Adjuvant Endocrine Therapy Research Articles

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki-67 in patients with locally advanced breast cancer

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker’s expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) – estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up.

Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates.

The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60mg via subcutaneous injection every 6months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes.

Factors Influencing Adherence to Adjuvant Endocrine Therapy After Breast Cancer Surgery.

Women with newly diagnosed hormone receptor-positive breast cancer are offered adjuvant endocrine therapy (AET). Despite the survival benefits of the therapy, a significant proportion of breast cancer patients do not adhere to the anti-hormonal medication. The purpose of this study was to analyse demographic, social, psychological and treatment-related factors influencing whether women diagnosed with early-stage breast cancer were adherent to offered therapy. This was a long-term retrospective, medical record study, supplemented with a questionnaire, including 81 women. Data from the Swedish Prescribed Drug Register were used to examine adherence. The women were followed for 5 years of offered AET. Out of 81 women, 67 (83%) were adherent (hade taken out 80% or more of the recommended dose), 10 (12%) were Partially Adherent and 4 (5%) never accepted AET. At baseline, the Never-Adherent group members were younger, more often considered themselves healthy and seemed much more satisfied with their lives. Baseline factors that positively affected adherence were satisfaction with the vocational situation (p = 0.023) and satisfaction with family life (p = 0.040). Cumulative musculoskeletal side effects were more frequently reported among women in the Adherent group than Partially Adherent women, after both 12 and 60 months (p = 0.018 and p = 0.011, respectively). There was also a significant difference in reported cumulative psychological side effects (p = 0.049) in disfavour of the Adherent group. Moreover, according to the questionnaire where the women retrospectively were asked which side effects, they experienced during the treatment period; sexual desire was significantly lower in the Adherent group (p = 0.0402) than in the Partially Adherent group. It is important to consider a woman's life situation, to support those who otherwise would not be able to complete AET and to help all women relieve side effects during AET. It should be investigated why some women did not start the recommended therapy.

Acceptability of Four Intervention Components Supporting Medication Adherence in Women with Breast Cancer: a Process Evaluation of a Fractional Factorial Pilot Optimization Trial

Adjuvant endocrine therapy (AET) reduces mortality in early-stage breast cancer, but adherence is low. We developed a multicomponent intervention to support AET adherence comprising: text messages, information leaflet, acceptance and commitment therapy (ACT), and side-effect website. Guided by the multiphase optimization strategy, the intervention components were tested in the ROSETA pilot optimization trial. Our mixed-methods process evaluation investigated component acceptability. The pilot optimization trial used a 24–1 fractional factorial design. Fifty-two women prescribed AET were randomized to one of eight experimental conditions, containing unique component combinations. An acceptability questionnaire was administered 4 months post-randomization, and semi-structured interviews with 20 participants further explored acceptability. Assessments were guided by four constructs of the theoretical framework of acceptability: affective attitude, burden, perceived effectiveness, and coherence. Quantitative and qualitative findings were triangulated to identify agreements/disagreements. There were high overall acceptability scores (median = 14–15/20, range = 11–20). There was agreement between the qualitative and quantitative findings when triangulated. Most participants “liked” or “strongly liked” all components and reported they required low effort to engage in. Between 50% (leaflet) and 65% (SMS) “agreed” or “strongly agreed,” it was clear how each component would help adherence. Perceived effectiveness was mixed, with 35.0% (text messages) to 55.6% (ACT) of participants “agreeing” or “strongly agreeing” that each component would improve their adherence. Interview data provided suggestions for improvements. The four components were acceptable to women with breast cancer and will be refined. Mixed-methods and triangulation were useful methodological approaches and could be applied in other optimization trial process evaluations.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole

BackgroundThe monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. MethodsBetween 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. ResultsAmong 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. ConclusionPatient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT trial).

The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience.

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.

