Aromatase Inhibitors Group Research Articles

Patient-reported outcome and survival in premenopausal hormone receptor-positive breast cancer patients at moderate to high risk: comparing toremifene with aromatase inhibitor in a real-world study.

Toremifene, a selective estrogen receptor modulator, is commonly used in China for premenopausal breast cancer patients. This real-world study aimed to compare patient-reported outcome (PRO) and survival between toremifene and aromatase inhibitor (AI) plus ovarian function suppression (OFS) in patients with moderate-/high-risk premenopausal hormone receptor (HR)-positive breast cancer. The primary endpoint was PROs, assessed using SF-36 and EQ-5D-5L questionnaires between January and March 2023. A total of 392 patients were included, with 171 receiving toremifene and 221 receiving AI. The toremifene group showed significantly higher scores in the role physical (p=0.034) and mental health (p=0.009) dimensions of SF-36 and lower anxiety/depression (AD) scores (p=0.038) in EQ-5D-5L compared to AI group. The estimated 5- and 8-year disease-free survival (DFS) rates were similar in toremifene and AI groups: 96.5% versus 91.9%, and 87.4% versus 87.8% (p=0.39), respectively. Adverse event rates were similar in two groups, except for a greater risk of endometrial thickening (p<0.001) and a lower occurrence of morning stiffness (p<0.001) in the toremifene compared to the AI group. Premenopausal HR-positive breast cancer patients receiving toremifene plus OFS had better role physical and mental health outcomes and lower AD dimensions than those receiving AI plus OFS. Both treatments had comparable DFS and favorable tolerability profiles.

Impact of aromatase inhibitors on mortality and hospitalization costs in patients with breast cancer: A National Inpatient Sample analysis 2020.

e13160 Background: Breast cancer is a significant public health concern globally, affecting millions of individuals each year. Aromatase inhibitors are a class of medications commonly used in the treatment of hormone receptor-positive breast cancer. The significance of the study lies in the impact of aromatase inhibitors on mortality and also healthcare-related costs for the treatment of breast cancer. Methods: The National Inpatient Sample database (2020) was used to identify adult patients with breast cancer using ICD-10 codes. Demographics (age, race, sex, region, and hospital size), co-morbidities, and hospitalization costs were compared between the two groups of patients: those who are on aromatase inhibitors and those who are not. The odds of mortality were analyzed. A p&lt;0.05 was considered statistically significant. Results: Out of 166870 patients who had breast cancer, 12975(7.7%) were on aromatase inhibitors. The aromatase inhibitors group was relatively older (median age, 69.4 years vs 64 years) and predominantly white (71.50% vs 66%) compared to the non-aromatase inhibitors group. The prevalence of heart failure and osteoporosis was greater in the aromatase inhibitors group than in the non-aromatase inhibitors group. The adjusted odds ratio of mortality in the aromatase inhibitors group was 0.45, 95% CI (0.39-0.50, p&lt;0.0001). Furthermore, the average total cost of hospitalization in the aromatase inhibitor group was $6426 less than the non-aromatase inhibitor group. Conclusions: Our study findings indicate that breast cancer patients treated with aromatase inhibitors experienced lower odds of mortality and lesser costs of hospitalization. However, the aromatase inhibitor group was found to have a higher prevalence of heart failure and osteoporosis. Hence, further research needs to be done on potential adverse effects and long-term effects of the aromatase inhibitors treatment.

Abstract PO2-17-03: Patient reported outcomes (PROs) and survival with toremifene versus aromatase inhibitors (AI) in patients with moderate/high-risk premenopausal hormone receptor (HR)-positive breast cancer: A real-world study

