Early-stage Breast Research Articles

Neoadjuvant sunitinib plus exemestane in post-menopausal women with hormone receptor-positive/HER2-negative early-stage breast cancer (SUT_EXE-08): a phase I/II trial

Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2− stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4–5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009

Is federal housing assistance associated with earlier-stage cancer diagnosis? Evidence from the new SEER-Medicare and US Department of Housing and Urban Development data linkage.

85 Background: Despite growing awareness that stable and affordable housing is a key social determinant of health, little research has examined the role of federal housing assistance in cancer outcomes. This study uses a novel data linkage to examine the association of federal housing assistance (i.e. various rent subsidy programs) on stage at diagnosis for the 4 most common cancers in the US. Methods: Individuals aged 66-95 years newly diagnosed with breast, colorectal, non-small cell lung (NSCLC) or prostate cancer in 2006-2019 with fee-for-service coverage were selected from SEER-Medicare Housing and Urban Development (HUD) administrative data. After identifying individuals with housing assistance at diagnosis, controls without housing assistance at diagnosis were propensity score matched in a 3:1 ratio by cancer site, age, sex, race/ethnicity, marital status, registry, year of diagnosis, area-level Yost socioeconomic status index, dual Medicaid eligibility, rural/urban residence, reason for Medicare entitlement, and pre-diagnosis comorbidity. Associations of housing assistance and diagnosis stage (SEER summary stage: localized vs. regional/distant) were examined with separate logistic regression models by cancer type. Results: A total of 7335 individuals with breast, 5660 with colorectal, 7399 with NSCL and 4309 with prostate cancer received housing assistance at diagnosis (Table). Compared to matched controls, a smaller percentage of individuals with housing assistance were diagnosed with regional/distant breast (36% vs. 33%), colorectal (59% vs. 57%), and NSCL (71% vs. 69%) cancers. Individuals receiving housing assistance were less likely to be diagnosed with later-stage breast (OR: 0.87; 95% CI: 0.83, 0.92) and NSCL (OR: 0.93; 95% CI: 0.88, 0.99) cancers. Housing assistance was not significantly associated with stage for individuals with colorectal or prostate cancers. Conclusions: Federal housing assistance is associated with earlier-stage breast and NSCL cancer diagnosis, highlighting its potential role in mitigating the adverse effects of housing insecurity on cancer outcomes. Housing assistance and cancer diagnosis stage. No Housing Assistance at Dx,N (%) Housing Assistance at Dx,N (%) OR [95% CI], P Breast Localized 14291 (64) 4890 (67) 1.0 (ref) Regional/Distant 8179 (36) 2445 (33) 0.87 [0.83, 0.92] P<0.001 Colorectal Localized 7046 (42) 2422 (43) 1.0 (ref) Regional/Distant 9934 (59) 3238 (57) 0.95 [0.89, 1.01] P=0.09 NSCLC Localized 6572 (30) 2298 (31) 1.0 (ref) Regional/Distant 15625 (71) 5101 (69) 0.93 [0.88, 0.99] P=0.02 Prostate Localized 10293 (80) 3401 (79) 1.0 (ref) Regional/Distant 2634 (20) 908 (21) 1.04 [0.96, 1.14] P=0.33 Dx=Diagnosis; OR=Odds Ratio; CI=Confidence Interval.

Evaluation of a complex survivorship intervention incorporating electronic patient-reported outcomes in early stage breast and gynecologic cancer: Results from the Linking You to Support and Advice (LYSA) randomized controlled trial.