The cardiovascular and metabolic effects of ovarian suppression in combination with tamoxifen or an aromatase inhibitor as adjuvant therapy for early estrogen receptor-positive breast cancer: a systematic review

Adjuvant endocrine therapy is a key treatment in oestrogen receptor positive early breast cancer (BC). For premenopausal women ovarian function suppression (OFS) in combination either tamoxifen or aromatase inhibitor (AI) is utilised in high-risk cases. The resultant suppression of circulating oestradiol from OFS could have adverse cardiovascular and metabolic effects, subsequently increasing the risk of cardiovascular disease. Our study highlights the potential cardio-metabolic impact endocrine therapy and OFS have on premenopausal women with BC. It also highlights the pressing need for standardisation of routine collection and recording of cardiometabolic history and risk factors as part of baseline assessment and adverse event reporting to better understand the cardiometabolic impact these treatment has on our patients. Further studies, with particular focus on baseline and subsequent development of cardiovascular risk factors are needed to explore the impact of these drugs on the cardiovascular health of these young women with BC

Factors influencing 5-year persistence to adjuvant endocrine therapy in young women with breast cancer

PurposeAlthough younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC). MethodsWe retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the “Helping Ourselves, Helping Others: The Young Women's BC Study” (IBCSG 43-09 HOHO). Women completed surveys at baseline, biannually for three years, and annually for another seven years. Data collection included sociodemographic information, QoL aspects assessed by the Cancer Rehabilitation Evaluation System-Short Form and symptoms assessed by the Breast Cancer Prevention Trial symptom scales. Cox regression models were applied to identify factors associated with non-persistence. ResultsThe cumulative risk of interrupting ET within 5 years was 27.7 % (95 % CI, 21.5–35.2). The QoL subscale scores remained stable over 5 years, with slight improvements in the physical subscale. Hot flashes decreased (p < 0.001), while vaginal problems intensified (p < 0.001) over time. Being married without children and having difficulties interacting and communicating with the medical team were significantly associated with non-persistence. ConclusionsDiscussing the desire to conceive with partnered childless women and establishing a good relationship with the medical team may be important in addressing the non-persistence in young BC survivors. As recent data suggests the safety of pausing ET to conceive, this approach may be a reasonable future option to limit non-persistence.

Is immediate breast reconstruction surgery safe for elderly women? Assessment of postoperative complications in women aged 70 years and older

IntroductionThe rate of immediate breast reconstruction (IBR) in elderly women (EW) is lower than in younger patients because of concerns related to postoperative complications (POC) and their consequences. ObjectiveWe assessed POC 30 days after IBR, readmissions rate within 30 days, and the time to start adjuvant therapy in EW aged ≥ 70 years. Materials and MethodsWe conducted an observational, retrospective, single-center study between January 2014 and May 2022 at the University Cancer Institute of Toulouse-Oncopole (IUCT-O), including patients over 70 years old treated with mastectomy and IBR. Patients’ characteristics, medical treatments with the time between therapies and POC were recorded. ResultsA total of 125 women aged 70 to 84 years old were included in our study. The rate of IBR was 13.7 %. The rate of major POC was 17.6 % (n = 22), including 9.8 % (n = 11) implant removal. There was significantly more skin necrosis in patients with a history of homolateral radiotherapy (p = 0.016) but less hematoma (p = 0.004). Overweight or obese EW tending to have more than one surgical POC (p = 0.019). EW with nipple-areola complex (NAC) conservation had significantly more skin necrosis (p = 0.01). The median time for initiation of adjuvant chemotherapy (ACT) and hormonal therapy was 5.7 [1.6–11.9] and 4.3 [1.6–78.9] weeks respectively. The median time to initiate adjuvant radiotherapy (ART) when preceded by ACT or not, was 9.2 [5.1–22] and 21.1 [16.9–21.4] weeks respectively. ConclusionOur study confirms that IBR in women aged ≥ 70 years is safe and does not delay adjuvant therapies.

Associations between HIV infection status, psychosocial factors, and adjuvant endocrine therapy adherence among South African women with early-stage breast cancer.

