitaxel for early stage high-risk TNBC showed manageable toxicity and encouraging antitumor activity. Immune-hot GSIS is associated with higher pCR rate and RCB class 0/1. This study provides an additional rationale for using nonanthracycline platinum-based therapy for future neoadjuvant trials in early stage TNBCs. Clinical trial identification number: NCT01525966Implications for PracticePlatinum is an important neoadjuvant chemotherapy agent for treatment of early stage triple-negative breast cancer (TNBC). In this study, carboplatin and nab-paclitaxel were well tolerated and highly effective in TNBC, resulting in pathological complete response of 48%. In univariate and multivariate analyses adjusting for age, race, tumor stage and grade, “immune-hot” GeparSixto immune signature (GSIS) and DNA repair defect (DRD) were associated with higher pathological complete response (pCR) and residual cancer burden class 0/1. The association of immune-hot GSIS with higher pCR holds promise for de-escalating neoadjuvant chemotherapy for patients with early stage TNBC. Although GSIS is not routinely used in clinic, further development of this immune signature into a clinically applicable assay is indicated.

PURPOSE OF REVIEW: Breast Self-Examination (BSE) remains controversial despite the 2009 United States Preventive Service Task Force (USPSTF) recommendation against teaching of BSE. The USPSTF recommendations were based on results from the Shanghai Study, high-quality randomized trial of BSE in 266,064 Chinese factory workers from 1989-1991; women instructed in BSE did not have a significant difference in mortality versus uninstructed controls. Regardless of the outcome of the Shanghai Study, the practice of BSE in the United States (U.S.) over the past 25 years has been associated with a marked reduction in the size of breast cancer identified by women. RECENT FINDINGS: In the Shanghai study, BSE was tested in China from 1989-1991. During this time period, Chinese breast cancer screening and treatment was not consistent with standard-of-care in U.S. and Europe. Breast cancer was a rare illness in China in the 1980’s. Treatment was not standardized; there was no breast imaging or margin assessment of the tumor. Tumor markers (e.g. estrogen receptor, progesterone receptor) were not reported. The Shanghai Study did not report in detail on the anti-cancer agents provided to women who enrolled in the trial. SUMMARY: BSE needs to be rigorously re-evaluated under current standard of care.

BACKGROUND AND PURPOSE: The Breast and Cervical Cancer Treatment Program (BCCTP) Act, passed by Congress in 2000, provides time-limited coverage to uninsured breast or cervical cancer patients. We examine survival differences between BCCTP cases and insured controls. METHODS: Stage I-III breast cancer patients, covered under California’s BCCTP from 2005–2009 (N=6,343), were 1:1 matched with California Cancer Registry (CCR) controls on age, race/ethnicity, and cancer stage. Overall and disease-specific (OS and DSS) survival were compared using multivariate regression. RESULTS: BCCTP cases were more often unmarried (Odds Ratio [OR]=2.47, 95% Confidence Interval [CI]=2.30–2.66), with poorly/undifferentiated tumors (OR=1.26, CI=1.13–1.40), classified as ER negative (OR=1.10, CI=1.02–1.20) and/or PR negative (OR=1.09, CI=1.01–1.17). Cases were more likely to undergo mastectomy (OR=1.13, CI=1.05–1.21) or no surgery (OR=1.64, CI=1.31–2.05) versus lumpectomy. Cases were also more likely to undergo radiation (OR=1.11, CI=1.03–1.19). Endocrine therapy rates were marginally lower in cases (OR=0.93, CI=0.86–1.00). OS and DSS were shorter in BCCTP cases on multivariate analysis (HR=1.29, CI=1.17–1.42 and HR=1.27, CI=1.14–1.42, respectively). When stratified by socioeconomic status (SES), cases had significantly shorter OS and DSS except in the lowest quintile. When stratified by stage, cases had significantly shorter OS and DSS, except for stage I. CONCLUSIONS: The BCCTP provides uninsured breast cancer patients with comprehensive and timely care. Although our results suggest that BCCTP delivers quality care, BCCTP patients have shorter survival rates, even after accounting for SES and stage differences. Further assistance to vulnerable populations is warranted, including longer duration of treatment coverage, and surveillance adhering to NCCN compliant surveillance programs.

