Receiving Aromatase Inhibitors Research Articles

A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

Effects of a 6-month aerobic exercise intervention on brain morphology in women with breast cancer receiving aromatase inhibitor therapy: a sub-study of the EPICC trial.

Physical exercise may increase brain volume and cortical thickness in late adulthood. However, few studies have examined the possibility for exercise to influence brain morphology in women treated for breast cancer. We conducted a nested sub-study within a randomized clinical trial to examine whether 6 months of moderate-intensity aerobic exercise in postmenopausal women with early-stage breast cancer influences brain morphology. We included twenty-eight postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (M age = 62.96 ± 5.40) who were randomized to either 45-60 min of supervised aerobic exercise 3 days/week (n = 16) or usual care (n = 12). Before beginning aromatase inhibitor aromatase inhibitor therapy, and the exercise intervention, and again at 6-month follow-up, volumetric and cortical thickness measures were derived from magnetic resonance imaging scans. There were no significant intervention effects on brain volume and cortical thickness. However, greater average exercise intensity (%) during the intervention was associated with greater post-intervention cortical volume, mean cortical thickness, precentral gyrus thickness, and superior parietal thickness (all p < 0.05). Finally, total supervised exercise time was associated with higher precentral gyrus thickness after the intervention (p = 0.042, R 2 = 0.263). The exercise intervention did not significantly affect brain volumes and cortical thickness compared to the control group. However, positive associations were found between exercise intensity and brain morphology changes after the 6-month intervention, indicating that exercise may reduce the vulnerability of the brain to the deleterious effects of breast cancer and its treatment.

Monocyte subsets in breast cancer patients under treatment with aromatase inhibitor and mucin-1 cancer vaccine

BackgroundMonocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models.MethodsTo elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry.ResultsWhen 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy.ConclusionsThis study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination.

Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.

Endocrine therapy is the standard treatment for hormone receptor-positive (HR+) breast cancer (BC). Yet, it is accompanied by treatment-related toxicities, leading to poor treatment adherence, high relapse, and low rates of survival. While pharmacogenomic variants have the potential to guide personalized treatment, their predictive value is inconsistent across published studies. To systematically assess the literature's current landscape of pharmacogenomics of endocrine therapy-related adverse drug effects, systematic searches in MEDLINE, Embase, Cochrane CENTRAL, Google Scholar and PharmGKB databases were conducted. We identified 87 articles. Substantial heterogeneity and variability in pharmacogenomic effects were evident across studies, with many using data from the same cohorts and predominantly focusing on the Caucasian population and postmenopausal women. Meta-analyses revealed Factor V Leiden mutation as a predictor of thromboembolic events in tamoxifen-treated women (p<0.0001). Meta-analyses also found that rs7984870 and rs2234693 were associated with musculoskeletal toxicities in postmenopausal women receiving aromatase inhibitors (p<0.0001 and p<0.0001, respectively). Overall, the current body of evidence regarding the potential role of pharmacogenomics in endocrine therapy-related toxicity in BC remains largely inconclusive. Key concerns include the heterogeneity in toxicity definitions, lack of consideration for genotype-treatment interactions, and the failure to account for multiple testing. The review underscores the necessity for larger and well-designed studies, particularly with the inclusion of premenopausal women and non-Caucasian populations.

The impact of non- and anthracycline-based chemotherapy on fatigue in breast cancer survivors: results from WF-97415

PurposeTo examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors.MethodsThis study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables.ResultsAmong 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point.ConclusionWomen with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

Adjuvant endocrine therapy choices in premenopausal patients with hormone receptor-positive early breast cancer: Insights from the prospective GIM23-POSTER study

BackgroundMost premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methodsThe Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. ResultsBetween October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. ConclusionsAI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

Overall survival analysis of first line CDK4/6 inhibitors in a large real-world cohort of patients with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer.