1505 Background: Expert consensus supports a multidisciplinary strategy in cancer survivorship care to enhance patient outcomes and quality of life. We hypothesized that introducing a women’s survivorship clinic into routine follow up care would be feasible, and associated with improved symptom management and quality of life (QOL). Methods: LYSA was a multisite randomized controlled trial with parallel arms (experimental and active comparator), co-designed with public and patient involvement. Eligibility: early-stage hormone receptor-positive breast or gynaecologic cancer (GYN) within 12 months of completing primary therapy, and internet access (NCT05035173). Experimental arm attended a nurse-led clinic targeting symptom management, and dietetic consultation. Electronic patient-reported outcome (ePRO) assessments were undertaken at baseline, and bimonthly to 12 months. An online trigger alert system facilitated symptom management. Active comparator arm attended the nurse-led clinic at baseline and end of study. Primary endpoint (feasibility): Proportions of participants completing baseline and follow up ePRO surveys, and engaging in healthcare consultations after ePRO triggers. Pilot efficacy endpoints: changes in cancer-related symptom (PROMIS, PRO-CTCAE, Fear of Cancer Recurrence), health-related QOL Questionnaires (EORTC-QLQ, EQ5D5L) . Sample size target (n=200) facilitated feasibility outcomes. Between arm differences were estimated using generalized linear model, adjusted for baseline outcome. Results: 200 women were randomized, March 2021-August 2022 across two sites; 84% breast and 16% GYN. Consent was obtained in clinic (51%), video call (33%) or phone (16%). Median age was 54 (range 23-78). Of the 173 participants completing the study (n = 90 experimental, 83 comparator), all completed both baseline and end of study surveys. Following symptom triggers (experimental arm), there were 322 study nurse visits across 86 participants, and 243 dietician visits across 73 participants. Engagement with healthcare and other supportive resources was approximately twice more than comparator arm, due to referral. There were no notable between-arm differences with respect to EQ5D5L items at study end. However, experimental arm participants had better EORTC Total scores at study end relative to comparator (difference in means -3.87 95%CI -6.58 to -1.16, p=0.005). There were also significant (p < 0.05) differences observed between the arms for 8/12 symptom items reflecting less fatigue, anxiety and depression in experimental arm at study end. Conclusions: The LYSA trial met its primary feasibility endpoint, with high rates of ePRO completion. Secondary endpoint analysis is ongoing including an economic analysis and future studies. Clinical trial information: NCT05035173 .

A pan-tumor prospective translational, Irish study, investigating the association of gut microbiome (GM) diversity with pathological complete response (pCR) after neoadjuvant treatment in early stage breast, rectal, and esophageal cancers.

TPS3188 Background: The gut microbiome (GM) is thought to influence host immunity by modulating multiple immunologic pathways. Studies have suggested that dysbiosis of the GM confers a predisposition to certain malignancies and influences response to immune checkpoint inhibitors. However, little is known about how the GM diversity influences complete pathological response to neo-adjuvant therapy in gastrointestinal (GI) and breast tumors. We hypothesize that a more diverse GM constitution at baseline will lead to improved pathological response at the time of definitive surgery. Methods: This is a cross institutional multi-centre Irish translational study investigating the impact of the GM diversity on the efficacy of neo-adjuvant therapy in GI and breast cancers by assessing its association with pathological response. The study population includes pts with early-stage breast, rectal or esophageal cancers commencing neo-adjuvant therapy (including chemotherapy, immunotherapy and chemo-radiation) and planned for definitive surgery. Exclusion criteria include prior allogenic tissue/solid organ transplantation and prior receipt of anti-cancer therapy. The study assessments will include fecal sampling of the GM prior to neo-adjuvant therapy, upon completion and again six months post completion of therapy. Fecal samples will be analysed by 16S RNA sequencing. Pathological response will be examined at time of surgery and patients will be classified as responders (complete pathological response) or non-responders. The primary endpoint of the study is to examine the association between the GM diversity and pathological response. Exploratory analysis will include the assessment of the association between cf-DNA and the GM diversity as well as an assessment of the association between cf-DNA at baseline and pCR. 120 patients will be recruited over 18 months. Species richness (Alpha Diversity) will be analysed using the Shannon diversity index and Jaccard similarity index will be used to calculate beta diversity. Following planned study recruitment, classification and clustering analysis will be performed with Principal Component Analysis (PCA) and Random Forest analysis. To assess the primary endpoint the association between GM and complete pathological response will be examined using logistic regression analysis adjusting for potential confounding factors in the final statistical analysis. Adjusted odds ratios (OR) and 95% confidence intervals will be presented. This is expected to read out in early 2025. Recruitment is ongoing, with 14 pts recruited to date. We demonstrate that it is feasible to accrue to translational studies in Ireland and we have streamlined screening and recruitment pathways to improve our methodology and recruitment numbers.

Time to treatment initiation of lung cancer and contributing factors from 2015-2020 utilizing Surveillance, Epidemiology and End Results program database.