Current cancer therapies target a limited set of tumor features, rather than considering the tumor as a whole. Systems biology aims to reveal therapeutic targets associated with a variety of facets in an individual’s tumor, such as genetic heterogeneity and its evolution, cancer cell-autonomous phenotypes, and microenvironmental signaling. These disparate characteristics can be reconciled using mathematical modeling that incorporates concepts from ecology and evolution. This provides an opportunity to predict tumor growth and response to therapy, to tailor patient-specific approaches in real time or even prospectively. Importantly, as data regarding patient tumors is often available from only limited time points during treatment, systems-based approaches can address this limitation by interpolating longitudinal events within a principled framework. This review outlines areas in medicine that could benefit from systems biology approaches to deconvolve the complexity of cancer.

OBJECTIVE To evaluate patient satisfaction scores as a function of physician and patient race and sex. BACKGROUND Patient satisfaction is increasingly used as a surrogate for physician performance. How patient and surgeon race and ethnicity affect perceptions of surgeon communication and care is not widely explored. METHODS Press Ganey patient satisfaction surveys collected from January 2019 to September 2020 were studied. Multivariate logistic regressions were used to identify factors associated with favorable surgeon performance as a function of patient and surgeon demographics. RESULTS A total of 4732 unique outpatient satisfaction survey responses were analyzed. The majority of patients were White (60.5%), followed by Asian (8.6%), Black (4.2%), and Hispanic (4.3%). URM accounted for 8.9% of the 79 surgeons evaluated, and 34% were female. Black, Hispanic, and Asian patients were more likely to report unfavorable experiences than their White counterparts (P < 0.01). Spanish-speaking patients were most likely to perceive that surgeon show less respect for patient concerns (13.9% vs 9.3%, P = 0.004) and inadequate time spent explaining health concerns (12.6% vs 9.2%, P < 0.001). Female surgeons were more likely to achieve the highest overall ratings for effective communication, whereas Asian surgeons received lower scores. Asian surgeons were more likely than non-Asian surgeons to receive lower scores in explanation (37.3% vs 44.1%, P = 0.003). After adjusting for confounding factors, Asian surgeons had 26% lower odds of receiving favorable scores for overall communication (odds ratio: 0.736, 95% confidence interval: 0.619-0.877, P = 0.001). CONCLUSIONS Both patient and surgeon race and sex drive negative perceptions of patient-physician communication. As URM report more negative experiences, further studies should focus on effects of surgeon cultural awareness on underrepresented patient satisfaction.

Blacks have the highest incidence and mortality from most cancers. The reasons for these disparities remain unclear. Blacks are exposed to adverse social determinants because of historic and contemporary racist polices; however, how these determinants affect the disparities that Blacks experience is understudied. As a result of discriminatory community policies, like redlining, Blacks have higher exposure to air pollution and neighborhood deprivation. Studies investigating how these factors affect tumor biology are emerging. We highlight the literature that connects racism-related community exposure to the tumor biology in breast, lung, prostate, and colorectal cancer. Further investigations that clarify the link between adverse social determinants that result from systemic racism and aggressive tumor biology are required if health equity is to be achieved. Without recognition that racism is a public health risk with carcinogenic impact, health care delivery and cancer care will never achieve excellence. In response, health systems ought to establish corrective actions to improve Black population health and bring medical justice to marginalized racialized groups.

BACKGROUND: Breast cancer mortality is substantially higher in Black compared to White women due in part to higher rates of poor prognosis triple-negative breast cancer (TNBC) in Black women. The influence of African ancestry on this disparity has not been adequately examined. METHODS: Using the Women’s Health Initiative cohort of 161,808 postmenopausal women, we examined risk of TNBC in 6,166 Black participants with information on African ancestry, of whom 374 had incident localized breast cancers. African ancestry was based on genetic information from 656,852 single nucleotide polymorphisms with ancestry groups stratified by

PURPOSE: Here we aim to review the association between mammographic density, collagen structure and breast cancer risk. FINDINGS: While mammographic density is a strong predictor of breast cancer risk in populations, studies by Boyd show that mammographic density does not predict breast cancer risk in individuals. Mammographic density is affected by age, parity, menopausal status, race/ethnicity, and body mass index (BMI). New studies normalize mammographic density to BMI may provide a more accurate way to compare mammographic density in women of diverse race and ethnicity. Preclinical and tissue-based studies have investigated the role collagen composition and structure in predicting breast cancer risk. There is emerging evidence that collagen structure may activate signaling pathways associated with aggressive breast cancer biology. SUMMARY: Measurement of film mammographic density does not adequately capture the complex signaling that occurs in women with at-risk collagen. New ways to measure at-risk collagen potentially can provide a more accurate view of risk.