e13095 Background: Multiple clinical trials have demonstrated the efficacy of the commercially available CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) as upfront therapy in patients (pts) with (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Recently, differences in overall survival (OS) benefit in MBC and invasive disease-free survival benefit in early-stage BC suggest greater potency of abemaciclib and ribociclib compared to palbociclib. Here we report a comprehensive OS analysis of a cohort of pts with HR+/HER2- MBC treated with ribociclib, palbociclib or abemaciclib and ET in 1st line setting. Methods: We retrieved medical records of pts with HR+/HER2- MBC receiving CDK4/6i as 1st line therapy between December 2013 and October 2023 at Memorial Sloan Kettering Cancer Center. We investigated the impact of clinico-pathological characteristics and treatment type as categorical variables on OS using uni- and multivariate Cox (proportional hazard) regression model. Any p-value (p) &lt;0.05 was deemed to be statistically significant. Results: 854 pts were included in the analysis, 838 females (98%) and 16 males at birth. The median age was 56 (IQR: 48-65). Overall, 722 (84%) pts received palbociclib, 88 (11%) abemaciclib, and 44 (5%) ribociclib. Most pts received aromatase inhibitor (AI) as ET backbone (n=634, 74%); 214 received fulvestrant (35%), and 6 received tamoxifen (1%). After a median follow-up of 3.14 years (range: 1.7-4.6), the median OS of the full cohort was 54.7 months (95%CI: 50-63.1). Clinico-pathological characteristics that resulted independently associated with worse OS were: male gender at birth (HR:2, 95%CI:1.4-4), disease-free interval ≤ 2 years (HR:1.64, 95%CI:1.11-2.44), ER-low status (HR: 2.27, 95%CI:1.42-3.63), high grade(HR: 1.28, 95%CI:1.01-1.62), liver involvement (HR: 1.48, 95%CI:1.08-2.03), and number of disease sites &gt;3 (HR:1.35, 95%CI:1.03-1.78). HER2-low status was associated with better OS (HR: 0.75, 95%CI:0.59-0.96). In terms of type of treatment, there was a trend toward improved OS in patients receiving AI rather than fulvestrant or tamoxifen (HR:0.76, 95%: 0.58-1), while the type of CDK4/6i did not affect the outcome. Conclusions: Clinical parameters of early relapse, high disease burden, and intrinsic tumor aggressiveness seem to be the main drivers of poor prognosis in patients with HR+/HER2- MBC in 1st line setting. In this analysis, type of CDK4/6i did not have a significant impact on OS, although pts treated with abemaciclib and ribociclib were underrepresented in the cohort due to the earlier and prevalent use of palbociclib as the first-in-class FDA-approved CDK4/6i. These data are reassuring about the use of palbociclib suggesting that a switch of CKD4/6i is not needed in pts with ongoing treatment and demonstrated benefit.

Efficacy and safety of eribulin-based chemotherapy in patients with advanced breast cancer: A single-centre retrospective study.

e13121 Background: Eribulin, a nontaxane microtubule dynamics inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. This retrospective study aimed to assess efficacy and safety of Eribulin-based chemotherapy in ABC patients, especially for patients exhibiting HER2-0 and HER2-low status (immunohistochemistry [IHC] 1+ or IHC 2+with a negative in situ hybridization assay). Methods: This single-center retrospective study planned to include 126 ABC patients from January 2020 to December 2023. Enrolled participants received Eribulin either as monotherapy or in combination with other regiments such as anti-angiogenic therapy, PD-1 inhibitor, or alternative chemotherapy in clinical practice. The primary outcomes included progression-free survival (PFS) and safety assessments. Results: A total of 84 patients with ABC received Eribulin were enrolled. Patients' baselines were summarized as follows: The median age was 53.3 years (range 30.0–86.0 years). 53 (63.1%) patients were HER2-low while 40 (47.6%) patients were hormone receptor (HR) positive. 63.1% patients have received at least one line chemotherapy before the use of Eribulin. According to the K-M survival analysis, the median PFS was 6.0 (range 3.2-11.3) months for all patients. The median PFS was longer for patients received aromatase inhibitors (AI) for over 6 months than patients with AI naive (median 10.1 vs 6.6 months; p=0.192) in HR positive patients. Patients who received CDK4/6 therapy had longer PFS than patients (median 10.7 vs 6.6 months; p=0.38). There was a trend toward prolonged PFS in the HER2-0 group compared with HER2-low group (median 10.13 vs 6.03 months; p=0.154), although there was no significant difference. A nonsignificant improvement of PFS was observed in HR-/HER2-0 patients, compare with HR-/HER2-low patients (median 16.4 vs 4.7mo; p=0.21). Meanwhile the median PFS of HER2-0 and HER2-Low was similar in HR positive patients. The objective response rate was 35.5% in HER2-0 group and 30.2% in HER2-low group. In multivariate cox regression, Eribulin as first line treatment (HR, 4.028; 95% CI, 1.131-14.337) and HER2-0 (HR, 2.903; 95% CI, 1.257-6.702) showed prognostic values regarding PFS. Common grade 3 or 4 adverse events that were reported in more than 10% were neutropenia (41.6%) and leukopenia (26.2%). No treatment-related deaths were reported. Conclusions: This single-center study demonstrated encouraging efficacy and safety in the ABC patients treated with Eribulin. Significant PFS benefit was associated with Eribulin treatment in patients with HER2-0 compared with HER2-low. This study still needs longer follow-up to evaluate its efficacy more comprehensively.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