1540 Background: Time from diagnosis of cancer to definitive therapy, or time to treatment initiation (TTI), has significant impact on prognosis. Kohorana et al performed an observational study in 2019 that found that TTI has increased in the United States with an absolute increased risk of mortality ranging from 1.2-3.2% per week in early-stage breast, lung, renal and pancreatic cancers. This study aims at identifying contributing factors and trends that can assist in shortening TTI of lung cancer. Methods: This is a retrospective cohort study conducted by review of Surveillance, Epidemiology and End Results Program database. Participants included 212,607 adults ages 18 and older diagnosed with lung cancer during 2015-2020. Variables contributing to TTI were studied like age, sex, race, marital status, geographic location, household income, stage and grade. TTI was measured as less than 30 days and greater than 30 days. ANOVA analysis was performed with SPSS and BlueSky Statistics, with p-value of <0.05 as significant. Results: TTI was 1.30 months in males and 1.31 months in females (p=0.038). In patients less than 65 years, TTI was 1.14 months, while those greater than 65 had a delay of 1.38 months (p<0.001). White patients had TTI of 1.26 months versus non-white patients, 1.44 months (p<0.001). Married patients had TTI of 1.24 months versus 1.44 months in widowed patients (P<0.001). Income less than $35,000 had less TTI (1.22 months) than income greater than $75,000 (1.33 months) (p<0.001), but the population earning <$35,000 was smaller (n=3,082) compared to >$75,000 (n=209,525), therefore not representative of the total population. Metropolitan had longer TTI than nonmetropolitan at 1.34 months versus 1.24 months, p<0.001. Grade IV had shorter TTI at 0.94 months with grades I and II having TTI of 1.42 and 1.46 months, respectively (p<0.001). Localized cancers had the longest TTI at 1.71 months versus distant at 1.01 months (p<0.001). More aggressive cancers had shorter TTI such as grade IV + distant at 0.76 months versus grade I + localized at 1.42 months. Association between grade and stage and impact on TTI was significant at p<0.001. Conclusions: This study revealed significant factors influencing the duration from cancer diagnosis to treatment among adult patients greater than 18 years old diagnosed with lung cancers. Shorter TTI intervals were observed for females, younger individuals (<65 years-old), white patients, married and those with higher tumor grades and distant cancer. Addressing these disparities requires targeted interventions that consider socioeconomic status, geographic location and cancer characteristics to ensure equitable access to timely and high-quality cancer care. Further investigation is warranted to fully understand the impact of factors such as household income and regional variations on treatment delays.

A prospective study to evaluate the prevelance of chemobrain (CB) in patients (pts) receiving adjuvant treatment.

e23174 Background: Although adjuvant chemotherapy (CT) significantly improves the clinical outcome of pts with early-stage (ES) cancer, it is also known to cause side-effects. CT-induced cognitive impairment or CB refers to a clinical condition characterized by lack of mental sharpness, memory and concentration impairment and difficulty in processing information and executing simple tasks. Prospective data regarding the emergence of CB are limited. We aimed to explore the prevalence and predictors for CB among pts receiving adjuvant CT and to evaluate its impact on their quality of life (QoL). Methods: This was a prospective cohort study conducted at the University Hospital of Larissa. Pts who were recently diagnosed with ES breast (BC) or colorectal (CRC) cancer and were about to receive adjuvant CT containing doxorubicin (D) or oxaliplatin (O), respectively, were eligible for this study (C1). The first control group (C2) consisted of ES cancer pts that were not eligible for adjuvant CT and the second group (C3) was recruited from a pool of healthy controls (HCs). All participants (pcs) met the following inclusion criteria: age > 50 years old, ability to speak and write in Greek. Pts with pre-existing dementia/anxiety disorder and severe anemia were excluded from the study. Pts in C1 were assessed before receiving CT and 3 months after CT initiation. All subjects in C2 and C3 were assessed in 3 months intervals as well. After completion of the informed consent process, all pts and age-matched noncancer controls completed the Greek Version of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to specifically assess CB. QoL was measured using the EORTC QLQ-C30. Results: Overall, 82 pts (53 with BC and 29 with CRC) were included in C1, 36 pts (24 with BC and 12 with CRC) in C2 and 15 pcs in C3. At baseline, pts in C1 and C2 had significantly lower FACT-Cog scores than healthy controls in C3 (p: 0.028 and p:0.038, respectively), indicating a higher prevalence of self-reported cognitive impairment among pts with cancer after a curative surgery compared to age-matched HCs. However, after 3 months of CT the majority of pts in C1 (59/82, 72%) demonstrated a decline in their cognitive performance (35/53, 66% in BC pts receiving D and 24/29, 82% in CRC pts receiving O). Pts with CRC receiving O experienced more severe cognitive deficits. On the contrary, 55% of the pts in C2 (20/36, 16 with BC and 4 with CRC) demonstrated an improvement. The presence of CB (decline in cognitive functioning in the absence of severe anemia) was associated with decreased QoL (p = 0.004). Pts were mostly frustrated by the difficulty in executing simple tasks. Conclusions: As demonstrated in one of the largest cohorts of pts with ES cancer, CB is a common problem among pts receiving adjuvant CT and is associated with detrimental impact on daily life. Creating awareness is crucial to offer cancer survivors the best care directed at improving QoL.

Intervening in the Cancer Care System: An Analysis of Equity-Focused Nurse Navigation and Patient-Reported Outcomes.