Abstract Background: The selective estrogen receptor modulator (SERM) toremifene, a synthetic analogue of tamoxifen, has shown similar efficacy to tamoxifen in patients with HR-positive breast cancer and is widely used in China for the treatment of premenopausal women with breast cancer. Multiple studies have confirmed the benefit of ovarian function suppression (OFS) combined with AI and SERMs in premenopausal women with HR-positive breast cancer. However, to date, there are no data comparing the efficacy and safety of toremifene plus OFS versus AI plus OFS. In this real-world study, we compared PROs and survival with toremifene or AI combined with OFS in patients with moderate/high-risk premenopausal HR-positive breast cancer. Methods: We enrolled premenopausal female patients with HR-positive, moderate/high-risk breast cancer who received OFS combined with toremifene or AI between January 1, 2010 and December 31, 2017 at the Breast Cancer Center of Sun Yat-sen Memorial Hospital. The primary endpoint was PROs, which were collected from January 1 to March 31, 2023, including the SF-36 and five-level EuroQol five-dimensional (EQ-5D-5L) questionnaires. Disease-free-survival (DFS) and safety were secondary endpoints. Associations between treatment group and SF-36 scores were evaluated using a Student’s t test and between treatment group and EQ-5D-5L scores using nonparametric tests. DFS was assessed using the Kaplan–Meier method and Cox regression. Results: A total of 392 patients were enrolled; 171 (43.6%) received toremifene and 221 (56.4%) received AI. Mean ± standard deviation scores for the role physical and general health dimensions of SF-36 were higher in the toremifene group versus the AI group (7.44±1.21 vs 7.15±1.48, P=0.034 and 22.90±3.95 vs 21.78±4.33, P=0.009, respectively). Scores on the anxiety/depression (AD) dimension of EQ-5D-5L were significantly different between the toremifene and AI treatment groups (mean rank: 184.14 vs 206.07, P=0.038); ‘no problems’ was selected by 49.7% and 37.1% of patients in the toremifene and AI groups, respectively. There were no significant differences in the other dimensions of SF-36 and EQ-5D-5L between the toremifene and AI groups (P&amp;gt;0.05). Similar estimated 5- and 8-year DFS rates were reported for the toremifene and AI groups; 96.5% (95% CI: 93.7-99.2) and 91.9% (95% CI: 88.2-95.5), and 87.4% (95% CI: 81.1-93.8) and 87.8% (95% CI: 81.1-94.4), respectively, and the hazard ratio for DFS was 0.75 (95% CI: 0.38-1.46), P=0.39. DFS was also comparable in the two treatment groups when stratified by HER2 status, age (≤40y vs &amp;gt;40y) and estrogen receptor expression level (≤20% vs &amp;gt;20%). Adverse event rates were generally similar in the two treatment groups, except for a higher rate of endometrial thickening (17.5% vs 1.8%, p&amp;lt; 0.001) and a lower rate of morning stiffness (7.6% vs 14.5%, p&amp;lt; 0.001) in the toremifene versus the AI group. Conclusion: Patients who received toremifene plus OFS had better role physical and general health dimensions on SF-36 and AD dimensions of EQ-5D-5L than those receiving AI plus OFS. There were no significant differences in 5- or 8-year DFS between the toremifene and AI groups. Both treatments were generally well tolerated. Citation Format: Yaping Yang, Fengxia Gan, Wenqian Yang, Yuan Xia, Qiang Liu, Chang Gong. Patient reported outcomes (PROs) and survival with toremifene versus aromatase inhibitors (AI) in patients with moderate/high-risk premenopausal hormone receptor (HR)-positive breast cancer: A real-world study [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 PO2-17-03.

Abstract PO1-02-04: The efficacy of endocrine therapy during the waiting period for surgery for hormone receptor-positive breast cancer