Multicenter Study on the Frequency of Low Bone Mineral Density in Young Women With Breast Cancer and Associated Factors

IntroductionYoung women with breast cancer (BC) may experience bone mineral density (BMD) loss secondary to cancer treatment effects on estrogen levels. Studies assessing BMD in BC patients have had a limited representation of young women. This multicenter retrospective study analyzed the frequency of low BMD and associated factors in this age group. MethodsWomen diagnosed with stage 0-III BC at ≤40 years, treated with chemotherapy and/or endocrine therapy between 2010 and 2020 at 5 Mexican BC referral centers were eligible. Demographic, clinical and treatment data were collected, as well as bone dual-energy X-ray absorptiometry (DEXA) results. Low BMD was defined as lumbar or femoral neck T-score < -1.0 or Z-score ≤ -2.0. ResultsA total of 1259 patients were included; median age at diagnosis was 36 years (21-40). Overall, 93% received chemotherapy and 65% endocrine therapy (tamoxifen was received at some point by 61%, aromatase inhibitors by 17%, and GnRH agonists/bilateral oophorectomy by 21%). DEXA scans were documented in 254 (20%), of which 163 (64%; 95% confidence interval [CI] 58%-70%) had a low BMD report. Low BMD was associated with receiving aromatase inhibitors (Odds ratio [OR] 1.92; 95% CI 1.13-3.24), and GnRH agonists/bilateral oophorectomy (OR 2.25; 95% CI 1.21-4.21). ConclusionThe suboptimal frequency of BMD monitoring observed displays an alarming disregard for bone health in young patients. Thus, a high proportion of women with low BMD are potentially being missed and precluded from the opportunity to receive timely interventions. Particular focus should be put on BMD monitoring among patients treated with aromatase inhibitors, GnRH agonists or bilateral oophorectomy.

Abstract PO4-27-08: A Phase II Multi-Institutional Study of Concurrent Radiotherapy, Palbociclib, and HormoneTherapy for Treatment of Bone Metastasis in Breast Cancer Patients