Nurse navigation can improve quality of cancer care and reduce racial disparities in care outcomes. Addressing persistent structurally-rooted disparities requires research on strategies that support patients by prompting structural changes to systems of care. We applied a novel conceptualization of social support to an analysis of racial equity-focused navigation and patient-reported outcomes. We applied an antiracism lens to create a theory-informed definition of system-facing social support: intervening in a care system on a patient's behalf. Participants were adults with early-stage breast or lung cancer, who racially identified as Black or White, and received specialized nurse navigation (n = 155). We coded navigators' clinical notes (n = 3,251) to identify instances of system-facing support. We then estimated models to examine system-facing support in relation to race, perceived racism in health care settings, and mental health. Twelve percent of navigators' clinical notes documented system-facing support. Black participants received more system-facing support than White participants, on average (b = 0.78, 95% confidence interval [CI]: [0.25, 1.31]). The interaction of race*system-facing support was significant in a model predicting perceived racism in health care settings at the end of the study controlling for baseline scores (b = 0.05, 95% CI [0.01, 0.09]). Trends in simple slopes indicated that among Black participants, more system-facing support was associated with slightly more perceived racism; no association among White participants. The term system-facing support highlights navigators' role in advocating for patients within the care system. More research is needed to validate the construct system-facing support and examine its utility in interventions to advance health care equity.

Assessing the Effect of Cancer Diagnosis on Beliefs about Comorbid Diabetes

ObjectivesIncreasingly, patients diagnosed with cancer also live with chronic comorbidities, and it is important to understand the impact of a new cancer diagnosis on perceptions about preexisting conditions. This study assessed the effect of cancer diagnosis on beliefs about comorbid diabetes mellitus and assessed changes in beliefs about cancer and diabetes over time. Data SourcesWe recruited 75 patients with type 2 diabetes who were newly diagnosed with early-stage breast, prostate, lung, or colorectal cancer and 104 age-, sex-, and hemoglobin A1c−matched controls. Participants completed the Brief Illness Perception Questionnaire four times over 12 months. The authors examined within-patient and between-group differences in cancer and diabetes beliefs at baseline and over time. ResultsOverall, diabetes beliefs did not differ between cancer patients and controls at baseline. Cancer patients’ beliefs about diabetes varied significantly over time; they reported less concern about cancer, less emotional effect, and greater cancer knowledge over time. Participants without cancer were significantly more likely to report that diabetes affected their life across all time points, though this effect did not persist after adjustment for sociodemographic variables. ConclusionWhile all patients’ diabetes beliefs were similar at baseline and 12 months, cancer patients’ beliefs about both illnesses fluctuated during the months following cancer diagnosis. Implications for Nursing PracticeOncology nurses can play a key role in recognizing the effects of cancer diagnosis on beliefs about comorbid conditions and fluctuations in these beliefs during treatment. Assessing and communicating patient beliefs between oncology and other practitioners could produce more effective care plans based on patients’ current outlook on their health.

Breast-conserving surgery without axillary surgery and radiation versus mastectomy plus axillary dissection in elderly breast cancer patients: A retrospective study.

The high relative mortality rate in elderly breast cancer patients is most likely the result of comorbidities rather than the tumor load. Foregoing axillary lymph node dissection or omitting radiotherapy after breast-conserving surgery (BCS) does not affect the prognosis of elderly breast cancer patients. We sought to assess the safety of breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) in elderly patients with early-stage breast cancer. We retrospectively included 541 consecutive breast cancer patients aged over 70 years with clinically negative axillary lymph nodes in one clinical center. Of these patients, 181 underwent mastectomy plus axillary lymph node dissection (MALND) with negative axillary cleaning and 360 underwent BCSNR. After a median follow-up of 5 years, there was no significant difference between the BCSNR and MALND groups in either distant recurrence-free survival (DRFS) (p=0.990) or breast cancer-specific survival (p=0.076). Ipsilateral axillary disease was found in 11 (3.1%) patients in the BCSNR group and 3 (1.7%) patients in the MALND group; this difference was not significant (p=0.334). We did not observe a significant difference in distant recurrence between the groups (p=0.574), with 25 (6.9%) patients in the BCSNR group experiencing distant recurrence compared to 15 (8.3%) patients in the MALND group. Our findings did show a significant difference in ipsilateral breast cancer recurrence (IBTR), with 31 (8.6%) patients in the BCSNR group experiencing IBTR compared to only 2 (1.1%) patients in the MALND group (p=0.003). BCSNR is a safe treatment option for elderly breast cancer patients with clinically negative axillary lymph nodes.

Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer

PurposeA previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer.MethodsAfter excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy.ResultsRegarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328).ConclusionIn cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

Predictors of surgery choices in women with early-stage breast cancer in China: a retrospective study

BackgroundThe breast-conserving surgery and reconstruction rate in China is relatively low when compared with those in Western countries. Moreover, predictors of surgical choices for women with breast cancer in China have not yet been explored. This study aims to explore differences in the surgical choices of women with different demographic and clinical characteristics and the predictors that influence surgical choices of women with early-stage breast cancer.MethodsThis retrospective study included women with early-stage (0-II) breast cancer who underwent surgeries at one of two Xiamen University-affiliated hospitals between 2009 and 2017. Using medical records, eleven variables were collected: the woman's age, year of diagnosis, hospital, marital status, payment method, cancer stage, presence of positive axillary lymph node, histology, neoadjuvant chemotherapy, radiotherapy, and the type(s) of surgery they chose. Binary logistic regression was used to analyse predictors of surgical choice.ResultsA total of 1,787 cases were included in this study. Of the total number of women with breast cancer, 61.3% underwent mastectomy without breast reconstruction, 26.4% underwent mastectomy with breast reconstruction, and the remaining 12.2% chose breast-conserving surgery. Women with different demographic and clinical characteristics underwent different types of surgery. Cancer stage, neoadjuvant chemotherapy, radiotherapy, and the choice of hospital were found to be predictors of breast-conserving surgery. Meanwhile, age, year of diagnosis, payment method, neoadjuvant chemotherapy, and the choice of hospital were found to be predictors of reconstruction after mastectomy in women with early-stage breast cancer.ConclusionsIn China, surgical choices for women with breast cancer have diversified. Healthcare workers should understand the surgical preferences of women of different ages. For early detection of breast cancer, knowledge of breast self-examination and breast cancer screening should be provided. Adequate information about the safety of reconstruction and advocacy for medical insurance coverage of reconstruction should be offer. Breast surgeons need specialised training and standardising protocols towards different types of breast surgery. These actions will help women make better, well-informed decisions about their breast surgeries.

Abstract C109: Testing Home-based Exercise Strategies in Underserved Minority Cancer Patients Undergoing Chemotherapy (THRIVE) Trial: A study protocol

Abstract Background: Higher rates of physical inactivity and comorbid conditions are reported in Hispanic and Black cancer patients receiving chemotherapy, compared to their White counterparts. Despite the beneficial effect of exercise training for cancer patients, rates of participation in clinical cancer trials are low among disadvantaged and racial and ethnic minority groups. This is possibly due to more barriers and less access to exercise training. Therefore, there is a crucial need for better understanding of how to apply exercise interventions using novel, accessible, and cost-effective home-based exercise approaches for Hispanic and Black communities, particularly during chemotherapy. In this study, we will examine the effect of supervised and unsupervised exercise on minutes of physical activity among Hispanic and Black cancer patients undergoing chemotherapy for breast, colorectal, and prostate cancer. Methods: The THRIVE trial is an 8-month prospective, three-arm study of 135 patients who are randomized in a 1:1:1 fashion to a supervised exercise intervention (SUP), unsupervised exercise (UNSUP), or an attention control group. Eligible patients include those with early-stage breast, colorectal, or prostate cancer, planning to receive chemotherapy, are sedentary, overweight or obese, and self-identifying as Hispanic or Black. Patients randomized to the SUP group participate in a home-based 16-week periodized aerobic and resistance exercise program performed three days per week, supervised through video conference technology. Patients randomized to the UNSUP group participate in an unsupervised 16-week, telehealth-based, periodized aerobic and resistance exercise program performed three days per week using the same exercise prescription parameters as the SUP group. The attention control group receive a 16-week home-based stretching program. The primary outcome is changes in minutes of physical activity assessed by 7-day accelerometry at month 4. Secondary outcomes include cardiovascular risk factors, patient-reported outcomes, and physical function. Outcome measures are tested at baseline, post-intervention at month 4, and after a non-intervention follow-up period at month 8. Discussion: The THRIVE trial is the first study to employ a novel and potentially achievable exercise intervention for a minority population receiving chemotherapy. In addition, this study utilizes an intervention approach to investigate the biological and behavioral mechanisms underlying exercise participation in these cancer patients. Results from this study will guide and inform large randomized controlled trials to test the effect of home-based exercise on treatment outcomes and comorbid disease risk in minority patients with cancer undergoing chemotherapy. Citation Format: Huimin Yan, Noelle Merchant, Ashley Desameau, Cherardi NeiraViscue, Paola Gonzalo-Encabo, Dong-Woo Kang, Rebekah L. Wilson, Mary K. Norris, Danny Nguyen, Daniel Gundersen, Laura L. Hayman, Rachel A. Freedman, Timothy Rebbeck, Christina M. Dieli-Conwright. Testing Home-based Exercise Strategies in Underserved Minority Cancer Patients Undergoing Chemotherapy (THRIVE) Trial: A study protocol [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 C109.