We aimed to evaluate for associations between HIV status, psychosocial factors, and adjuvant endocrine therapy (AET) adherence in South African (SA) women with estrogen receptor positive (ER+) breast cancer (BC). We enrolled South African women with early-stage ER + BC in remission and prescribed tamoxifen or an aromatase inhibitor to the prospective observational study. We performed AET pill counts at enrollment, 12 weeks, and 24 weeks, and calculated adherence ratios of pills consumed between visits to days between visits. Women completed questionnaires on social support, attitude towards medication, health literacy, self-efficacy, mental health, and AET toxicity. We collected household wealth data. We used hierarchical linear (HLM) and structural equation modelling (SEM) to compare adherence ratios between women with and without HIV while adjusting for psychosocial factors. We collected adherence data from 239 women, 63 (26.4%) with co-morbid HIV. Comparing women with and without HIV, median AET adherence ratio was 0.88 vs 0.89, respectively (HLM p = 0.31). In our SEM model for the full cohort, mental health, healthcare savvy, and side effect burden latent variables were not significantly associated with adherence. In the subgroup of women living with HIV, lower SES quintile (β 0.04, SE 0.02, p = 0.08) and poorer mental health (β -0.02, SE 0.01, p = 0.10) showed trends toward association with adherence. HIV status is not predictive of AET adherence among SA women with ER + BC, though decreasing SES status and increasing mental health symptoms are marginally associated with adherence in women with BC and HIV.

Social Characteristics and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women With Breast Cancer.

PURPOSESocial characteristics, including cohabitation/marital status and socioeconomic position (SEP)-education level, employment status, and income-influence breast cancer prognosis. We investigated the impact of these social characteristics on adherence to adjuvant endocrine therapy (AET) from treatment initiation to 5 years after diagnosis.METHODSWe assembled a nationwide, population-based cohort of premenopausal women diagnosed in Denmark with stage I-III, estrogen receptor-positive breast cancer during 2002-2011. We ascertained prediagnostic social characteristics from national registries. AET adherence was based on information from the Danish Breast Cancer Group and operationalized as (1) adherence trajectories (from group-based trajectory modeling) and (2) early discontinuation. We computed odds ratios (ORs) and associated 95% CI to estimate the association of cohabitation and SEP with AET adherence using multinomial and logistic regression models adjusted according to directed acyclic graphs.RESULTSAmong 4,353 patients, we identified three adherence trajectories-high adherence (57%), slow decline (36%), and rapid decline (6.9%). Compared with cohabiting women, those living alone had higher ORs of slow (1.26 [95% CI, 1.08 to 1.46]) or rapid decline (1.66 [95% CI, 1.27 to 2.18]) versus high adherence. The corresponding ORs for women not working versus employed women were 1.22 (95% CI, 1.02 to 1.45) and 1.76 (95% CI, 1.30 to 2.38). For early discontinuation (17%), the ORs were 1.48 (95% CI, 1.23 to 1.78) for living alone and 1.44 (95% CI, 1.17 to 1.78) for women not working.CONCLUSIONAdherence to AET was lower among women living alone or unemployed than cohabiting or employed women, respectively. These women may benefit from support programs to enhance AET adherence.

(054) OPTIMIZING INTERNET-BASED PSYCHOSOCIAL INTERVENTION FOR BREAST CANCER-RELATED SEXUAL MORBIDITY: PROTOCOL FOR A FACTORIAL TRIAL