Abstract Background: Although neoadjuvant endocrine therapy has been used to improve breast conservation rate, its prognostic relevance is unknown. The search for a valid prognostic factor equivalent to pCR in neoadjuvant chemotherapy is a current challenge in neoadjuvant endocrine therapy. In this study, we investigated the efficacy of short term neoadjuvant endocrine therapy utilizing the waiting period for surgery and the prognostic factor including Preoperative Endocrine Prognostic Index (PEPI) score. Methods: A total of 480 patients with StageⅠ-Ⅲ hormone receptor-positive, HER2-negative breast cancer was treated with endocrine therapy during the waiting period for surgery between October 2012 and December 2021. Premenopausal and postmenopausal patients received tamoxifen (TAM) and non-steroidal aromatase inhibitor (AI), respectively. The primary endpoint was change in tumor size by ultrasound and Ki67 expression before and after short term endocrine therapy. The secondary endpoint was prognosis of patients divided by PEPI score which was calculated using tumor size, lymph node metastasis, Ki67 expression, and ER Allred score. This study was approved by the institutional review board of Teikyo University. Results: Median age and tumor size of the entire 480 patients was 55 years (range, 31 - 89), 1.65 cm (range, 0.4 – 7.5), respectively. The median duration of endocrine therapy was 39 days (range, 1-90). 19 (0.3 %) pts were clinically node-positive. Of the entire 480 patients, 211 and 269 patients had TAM and AI, respectively. After short term endocrine therapy, the tumor size was significantly reduced from 1.83cm to 1.62cm in AI group (p=0.02), although TAM did not decrease the tumor size (p=0.89). The Ki67 expression was significantly decreased from 16.4% to 11.3% in TAM group (p=0.002), and from 15.9% to 6.98% in AI group (p &amp;lt; 0.001). There were significant differences in the distribution of PEPI scores between TAM and AI group (p &amp;lt; 0.05) (Table). At the median follow-up of 1012 days, patients with PEPI score ≥ 4 showed worse disease-free survival compared with patients with PEPI score &amp;lt; 4 in TAM group (Figure1). Overall survival is not available because there were no deaths in TAM group. At the median observation period of 833 days, patients with PEPI score ≥ 4 showed worse disease-free survival compared with patients with PEPI score &amp;lt; 4 in AI group (Figure2). In terms of mortality, patients with PEPI score ≥ 4 had worse overall survival than patients with PEPI score 0 and 1-3 (p=0.07). Conclusions: These results suggested that neoadjuvant endocrine therapy during the waiting period for surgery might be effective in reducing Ki67 expression level and PEPI score might be useful in predicting the prognosis of hormone receptor positive breast cancer patients. Table. Distribution of PEPI score Figure 1. Disease-free survival in patients treated with tamoxifen Figure 2. Disease-free survival in patients treated with non-steroidal aromatase inhibitor Citation Format: Yuka Maeda, Saki Naruse, Yuka Isono, Ayana Sato, Akiko Matsumoto, Tatsuhiko Ikeda, Hiromitsu Jinno. The efficacy of endocrine therapy during the waiting period for surgery for hormone receptor-positive breast cancer [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 PO1-02-04.

Lipid changes during endocrine therapy in early-stage breast cancer patients: A real-world study

BackgroundEndocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs.MethodsThe changing trend of blood lipid during endocrine therapy in 2756 BC patients from January 2013 to December 2021 was retrospectively analyzed. The changes in four lipid parameters were assessed by the Generalized Linear Mixed Model, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). These parameters were quantified at baseline and at 6, 12, 18, 24, 36, 48, 60, and 72 months after endocrine therapy initiation. Furthermore, a subgroup analysis according to menopausal status or medication types was conducted.ResultsA total of 1201 patients taking aromatase inhibitors (AIs), including anastrozole (ANA), letrozole (LET), or exemestane (EXE), and 1555 patients taking toremifene (TOR) were enrolled. TC and TG levels showed a significantly elevated trend during 5 years of treatment (P < 0.05). HDL-C levels increased from baseline in the TOR group (P < 0.05). Compared with the postmenopausal AI group, the increasing trends of TC, TG, and LDL-C in the premenopausal AI group were more evident with the extension of time (β = 0.105, 0.027, 0.086, respectively). Within 3 years, TC, TG, and LDL-C levels in the ANA and LET groups were significantly higher than baseline (P < 0.05). Moreover, the levels of TG in the EXE group were significantly lower than that in the ANA or LET group (P < 0.05), but this significant difference disappeared after 3 years.ConclusionsAIs significantly influenced lipid profiles more than TOR. AIs had a greater effect on blood lipids in premenopausal patients. Steroidal AIs (EXE) may affect lipid levels less than nonsteroidal AIs (ANA and LET).

Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older.

Elderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data are needed to inform clinical management of elderly patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This subanalysis of the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness of palbociclib plus an aromatase inhibitor (AI) versus an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years treated in routine clinical practice in the United States. This retrospective observational cohort study used electronic health records from the Flatiron Health Analytic Database. Palbociclib treatment patterns, overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Three methods were used for comparative analyses: (1) an unadjusted analysis, (2) stabilized inverse probability treatment weighting (sIPTW; primary analysis), and (3) propensity score matching (PSM; sensitivity analysis). A total of 961 patients aged ≥ 75 years with HR+/HER2- mBC were identified who started palbociclib plus an AI (n = 313) or an AI alone (n = 648) as first-line (1L) therapy between February 2015 and March 2020 (data cut-off: September 30, 2020). Among patients in the palbociclib plus an AI group with a documented palbociclib starting dose (n = 306), approximately 75% started palbociclib at 125 mg/day, and approximately 40% experienced dose adjustment. After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51-0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59-0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55-0.87]; P = 0.0014). These significant improvements in OS, rwPFS, and TTC remained consistent in the unadjusted analysis and after PSM. This real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years. These findings support palbociclib plus an AI as a standard-of-care 1L treatment for elderly patients with HR+/HER2- mBC.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. NCT05361655.

Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer.

(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand-foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.

Abstract P3-03-26: Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data

Abstract Purpose: Osteopenia and osteoporosis are commonly encounter in elder women. One third of women elder than fifty years suffer a fracture second to osteoporosis around the world. Standard treatments for breast cancer such as chemotherapy or hormonal therapy may increase the risk of both osteopenia and osteoporosis. Premenopausal women treated with standard adjuvant chemotherapy frequently develop ovarian failure, or early menopause, which is associated with accelerated bone loss. Trabecular bone score (TBS), an index extracted by DXA that provides an indirect measurement of bone axial microarchitecture. In addition to the BMD, TBS are warranted to improve the prediction of fracture risk at the individual level. However, due to regulations of National Health Insurance in Taiwan, data are limited on the incidence of osteopenia and osteoporosis in women with breast cancer in Taiwan. In this study, we investigated the proportion of osteopenia and osteoporosis in women with breast cancer in Taiwan. Materials and Methods: There were enrolled 201 female who diagnosed with breast cancer between May 2019 and December 2020 in this retrospective study. Patients with bone metastasis (n=11) and double cancer(n=3) were excluded. All patients received dual energy X-ray absorptiometry (DXA) at least once, including bone mineral density (BMD), T-score (spine and total hip) and trabecular bone score (TBS) data. The data were retrospectively analyzed baseline age, BMD, breast cancer type, aromatase inhibitors (AIs) usage status by Kruskal-Wallis test. Results: Basing on the lowest T-score from measurements at the spine or total hip, 58.8% (n=110) of osteopenia (-2.5≤T←1) and 27.8%(n=52) of osteoporosis (T←2.5) were identified in women with breast cancer (figure1). Statistics significance was noted in patients’ age and BMI between three groups. There was no difference in bone mineral density according to breast cancer subtype. (table 1) Patients who ever use aromatase inhibitors (n=90) had lower BMD (T=-2.14) and trabecular bone score (TBS=1.3) than non-AI group (n=97, T=-1.84, TBS=1.34). (figure 2) (table 2) Conclusions: According to Taiwan’s NHI sampling data from 1999 to 2001, the averaged prevalence of osteoporosis in those aged ≥50 years was 11.35% for women. Breast cancer survivors are at higher risk for osteopenia and osteoporosis compared to cancer-free women in Taiwan. Aromatase inhibitors (AIs) group had lower BMD and TBS (p&amp;lt; 0.05). In our study, forty percent of TNBC patients diagnosed osteoporosis, which is compatible with increased bone loss due to chemotherapy-induced ovarian failure. Therefore, clinicians should be aware not only of AI-associated bone loss but also of patients who ever accepted long-term chemotherapy. A normal range for TBS values in postmenopausal women has been proposed: a TBS of ≥1.350 is considered normal; a TBS between 1.20 and 1.35 is considered consistent with partially degraded microarchitecture, and a TBS of ≤ 1.200 defines degraded microarchitecture. In our study, mean TBS in women with breast cancer (n=187) is 1.32. Further research is needed to determine the validity of cut-points for guiding treatment decisions. Figure 1. Inclusion/exclusion criteria and flow chart Figure 1. Inclusion/exclusion criteria and flow chart Table 1 Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Citation Format: Chia-Hua Liu, Chih-Chiang Hung, I-Chen Tsai. Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-26.

Abstract P3-01-14: Real-world treatment patterns of Palbociclib plus an aromatase inhibitor or aromatase inhibitor alone for metastatic breast cancer in the Flatiron database