Examining ACCURE's Nurse Navigation Through an Antiracist Lens: Transparency and Accountability in Cancer Care.

There are persistent disparities in the delivery of cancer treatment, with Black patients receiving fewer of the recommended cancer treatment cycles than their White counterparts on average. To enhance racial equity in cancer care, innovative methods that apply antiracist principles to health promotion interventions are needed. The parent study for the current analysis, the Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) intervention, was a system-change intervention that successfully eliminated the Black-White disparity in cancer treatment completion among patients with early-stage breast and lung cancer. The intervention included specially trained nurse navigators who leveraged real-time data to follow-up with patients during their treatment journeys. Community and academic research partners conducted thematic analysis on all clinical notes (n = 3,251) written by ACCURE navigators after each contact with patients in the specialized navigation arm (n = 162). Analysis was informed by transparency and accountability, principles adapted from the antiracist resource Undoing Racism and determined as barriers to treatment completion through prior research that informed ACCURE. We identified six themes in the navigator notes that demonstrated enhanced accountability of the care system to patient needs. Underlying these themes was a process of enhanced data transparency that allowed navigators to provide tailored patient support. Themes include (1) patient-centered advocacy, (2) addressing system barriers to care, (3) connection to resources, (4) re-engaging patients after lapsed treatment, (5) addressing symptoms and side effects, and (6) emotional support. Future interventions should incorporate transparency and accountability mechanisms and examine the impact on racial equity in cancer care.

Mechanisms to enhance racial equity in health care: Developing a model to facilitate translation of the ACCURE intervention

BackgroundAs medical and public health professional organizations call on researchers and policy makers to address structural racism in health care, guidance on evidence-based interventions to enhance health care equity is needed. The most promising organizational change interventions to reduce racial health disparities use multilevel approaches and are tailored to specific settings. This study examines the Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) intervention, which changed systems of care at two U.S. cancer centers and eliminated the Black-White racial disparity in treatment completion among patients with early-stage breast and lung cancer. PurposeWe aimed to document key characteristics of ACCURE to facilitate translation of the intervention in other care settings. MethodsWe conducted semi-structured interviews with participants who were involved in the design and implementation of ACCURE and analyzed their responses to identify the intervention's mechanisms of change and key components. ResultsStudy participants (n ​= ​18) described transparency and accountability as mechanisms of change that were operationalized through ACCURE's key components. Intervention components were designed to enhance either institutional transparency (e.g., a data system that facilitated real-time reporting of quality metrics disaggregated by patient race) or accountability of the care system to community values and patient needs for minimally biased, tailored communication and support (e.g., nurse navigators with training in antiracism and proactive care protocols). ConclusionsThe antiracism principles transparency and accountability may be effective change mechanisms in equity-focused health services interventions. The model presented in this study can guide future research aiming to adapt ACCURE and evaluate the intervention's implementation and effectiveness in new settings and patient populations.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer

BackgroundIn the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients’ quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called ‘single-port insufflation endoscopic breast-conserving surgery’ (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer.MethodsA total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale.ResultsThe mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis.ConclusionThe novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients’ postoperative comfort and psychological well-being, as compared to the conventional technique.

The relationship between adjuvant chemotherapy and thiol-disulfide compounds.

Thiols are the organic compounds of the antioxidant system. There is limited data in the literature concerning chemotherapy (CT) in cancer and thiol balance. In this study, we aimed to evaluate the possible changes of thiol/disulfide levels with the recurrent CT cycles and type of cancer. The 40 healthy individuals and 40 patients who had been newly diagnosed with early-stage breast, ovary and endometrium cancer receiving adjuvant CT. Blood samples were taken from all patients three times as basal and after the first and second CT sessions. We compared preadjuvant treatment levels of thiol and disulfide parameters in the patients group with the control group. The median of native thiol and total thiol was found to be higher in the control group than in the study group (P < 0.001). In addition, disulfide/native thiol and disulfide/total thiol rates were found to be higher in the patient group (P = 0.001). When we look at the comparison before and after CT in the patient group, disulfide/native thiol and disulfide/total thiol rates, which represent increased oxidative stress (OS) levels were found to be higher after CT than before CT measurement (P < 0.016). This is the first study, which has researched the relationship between cancer type and thiol compounds and changes of thiol compounds during CT therapy, by using the method designed by Erel and Neşelioğlu. In this study, we found that pre-CT thiol disulfide balance in cancer patients shifted toward disulfide direction and OS levels may increase after repetitive CT sessions.