Background: Response to neoadjuvant therapy is a predictor of progression-free and overall survival in HER2+. To decrease treatment associated toxicities in patients with HER2+ breast cancers we utilized a non-anthracycline regimen with pertuzumab (pert), trastuzumab (trast), and nab-paclitaxel (nab). Pre- neoadjuvant therapy biopsies were procured to evaluated possible biological predictors of pathologic complete response (pCR). Methods: Women with locally advanced HER2 positive breast cancers were recruited from our breast cancer clinics. After obtaining informed consent for this IRB-approved trial, patients were treated with 6 cycles of pertuzumab (day 1 every 21 days [d]), and weekly trastuzumab 2 mg/kg with and nab-paclitaxel 100 mg/m2. Formalin fixed paraffin embedded (FFPE) or frozen biopsies pre-NT and post-NT were collected, along with blood samples at pre-treatment, and at the end of study for correlative analysis. Results: Accrual is complete, with 42 of the 45 HER2+ patients assessed for pCR rate (3 too early to evaluate). The median age was 54 yrs (range 31-77 years). 12 patients were stage 3, 26 stage 2, and 1 stage 1 patient. The pCR rate was 64.2% (27/42), with 73.7% (14/19) in ER/PR negative patients and 56.5% (13/23) in ER/PR positive patients. The initial primary tumor size was similar for in those who achieved pCR and non-pCR patients (mean 4.1 cm vs 3.2 cm, respectively). Most patients required dose modifications. Grade 3 AEs reported included 6 patients with hypertension, 3 patients with hematological AEs, 3 patients with elevated LFTs, and 2 patients with diarrhea. Conclusions: This anthracycline-free regimen in HER2+ BC can achieve promising pCR response rates, with toxicities well-managed with dose modifications. Results of correlative analysis will be presented. Citation Format: Somlo G, Waisman J, Yuan Y, Kruper L, Frankel P, Jones V, Lusi T, Schmolze D, Yim J, Hurria A, Mortimer J. Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-18.

Background: Response to neoadjuvant therapy (NT) predicts progression-free and overall survival in triple negative breast cancer (TNBC). Carboplatin has shown efficacy in patients with TNBC. The current phase II prospective neoadjuvant trial was designed to decrease toxicities and improve efficacy. Methods: Patients with TNBC received carboplatin (carb) and nab-paclitaxel (nab). Pre-NT biopsies were procured to evaluate for biological predictors of pathological complete response (pCR). Newly diagnosed stage II-III patients with TNBC were treated with 4 cycles of carb (AUC 6, day 1 of 28 day cycle) and weekly nab 100 mg/m2 x 16. Targeted accrual goal is 70. RNA extracted from formalin fixed paraffin embedded (FFPE) biopsies pre-NT was tested for MammaPrint/BluePrint and custom Agilent full genome microarrays for gene expression (GE, by Agendia Inc). The raw gMeanSignal was log2 transformed and normalized to the 75thpercentile for GE analysis. Association between MammaPrint/ BluePrint results and pCR was tested by Fisher exact test. The linear model from R limma package was applied. Ingenuity Pathway Analysis (IPA) was applied to assess functional pathways associated with pCR. Cellular distribution by CIBERSORT analysis was carried out to estimate the abundance of 22 different cell types in each patient sample, and test whether the distribution of cell types is different between pCR and non-responders. Results: A total of 64 patients were enrolled. Two patients were deemed ineligible (Her2+), and three were too early, resulting in 59 patients evaluable for pathological response. The pCR rate was 47% (RCB0, 28/59). Eight patients had RCB I. RCB0 plus RCBI reached 61%. Sufficient quality RNA and DNA were available from the first 43 of 55 pts with TNBC. 44/59 (75%) required dose modifications (mostly hematologic), 5 patients had grade 3 peripheral neuropathy (PN), 3 had grade 2 PN, and 3 patients had grade 2 LFTs. In the 53 pts with GE assessment, pCR was inversely associated with luminal BluePrint type (p=0.04). With fold change >1.5 and p-value < 0.05, 36 genes were differentially expressed (DE) in TNBC. CIBERSORT analysis suggested that T-cell regulatory cells (TREGS) were associated with pCR in TNBC, and 5 cell types (plasma cells, TREGS, macrophage, dendritic cells and neutrophils) presented differently between all pCR and non-pCRs with P-value Conclusions: The combination of carboplatin and nab-paclitaxel given in the neoadjuvant setting reached a promising pCR rate of 47%. The MammaPrint non-luminal BluePrint subtype was predictive of pCR in TNBC. Preliminary analysis suggested that a 36-gene signature for TNBC was associated with pCR. CIBERSORT analysis revealed 5 cell types with different abundance between the pCR and non-responders, suggesting the need to target the tumor microenvironment. Citation Format: Yuan Y, Frankel P, Li M, Kruper L, Jones V, Treece T, Waisman J, Yim J, Tumyan L, Schmolze D, Hurria A, Yeon C, Mortimer J, Somlo G. Phase II trial of neoadjuvant carboplatin and nab-paclitaxel in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-07.