Abstract Background: CDK4/6 inhibitor in combination with an aromatase inhibitor (AI) or fulvestrant as initial endocrine therapy are standard of care for patients with HR+/HER2– advanced/metastatic breast cancer (mBC). This analysis describes treatment patterns including dosing patterns and time to subsequent treatment in patients receiving first line Palbociclib (PB)+AI therapy compared to AI alone, for HR+/HER2– mBC in the US routine clinical setting. Methods: This was a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records from over 280 cancer clinics representing more than 3 million actively treated cancer patients in the US. Between February 2015 and March 2020, 2888 postmenopausal mBC women and men aged ≥18 years started first-line PB+AI or AI therapy. Patients were followed from start of therapy to September 2020, death, or last visit, whichever came first. PB treatment patterns were captured as starting dose and dose adjustments from medical records during the observation period. Comparative time to subsequent therapy (TTNT) or chemotherapy (TTC) was defined as length of time from the start of treatment to next line of anticancer therapy/chemotherapy, death from any cause, last visit, or end of study, whichever came first. Cox proportional-hazards models were used to estimate the relative effectiveness of PB+AI vs AI. Stabilized inverse probability treatment weighting (sIPTW) and propensity score matching (PSM) statistical methods were used to balance of baseline demographics and clinical characteristics. Results: Of the 2888 eligible pts (1324 with PB+AI and 1564 with AI), median age was 70.0 years, 67.8% were white, 34.8% had de novo mBC, 29.4% had lung or liver involvement, 38.7% had bone-only disease. Median follow-up was 25.0 months in the PB+AI arm and 23.3 months in the AI alone arm. Of the 1342 patients receiving PB, therapy was started at 125 mg, 100 mg, and 75 mg/day in 83.8%, 10.9%, 3.6%, respectively (1.7% undocumented PB dose) with dose changes in 41.1%, 36.8%, 31.3% of patients in each starting dose category with dosing information. After sIPTW median TTNT was 18.4 months (95%CI: 16.3-20.3) in the PB +AI group and 8.3 months (95%CI: 7.2-10.0) in the AI group; HR=0.56 (95%CI: 0.51-0.62), p&amp;lt; 0.0001. After sIPTW median TTC was 37.4 months (95%CI: 33.7-40.7) PB+AI group and 29.2 months (95%CI: 26.8-33.5) in the AI group; HR=0.77 (95%CI: 0.69-0.86), p&amp;lt; 0.0001. Results for the PSM analyses were similar. The table presents full results in detail. Conclusions: These treatment patterns analyses in a heterogeneous mBC patients from real world US clinical practice, provide support for first line PB+AI treatment for HR+/HER2– mBC. The majority of patients initiated therapy at the 125 mg/daily dose (84%). Importantly, these analyses also report meaningful differences in the delay to next line of therapy and chemotherapy in the PB+AI compared to AI therapy arm. Table. Median time to next line of therapy or chemotherapy Citation Format: Hope Rugo, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M. Layman, Adam M. Brufsky. Real-world treatment patterns of Palbociclib plus an aromatase inhibitor or aromatase inhibitor alone for metastatic breast cancer in the Flatiron database [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-14.

Abstract P1-02-06: Improved survival with ovarian function suppression in premenopausal hormone receptor-positive breast cancer: a propensity score matching of ASTRRA-trial participants with single-center postmenopausal patients

Abstract Background: Poor survival outcome in young women with hormone-sensitive breast cancer was reported. And previous studies have demonstrated that the addition of ovarian function suppression (OFS) significantly improved disease-free survival (DFS) in patients with premenopausal hormone receptor–positive breast cancer. In this study, we examined whether ovarian function suppression treatment in premenopausal women is effective in survival comparable to postmenopausal status. Methods: We evaluated 1,298 breast cancer patients included in the post-trial follow-up of the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial who received either tamoxifen (TAM) only (n=647) or TAM + OFS (n=635), randomly assigned in a 1:1 ratio and postmenopausal patients in AMC (Asan Medical Center; Seoul, Korea) treated with aromatase inhibitor (AI) (n=603). All patients analyzed in this study underwent surgery between March 2009 and November 2011. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was overall survival (OS). We use propensity-score matching by lymph node status, tumor size, tumor grade, histologic type of cancer, human epidermal growth factor receptor-2 (HER2) status, chemotherapy regimen, surgical modality, and radiotherapy in the overall cohort and in separate subgroups according to anti-hormonal therapy regimens. Results: In the overall matched cohort, there was a significant difference between the postmenopausal AI group and premenopausal Tam only group in DFS (hazard ratio for the postmenopausal AI group, 0.654; 95% CI, 0.432 to 0.991) and OS was not significantly different between the premenopausal Tam only group and postmenopausal AI group (p=0.061). On the other hand, there was no significant difference between the postmenopausal AI group and premenopausal Tam+OFS group in disease free survival (hazard ratio for the postmenopausal AI group, 1.156; 95% confidence interval [CI], 0.735 to 1.820) or the overall survival (hazard ratio for the postmenopausal AI group, 1.04; 95% CI, 0.553 to 1.956). Conclusion: This study’s findings suggest that the poor prognosis of young women with hormone-sensitive breast cancer is improved by adding OFS to Tam and the effect is not inferior to that of using AI in post-menopausal women. Outcomes in a Cohort of Patients Matched for Propensity Scores postmeno AI, postmenopausal patients who treated with aromatase inhibior in Asan Medical Center; premeno Tam+OFS, premenopausal ASTRRA participants who treated with tamoxifen and ovarian function suppression; premeno Tam, premenopausal ASTRRA participants who treated with tamoxifen only Citation Format: Young-jin Lee, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Seonok Kim, Hee Jeong Kim. Improved survival with ovarian function suppression in premenopausal hormone receptor-positive breast cancer: a propensity score matching of ASTRRA-trial participants with single-center postmenopausal patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-02-06.