PCR72 Health State Utility Values for Patients with Chemotherapy-Induced Myelosuppression: A Systematic Review

Cytotoxic chemotherapy can induce myelosuppression and have an influence on a cancer patient’s quality of life (QOL). Two newer products developed to prevent chemotherapy-induced myelosuppression, plinabulin and trilaciclib, have primarily been studied in early-stage breast and advanced lung cancer. This systematic literature review sought to characterize empirically derived health state utility values (HSUVs) of chemotherapy-induced myelosuppression at any stage of breast cancer (BC), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC).

Abstract 5918: The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer

Abstract Background: Breast cancer (BC) is one of the three most common cancers worldwide, which is a heterogeneous group of different disease subtypes, each with its own biology and clinical characteristics. Approximately 60% of patients with early-stage BC receive adjuvant treatment, however, only a small number derive a benefit. Recurrence remains a major obstacle. Comprehensive profiling analysis in early-stage (T1-2N0-1M0) BC with different disease subtypes might help understand the tumorigenesis mechanisms and pave the way to evaluate the recurrence risk in early-stage BC. Methods: A total of 418 patients diagnosed with early-stage BC were enrolled, including 82 patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC, 49 HR-/HER2+ patients, 239 HR+/HER2- patients, and 48 HR-/HER2- patients. Capture-based targeted sequencing was performed on tumor tissue samples using a panel consisting of 520 cancer-related genes. The genomic profiling among different disease subtypes were investigated and tumor mutational burden (TMB) was calculated. Results: Besides HER2, TP53, CDK12, and PIK3CA were the most frequently mutated genes in both HR2-/HER2+ (75.5%, 65.3%, and 36.7%) and HR2+/HER2+ BC (67.1%, 57.3%, and 36.6%). PIK3CA and TP53 were also the most frequently mutated gene in both HR-/HER2- (22.9% and 81.3%) and HR+/HER2- (54% and 23.4%) BC. Moreover, alterations in KRAS (12.5%) and GATA3 (26.8%) were frequently occurred in HR-/HER2- and HR+/HER2- BC, respectively. Furthermore, a comparable TMB level was observed among four subtypes (median TMB: 3.0 mutations/Mb for HR+/HER2- BC; 3.7 mutations/Mb for other subtypes). Next, the genomic profiling was compared between T1-2N0 and T1-2N1 disease in four subtypes, respectively. No different mutation frequencies in cancer-related genes were observed between T1-2N0 and T1-2N1 disease in both HR+/HER2+ and HR-/HER2- BC. In HR+/HER2- BC, T1-2N1 disease had a higher mutation frequency of TRRAP (4% vs. 0%, p&amp;lt;0.05) and a lower mutation frequency in CHD4 (0% vs. 6%, p&amp;lt;0.01), ERBB3 (0% vs.5%, p&amp;lt;0.05), and CTCF (1% vs.6%, p&amp;lt;0.05) than T1-2N0 disease. In HR-/HER2+ BC, patients with T1-2N1 disease had more alterations occurring in HNF1B (23% vs. 0%, p&amp;lt;0.05) and CDK12 (77% vs.48%, p&amp;lt;0.05), and less alterations occurring in NCOR1 (0% vs. 13%, p=0.096) than those with T1-2N0 disease. Moreover, a higher mutation frequency in homologous recombination signaling pathway was associated with the presence of node metastases in HR-/HER2+ BC (52.2% vs. 76.9%, p=0.082). A comparable TMB level was observed between T1-2N0 and T1-2N1 in four subtypes, respectively. Conclusions: Our work reveals the molecular heterogeneity among four subtypes, and between T1-2N0 and T1-2N1 disease in a certain subtype. These findings suggest that molecular features may also need to be taken into consideration for recurrence risk assessment in early-stage BC. Citation Format: Bo Chen, Yingzi Li, Yuchen Zhang, Guochun Zhang, Haiwei Du, Dailin Sun, Junjun Li, Ning Liao. The comprehensive genomic profiling in early-stage (T1-2N0-1M0) breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5918.

Abstract 650: Reparixin, CXCR1/2 inhibitor in combination with CDK4/6 inhibitors attenuates endocrine resistant breast cancer growth and metastasis