Abstract Introduction Although 3 in 4 breast cancer survivors report significant sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to breast cancer survivors via the Internet could overcome many of the barriers to in-person interactions, including limited availability of resources and stigma. Prior research on telehealth interventions for breast cancer survivors’ sexual health has limitations. First, survivors continue to endorse time burden as a leading reason for declining telehealth sexual health interventions. Second, prior trial designs have not been able to determine which intervention components work best for which survivors. This knowledge is crucial to refine and personalize sexual health care for survivors. Objective Use the Multiphase Optimization Strategy (MOST) methodological framework to achieve the following aims: (1) develop an Internet intervention for breast cancer-related sexual health that is optimized for greatest impact; and (2) determine how intervention components work (i.e., mediators) and for whom they work best (i.e., moderators). Methods 320 partnered, post-treatment female breast cancer survivors who endorse at least one bothersome sexual symptom (i.e., pain with sex, vaginal dryness, low sexual desire, difficulty with orgasm) related to their breast cancer treatment will be enrolled. Recruitment will be conducted via a US-national community oncology research program representing more than 1,000 individual practice locations. In this factorial trial, participants will be randomized to receive a combination of 4 intervention components: psychoeducation about cancer-related sexual morbidity, training for communication with their health care team, training for communication with their partners, and intimacy promotion skills training. These components were selected as they are supported by our intervention research, are consistent with survivorship guidelines, and align with survivors’ preferences found in our qualitative research. Components will be implemented using a robust Internet intervention platform with tailoring and highly-engaging elements like animation, video, and automated email prompts. Survivors will complete assessments at baseline (pre-randomization) and 3- and 6-month post-assessments. First, the impact of intervention components on survivors’ sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Inventory) will be tested. Next, a select set of mediators (i.e., sexual functioning knowledge, sexual communication self-efficacy with clinicians and partner, emotional intimacy with partner) and moderators (i.e., menopausal status, adjuvant endocrine therapy use, psychological distress, relationship duration and satisfaction) will be evaluated. Results Institutional review board approvals are in progress, with clinical trial registration to follow. Data collection is anticipated to begin in Spring 2024 and be completed in 2027. Conclusions Findings from this trial will accelerate the development of more effective sexual health interventions for breast cancer survivors by determining how intervention components work and for whom various components work best. By identifying the combination of intervention components likely to provide breast cancer survivors the greatest sexual health benefit for the least burden, this study will result in the first Internet intervention optimized for maximum impact for the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: AHC: grants from Janssen, Relmada Therapeutics, Inc., and Sage Therapeutics; personal fees from Acadia, Alkermes, Allergan, AMAG Pharmaceuticals, Inc., Fabre-Kramer, Ovoca Bio plc, Pure Tech Health, Sage Therapeutics, Takeda/Lundbeck, WCG MedAvante-ProPhase, Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, Guilford Publications; personal fees and other from S1 Biopharma; and other from Euthymics and Mediflix LLC. GL: consultant or research affiliation with Agios Pharmaceuticals, Inc; Denovo Biopharma; IN8bio; Incyte Corporation; Novocure Inc.; oblato; ONO Pharma; Sumitomo Dainippon Pharma Co., Ltd. LR: financial and/or business interest in BeHealth Solutions and is a consultant to Mahana Therapeutics.

Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06).

LBA1000 Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P&lt;0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC. Conclusions: T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425 .[Table: see text]

Prognostic utility of ctDNA detection in the monarchE trial of adjuvant abemaciclib plus endocrine therapy (ET) in HR+, HER2-, node-positive, high-risk early breast cancer (EBC).

LBA507 Background: In monarchE (NCT03155997), 2 years of adjuvant abemaciclib + ET resulted in sustained improvement in invasive disease-free survival (IDFS; HR=0.680, 7.6% absolute benefit at 5 years) in patients (pts) with HR+, HER2-, node-positive, high-risk EBC. Here, we investigate the prognostic value of ctDNA detection and dynamics in pts from monarchE. Methods: Samples were analyzed from a selected pt subset (n=1397; abemaciclib + ET arm, n=685; ET arm, n=712), enriched for overall IDFS events compared to the total monarchE study population (IDFS event rate: 31% [433/1397] vs 18% [992/5637]). Pts had blood collected pre-study treatment (baseline) and at 3, 6, or 24 months. ctDNA detection was performed using the personalized, tumor informed Signatera ctDNA assay (Natera, Inc) and whole exome sequencing (WES) of matched primary tumor and normal required for assay design was performed. Results: Among 1397 pts, 65% (n=910) had sufficient plasma samples and WES performed, and all 910 had successful ctDNA assay testing. Among these 910 pts, the IDFS event rate was 27% (abemaciclib + ET, 23% [101/438]; ET alone, 31% [146/472]). Rates of ctDNA positivity (at baseline and any change from baseline) and associated IDFS events are shown in Table. Among pts with ctDNA positivity, 87% had an IDFS event in comparison to 15% with persistent ctDNA negative (-) status during the study. Conclusions: In a pt subset from monarchE enriched for IDFS events, ctDNA detection was relatively infrequent (&lt;20%); however, its detection at any time during the 24 months of study therapy was adversely prognostic. As compared to pts who had remaining ctDNA positive (+), pts who had clearance of ctDNA on therapy had lower risk of IDFS events, but the event risk still remained clinically meaningful in these pts. Clinical trial information: NCT03155997 . [Table: see text]