Risk of Cardiovascular Events and Lipid Profile Change in Patients with Breast Cancer Taking Aromatase Inhibitor: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) is one of the most common comorbidities in breast cancer survivors. Recently, the target population and treatment period for aromatase inhibitor (AI) treatment in breast cancer patients has been expanding. However, information on adverse CVD events from the long-term use of AI is still lacking. The aim of this study was to investigate the CVD side effects of AI treatment and to evaluate the changes in lipid profile during AI treatment. A systematic search of PubMed (Medline), EMBASE, and Cochrane Library databases reporting on cardiovascular outcomes or lipid profiles change in adult female breast cancer patients (>19 years old) with AI was performed. The pooled analysis of 25 studies showed that the prevalence rate of any type of cardiovascular disease was 6.08 per 100 persons (95% CI 2.91-10.31). Angina was the most common type of heart-related cardiovascular event accounting for 3.85 per 100 persons, followed by any type of stroke (3.34) and venous thromboembolism (2.95). Ischemic stroke (OR 1.39, 95% CI 1.07-1.81) and myocardial infarction (OR 1.30, 95% CI 0.88-1.93) were more common in AI compared with tamoxifen, whereas the prevalence of venous thromboembolism (OR 0.61, 95% CI 0.37-1) was significantly lower in the AI group. In addition, treatment with AI for 6-12 months showed a decrease in HDL-cholesterol and an increase in LDL-cholesterol and total cholesterol. Various CVDs can occur when using AI, and in particular, the risk of MI and ischemic stroke increases in comparison with the adverse effect of tamoxifen. The occurrence of CVD might be related to the deterioration of the lipid profile after AI treatment. Therefore, a customized individualization strategy considering each patient's CV risk factors is needed during AI treatment.

Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients.

Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient-physician communication and a good-quality care network.

The effect of aromatase inhibitor on controlled ovarian stimulation for oocyte cryopreservation in adolescent and young cancer patients.

To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.

Comparison of changes in lipid profiles of premenopausal women with early-stage breast cancer treated with different endocrine therapies

Adjuvant endocrine therapy improves the prognosis of early breast cancer with hormone receptor positivity. However, there is no systematic report on the effect of endocrine therapy (particularly ovarian function suppression, OFS) on serum lipids in premenopausal women. This retrospective cohort study aimed to determine whether various endocrine treatments had different effects on blood lipids. This study enrolled 160 premenopausal patients with stage I–III breast cancer in eastern China. The initial diagnostic information was retrieved from patient's medical records, including age at the time of diagnosis, tumor characteristics, anticancer treatment and past medical history. The changes in blood lipids in patients receiving different types of endocrine therapy were compared at the 3rd, 6th, 12th, and 24th months after initiating endocrine therapy. Generalized linear mixed model was used in our analyses. Our data revealed that low-density lipoprotein cholesterol (LDL-C) levels in patients with tamoxifen (TAM) were significantly lower in the 6th, 12th, and 24th months than that in the 3rd month, while high-density lipoprotein cholesterol (HDL-C) levels in the 6th, 12th, and 24th months were significantly higher than that in the 3rd month, indicating that blood lipid levels generally improved with time. While in TAM plus OFS group, HDL-C levels were significantly higher in the 24th month than in the 3rd month, total cholesterol (TC) levels were significantly higher in the 24th month than in the 6th month. The lipid profiles of OFS plus aromatase inhibitor (AI) group did not show significant differences at any time point but were significantly higher than those of the other two groups especially in LDL and TC. TAM group tended to have lower serum lipid levels. With longer follow-up, no statistically significant difference in values was observed between TAM and TAM plus OFS groups at various time points. Compared with the other two groups, OFS plus AI group presented an increasing trend toward LDL-C and TC. The risk of dyslipidemia requires further investigation using a large sample size.