This study addresses the core issue facing a surgical team during breast cancer surgery: quantitative prediction of tumor likelihood including estimates of prediction error. We have previously reported that a molecular probe, Laser Raman spectroscopy (LRS), can distinguish healthy and tumor tissue. We now report that combining LRS with two machine learning algorithms, unsupervised k-means and stochastic nonlinear neural networks (NN), provides rapid, quantitative, probabilistic tumor assessment with real-time error analysis. NNs were first trained on Raman spectra using human expert histopathology diagnostics as gold standard (74 spectra, 5 patients). K-means predictions using spectral data when compared to histopathology produced clustering models with 93.2–94.6% accuracy, 89.8–91.8% sensitivity, and 100% specificity. NNs trained on k-means predictions generated probabilities of correctness for the autonomous classification. Finally, the autonomous system characterized an extended dataset (203 spectra, 8 patients). Our results show that an increase in DNA|RNA signal intensity in the fingerprint region (600–1800 cm−1) and global loss of high wavenumber signal (2800–3200 cm−1) are particularly sensitive LRS warning signs of tumor. The stochastic nature of NNs made it possible to rapidly generate multiple models of target tissue classification and calculate the inherent error in the probabilistic estimates for each target.

Importance: Access to perioperative breast surgery occupational therapy services remains limited in remote areas. Objective: To assess the feasibility and acceptance of occupational therapy services using a “hub-and-spoke” telemedicine model. Design: Prospective study using videoconferencing to connect the occupational therapist, located at the hub site, with the patient, located at the spoke site. Setting: National Cancer Institute Comprehensive Cancer Center (hub site) and affiliated community cancer center (spoke site). The sites are 75 mi apart. Participants: Female breast cancer patients (N = 26) scheduled for breast surgery were asked to participate in telemedicine occupation therapy sessions. Patients lived in a geographically remote region and travelled a mean of 16 miles (range = 3–85) to the hub site. The majority (56%) of the patients had public insurance. Intervention: Perioperative occupational therapy sessions completed through videoconferencing. Outcomes and Measures: Outcome measures were participation in and completion rate for the sessions, number of sessions required to return to baseline, and time interval from surgery to return to baseline function. Patient satisfaction was assessed with a questionnaire. Results: Of the patients who enrolled in the study, 18 completed all postoperative sessions in which functional assessments, exercises, and education were provided. Patients regained baseline function within a mean of 42.4 days after surgery and after an average of three sessions. Patients reported high satisfaction with the sessions. Conclusions and Relevance: Videoconference telemedicine in breast perioperative rehabilitation is feasible, effective, and acceptable to patients. This study adds to the emerging use of telemedicine for rehabilitative services. What This Article Adds: This study, by demonstrating the acceptability, practicality, and efficacy of breast perioperative occupational therapy services offered through a videoconferencing platform, supports continued research to evaluate the value of telemedicine. Issues with access to medical care may be mitigated through creative use of technology.

Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Breast cancers that rapidly develop between breast image screening are called "interval cancers." The efforts of our team focus on identifying multiscale integrated strategies to identify biologically aggressive precancerous breast lesions. Our goal is to identify spatiotemporal changes that occur prior to development of interval breast cancers. To accomplish this requires integration of new technology. Our team has the ability to perform single cell in situ transcriptional profiling, noncontrast biological imaging, mathematical analysis, and nanoscale evaluation of receptor organization and signaling. These technological innovations allow us to start to identify multidimensional spatial and temporal relationships that drive the transition from biologically aggressive precancer to biologically aggressive interval breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics.

Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen, coupled with lack of a survival benefit, potential for genotoxicity, and failure to provide a significant risk-reduction for estrogen receptor-negative breast cancer, all contribute to the low acceptance of tamoxifen chemoprevention in premenopausal women at high-risk for breast cancer. While other prevention options exist for postmenopausal women, there is a search for well-tolerated prevention agents that can simultaneously reduce risk of breast cancers, cardiovascular disease, and type-2 diabetes. Metformin is a well-tolerated oral biguanide hypoglycemic agent that is prescribed worldwide to over 120 million individuals with type-2 diabetes. Metformin is inexpensive, safe during pregnancy, and the combination of metformin, healthy lifestyle, and exercise has been shown to be effective in preventing diabetes. There is a growing awareness that prevention drugs and interventions should make the "whole woman healthy." To this end, current efforts have focused on finding low toxicity alternatives, particularly repurposed drugs for chemoprevention of breast cancer, including metformin. Metformin's mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin. Signaling pathways activated by insulin also drive biologically aggressive breast cancer and predict poor survival in women with breast cancer. The mechanistic rationale for metformin chemoprevention is well-supported by the scientific literature. Metformin is cheap, safe during pregnancy, and has the potential to provide heart-healthy breast cancer prevention. On-going primary and secondary prevention trials will provide evidence whether metformin is effective in preventing breast cancer.

The higher education community often views international students through a homogenous lens. To challenge the cultural norms set by the dominant group, researchers need to explore how these norms affect international teaching assistants (ITAs). The following questions guided the current study: (a) How do ITAs construct intersecting identities of teacher and learner that reflect the presence of dominant cultural norms within a predominantly White institution? (b) What strategies do ITAs use to navigate cultural and linguistic power dynamics within a predominantly White institution as they seek to establish authority? We conducted a case study through an intersectionality framework. Findings revealed participants’ marginalization, authority, and strategies to overcome oppression. We offer recommendations about power dynamics that require increased institutional support.

During puberty, a woman’s breasts are vulnerable to environmental damage (“window of vulnerability”). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.

Gross intraoperative assessment can be used to ensure negative margins at the time of surgery. Previous studies of this technique were conducted before the introduction of consensus guidelines defining a “positive” margin. We performed a retrospective study examining the accuracy of this technique since these guidelines were published. We identified all specimens that were grossly examined at the time of breast conserving surgery from January 2014 to July 2020. Gross and final microscopic diagnoses were compared and the performance of intraoperative examination was assessed in terms of false positive and false negative rates. Logistic regression models were used to examine the effect of clinicopathologic covariates on discordance. 327 cases were reviewed. Gross exam prompted re-excision in 166 cases (61%). The rate of false negative discordance was 8.6%. In multivariate analysis, multifocality on final pathology was associated with discordance. We consider the false negative rate acceptable for routine clinical use; however, there is an ongoing need for more accurate methods for the intraoperative assessment of margins.

Distress screening is now required for cancer center accreditation. Understanding patient and caregiver stress is critical to successful cancer care. This study examines the perceived emotional impact of breast cancer on both patients and partners.From March 2011-February 2016, patients and partners undertook an electronic, 48-point distress screen during their first visit at a surgical breast clinic. Distress was measured via self-reported concerns on a five point Likert scale. Respondents were also asked about preferred interventions. The ability of the patient and partner to manage emotions was assessed in relation to education, ethnicity, fatigue, anxiety, and depression using ordered logistic regression.Of the 665 individuals screened, 51.7%(n = 344) were patients, while 48.3%(n = 321) were partners. Patients were more distressed than partners regarding fatigue, anxiety, depression, and worrying about the future (p 0.005). Only 19.7% of partners requested information with regards to "managing emotions" compared to 46.3% of patients. In the univariate analysis, being a partner was protective (OR 0.49 (95%CI 0.34-0.70, p 0.000) as was holding an advanced educational degree (OR 0.36 (95%CI 0.14-0.93) p = 0.035). In the multivariate regression, having more education remained protective, while being a partner was no longer protective (OR 0.93(95%CI 0.62-1.39, p = 0.789). Financial concerns, anxiety, depression, and worrying about the future remained statistically significant. Partners asked for help less than patients (OR 0.28 (95%CI 0.17-0.48), p 0.000).While partners have similar concerns as patients, they do not seek information or help in managing emotions as often as do patients. Both patient and partners with less education and increased financial distress were likely to report difficulty in managing emotions. This study identifies groups who would benefit from supportive measures even in the absence of a request for help.