Remote Monitoring App for Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer

Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence. To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET. This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had a mobile device with a data plan and an email address and were asked to use an electronic pillbox to monitor AET adherence and to complete surveys at enrollment and 1 year. Participants were randomized into 3 groups: (1) an app group, in which participants received instructions for and access to the study adherence and symptom monitoring app for 6 months; (2) an app plus feedback group, in which participants received additional weekly text messages about managing symptoms, adherence, and communication; or (3) an enhanced usual care (EUC) group. App-reported missed doses, increases in symptoms, and occurrence of severe symptoms triggered follow-ups from the oncology team. The primary outcome was 1-year, electronic pillbox-captured AET adherence. Secondary outcomes included symptom management abstracted from the medical record, as well as patient-reported health care utilization, symptom burden, quality of life, physician communication, and self-efficacy for managing symptoms. Among 304 female participants randomized (app group, 98; app plus feedback group, 102; EUC group, 104), the mean (SD) age was 58.6 (10.8) years (median, 60 years; range, 31-83 years), and 60 (19.7%) had an educational level of high school diploma or less. The study completion rate was 87.5% (266 participants). There were no statistically significant differences by treatment group in AET adherence (primary outcome): 76.6% for EUC, 73.4% for the app group (difference vs EUC, -3.3%; 95% CI, -11.4% to 4.9%; P = .43), and 70.9% for the app plus feedback group (difference vs EUC, -5.7%; 95% CI, -13.8% to 2.4%; P = .17). At the 1-year follow-up, app plus feedback participants had fewer total health care encounters (adjusted difference, -1.23; 95% CI, -2.03 to -0.43; P = .003), including high-cost encounters (adjusted difference, -0.40; 95% CI, -0.67 to -0.14; P = .003), and office visits (adjusted difference, -0.82; 95% CI, -1.54 to -0.09; P = .03) over the previous 6 months compared with EUC participants. This RCT found that a remote monitoring app with alerts to the patient's care team and tailored text messages to patients did not improve AET adherence among women with early-stage breast cancer; however, it reduced overall and high-cost health care encounters and office visits without affecting quality of life. ClinicalTrials.gov Identifier: NCT03592771.

The impact of adjuvant endocrine therapy (AET) omission in ER-low (1-10%) early-stage breast cancer.

513 Background: Adjuvant endocrine therapy (AET) improves overall survival (OS) in patients (pts) with hormone receptor (HR) positive early-stage breast cancer (BC). For pts with estrogen receptor (ER)-low BC (defined as ER 1-10%), there is controversy regarding AET benefit, given tumor heterogeneity (&gt;40% basal; (1)), and similar chemotherapy response and prognosis to ER-negative (neg) BC. Current guidelines categorize ER-low BC as a separate entity and suggest equipoise regarding AET benefit. We previously determined that AET omission in chemotherapy-treated pts with ER+ BC resulted in a nearly 2-fold increase in death (2). However, the impact of AET omission in patients with ER-low BC is unknown. Methods: Beginning in 2018, the National Cancer Database (NCDB) began to abstract ER as a continuous variable, allowing classification of ER+ tumors as 1-10% or &gt;10%. Therefore, we queried the NCDB 2018-2020 for patients with stage I-III ER+BC treated with neoadjuvant or adjuvant chemotherapy, as these pts have the highest risk of recurrence. ER was assessed as ER-neg (0%), low (1-10%) and ER &gt;10%. OS was analyzed with AET as a time-dependent covariate using Cox proportional hazards regression. Results: 357,085 pts with stage I-III ER+BC were identified, with 10,396 (3%) classified as ER-low. Among pts with ER-low disease, 69% had PR-neg BC and 67% had HER2-neg BC. The majority (77%) were treated with chemotherapy (32% neoadjuvant, 44% adjuvant, 1% unknown timing) and formed our analysis cohort. Among these 7,956 pts, AET was omitted in 3,233 (41%). AET omission was more common for pts with tumors that were PR-neg vs positive (46% vs 30%, p&lt;0.001), HER2-neg vs positive (44% vs 37%, p&lt;0.001), and Ki67≥20% (44% vs 35%, p&lt;0.001). With median follow-up of 3 years, 648 deaths were observed. OS was 94.3% (95% CI: 93.8-94.9%) at 2 years and 87.6% (95% CI: 86.5-88.7%) at 4 years. In unadjusted analysis, omission of AET was associated with worse OS (HR 1.40, 95% CI: 1.19-1.65, p&lt;0.001), with similar effects regardless of PR, HER2, or Ki67 (each interaction test p&gt;0.3). When controlling for age, comorbidity score, year of diagnosis, PR, HER2, and pathologic stage, the adjusted effect of AET omission on OS was HR 1.22 (95% CI: 1.00-1.48, p=0.05). Given assessment of OS was performed during pandemic years, with 1/3 of deaths occurring during the first year of follow-up, we performed a sensitivity analysis to analyze pts who survived to one year after definitive surgery. In this analysis, the adjusted effect of AET omission on OS was 1.24 (95% CI: 1.02-1.51, p=0.03). Conclusions: Omission of AET in pts treated with chemotherapy for ER-low, early-stage BC is associated with significantly worse OS. These data strongly suggest that pts with ER low BC should be counseled regarding the benefit of AET and practice guidelines should recommend AET in this setting. 1. Benefield JNCI 2020. 2. Choong SABCS 2022.