Increased Clinical Pain Locations and Pain Sensitivity in Women After Breast Cancer Surgery: Influence of Aromatase Inhibitor Therapy.

Aromatase inhibitors (AIs), which potently inhibit estrogen biosynthesis, are a standard treatment for hormone sensitive early-stage breast cancer. AIs have been associated with substantial joint pain and muscle stiffness (aromatase inhibitor-associated musculoskeletal syndrome). However, the link between AIs and number of clinical pain locations and pain sensitivity are less well understood. The aim of this study was to compare longitudinal changes in clinical pain and quantitative pain sensitivity between women who did or did not receive AI therapy. Women with early-stage breast cancer were prospectively enrolled and assessed for clinical pain in surgical and nonsurgical body areas using the Brief Pain Inventory and Breast Cancer Pain Questionnaire, and for pain sensitivity using quantitative sensory testing preoperatively and at 1 year postoperatively. Pain outcomes between participants who did and did not begin adjuvant AI therapy were compared using Wilcoxon Signed-Ranks and generalized estimating equation linear regression analyses. Clinical pain and pain sensitivity were comparable between AI (n=49) and no-AI (n=106) groups preoperatively. After adjusting for body mass index, AI therapy was associated with a greater increase in the number of painful nonsurgical body sites (significant time by treatment interaction, P =0.024). Pain location was most frequent in knees (28%), lower back (26%), and ankles/feet (17%). Quantitative sensory testing revealed a significant decrease in pain sensitivity (increased pressure pain threshold) in the no-AI group over time, but not in the AI group. AI therapy was associated with increased diffuse joint-related pain and greater post-treatment pain sensitivity, potentially implicating central sensitization as a contributing pain mechanism of aromatase inhibitor-associated musculoskeletal syndrome worthy of future investigation.

Real-World Patient Characteristics, Utilization Patterns, and Outcomes of US Patients with HR+, HER2- Metastatic Breast Cancer Treated with Abemaciclib.

Abemaciclib is the most recent oral cyclin-dependent kinase 4 and 6 inhibitor (CDK4 & 6i) to receive US Food and Drug Administration (FDA) approval to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC). Administrative claims data were used to describe patient characteristics and select clinical and economic outcomes in US patients treated in routine clinical practice. Prior analyses from electronic health records data indicate approximately 25% of patients received either palbociclib or ribociclib for MBC before initiating abemaciclib treatment; this work further explored these findings and associated outcomes. This retrospective study analyzed medical and pharmacy claims from the IBM® MarketScan® Research Databases between 1 January 2007 to 31 January 2020. Patients with HR+, HER2- MBC newly initiating abemaciclib between 1 September 2017 and 31 October 2019 were included and grouped by concomitant therapy (+aromatase inhibitor (AI), +fulvestrant (F), 200mg abemaciclib monotherapy (Mono), or +other), and outcomes were analyzed by prior CDK4 & 6i use. Patient and treatment characteristics were summarized with descriptive statistics. Kaplan-Meier methods assessed time-to-discontinuation (TTD; i.e., persistency) and time-to-chemotherapy (TTC). Adherence (defined by the medication possession ratio) and drug wastage were determined. This analysis included 454 patients (mean age 57.7years), with 35.0% (n = 159) in the +F group, 29.3% (n = 133) in the +AI group, 10.4% (n = 47) in the 200 mg Mono group, and 25.3% (n = 115) in the +other group. Prior chemotherapy and CDK 4 & 6i use were present in 23.8% and 49.8% of all patients, respectively. Visceral metastases were present at abemaciclib initiation in 50.4% in the +AI group; 49.7% in the +F group; and 55.3% in the 200 mg Mono group. Liver metastases were present in 33.7% of the overall population. Among patients without prior CDK4 & 6i use, the median TTD for patients receiving abemaciclib + AI was not reached [95% CI 430-not reached (NR) days], abemaciclib + F [531 days (95% CI 281-NR)], and abemaciclib mono [141 days (95% CI 80-NR)]. Median TTC for abemaciclib + AI and abemaciclib + F groups were not reached and the median TTC for abemaciclib mono was 535 days (95% CI 181-NR). Medication adherence was 88.7% and medication wastage costs among those with at least one dose modification were $808.12 and $452.2 per patient per month based on amount paid and wholesale acquisition cost (WAC), respectively. Mean length of follow-up for all patients was 350 days (SD 187). These real-world data complement clinical trial results by examining abemaciclib use among patients treated in routine clinical practice. The sizeable number of patients treated with prior CDK4 & 6i, chemotherapy, and/or visceral metastases at abemaciclib initiation suggest that many patients had very advanced disease and/or were in later stages of their treatment. These data confirm a higher percentage of patients treated with previous CDK4 & 6i than reported previously, reinforcing the importance of the ongoing, prospective clinical trials evaluating outcomes following progression on CDK4 & 6i.

