ER-positive Research Articles

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

MO53-2 Harnessing artificial intelligence and big data for prognostic advancements in hormone receptor-positive breast cancer

MO53-2 Harnessing artificial intelligence and big data for prognostic advancements in hormone receptor-positive breast cancer

Coping With Side Effects: A Daily Diary Study in Women With Breast Cancer Living With Adjuvant Endocrine Therapy.

Adjuvant endocrine therapy (AET) is increasingly being prescribed for up to 10years to people diagnosed with hormone receptor-positive breast cancer. AET intake is often accompanied by side effects that significantly impact the well-being of people. The way individuals cope with medication-related side effects might play a pivotal role in their emotional adaption. This intensive-longitudinal study investigated the association between self-reported coping strategies (Brief COPE) and psychological well-being (Patient Health Questionnaire-4) among women undergoing AET. A multilevel factor analysis resulted in the identification of four coping factors, namely, problem-focused, support-focused, meaning-focused, and avoidance-focused coping. Daily coping efforts and experienced side effects were analyzed as predictors of psychological well-being using multilevel modeling. A total of 215 women (Mage=56.5±10.9years) participated, resulting in a total of n=2080 daily surveys (M=9.67±1.08). On average, women reported 3.7±2.2 different side effects per day. Days characterized by an elevated frequency of side effects and increased burden were associated with diminished well-being. Using more problem- and meaning-focused strategies than usual to cope with side effects correlated positively with well-being. Conversely, employing more support- and avoidance-focused coping strategies than usual was linked to reduced psychological well-being. Exploratory analyses focusing on individual coping strategies provided nuanced insights into coping behaviors. The present findings underscore the relationship between women's coping efforts concerning medication-related side effects during AET and their daily well-being. Psychosocial education (e.g., cognitive behavioral therapy) may offer valuable benefits for patients by helping them develop adaptive coping strategies to manage side effects.

Site specific O-GlcNAcylation of progesterone receptor (PR) supports PR attenuation of interferon stimulated genes (ISGs) and tumor growth in breast cancer

Hormone receptor (HR) positive breast cancer, defined by expression of estrogen (ER) and/or progesterone (PR) receptor expression, is the most commonly diagnosed type of breast cancer. PR alters the transcriptional landscape to support tumor growth in concert with or independent of ER. Thus, understanding the mechanisms regulating PR function are critical to developing new strategies to treat HR+ breast cancer. O-GlcNAc is a post-translational modification responsible for nutrient sensing that modulates protein function. Although PR is heavily post-translationally modified, through phosphorylation and O-GlcNAcylation, specific sites of O-GlcNAcylation on PR and how they regulate PR action, have not been investigated. Using established PR-expressing breast cancer cell lines, we mapped several sites of O-GlcNAcylation on PR. RNA-sequencing after PR O-GlcNAc site mutagenesis revealed site-specific O-GlcNAcylation of PR is critical for ligand-independent suppression of interferon signaling, a regulatory function of PR in breast cancer. Furthermore, O-GlcNAcylation of PR enhances PR-driven tumor growth in vivo. We have delineated one contributing mechanism to PR function in breast cancer that impacts tumor growth, and provided additional insight into the mechanism through which PR attenuates interferon signaling.

Understanding health literacy's moderating role in remote monitoring for adjuvant endocrine therapy: Findings from a randomized clinical trial.