Adherence to adjuvant hormone therapy in hormone-sensitive breast cancer: Insights from the Medical Oncology Department at Hassan II University Hospital, Morocco.

e12505 Background: Adjuvant endocrine therapy (AET) improves long-term survival for hormone-sensitive breast cancer; However, suboptimal adherence is prevalent, with many women failing to follow prescribed dosage and frequency. Long-term adherence patterns to AET are poorly understood. Additionally, there is a lack of data regarding the adherence to AET among Moroccan women and the factors that may influence it. Objectives: The primary objective of the study was to assess the adherence rate to AET in patients with HR-positive early breast cancer being treated at Hassan II University Hospital of Fez, Morocco. Secondary objectives included determining factors associated with poor adherence and assessing the adverse events associated with AET and their prevalence. Methods: We conducted a cross-sectional study involving 335 breast cancer patients undergoing AET. Eligible patients, who had received at least one dispensing of AET, participated in the study through a direct questionnaire survey after providing signed consent. The questionnaire comprised sections covering patient demographics, clinical data (stage, type of AET, duration of therapy), side effects or symptoms related to AET, other factors that may impact adherence. Adherence to AET was assessed at three points of measurement: 1 year, 3 years, and ≥ 5 years after the initiation of therapy. The study was carried out with respect to the Moroccan regulation in effect. Results: The study included 335 cases with an average age of 54 years. Participants were predominantly illiterate (62%) and post-menopausal (50.7%). Most were classified as stage II UICC (53.5%). Mastectomy was performed in the majority (74%). Neo(adjuvant) CMT was given to 79.4%, and adjuvant radiotherapy to 86.9%. Tamoxifen was administered to 55.4%, and aromatase inhibitors to 44.6%. Medical castration was associated with 12.5%, and 35 patients switched AET over time. Only 12.8% exceeded 5 years of AET during recruitment. Adherence assessment revealed an overall adherence rate of 53.4%. Notably, 67.2% claimed never to forget their medication, and about 20% temporarily stopped it, primarily due to lack of information. Most participants used a reminder strategy, notably alarms (43.3%). Treatment tolerance varied, with hot flushes and arthralgia being predominant side effects. Statistical analyses found a significant link between treatment lasting over 5 years and non-adherence (p = 0.003). However, the use of an alarm as a reminder strategy strengthened adherence (p = 0.021). No statistically significant differences were noted in other variables. Conclusions: Despite the benefits, ensuring adjuvant hormone therapy adherence is challenging. Our analysis, estimating a 53.4% global adherence, found that only treatment duration and recall strategy significantly correlated with adherence.

Comprehensive clinical characteristics and ctDNA mutational profile analysis of endocrine resistance/sensitivity to adjuvant ET therapy in luminal breast cancer from the GEICAM/2014-03_RegistEM registry.