Abstract Background: This Phase II study aimed to determine the efficacy and safety of administering palliative radiotherapy (RT) to bone metastases (mets) in patients (pts) receiving concurrent palbociclib and hormone therapy (HT) for hormone receptor positive, Her2/neu negative breast cancer. The primary endpoint was response rate 3 months after RT. Methods: Pts with painful bone mets or asymptomatic bone mets with risk for impending clinical event were treated with RT to 30 Gy in 10 fractions or 20 Gy in 5 fractions with concurrent palbociclib and HT. Change in maximum pain score on the Brief Pain Inventory was used to assess pain response 3 months post RT relative to baseline. Among pts with asymptomatic bone lesions, response was defined as prevention of a clinical event (e.g., bone fracture) without evidence of local tumor growth on surveillance imaging. Patient reported outcomes (PROs) of fatigue, depression, anxiety, and quality of life were collected. Blood-based biomarkers were examined to determine their relationship with response and PROs. Using a non-inferiority study design, a sample size of at least 33 pts was needed to achieve 80% power to detect a non-inferiority proportion of 60% using a one-sided binomial test and assuming a Type I error of 0.05. Results: Among 38 patients enrolled, 79% had painful bone mets. 35 pts completed baseline and 3-month post RT assessments. 61% and 37% of pts received aromatase inhibitors and fulvestrant, respectively, with palbociclib. Median age was 60 years (31-83) and 25% of pts were non-Hispanic Black. The majority (72%) of pts received 5 fraction RT and 69% received RT to one bone region. 29 patients (83%) were responders [95% CI: 66%-93%, p=.003]. Median progression free survival (PFS) was 30.4 months (1.3 - 44.0). Three-year PFS and overall survival were 45.6% and 67.2%, respectively. Grade 3 neutropenia developed in 4 (11%), 4 (11%), and 7 (20%) pts at end of RT, 1 month, and 3 months post RT, respectively. No pts developed Grade 4 neutropenia. One patient developed Grade 3 gastrointestinal toxicity during RT, another developed Grade 3 dyspnea 1 month post XRT, and another developed a bone fracture 6 months after RT. &amp;gt;While patient reported measures of fatigue, depression, and overall quality of life did not significantly change during or after RT relative to baseline, pain scores (i.e., BPI pain severity and interference, BM22 pain characteristics and pain site subscales, EORTC C15 pain) significantly decreased 3 months post XRT relative to baseline. Heightened inflammatory marker levels (e.g., TNFRII, IL1ra, CRP, TNF alpha) were significantly associated with worse symptoms of fatigue (MFI) and depression (HADS), increased pain interference (BPI), and lower overall quality of life (SF-36), controlling for age and time using mixed effect models. Patients with improved pain symptoms and lower pain scores had significantly lower inflammatory marker levels relative to baseline (e.g., interleukin-6). Conclusions: Our study demonstrated high rates of response to concurrent RT with palbociclib and HT with acceptable levels of toxicity. These results suggest that RT to bone mets effectively alleviates pain in patients taking palbociclib and pain response to treatment is associated with decreased inflammatory markers. RT may be given to pts receiving palbociclib and HT for breast cancer. Clinical Trial Identification: NCT03691493 Citation Format: Mylin Torres, Jolinta Lin, Sarah Friend, Canhua Xiao, Yichun Cao, Shannon Kahn, Karen Godette, Sheela Hanasoge, David Yu, Tony Eng, Matthew Cheney, Nancy Wiggers, Andrew Pippas, Keerthi Gogineni, Jane Meisel, David Schuster, Aditya Bardia, Andrew Miller, Jennifer Felger, Jeffrey Switchenko, Amelia Zelnak, Kevin Kalinsky, Manali Bhave. A Phase II Multi-Institutional Study of Concurrent Radiotherapy, Palbociclib, and HormoneTherapy for Treatment of Bone Metastasis in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-08.