45 Background: Despite the efficacy of oral adjuvant endocrine therapy (AET) for improving survival among women with hormone receptor-positive early-stage breast cancer, adherence rates remain low. Our THRIVE study (NCT03592771) investigated the effectiveness of a mobile health remote monitoring app with and without tailored educational messages on AET adherence among women with breast cancer and found no statistically significant treatment effects on 1-year AET adherence overall. Health literacy contributes to patients’ understanding of their treatment plans. We conducted a post hoc analysis of the THRIVE study to examine if health literacy moderates the effectiveness of this intervention. Methods: This non-blinded randomized controlled trial included women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across three states. Participants used a pillbox to electronically monitor AET adherence for 1 year and completed surveys at enrollment. Consented participants were randomized into (1) “App”, receiving access to the study adherence and symptom monitoring app for 6 months, with increasing/severe symptoms and missed doses reported in the app triggering follow-ups from the oncology team; (2) “App+Feedback”, receiving additional weekly text messages about managing symptoms, adherence, and communication for 6 months; or (3) “Enhanced Usual Care (EUC).” The primary outcome was 1-year AET adherence captured with the pillbox (≥80% Proportion of Days Covered [PDC] vs. < 80%). The enrollment survey captured participant’s sociodemographic characteristics, including race and ethnicity, education, household income, and health literacy. We used a linear probability model to measure the interaction between the study arm and health literacy on AET adherence. Results: Among 304 women randomized (104 EUC, 98 App, and 102 App+Feedback), the 12-month follow-up retention rate was 88% (n = 266) and 19.4% reported low health literacy at enrollment. Low health literacy was more prevalent among Black (29.4%) vs. White (13.4%) participants (p < 0.001), those with incomes below the federal poverty level (34.4% vs. 17.2% of those with higher incomes, p = 0.02), and those with only a high school degree or lower education (31.7%) vs. with those with some college or higher education (16.4%, p < 0.01). In the low health literacy group, 80.0% of App+Feedback were AET adherent vs. 42.1% of EUC, a 37.9 percentage point (ppt) difference (95% CI: 4.1 to 71.7, p = 0.03); in higher literacy group adherence, 47.1% of App+Feedback vs. 59.0% of EUC were adherent, a -11.8 ppt difference (95% CI: -27.9 to 4.3, p = 0.15). Conclusions: A remote monitoring app with tailored educational text messages led to higher 1-year AET adherence among participants with low health literacy, but not for those with high health literacy. Clinical trial information: NCT03592771 .

The Systemic Immune-Inflammation Index is a Predictor of Chemotherapy Sensitivity and Disease-Free Survival in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

BackgroundThe relationship between the systemic immune-inflammation index (SII), chemotherapy sensitivity, and prognosis in HR+HER2– breast cancer (BC) has not been extensively studied. Patients and methodsClinical data from 980 patients diagnosed with HR+HER2– BC between June 2012 and June 2016 were collected. Patients were divided into low- and high-SII groups according to median SII value. Differences among variables were assessed using the chi-squared test. The inverse probability of treatment weighting (IPTW) method was used to control bias. The associations between clinicopathological factors, baseline SII, and disease-free survival (DFS) were analyzed using Kaplan–Meier curves and Cox analyses. ResultsThe median follow-up period was 37 months (5-77). 480 patients underwent neoadjuvant chemotherapy, and low baseline SII values were associated with higher pathological complete response (pCR) rates than those in the high SII group (16.4% vs. 9.2%; P = .019). Multivariate analyses revealed that larger tumor size, more lymph node involvement, high Ki-67 score, and high baseline SII were independent prognostic factors for worse outcomes in patients with HR+HER2– BC. The risk for metastasis/recurrence was higher in the high SII group compared with that in the low SII group (hazard ratio 2.07 [95% CI, 1.35-3.19]; P = .001). After IPTW, a similar result was obtained, in that a high SII value was significantly associated with worse DFS among patients with HR+HER2– BC. ConclusionA low baseline SII was associated with higher pCR rates after neoadjuvant chemotherapy and was an independent prognostic factor for better DFS outcomes in patients with HR+HER2– BC.

Regional Variation in Deescalated Therapy in Older Adults With Early-Stage Breast Cancer