Abstract Various endocrine therapies have been developed such as selective estrogen receptor modulation (SERM), selective estrogen receptor downregulator (SERD) and ligand deprivation using aromatase inhibitors (AI). Tamoxifen (TAM), a SERM and AIs are the most commonly used adjuvant treatment for postmenopausal women with early-stage estrogen receptor positive breast cancer. Despite the relative safety and significant anti-neoplastic and chemopreventive activities of tamoxifen and AIs, many initially responsive breast tumors develop resistance and ultimately recur. Many underlying molecular events that confer resistance are known, but a unifying theme is yet to be revealed. While the tumor microenvironment is being increasingly recognized as a key factor in multiple stages of disease progression, particularly local resistance, immune-escaping, and distant metastasis, our previous work shows that the critical molecular and cellular players secreted from a crosstalk between breast cancer cells and stromal cells can regulate the tumor growth and process of metastasis in breast cancer. In this report, using established endocrine resistant breast cancer (ERBC) cells and ESR1 mutant cells (Y537S and D538G), we screened the secreted factors in crosstalk between cancer cells and fibroblasts using cytokine antibody arrays and found that CXCL1 is highly upregulated in fibroblasts. To investigate a potential impact given the current clinical landscape of endocrine resistant breast cancer, we performed a high throughput cell-based screen to identify effective combinations of drugs that will be tested in vivo using reparixin, CXCR1/2 inhibitor, tamoxifen (SERM), fulvestrant (SERD), and CDK4/6 inhibitors (Palbociclib and Ribociclib) in co-culture with ERBC cells and fibroblast. Significantly, reparixin decreased ERBC cell viability compared to vehicle while reparixin in combination with tamoxifen and fulvestrant, enhanced the inhibitor effects in ERBC cell growth. We found that the combination treatment of reparixin and Palbociclib and ribociclib significantly inhibited ERBC cell growth and migration compared the single treatment. The inhibitory effect of reparixin was higher in combination with CDK4/6 inhibitors that the combination with tamoxifen and fulvestrant. Furthermore, reparixin in combination with CDK4/6 inhibitors decreased ERBC cell migration and promotes apoptosis.These findings implicate CXCL1 signaling as a critical event in ERBC tumor growth and metastasis via crosstalk between cancer cells and stromal components. Further, these studies suggest that CXCL1 act as key regulators orchestrating ERBC. Therefore, we have provided evidence that supports the hypothesis that functional inhibition of the CXCL1 and CDK4/6 signaling pathway has the potential to circumvent ERBC growth and metastasis. Citation Format: Sneha Pandithar, Olivia Reff, Kideok Jin. Reparixin, CXCR1/2 inhibitor in combination with CDK4/6 inhibitors attenuates endocrine resistant breast cancer growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 650.

Intratumoral (IT) INT230-6 can cause tumor necrosis in vivo: Preliminary results of a phase II randomized presurgical window-of-opportunity study in early breast cancers (the INVINCIBLE study).

605 Background: The INVINCIBLE study is a randomized, Phase 2 presurgical Window-Of-Opportunity trial for IT INT230-6 (comprising VINblastine (VIN) Cisplatin (VIN)) evaluating clinical and BioLogical Effects in patients with early-stage operable Breast Cancer. INT230-6 also contains a dispersion enhancer molecule designed to facilitate diffusion of the cytotoxic agents into cancer cells and cause tumor necrosis. We have previously demonstrated that INT230-6 halts cancer cell replication and induces apoptosis while maturing dendritic cells and recruiting T-cells to the tumor microenvironment. In this trial, IT injections of INT230-6 are conducted to 1) exploit the potential of regional cytotoxic chemotherapy on breast cancer in vivo and 2) assess the potential for an immune response in the tumor microenvironment and host prior to surgical resection. Methods: Up to 90 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers are randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham. This study has two parts. Part I (N=29) was a randomized trial comparing 1-3 doses of INT230-6 injected weekly vs no treatment prior to surgery to evaluate safety, feasibility, and optimal drug dosing. Part II is a double-blinded randomized trial of up to 60 patients where patients will receive one IT dose of INT230-6 vs saline injection (2:1). The primary endpoint is to estimate the proportion of patients who achieve a complete cell cycle arrest post-surgery compared to the diagnosis biopsy. Secondary endpoints include an evaluation of the rate of pathological complete response, the percent of residual cancer, and safety. The study will also profile changes in CD4/CD8 and the T-cell repertoire. Results: Part I demonstrated feasibility, safety and tolerability of presurgical IT injections in breast cancer patients. Twenty patients with tumors ranging from 1-4.4cm were injected with at least one dose up to 48 hours prior to surgery. No surgeries were delayed or altered and the most common (&gt;10%) AEs were injection site pain (100%), infusion site extravasation, injection site reaction and vomiting (10% each). Preliminary data show histologic evidence of up to 95% tumor necrosis in varying biologic subtypes and an increase in intratumoral TILs in injected tumors compared to controls. Part II is ongoing. Conclusions: Preliminary evidence shows that a single dose of INT230-6 can cause intratumoral necrosis and stimulate an immune response in breast cancers prior to surgery with minimal adverse effects and good tolerability. The results of Part II of the study will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. Clinical trial information: NCT04781725.