Nipple-areola sparing mastectomy (NSM) may be offered to some women with breast cancer as an alternative to skin sparing (SSM) or total mastectomy (TM) with excellent cosmetic results and acceptable recurrence risk. The aim of this study is to determine the local/regional recurrence rate of NSM in comparison to SSM and TM at our institution and to determine the factors that may be associated with risk of recurrence. Women who underwent NSM (n=148), SSM (n=660) or TM (n=443) at City of Hope National Medical Center between May 2007 and December 2014 for Stage 0-III breast cancer were identified retrospectively. Exclusions were: women with inflammatory breast cancer and those who had mastectomy for recurrent breast cancer. Overall survival (OS) and disease free survival (DFS) were analyzed using Cox regression controlling for age, race/ethnicity, stage, histology, grade, hormone receptor and Her2 receptor status. There were total of 165 NSMs, 704 SSMs and 466 TMs performed for cancer, accounting for the patients with bilateral cancers. The median follow up time was 38, 58 and 55 months for NSM, SSM and TM, respectively. Median (range) age at diagnosis was 49 (23-74) for NSM, 51 (23-90) for SSM and 59 (26-92) for TM. In the NSM group, 76% of patients had invasive ductal cancer (IDC) and 15% had ductal carcinoma in-situ (DCIS); this was comparable to 73% and 13% in the SSM group and 78% and 9% in the TM group, respectively. The majority of patients who underwent NSM had Stage II disease (45%), which was similar to SSM (43%) and TM (44%). Only 3% of NSM patients had Stage III disease compared to 17% of SSM patients and 29% of TM patients. Most of the patients in all 3 surgical groups received adjuvant chemotherapy (NSM 59%; SSM 52%; TM 51%). Of patients who underwent NSM, 20% received neoadjuvant chemotherapy, compared with 29% of SSM patients and 35% of TM patients. The local/regional recurrence rate per breast was 12/165 (7.3%) for NSM, 23/704 (3.3%) for SSM and 11/466 (2.4%) for TM (n=11). Median time to recurrence was 20, 26 and 16 months for NSM, SSM and TM, respectively. Of the NSMs performed only 1 recurrence occurred at the nipple-areolar complex (0.6%), 9 recurrences were at the chest wall (5.5%) and 2 were at the axilla (1.2%). Eight recurrences after NSM had DCIS in addition to IDC at the time of initial diagnosis while 2 had pure DCIS, 1 had pure IDC and 1 had invasive lobular cancer. There were 8 recurrences with estrogen receptor (ER) and progesterone receptor (PR) positivity at the time of initial diagnosis, that converted to ER+, PR-. One third of recurrences after NSM had multifocal disease. There was no significant difference found in adjusted overall survival (p=0.49) and adjusted disease free survival (p=0.10) among NSM, SSM and TM patients. Even though there is higher rate of local/regional recurrence with NSM, there is no difference in overall and disease-free survival at our institution. Presence of DCIS may be an important factor for recurrence. From these data we conclude that NSM is an oncologically acceptable alternative to SSM and TM, with excellent cosmetic results. Citation Format: Bostanci Z, Wang X, Ottesen R, Nikowitz J, Jones VC, Springer L, Lai L, Taylor L, Vito CA, Paz IB, Niland J, Kruper L, Yim JH. Oncological safety of nipple-areola sparing mastectomy in comparison with skin sparing and total mastectomy: Results from a NCI-designated comprehensive cancer center [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-12.

This abstract was not presented at the symposium.