Although trial data support the omission of axillary surgery and radiation therapy (RT) in women aged 70 years or older with T1N0 hormone receptor-positive (HR+) breast cancer, potential overtreatment in older adults with frailty persists. To determine how much geospatial variation in locoregional therapy may be attributed to region vs patient factors. This retrospective cross-sectional study included women aged 70 years or older who were diagnosed with HR+/ERBB2-negative (ERBB2-) breast cancer from January 1, 2013, to December 31, 2017. Data came from Surveillance, Epidemiology, and End Results-Medicare. Hierarchical multivariable modeling was used to evaluate the variance in deescalated care attributable to 4 domains, ie, (1) random, (2) region (health service area [HSA]), (3) patient factors, and (4) unexplained. Patient factors included age, frailty (validated claims-based measure), Charlson Comorbidity Index (CCI), and socioeconomic status (Yost index). Analyses were performed from January to October 2023. HSA. Deescalated care, defined as omission of axillary surgery, RT, or both. Standard therapy was defined as lumpectomy, axillary surgery, and RT or mastectomy with axillary surgery. Multivariable logistic regression was used to identify factors associated with deescalated care receipt. Of 9173 patients (mean [SD] age, 76.5 [5.2] years), 2363 (25.8%) were aged 80 years or older, 705 (7.7%) had frailty, and 419 (4.6%) had a CCI of 2 or greater. While 4499 (49.1%) underwent standard therapy, 4674 (50.9%) underwent deescalated therapy (1193 [13.0%] of the population omitted axillary surgery and 4342 [55.5%] of patients undergoing lumpectomy omitted RT). Of the total variance, random variation explained 27.3%, region/HSA explained 35.3%, patient factors explained 2.8%, and 34.5% was unexplained. In adjusted models, frailty and increased age were associated with a higher likelihood of undergoing deescalated therapy (frailty: odds ratio [OR], 1.70; 95% CI, 1.43-2.02; age, by 1-year increment: OR, 1.10; 95% CI, 1.09-1.11), but CCI was not. Patients in rural areas compared with those in urban areas (OR, 0.82; 95% CI, 0.68-0.99) and Asian and Pacific Islander patients compared with non-Hispanic White patients (OR, 0.68; 95% CI, 0.54-0.85) had a lower likelihood of undergoing deescalated therapy. In this retrospective cross-sectional study of women aged 70 years or older diagnosed with T1N0 HR+/ERBB2- breast cancer, region/HSA contributed more to the variation in deescalated therapy use than patient factors. Unexplained variation may be attributed to unmeasured characteristics, such as multidisciplinary environment and patient preference. Decision support efforts to address overtreatment should target regions with low rates of evidence-based deescalation.

Incidence of Graves' Disease with Validation and Completeness of the Diagnosis for Registry Extracts in the Danish National Patient Register.

Graves' disease (GD) is one of the most common causes of thyrotoxicosis. It has been proposed to identify incident GD by using the GD-specific code, E05.0, of the 10th revision of the International Classification of Disease (ICD-10) in the Danish National Patient Register (DNPR). We aimed to report the incidence of GD and to investigate the validity and completeness of E05.0 registration using Aalborg University Hospital (AaUH) as a single centre-sample. The study included registry data from 2020 to 2022. The study population (n=2,893) comprised all people (15-99 years) in the catchment area of AaUH (n=244,872) with either positive anti-thyroid stimulating hormone receptor antibodies (TRAb), or registered with a thyroid disease related ICD-10 code E03.0-E07.9, O99.2 or O90.5 at the Department of Endocrinology, AaUH. To identify incident cases, all subjects occurring for the first time in 2020 were excluded (n=2,339). The incident subjects were categorized into a general practice (n=63) or hospital care group (n=491) and underwent GD verification by biochemical tests and thyroid imaging. Validity was evaluated by positive (PPV) and negative (NPV) predictive values and completeness of E05.0 registration was estimated to the total number of verified GD subjects in hospital care only and in overall (groups combined). One hundred thirty-one incident GD subjects were identified corresponding to an incidence of 26.8 per 100,000/year. E05.0had a PPV of 90% [95% CI: 81;96] and a NPV of 90% [95% CI: 85;93] to identify incident cases of GD. Completeness was estimated to be 73% [95% CI: 63;82] in hospital care and 50-60% [95% CI: 41;68] in overall. We report on a similar incidence of GD as previous studies in Denmark. Despite a high PPV, incident cases of GD could not adequately be identified by E05.0 in DNPR due to low completeness. Researchers should rely on biochemical test results to identify incident GD.

A study of the prevalence of PGR gene expression with ER and PR Receptor markers positivity in female breast cancer cases in Al-Najaf province, Iraq

A study of the prevalence of PGR gene expression with ER and PR Receptor markers positivity in female breast cancer cases in Al-Najaf province, Iraq

Survival outcomes of Black/African American (B/AA) patients with HER2-negative (IHC 0, 1+, 2+ and ISH-), advanced breast cancer (HER2-neg aBC) across three academic cancer centers in the United States.