Abstract PO5-01-12: Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens

Abstract Late recurrence of breast cancer remains a significant challenge in patient management. Despite the established efficacy of hormone therapy, factors influencing late recurrence and the impact of different hormone therapy regimens on this outcome are not yet fully understood. This study aims to investigate the key determinants contributing to late recurrence within the context of different hormone therapy regimens. This study is a retrospective analysis of medical records from two institutions between 1988 and 2018, specifically examining patients who had HR-receptor positive breast cancer who underwent surgery and completed a 5-year course of standard hormone therapy. Primary endpoint is to identify the demographic, clinical and pathologic factors as associated with late recurrence. Out of 1929 eligible patients, 49.6% (956) received Tamoxifen (TMX), 37.6% (726) received Aromatase inhibitors (AI), and 12.8% (247) switched between regimens (TMX to AI or AI to TMX). Median follow-up was 12.1 years (3.75 - 21.41 years). During this period, all-type recurrence (ATR) occurred in 9.3% of all patients, with higher rates in the TMX recipients (12.2%). Locoregional and contralateral recurrence were identified in 10.6% of TMX recipients, 6.5% of patients who switched regimens, and 5% of AI recipients. In all patients, 5.4% were diagnosed with distant metastasis, with slightly higher rates in the TMX recipients (6.4%). Multiple sites in the bone, lung, liver and brain (34.3%) was the most prevalent location of distant metastasis (DM), followed by soft tissue (20%), liver (16.2%), bone (10.5%), lung (8.6%), and other locations. Significant differences in recurrence-free survival (RFS) were observed between hormone therapy groups (p=0.004, log-rank test). Mean overall RFS was 20.4 years (95% C.I. 20.1-20.9 years). TMX recipients had a mean RFS of 19.8 years, AI recipients had a mean RFS of 18.3 years and those who switched regimens had a mean RFS of 21.9 years. Further analysis showed premenopausal patients who switched regimens had higher RFS (p=0.014). No significant difference in RFS was seen between premenopausal patients receiving AI or Tamoxifen, or amongst post-menopausal patients with different hormone therapy regimens. No significant difference in distant metastasis-free survival (DMFS) was observed between hormone therapy groups (p=0.442). Mean overall DMFS was 21.5 years (95% C.I. 21.2 - 21.8 years), with TMX patients 21.1 years, AI patients at 18.6 years, and those who switched regimens at 21.4 years. Sub-analyses of DMFS in pre and postmenopausal patients with different hormone therapy regimens showed no significant differences. Multivariate analysis showed tumor size ≤ 2cm (p= 0.0001) and negative axillary node involvement (p= 0.0001) significantly decreased odds of developing late all-type recurrence (ATR) in TMX recipients. In patients who switched regimens, Her2 positivity (p=0.04) significantly decreased the odds of late ATR. In AI recipients, not undergoing axillary operation (p = 0.008) significantly increased the odds of late ATR. For TMX recipients, negative axillary node involvement (p=0.004), tumor size ≤ 2cm (p=0.03), and undergoing mastectomy (p=0.02) significantly decreased odds of distant metastasis (DM). Among patients who switched regimens, adjuvant anti-Her2 therapy (p=0.02) significantly decreased odds of DM. For AI recipients, high PR score (p=0.02) and undergoing sentinel lymph node biopsy significantly decreased odds of DM, while age &amp;lt; 50 years significantly increased odds of developing DM. These findings emphasize the significance of the relationship between hormone therapy regimens and factors affecting late recurrence, thereby providing valuable insights for clinical decision-making. Risk stratification based on identified factors can help in identifying patients at higher risk of late recurrence allowing for more intensive surveillance and potentially early intervention. Univariate (Chi-square, Logistic Regression) and Multivariate Analysis (Logistic Regression) for Clinicopathologic factors associated with all-type recurrence and distant metastasis after surgery and completion of 5-years endocrine therapy Table. a. LN lymph node b. SLNB, Sentinel lymph node biopsy c. ALND, Axillary lymph node dissection d. Cutoff values of Ki67 14% in KUAH and 10%in SNUH e. ER and PR cutoff value is 10% f. UV, Univariate analysis, MV multivariate analysis, O.R. Odds Ratio, C.I. Confidence Interval Citation Format: Mary Rose Mendoza, Eun-Shin Lee. Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-12.

Abstract PO2-12-10: Age-specific outcomes in breast cancer patients treated with aromatase inhibitors - A national inpatient sample database analysis

Abstract Background: This study aims to investigate the age-specific outcomes of breast cancer patients undergoing aromatase inhibitors therapy. Currently, no research exists on the age-specific differences in outcomes for this patient population. This study seeks to fill this knowledge gap and provide valuable insights into the various outcomes of these patients. Methods: This retrospective study analyzed hospitalization data from the National Inpatient Sample (NIS) between January 2016 and December 2019 using STATA/BE 17.0 for statistical analysis. It focused on breast cancer patients treated with aromatase inhibitors, evaluating outcomes like mortality, length of stay, charges, and clinical outcomes. We used univariate regression and logistic analysis, with ICD-10 codes utilized for data classification. Results: A total of 5,994 weighted hospitalizations were identified, consisting of breast cancer patients being treated with aromatase inhibitors. For patients aged below 65 (n=1,919), the inpatient mortality rate was 1.8% (n=35), while for patients aged 65 and above (n=4,075), it was slightly higher at 2.3% (n=94). However, there was no statistically significant difference in inpatient mortality between the two age groups (adjusted odds ratio [aOR] = 1.21 [0.82-1.78], p=0.339). The average length of stay (LOS) was similar for both age groups, with patients below 65 having a mean LOS of 4.75 days and those aged 65 and above having a mean LOS of 4.71 days. Total charges ($) in the younger population ( &amp;lt; 65) were incurred at a mean of $60,782.73 (56,764.18-64,801.27), compared to lesser charges in the elderly at a mean of $54,734.38 (52,339.83-57,128.94). The occurrence of pathological fractures was higher in patients below 65, with a rate of 1.6% (n=31), compared to 0.8% (n=33) in patients aged 65 and above (aOR = 0.47 [0.28-0.78], p=0.004). Regarding venous thromboembolism (VTE), the occurrence was 5.5% (n=105) in patients below 65 and 4.8% (n=195) in patients aged 65 and above. There was no significant difference between the two age groups (aOR = 0.86 [0.68-1.10], p=0.237). The occurrence of acute cerebrovascular accidents (CVA) was 0.6% (n=11) in patients below 65 and 1.6% (n=65) in patients aged 65 and above, with an aOR of 2.58 (1.38-4.80), indicating a significantly higher likelihood of CVA in the older age group (p=0.003). Patients aged 65 and above had a higher occurrence of myocardial infarction (MI) compared to patients below 65, with rates of 2.1% (n=85) and 0.1% (n=2), respectively. The aOR for MI was 2.35 (1.39-3.98), indicating a significantly higher likelihood of MI in the older age group (p=0.001). There was no statistically significant difference in the occurrence of hypertensive crisis (HTN crisis) between the two age groups (aOR=1.47 [0.93-2.34], p=0.09). Conclusion: Among breast cancer patients receiving aromatase inhibitors, there was no significant difference in in-patient mortality between those aged below 65 and those aged 65 and above. Both age groups had similar lengths of stay and charges incurred. There was no statistically significant difference in VTE and HTN crisis odds. However, patients below 65 had a higher occurrence of pathological fractures, while patients aged 65 and above had a higher likelihood of acute cerebrovascular accidents and myocardial infarction. Further guidelines must be established to improve inpatient morbidity and mortality in this patient population. Breast cancer patients on aromatase inhibitors therapy Citation Format: Rushin Patel, Akshit Chitkara, Zalak Patel, Mrunal Patel, Darshil Patel, Himanshu Kavani, FNU Anamika, Femina Patel. Age-specific outcomes in breast cancer patients treated with aromatase inhibitors - A national inpatient sample database analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-10.