1011 Background: Patients (pts) with hormone receptor-positive (HR) early breast cancer (BC) may develop resistance to adjuvant endocrine therapies (ET), with relapse occurring months (m) to decades after surgery. Our study explores clinical characteristics, prognosis, and oncogenic drivers in circulating tumor DNA (ctDNA) at relapse in HR+ BC pts, based on their sensitivity to adjuvant ET. Methods: In the REGISTEM study, we identified 805 primary HR-positive BC pts who developed metastatic relapse. These cases were classified based on their sensitivity to adjuvant ET, according to the 5th ESO-ESMO ABC Guidelines: 1ET-resistance (1ET-R, relapse within the first 2 years of adj ET; n=138), 2ET-resistance (2ET-R, relapse after the first 2 years or &lt;12 m after completing adj ET; n=284), and ET-sensitive (ET-S, relapse after &gt;12 m of completing adj ET; n=383). Out of this cohort, 139 individuals had plasma samples obtained prior to the initiation of the first-line treatment for advanced disease, and these samples were analyzed using the AVENIO ctDNA assay. Results: Pts with 1ET-R were significantly more likely to have grade 3, stage III, and highly proliferative tumors (Ki67&gt;20%). The median time to distant relapse was 24 m for 1ET-R, 52.8 m for 2ET-R, and 124 m for ET-S cases. For first-line treatment, the median PFS was 8.1 m for 1ET-R, 13 m for 2ET-R, and 21.2 m for ET-S relapse (p&lt;0.0001). With a median follow-up in the advanced setting of 34 m, median OS was 28 m for 1ET-R, 46 m for 2ET-R, and 55 m for ET-S relapses (p&lt;0.0001). Pts with ET resistance had more mutations (mut) and higher mut allele frequency than ET-sensitive relapse. Pts with ET resistance showed higher incidence of mut in TP53, ESR1, PTEN, andhigh copy number in EGFRand ERBB2 than ET-sensitive, but similar incidence of mut in PIK3CA.Mut in ESR1 and high copy number in EGFR were correlated with poorer PFS, while ESR1 mut were additionally associated with worse OS, although these associations were not independent of the ET relapse groups (Table). Furthermore, mut in PIK3CA were associated to worse PFS only in ET-R pts. Conclusions: In HR-positive BC, both primary and secondary resistance to adjuvant ET represents a highly aggressive disease with enriched actionable genetic alterations detected at the time of diagnosis of metastatic relapse. Addressing these alterations has the potential to mitigate the unfavorable prognosis associated with these cases. Clinical trial information: NCT02819882 .[Table: see text]

Exploring factors impacting quality of life in patients with breast cancer undergoing adjuvant hormone therapy: Experience of the Medical Oncology Department-CHU Hassan II-FEZ University Hospital.

e12507 Background: Considering that the recommended duration of adjuvant hormone therapy in localized breast cancer is at least 5 years, it becomes crucial to investigate the quality of life (QOL) of these patients and the factors influencing it. Objectives: To assess the quality of life (QOL) and identify factors impacting it in patients with localized hormone-sensitive breast cancer receiving adjuvant hormone therapy. Methods: We surveyed 335 patients with localized hormone-sensitive breast cancer undergoing adjuvant hormone therapy using the Moroccan Arabic dialect version of the EORTC QLQ-C30 questionnaire. Written informed consent was obtained from all participants. Confidentiality of participant data was maintained. The study was carried-out with respect to the Moroccan regulation in effect. Results: The overall quality of life (QOL) in our patient population was moderate, with positive scores for social functioning, followed by physical, cognitive, and emotional functioning. Financial difficulties emerged as the most influential factor affecting patients' QOL, followed by fatigue, pain, and other symptoms. Age-related declines in physical functioning were observed, with symptoms more prevalent, especially diarrhea, in patients aged 70 and above (p = 0.009). Urban patients faced a greater financial impact on QOL than rural patients (p = 0.025). Higher education correlated with improved QOL, particularly in physical functioning (p = 0.025). Married individuals demonstrated better overall QOL and fewer symptoms (p = 0.027). Menopausal patients exhibited lower ability and a higher loss of appetite (p = 0.027). No significant correlation was found between UICC stage and QOL. Patey-mastectomy was associated with more pain than tumorectomy (p = 0.024). Previous chemotherapy had no overall QOL impact, but users reported less diarrhea (p = 0.016). Hormone therapy type did not significantly affect overall health status, except for tamoxifen users who demonstrated improved functional roles (p = 0.008). The duration of adjuvant hormone therapy (&lt;5 years or &gt;5 years) showed no significant difference in patient QOL. Associated castration had a significant impact on overall health and role functioning, favoring non-castration (p = 0.034 and p = 0.011). Effective treatment tolerance positively influenced overall QOL, leading to better physical, emotional, and cognitive functioning (p &lt; 0.0001), with fewer pronounced symptoms. Conclusions: Our study indicate that the overall QOL of patients with localized breast cancer under AET was moderate, and several factors were identified as major influences, each affecting the QOL in distinct ways.