129 Background: As B/AA patients are underrepresented in clinical research, data is limited on survival outcomes of B/AA patients with HER2-neg aBC. This study compared survival outcomes of these patients against those of non-B/AA patients. Methods: This was a retrospective cohort study at Huntsman Cancer Institute, H. Lee Moffitt Cancer Centre and Research Institute, and Winthrop P. Rockefeller Cancer Institute. Adult patients diagnosed with HER2-neg aBC from 2010 to 2021 were eligible. Patient data were extracted via chart review, including self-reported race from clinical records. HER2-low status was defined as immunohistochemistry (IHC) scores 1+ or 2+ and negative fluorescence in situ hybridization test; HER2-neg comprised HER2-low and IHC 0. Overall survival (OS), i.e. time until death, and progression-free survival (PFS), i.e. time until death or disease progression, were estimated using Kaplan-Meier methods with treatment start as index date and censoring at date of last follow-up or 12/31/2021, whichever earlier. Association between B/AA race and survival was evaluated using multivariable Cox regression. Results: A total of 869 patients were HER2-neg, 95 were B/AA, and 64 (67%) were HER2-low while 31 (33%) had IHC 0 disease. Compared to non-B/AA patients (85% non-Hispanic White), fewer B/AA patients had stage IV disease (38% vs 57%, p=0.001), lobular histology (3% vs 14%, p=0.001) and positive hormone receptor status (HR) (60% vs 78%, p<0.001). B/AA patients showed shorter median OS and PFS than non-B/AA patients overall and in subgroups defined by stage and HR but 95% confidence intervals (CI) overlapped (Table). Controlling for stage and HR, B/AA patients had shorter OS (Hazards ratio: 1.4, 95% CI: 1.0-1.9) but no difference in PFS (Hazards ratio: 1.2, 95% CI: 0.9-1.6). Conclusions: OS of B/AA patients with HER2-neg aBC was shorter than that of non-B/AA patients controlling for staging and HR. A sizable proportion of B/AA patients have HER2-low disease and more studies are needed to confirm if this patient population has different outcomes compared to non-B/AA. Survival outcomes of B/AA patients vs non-B/AA patients. Overall Survival (months) Progression-free Survival (months) B/AA Non-B/AA B/AA Non-B/AA n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) Overall 95 41.4 (28.3 to 69.4) 774 56.7 (50.0 to 66.2) 95 9.9 (8.0 to 20.3) 773 16.1 (13.9 to 18.3) Staging IIIB/IIIC 60 69.4 (39.1 to NR) 339 NR (110.1 to NR) 60 10.2 (8.0 to 23.8) 339 22.5 (15.0 to 37.8) IV 35 28.1 (18.2 to 40.9) 435 39.4 (35.5 to 44.0) 35 9.6 (7.3 to 25.7) 434 13.9 (11.6 to 17.0) Hormone receptor Positive 57 41.4 (27.8 to 69.4) 609 62.0 (55.1 to 69.7) 57 8.6 (7.8 to 20.3) 609 17.1 (14.1 to 19.7) Negative 38 40.9 (23.1 to NR) 162 41.6 (24.2 to 68.3) 38 10.2 (7.7 to NR) 161 11.8 (9.3 to 17.2) B/AA – Black/African American, Mdn – median, NR – not reached.

Nanoemulsion-based transdermal delivery of third-generation steroidal and non-steroidal aromatase inhibitors in preclinical models.