Abstract PO5-17-07: MUCINOUS BREAST CARCINOMA: REAL WORLD DATA IN A REFERENCE CENTER IN SÃO PAULO

Abstract BACKGROUND: Mucinous breast carcinoma (MC) is a subtype of invasive carcinoma that corresponds to 1 to 6% of all types of breast cancer. It occurs when the mucinous component accounts for more than 50% of the tumor producing extracellular mucin in large scale. Mucin is a complex carbohydrate engaged in processes such as epithelial differentiation, adhesion modulation and cell signaling. Along with other special types of breast neoplasia, MC appears to have an unique behavior and, since it’s low amount of cases, a detailed clinical evaluation has been difficult. OBJECTIVES: To describe the profile of patients with breast MC that were treated in a reference center in São Paulo, Brazil as well as evaluate its management and outcomes. METHODS: A descriptive longitudinal observation study conducted at São Paulo’s Women’s Health Reference Center - Hospital da Mulher from July 2022 to January 2023, based on 192 medical records of patients diagnosed with MC from 2003 to 2018. RESULTS: 192 patient’s records were included. The age range was 31-93 years, out of which 74,3% of the patients were older than 50 when diagnosed. 48,7% identified as white and 43,7% showed earlier diagnoses of systemic hypertension. The time range between diagnosis and first treatment was 4,5 months. Out of the histopathological features, the nuclear grade was 3 in 69 patients (34,6% of the cases), and histological grade 1 in 52,7%. About pathological staging, the size of the tumors went form 0,5 to 9,5 cm, with an average of ± 4,7cm, the majority of them showed positive ER (89,4%), negative PR (85%), and were negative for Her-2 (76%). Greater number of patients (92,4%) went through both clinical and surgical treatment. Only 15 (7,5%) had isolated clinical treatment. 31% of the patients received systemic chemotherapy treatment, 25% of those were neoadjuvant. 81,9% of patients received aromatase inhibitor and only 17% radiotherapy. Distant metastasis were diagnosed in 27 patients (13,5%) and the local recurrence was observed in 15,3%. Out of distant metastasis, pulmonary type was more prevalent, registered in 45,7% of patients, followed by osseous (22,88%) and hepatic (14,2%). 33 patients (16,5%) progressed to death, however, the specific cause was not determined. CONCLUSION: MC is a rare subtype of breast cancer, more prevalent in post-menopausal and white women. Frequently shows low histological grade and positive hormonal receptors, which reinforces the idea of a indolent behavior. The treatment is mostly surgical, with adjuvance if necessary. Metastasis are infrequent and knowing the profile of patients with MC, as well as it’s behavior, allows the better management when facing this diagnosis. Citation Format: Marina Fleury De Figueiredo, Andre Mattar, Felipe Cavagna, Ana Lígia Minatel da Silva, Rafaella Nadai, Juliana Medeiros de Oliveira, Luma Fleury de Figueiredo. MUCINOUS BREAST CARCINOMA: REAL WORLD DATA IN A REFERENCE CENTER IN SÃO PAULO [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-07.