Background: Molecular tumor boards (MTB) are a key component of most precision oncology programs, designed to provide a structured multidisciplinary approach to evaluating cancer patients (pts) for therapy (Tx), clinical trial (CT) enrollment, and genetic counseling (GC) services. Two health systems separately instituted MTB in 2017, and through a bio-informatics platform have been tracking the impact of these on pt care. We describe the collective experience in tracking MTB impact. Methods: This is a retrospective cohort study of pts reviewed for the first time by MTB between September 1, 2017 and September 30, 2020 at either of the two health systems (HS). Follow up data were obtained by a certified tumor registrar at a median time of 109 days after presentation. Demographics and clinical characteristics of MTB pts were obtained. Pts were identified for whom Tx or CTs were recommended and subsequently administered after MTB review, along with pts for whom GC was recommended and subsequently had genetic testing performed. Results: 351 pts were evaluated. Pt demographics included: median age of 65 years; 61% female; 83% White, 13% Black, 3% Asian, with 2% of Hispanic/Latino ethnicity. The most common primary sites observed were lung (75 pts; 21%), breast (44 pts; 13%) and central nervous system (26 pts, 7%). 334 pts (95%) had data regarding Tx and CT recommendations. 124 pts (37%) received a Tx recommendation and 36 (29%) of these received Tx. 73 pts (22%) received a CT recommendation and 4 (6%) of these pts were enrolled on CTs. 340 pts (97%) had data regarding GC recommendations. 94 pts (28%) received a GC referral and 28 (30%) of these received GC. 25 (89%) of these received a molecular test for germline cancer risk, and 10 (40%) of these had a risk mutation identified in one of the following: ATM (4), BRCA2 (2), BARD1 (1), CHEK2 (1), RAD51C (1), and RET (1). Conclusions: MTB was successful in matching pts to Tx and CT, and in providing appropriate referrals to GC and identifying germline risk mutations. The bio-informatics platform provided a uniform format and structure to collate and analyze data between programs. These parameters will serve as a baseline to monitor future MTB impact and trends as these precision oncology programs continue to grow. The relatively low percentage of patients of color whose cases were reviewed in this MTB analysis merits further understanding. Citation Format: Igor I. Rybkin, Michael A. Thompson, Frank M. Wolf, Kristen Collins, Louisa Laidlaw, Tom Mikkelsen, Jennifer Godden, Mary Walters, James L. Weese, Ronda Broome, Joe Burkhart, Veronica Jones, Chenan Zhang, Thomas D. Brown, Anna Berry. Molecular tumor board impact at two large health systems [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P159.

Background: Pathologic complete response (pCR) to HER2-targeting neoadjuvant therapy (NT) predicts for improved survival (Cortazar et al, Lancet, 2014). The addition of pertuzumab to trastuzumab and docetaxel increased pCR rates, and, as first line treatment for MBC led to longer overall survival ([OS] Swain et al, NEJM 2015). Avoidance of anthracyclines in the adjuvant setting for HER2+ BC reduced the risk of secondary hematologic malignancies without a detriment to OS (Slamon et al, NEJM, 20111). Finally, nab-paclitaxel (nab) might provide an advantage over other taxanes via decreased use of steroids and may lead to increased response rates (RR). We designed a study of pertuzumab (pert), trastuzumab (trast), and nab, testing the feasibility and efficacy of this regimen in the LABC and metastatic breast cancer settings. Materials and Methods: Pts with Stages II-III LABC received six cycles of NT with pert (day 1 q 21 days), trast, and nab 100 mg/m2 (both given IV, weekly). Pts with untreated MBC received the same regimen until progression, toxicities, or patient or physician preference led to stopping therapy. Primary endpoints included pCR (LABC) and RR and progression-free survival (PFS) in MBC. Forty pts with LABC and 25 pts with MBC were to be accrued. The study was designed to test whether the pCR rate of Neosphere (Gianni et al, Lancet Oncol, 2012, > 45.8%) and the PFS rate of CLEOPATRA (median of > 18.5 months) can be matched or exceeded. Procurement of serial samples for assessment of tumor gene expression, circulating tumor cells, miRNA, and serum DNA profiling for exploratory biomarker analysis was carried out. Results:Twenty-two of 28 already enrolled pts with LABC (clinical stage II:15, stage III: 7) completed NT. The median age was 53 (34-77). The pCR rate was 86% (6/7) for hormone receptor negative (HR-) and 40% (6/15) for HR+ pts, with an overall pCR of 55%. Three pts without pCR following NT had residual BC with a HER2 negative phenotype. Eighteen of 22 pts required nab dose modifications. The most frequent toxicities following NT included elevated liver function tests:27%, peripheral neuropathy:23%, hematological toxicities:17%, diarrhea:18%, infusion reactions:18%. In the MBC cohort there were 13 of 16 enrolled pts with > 2 months of follow-up. The median age was 47 (31-65), 62% had HR+ disease. A CR rate of 4/13 (31%) and confirmed RR of 77% were observed. The median number of cycles with pert, trast, nab was 9 (3+ to 41); 11 of 13 pts required dose modifications or delays (3 of the delays were due to primary breast surgery performed upon response to treatment). At a median follow-up of 19 months, PFS and OS estimates are 63% (95% CI 0.09-0.93), and 89% (95% CI 0.61-1.0). Conclusion: The non-anthracycline-containing regimen of pertuzumab, trastuzumab, and nab-paclitaxel induced a high pCR rate in HER2+ BC. PFS is encouraging in MBC. Outcome of the fully accrued cohorts inclusive of residual cancer burden scores in the LABC cohort, and correlative data with exploratory biomarker analysis will be presented. Citation Format: Somlo G, Frankel P, Yeon C, Yuan Y, Yim J, Kruper L, Taylor L, Mortimer J, Waisman J, Jones V, Vito C, Paz B, Huria A, Li D, Gaal C, Tong T, Tumyan L. Phase II trial of pertuzumab, trastuzumab, and nab-paclitaxel in patients (pts) with HER2 overexpressing (HER2+) locally advanced or inflammatory breast cancer (LABC) or untreated stage IV metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-35.