Aromatase inhibitors are effective in treating hormone receptor-positive breast cancer, particularly in postmenopausal women. However, the challenges of inconsistent dissolution, variable absorption and side effects with oral administration persist. To address these issues, transdermal delivery has emerged as a viable alternative. In our study, we have developed nanoemulsion-based transdermal creams containing third-generation aromatase inhibitors Exemestane (EXE) or Letrozole (LE) and evaluated their toxicity, anti-tumour effects and androgenic potency using preclinical models including Bama minipigs, DMBA-induced breast cancer rats and orchidectomized male rats. The results of our study are significant, suggesting that both creams effectively penetrated the skin, demonstrating an impressive anti-breast cancer effect. Importantly, EXE cream had no organ toxicity at the tested dose, providing a reassuring safety profile for its use. In contrast, LE cream displayed reversible toxicity from drug molecule itself in animals at the given dose, dissipating after 3 weeks of withdrawal and recovery. This study establishes a solid foundation for the safe clinical use of third-generation aromatase inhibitors. It highlights transdermal creams as a promising drug delivery carrier for administering them.

Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers

BackgroundBreast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive.MethodsIn this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities.ResultsWe observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy.ConclusionsOur findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

MammOnc-DB, an integrative breast cancer data analysis platform for target discovery.

Breast cancer (BCa) is one of the most common malignancies among women worldwide. It is a complex disease that is characterized by morphological and molecular heterogeneity. In the early stages of the disease, most BCa cases are treatable, particularly hormone receptor-positive and HER2-positive tumors. Unfortunately, triple-negative BCa and metastases to distant organs are largely untreatable with current medical interventions. Recent advances in sequencing and proteomic technologies have improved our understanding of the molecular changes that occur during breast cancer initiation and progression. In this era of precision medicine, researchers and clinicians aim to identify subclass-specific BCa biomarkers and develop new targets and drugs to guide treatment. Although vast amounts of omics data including single cell sequencing data, can be accessed through public repositories, there is a lack of user-friendly platforms that integrate information from multiple studies. Thus, to meet the need for a simple yet effective and integrative BCa tool for multi-omics data analysis and visualization, we developed a comprehensive BCa data analysis platform called MammOnc-DB (http://resource.path.uab.edu/MammOnc-Home.html), comprising data from more than 20,000 BCa samples. MammOnc-DB was developed to provide a unique resource for hypothesis generation and testing, as well as for the discovery of biomarkers and therapeutic targets. The platform also provides pre- and post-treatment data, which can help users identify treatment resistance markers and patient groups that may benefit from combination therapy.

Desire for pregnancy and fertility preservation in young patients with breast cancer.

Data on the desire for pregnancy and the status of fertility preservation (FP) in patients with breast cancer remain unclear. This study aimed to determine the status of patients with breast cancer who desired pregnancy and FP implementation before systemic therapy. This retrospective study surveyed the institutional clinical databases and electronic medical records of patients aged < 43years with stages 0-III primary breast cancer during surgery and treated between April 2020 and March 2021. All patients were enquired about their desire for pregnancy in a questionnaire by "present," "absent," and "unsure" at their first visit. The correlation between the desire for pregnancy, implementation of FP, and clinicopathological factors was investigated. Among 1005 patients who underwent surgery for primary breast cancer, 146 were included in the analysis. Of them, 34 (23.3%) patients had a desire for pregnancy, and 45 (30.8%) chose "unsure." Factors associated with the desire for pregnancy were younger age during surgery (p < 0.0022), unmarried status (p < 0.001), nulliparity (p < 0.001), early-stage disease (p = 0.0016), and estrogen receptor positivity (p = 0.008). Among 115 patients who underwent systemic therapy, 13 (11.3%) underwent FP before systemic therapy. Patients who were nulliparous frequently pursued FP (p = 0.0195). The proportion of FP implementation was low in patients who received neoadjuvant chemotherapy (p = 0.0863). Our study suggests that unmarried, nulliparous, and younger patients were more interested in pregnancy, and nulliparous patients frequently pursued FP.

Spectrum of Ductal Carcinoma In Situ (DCIS) Lesions of the Breast: From Morphology to Molecular Characteristics.