The effects of low HER2 expression on survival in patients with metastatic breast cancer treated with CDK 4/6 inhibitors: a multicenter retrospective study

PurposeEndocrine therapy (ET) in combination with CDK 4/6 inhibitors (CDK 4/6i) is the standard treatment modality for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (mBC). There is uncertainty about the prognostic and predictive value of HER2-low status and whether HER2-low BC is an individual biologic subtype. In this study, we aimed to investigate the prognostic effect of HER2 expression status on survival in mBC patients treated with first-line ET plus CDK 4/6i.MethodsThis multicenter retrospective study included patients with HR + /HER2-negative mBC cancer who were treated with first-line CDK 4/6i in combination with ET from January 2016 to March 2023. Patients were divided into two groups (HER2-low and zero), and survival and safety analyses were performed.ResultsA total of 201 patients were included in this study; of these, 73 (36.3%) had HER2-low disease and 128 (63.7%) had HER2-zero. There were 135 patients (67.2%) treated with ribociclib and 66 (32.8%) with palbociclib. Most of the patients (75.1%) received aromatase inhibitors as combination-endocrine therapy. Baseline characteristics were similar between the two groups. The median follow-up was 19.1 months (range: 2.5–78.4). The most common side effect was neutropenia (22.4%). The frequency of grade 3–4 toxicity was similar between the HER2-zero and low patients (32% vs 31.5%; p = 0.939). Visceral metastases were present in 44.8% of patients. Between the HER2-low and zero groups, median PFS (25.2 vs 22.6 months, p = 0.972) and OS (not reached vs 37.5 months, p = 0.707) showed no statistically significant differences.ConclusionThe prognostic value of HER2-low status remains controversial. Our study showed no significant effect of HER2 low expression on survival in patients receiving CDK 4/6i plus ET.

Chemical Shift-Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors.

Osteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift-encoded MRI (CSE-MRI) in detecting OLB needs to be investigated. To assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE-MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy. Prospective. 126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery. 1.5-T, three-dimensional CSE-MRI (six echoes), T1-weighted Dixon, short tau inversion recovery, and diffusion-weighted images. Both CSE-MRI and dual-energy x-ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T-score ≤ -2.5 from BMD measurements indicated osteoporosis, whereas T-scores of ≤ - 2.5 plus TBS ≤-3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed. Student's t-test; Mann-Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P-value <0.05 was considered statistically significant. For detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*). R2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs. 2 TECHNICAL EFFICACY: Stage 4.

Quality improvement initiative to increase bone mineral density screening with DEXA scans among patients receiving aromatase inhibitors or androgen deprivation therapy at an urban safety-net hospital.

468 Background: Patients on aromatase inhibitors (AI) or androgen deprivation therapy (ADT) are at increased risk for osteopenia and osteoporosis. Guidelines recommend baseline and regular bone mineral density (BMD) assessment with dual-energy x-ray absorptiometry (DEXA) scans for these patients. Baseline data for BMD assessment for patients on either AI or ADT at our institution was reviewed and interventions were subsequently developed to improve screening rates. Methods: A retrospective chart review was performed for patients seen in the medical oncology clinic at Denver Health from 2018 through the first 2 quarters of 2020. Patients had a diagnosis of breast cancer or prostate cancer and were prescribed AI or ADT. The review evaluated whether DEXA scans had been ordered for this population. In September 2020, interventions were implemented including: an electronic reminder for ordering providers, education for pharmacists, and education for all nurses who worked in the clinic and the infusion center. Primary care providers who work outside of the oncology clinic were also contacted. An alert in Denver Health’s electronic medical software (EPIC) was launched successfully in September 2020. The alert reminded all providers ordering AI or ADT that a DEXA scan should be performed. The data for DEXA scan monitoring post-intervention was then tracked and measured through the second quarter of 2022. Results: A total of 282 patients were prescribed AI or ADT during the initial retrospective study, out of which 88 had baseline DEXA scans performed, accounting for 31.2% of the patients. After the intervention was implemented in 2020, the rate of DEXA scans performed increased to 44.2% in 2020, 59.4% in 2021 and 54.1% in 2022. The main barriers to the completion of DEXA scans were issues with transportation, multiple appointments leading to patient confusion and time constraints, and health literacy. Conclusions: Although BMD screening remains a very important part of cancer treatment and survivorship, it remains underutilized. In addition to the EPIC alert that was implemented, we are optimistic that continued education and reminders for all clinical staff will help ensure that the utilization of DEXA scans for BMD screening for patient on AI or ADT continues to increase. Community outreach is being planned to provide education about the importance of bone health.