Failure to precisely distinguish malignant from healthy tissue has severe implications for breast cancer surgical outcomes. Clinical prognoses depend on precisely distinguishing healthy from malignant tissue during surgery. Laser Raman spectroscopy (LRS) has been previously shown to differentiate benign from malignant tissue in real time. However, the cost, assembly effort, and technical expertise needed for construction and implementation of the technique have prohibited widespread adoption. Recently, Raman spectrometers have been developed for non-medical uses and have become commercially available and affordable. Here we demonstrate that this current generation of Raman spectrometers can readily identify cancer in breast surgical specimens. We evaluated two commercially available, portable, near-infrared Raman systems operating at excitation wavelengths of either 785 nm or 1064 nm, collecting a total of 164 Raman spectra from cancerous, benign, and transitional regions of resected breast tissue from six patients undergoing mastectomy. The spectra were classified using standard multivariate statistical techniques. We identified a minimal set of spectral bands sufficient to reliably distinguish between healthy and malignant tissue using either the 1064 nm or 785 nm system. Our results indicate that current generation Raman spectrometers can be used as a rapid diagnostic technique distinguishing benign from malignant tissue during surgery.

To optimize breast cancer care, several organizations have crafted guidelines to define best practices for treating breast cancer. In addition to recommended therapies, 'timeliness of treatment' has been proposed as a quality metric. Our study evaluates time to surgical treatment and its effect on overall survival (OS).The National Cancer Data Base (NCDB) was used to identify women diagnosed with invasive breast cancer between 2004 and 2012. Time from diagnosis to surgical treatment was calculated and grouped according to predetermined time intervals. Univariate and multivariate Cox proportional hazard models were used to assess patient and treatment factors related to OS.Overall, 420,792 patients initially treated with surgery were identified. Increased time to surgical treatment12 weeks was associated with decreased OS [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 1.09-1.20]. When stratified by pathologic stage, stage I patients treated at 8 to12 weeks (HR 1.07, 95 % CI 1.02-1.13) and12 weeks (HR 1.19, 95 % CI 1.11-1.28), as well as stage II patients treated at12 weeks (HR 1.16, 95 % CI 1.08-1.25), had decreased OS compared with patients treated at4 weeks. Other variables associated with decreased survival were treatment at a community cancer program, Medicaid or Medicare insurance, Black race, increasing age, mastectomy, moderately and poorly differentiated tumor grade, increasing T and N stage, and higher Charlson Index Group.The survival benefit of expedited time to initial surgical treatment varies by stage and appears to have the greatest impact in early-stage disease. Prior to establishing standard metrics, further quantification of the impact on patient outcomes is needed.