Background Specific molecular characteristics of invasive breast cancer have been linked to an increased risk of early relapse. Similarly, ductal carcinoma in situ (DCIS) displays a comparable molecular profile, although their prevalence and implications are not yet fully understood. Aims and objectives The study design defined a multivariable statistical approach aimed at describing the interplay between the histopathological features of ductal carcinoma in situ (DCIS) and their molecular profile. The objective was to explore the correlations between the histopathological features of DCIS (tumor location, DCIS grade, DCIS type, and presence or absence of comedo necrosis) and various biomarkers like estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2/neu), androgen receptor (AR), and epidermal growth factor receptor (EGFR), in addition to the Ki-67 labeling index. Methods In this retrospective study, we selected and analyzed 100 diagnosed cases of ductal carcinoma in situ (DCIS) to represent various subtypes, grades, and morphological characteristics. A detailed histopathological review and immunohistopathological staining for ER, PR, HER2/neu, AR, EGFR, and Ki-67 were performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Molecular subtyping was done based on the biomarker analysis into luminal A, luminal B, luminal HER2/neu, HER2/neu enriched, and triple-negative subtypes. Statistical analysis was done to examine the correlation between tumor location, histopathological features of ductal carcinoma in situ (DCIS), and the expression of the immunohistochemical markers and the molecular subtypes. Results The majority of cases exhibited positivity for estrogen receptor (ER) and progesterone receptor (PR). A strong association was observed between histopathological features (DCIS grade, type, and comedo necrosis) of DCIS and ER/PR status. Additionally, a significant correlation was found between ductal carcinoma in situ (DCIS) grade and HER2/neu status. However, no association was identified between histopathological features and AR or EGFR status. Contrary to expectations, triple-negative DCIS did not show the most aggressive behavior, whereas HER2/neu-positive tumors, particularly high-grade ones, exhibited more aggressive features. No low-grade cases of luminal HER2/neu and HER2/neu-enriched tumors were found. A higher Ki-67 labeling index was found in cases with grade 3 and solid and comedo architectural types of DCIS, while low-grade tumors had a lower Ki-67 labeling index. Conclusion These findings suggest that hormone pathways play a crucial role in ductal carcinoma in situ (DCIS) progression, but the molecular interactions are complex and extend beyond simple binary associations. The complex relationship between the histopathological features of ductal carcinoma in situ (DCIS) and its hormone receptor status warrants further investigation with a larger sample size to fully understand the underlying mechanisms. The results challenge the expectation that triple-negative DCIS is the most aggressive subtype, highlighting the need for further research into the prognostic significance of different DCIS subtypes.

Pathological complete response after neoadjuvant cyclin-dependent kinase 4/6 inhibitor and neoadjuvant endocrine therapy in locally advanced hormone receptor-positive breast cancer

Breast cancer (BC) comprises different molecular subtypes, each having its own individual prognostic factors and thus having a distinct treatment algorithm. With the advent of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, hormone receptor-positive (HR+) BC now has an additional targeted therapeutic option apart from endocrine therapy. As of now, CDK 4/6 inhibitors are Food and Drug Administration (FDA) approved in the metastatic and adjuvant settings. However, for the neoadjuvant setting, systemic chemotherapy is the standard of care. Systemic chemotherapy may not be a suitable option for elderly and frail patients in terms of associated side effects. Thus, due to tailored oncological management, many phase II and III trials of neoadjuvant CDK 4/6 inhibitors are ongoing. CDK 4/6 inhibitors are better tolerated than systemic chemotherapy and have less reported adverse events. Here, we report a case of locally advanced BC (HR+) achieving pathological complete response from neoadjuvant CDK 4/6 inhibitor with minimal toxicity. Thus, CDK 4/6 inhibitors appear to have a promising and upcoming role in the neoadjuvant setting for hormone-positive BC.

Abstract C053: Racial differences in adverse sexual symptoms and implications for quality of life and adjuvant endocrine therapy adherence among women with early-stage breast cancer