Real-world assessment of quality-of-life in patients with breast cancer treated with adjuvant endocrine therapy.

Objective: The aim of this study was to investigate quality-of-life (QoL) in breast cancer (BC) patients treated with adjuvant endocrine therapy (AET). Methods: Wedesigned a cross-sectional study of 233 BC patients treated with AET andused the Functional Assessment of Cancer Therapy - Breast questionnaire. Results: No significant difference was observed between endocrine agents. Duration of AET did not affect QoL. In the entire cohort, multivariate analysis determined age (p=0.034) and switching treatment from tamoxifen to aromatase inhibitors (p=0.049) as significant positive coefficients of QoL, while comorbidity (p=0.072) tended to be associated with lower scores. Education level (p=0.001) and chemotherapy (p=0.04) were significant predictors of QoL in the tamoxifen group, while comorbidity (p=0.04), surgery type (p=0.02), radiotherapy (p=0.006) and stage (p=0.009) had a significant impact on QoL in aromatase inhibitors group. Conclusion: Evaluating the well-being of BC patients by QoL questionnaires is of great importance to identify particular subgroups that may require supportive care.

Association of Obesity and Luminal Subtypes in Prognosis and Adjuvant Endocrine Treatment Effectiveness Prediction in Chinese Breast Cancer Patients.

PurposeTo evaluate the influence of obesity on clinicopathological characteristics of breast cancer; to explore the effect of obesity on the prognosis and performance of endocrine therapy in breast cancer patients.MethodsPatients with luminal/HER2-negative early breast cancer were included and categorized into the non-obese (BMI<28kg/m2) and obese (BMI≥28kg/m2) groups according to body mass index (BMI). Clinicopathological characteristics and treatment modalities were compared between groups. Interaction of adjuvant endocrine therapy with obesity was analyzed.ResultsA total of 2,875 patients were included: 2,598 non-obese and 277 obese. A higher rate of patients with comorbidities (OR: 2.83, 95%CI 2.13-3.74, P<0.001) or PR-positive tumor (OR: 1.63, 95%CI 1.03-2.58, P=0.037) were identified in the obese group. Obesity was not associated with disease recurrence (P=0.839) or overall survival (P=0.140) in the whole population. Subgroup analysis did show an association with worse relapse-free survival (RFS, HR 3.48, 95%CI 1.31-9.22, P=0.012) and overall survival (OS, HR 4.67, 95%CI 1.28-16.95, P=0.019) in luminal A breast cancer. These results could not be reproduced in the luminal B subtype with a RFS (HR 0.78, 95%CI 0.41-1.49, P=0.454) or OS (HR 1.17, 95%CI 0.50-2.74, P=0.727). Furthermore, obesity did not impact endocrine therapy effectiveness in Tamoxifen or the aromatase inhibitor group (RFS: interact P=0.381; OS: interact P=0.888).ConclusionsThe impact of obesity on prognosis interacted with luminal subtype status in Chinese breast cancer patients which was not related with endocrine treatment modality.

Cognitive complaints during breast cancer endocrine therapy: aromatase inhibitors versus tamoxifen

ObjectivePrevious data hypothesise that women receiving aromatase inhibitors (AIs) exhibit worse cognitive functioning than patients on tamoxifen (TAM) since their oestrogen levels are lower. We aimed to compare cognitive complaints...