Variability of DNA Repair and Oxidative Stress Genes Associated with Worst Pain in Breast Cancer Survivors on Aromatase Inhibitors.

Pain is a problem affecting women with breast cancer (HR+BrCa) receiving aromatase inhibitor (AI) therapy. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in DNA repair and oxidative stress genes and perceived worst pain after 6 months of AI therapy. We explored 39 SNPs in genes involved in DNA repair (ERCC2, ERCC3, ERCC5, and PARP1) and oxidative stress (CAT, GPX1, SEPP1, SOD1, and SOD2) in women with HR+BrCa receiving adjuvant therapy (AI ± chemotherapy; n = 138). Pain was assessed via the Brief Pain Inventory. Hurdle regression was used to evaluate the relationship between each associated allele and (1) the probability of pain and (2) the severity of worst pain. ERCC2rs50872 and ERCC5rs11069498 were associated with the probability of pain and had a significant genetic risk score (GRS) model (p = 0.003). ERCC2rs50872, ERCC5rs11069498, ERCC5rs4771436, ERCC5rs4150360, PARP1rs3219058, and SEPP1rs230819 were associated with the severity of worst pain, with a significant GRS model (conditional mean estimate = 0.45; 95% CI = 0.29, 0.60; p < 0.001). These results suggest DNA repair and oxidative stress pathways may play a role in the probability of pain and the severity of worst pain. As healthcare delivery moves towards the model of precision healthcare, nurses may, in the future, be able to use these results to tailor patient care based on GRS.

Breast Cancer Survivors with Genitourinary Syndrome of Menopause Receiving Aromatase Inhibitors Are Willing to Sexual Assessment: Is a Dyspareunia Approach Enough?

Breast Cancer Survivors with Genitourinary Syndrome of Menopause Receiving Aromatase Inhibitors Are Willing to Sexual Assessment: Is a Dyspareunia Approach Enough?

Adjuvant Endocrine Therapy in Premenopausal Women With Hormone Receptor-Positive Early-Stage Breast Cancer: Risk Stratification in a Real-World Setting

BackgroundOvarian function suppression (OFS) and hormone therapy (HT) represent an adjuvant option in premenopausal hormone receptor-positive early breast cancer (HR+EBC). The SOFT-TEXT trials showed improved outcomes upon receiving aromatase inhibitors (AIs)/OFS. MethodsIn order to estimate the magnitude of absolute improvements, we conducted a retrospective study applying composite risk (CR) to 237 premenopausal HR+EBC patients. ResultsOverall, 119 of these received tamoxifen (T)/OFS and 118 received AIs/OFS. The median age was 45 years (ys). After a median follow up of 65 months, recurrence was 6.7% in T patients and 10.2% in AI ones. CR (cutoff: 2.67) and ET duration (five-year cutoff) was found to have a significant impact on DFS. Invasive disease-free survival (IDFS) at 5 ys amounted to 82.9% for a CR>2.67 and 95% with CR</=2.67 (p 0.0046). Five-year IDFS was 98.3% in patients who had completed 5-year HT compared to 54.6% of those who had stopped before 5 years (P < .0001). Excluding patients who had discontinued therapy due to disease relapse, IDFS difference at 5 years remained statistically significant (p=0.03) between the two groups, with an iDFS rate of 86.5% at 5 years in the second group. Adverse events of different grades were reported in 116 and 112 patients in the T/OFS group and the AIs/OFS, respectively. Early discontinuation due to toxicity was 3.8%. Seven patients (19.4%) discontinued therapy due to pregnancy desire (6 in the T group, 1 in the AI one); of these, one patient relapsed. ConclusionIn a real-world setting, treatment options for premenopausal patients who are candidates for HT and OFS should take risk status into account. Therefore, every effort should be made to maintain patient adherence to treatment in order to manage toxicities and improve outcomes.