Abstract Background Adjuvant endocrine therapy (AET) is effective at reducing breast cancer recurrence risk. It is associated with adverse symptoms, including sexual symptoms (e.g., vaginal dryness, reduced libido, dyspareunia), that can contribute to medication nonadherence and poor quality of life (QoL). Black women are least likely to start and maintain AET. We conducted post hoc analysis of a randomized clinical trial (RCT) to examine racial differences in how sexual symptoms affect sexual satisfaction and how these contribute to differences in AET adherence for Black and White women with early-stage breast cancer. Methods We used data from a nonblinded RCT of women diagnosed with early-stage (Stage I-III), hormone receptor-positive breast cancer and prescribed AET at a regional cancer center in the U.S. Mid-South. We restricted to Black and White participants who completed surveys at enrollment, 6-, and 12-months (N=275). The Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) captured sexual symptoms (e.g., vaginal itchiness, bleeding, dryness, discharge, change in interest in sex, and pain with intercourse) and PROMIS Sexual Function and Satisfaction captured changes in sexual satisfaction with 5-item options ranging from “not at all” to “very much.” The 12-item Short Form Health Survey measured QoL with physical and mental health component summaries (higher scores indicated better QoL). AET adherence, captured by an electronically monitored pillbox, was measured as the proportion of days participants took their medication as prescribed over the 1-year follow-up. We conducted race-stratified linear regressions to examine associations of sexual symptoms with QoL and adherence. Results Among 275 participants, 102 (37%) were Black. Black women reported greater severity of vaginal discharge and that loss of sexual satisfaction was due to sexual symptoms at 6- and 12-months (p&amp;lt;0.05). Vaginal itchiness, vaginal discharge, painful intercourse, and loss of interest in sex were associated with lower mental QoL for Black and White women at all three time points. However, loss of interest in sex was associated with lower physical QoL at all three time points for Black women only. Worsening vaginal dryness was associated with lower 6-month AET adherence for Black (p=0.018) but not for White women (p=0.90). Similarly, lower sexual interest and lower sexual satisfaction was associated with lower 12-month AET adherence for Black women (p&amp;lt;0.05) but not for White (p=0.21 and p=0.13, respectively). Conclusion Women with early-stage breast cancer on AET reported adverse sexual symptoms with associated reductions in their sexual satisfaction and physical and mental QoL. Vaginal dryness, reduced libido, and lowered sexual satisfaction are associated with AET nonadherence among Black women, a group with known adherence barriers and recurrence risks. Our findings suggest that adverse sexual symptoms and sexual health challenges contribute to racial disparities in AET adherence and QoL. Oncosexuality care interventions for Black women are needed. Citation Format: Janeane N. Anderson, Freddie Yang, Xin Hu, Gregory A. Vidal, Ilana Graetz. Racial differences in adverse sexual symptoms and implications for quality of life and adjuvant endocrine therapy adherence among women with early-stage breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C053.

Abstract B117: HT Helper Study: A phone application + patient navigation to improve medication adherence among Latina breast cancer patients experiencing social determinants of health

Abstract Background: Hormone therapy (HT) is highly effective for nearly all breast cancer patients with hormone receptor-positive tumors, which are about 80% of all breast cancer diagnoses. Long-term use of HT reduces cancer recurrence rates and cuts the risk of mortality nearly in half during the second decade after diagnosis. Despite proven benefits, 33% of women who are prescribed HT do not take it as prescribed by their doctor (&amp;lt;80% take their daily dosage). Latina patients are disproportionately affected by Social Determinants of Health (SDoH) that keep them from adhering to HT and are at higher risk of breast cancer recurrence and mortality. Objective: The goal of this 4-year randomized controlled study is to assess the effectiveness of the existing bilingual, culturally tailored, interactive HT Helper App, in combination with patient navigation (PN), on improving adherence to HT among Latina breast cancer patients experiencing SDoH barriers, i.e., income, health insurance, education, health literacy, and language, that impacts their medication adherence. This theory-based intervention will increase patient education, enhance self-efficacy, facilitate communication with the medical team and coordination of resources to address SDoH barriers and help patients develop self-care skills for optimal adherence to HT, ensuring patients the most equitable treatment outcomes possible, including improvement in quality of life, survival, and life expectancy. Study Design. The proposed study involves a parallel 3-group randomized controlled trial with 5-time assessments (baseline, 3, 6, 12, and 18 months) and will enroll 159 breast cancer patients who are prescribed HT and are attending the breast clinic at the Mays Cancer Center at UT Health San Antonio. Intervention components are based on Social Cognitive Theory and elements of Motivational Interviewing. Methods: We will compare the effectiveness of 3 groups on HT adherence: 1) the HT Helper App + PN group vs. the PN alone group vs. the usual care group, and will assess the effect of each study condition on patient self-efficacy to identify side effects, use self-care to manage side effects, and communicate with the medical team. We hypothesize that the HT Helper App + PN and the PN alone groups will have greater rates of HT adherence and higher patient self-efficacy than the usual care group, with the HT Helper App + PN achieving better results than both PN alone and the usual care groups. Conclusion: This proposed multi-level intervention involving a unique combination of mHealth technology + PN has the potential to improve adherence to HT by addressing SDoH and promote equitable breast cancer outcomes, including reduced recurrence and improved quality of life, overall survival and life expectancy among underserved Latina patients. The anticipated outcome is a scalable, evidence-based, and easily disseminated intervention with potentially broad use to patients using oral anticancer medications. Citation Format: Patricia Chalela, Vivian Cortez, Sandra Sivak, Armida Flores, Martha De La Mora, Zully Garcia, Byeongyeob Choi, Edgar Muñoz, Qurathul Ahmed, Audrey Cordova, Maria I Sung-Cuadrado, Asra Aslam, Cliff Despres, Alyssa Gonzales, Virginia G Kaklamani, Kate I. Lathrop, Marcela Mazo Canola, Devasena Inupakutika, David Akopian, Amelie G. Ramirez. HT Helper Study: A phone application + patient navigation to improve medication adherence among Latina breast cancer patients experiencing social determinants of health [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B117.

Postmarketing adverse events of tamoxifen in male and female patients with breast cancer

AbstractTamoxifen (TAM), a selective estrogen receptor (ER) modulator, has received approval for use in patients with breast cancer (BC) exhibiting positive ER expression. Given the widespread clinical use of TAM, a comprehensive real‐world study of its adverse events (AEs) is warranted. The database for analysis, sourced from the Food and Drug Administration Adverse Event Reporting System (FAERS), covers the period from the first quarter of 2014 to the third quarter of 2023. A disproportionality analysis was conducted to quantify the correlation between TAM and AEs. Subgroup analyses were performed to identify differences between BC AEs in males and females receiving TAM, aiming to assess the risk factors of male BC AEs. Total 4890 reports indicated BC, with 91 and 4190 specifically linked to AEs in male and female patients with BC, respectively. Male‐specific AE was libido decreased (reporting odds ratio [ROR]: 43.33), and female‐specific AE was uterine disease, including sarcoma uterus (ROR: 519.51), endometrial cancer (ROR: 131.26), uterine polyp (ROR: 40.83), endometriosis (ROR: 11.39), among others. A notably higher risk of AEs in male patients with BC was observed in individuals aged &gt;65 years (χ2 = 20.83, p &lt; .001). Male patients with BC had a relatively higher risk of hospitalization (χ2 = 4.83, p = .03) and a lower risk of deaths (χ2 = 5.32, p = .02). Theses finding may assist healthcare professionals in recognizing the TAM‐associated AEs and understanding gender differences, potentially improving safety in clinical applications.

Effectiveness of combined targeted and hormonal therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer: A systematic review and meta-analysis of RCTs.

we aim to synthesize available evidence on the effectiveness of hormonal plus targeted therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer. We searched the following databases: Medline, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, and African Journal. Only studies that investigated the effectiveness of hormonal therapy combined with targeted therapy for HR+/HER2- advanced breast cancer treatment were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. Statistical analysis was performed using Comprehensive Meta-analysis version 3. 24 studies were included in the meta-analysis with an overall sample size of 7635. Median PFS, OS and ORR were found to be significantly increased in the combination group compared to hormonal monotherapy [SMD = 6.072 (95% CI = 3.785-8.360), p < 0.001], [SMD = 1.614 (95% CI = 0.139-3.089), p = 0.032] and [OR = 1.584 (CI 1.134-2.213), p = 0.007] respectively. Subgroup analysis showed a significant difference in PFS and ORR between patients who received "hormonal therapy + CDK4/6 inhibitors" vs hormonal therapy only [SMD = 6.015 (CI 3.069-8.960), p < 0.001], (OR = 1.828 (CI 1.030-3.243), p = 0.039] respectively. Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.