Adjuvant Endocrine Treatment Research Articles

Tamoxifen Effects on Cognition and Language in Women with Breast Cancer.

Cognitive changes following adjuvant treatment for breast cancer (BC) are well documented following chemotherapy. However, limited studies have examined cognitive and/or language functions in chemotherapy-naive women with BC taking tamoxifen (TAM). Using ambulatory cognitive assessment, we investigated the trajectory of cognitive and language changes during early period of adjuvant endocrine treatment (TAM) in women with BC at two time periods (pretreatment and 2 months after treatment began). Four women with BC and 18 cognitively healthy age-matched controls completed three cognitive tasks using smartphones, during a short time period (5 days) and repeated them at two time periods. To determine language ability, language samples were collected at two time periods, where the participants described two stories from two wordless picture books and samples were assessed using core lexicon analyses. Wilcoxon-signed rank tests were computed to identify differences in linguistic and cognitive performances of both the groups at two time periods. No significant within-group or between-group differences were seen on the cognitive and language tasks at the two time periods; however, women with BC performed more poorly compared to the control group. We did see decline in some women with BC and not in others, in cognition and language during initial course of TAM treatment. However, the approach we used to assess these changes is valuable and innovative. This approach will help refine current research paradigms for determining cognitive and linguistic changes and will help determine if women with BC might require language intervention in the future.

Audit to Evaluate Recurrence Rates in Patients with DCIS Treated with Adjuvant Radiotherapy and the Role of Endocrine Treatment

Purpose: Ductal carcinoma-in-situ (DCIS) comprises 20–25% of screening detected breast cancers [1], with a low 20-year mortality rate of 3% [2]. Radiotherapy has been found to halve the likelihood of recurrence, versus breast-conserving surgery (BCS) alone, to 15% at 10 years [3–5]. There is conflicting evidence if endocrine therapy gives a significant benefit in patients treated with BCS and radiotherapy [6,7]. Furthermore, endocrine therapy can cause significant morbidity and up to 20% of patients do not tolerate the full course of treatment [8]. In this cohort of patients, we audited the rate of disease recurrence and determined the additional benefit of adjuvant endocrine treatment over a 10-year period.

109P Updated long-term overall survival of older adjuvant ibandronate-treated patients with intermediate- or high-risk early breast cancer compared with additional adjuvant capecitabine treatment: The ICE randomized clinical trial

The majority of breast cancers occur in women over the age of 65, but older breast cancer patients are largely underrepresented in clinical trials. We investigated the effect of adding capecitabine to adjuvant treatment with ibandronate in elderly breast cancer patients. The multicenter phase III ICE trial enrolled women ≥65 years with early node-positive/high-risk node-negative breast cancer and a Charlson Comorbidity Index (CCI) ≤2. Patients were randomized to capecitabine 2000 mg/m2 day 1-14 q3w for 6 cycles plus ibandronate (50 mg p.o. daily or alternatively 6 mg i.v. q4w) or ibandronate alone for 2 years. We present here an update on long-term follow-up for the secondary endpoint of overall survival (OS). 1358 (96.4%) from 1409 randomized patients started treatment. 564 (83.4%) completed 6 cycles of capecitabine. 513 (77.7%) and 516 (78.8%) completed ibandronate in the capecitabine/ibandronate and ibandronate arm, respectively. Median age was 71 (range 64-88) years, 1099 (81%) were hormone receptor (HR)-positive, 705 (51.9%) node-negative, 794 (58.5%) had a CCI of 0. HR-positive patients received additional adjuvant endocrine treatment. After an updated median follow-up time of 74 (IQR 56-126) months for OS in the entire cohort, 7-year OS was 83.5% for capecitabine/ibandronate versus 80.9% for ibandronate, and 10-year OS was 73.1% for capecitabine/ibandronate versus 70.8% for ibandronate (P=0.413). Lack of effect was independent from age, nodal and HR status. Addition of capecitabine caused significantly higher skin and gastrointestinal toxicities. The adjuvant combination of capecitabine and ibandronate did not show significantly better OS than ibandronate alone in elderly breast cancer patients.

Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update.

(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.

Abstract 5460: Novel immunohistochemistry-based predictive and prognostic tests for hormone receptor-positive breast cancer

Abstract Background: Breast cancer (BC) is the most diagnosed cancer worldwide and the most common cancer diagnosed in American women. Despite successes of adjuvant endocrine therapies in treating the most common subtype of hormone receptor-positive (HR+) BC, de novo and emergent resistance to these therapies, i.e., endocrine resistance, remains a significant concern with patients experiencing recurrences during and after adjuvant treatment. We report here unique patterns of expression (UPE) of N-myristoyltransferase 1 (NMT1) protein that are prognostic and predictive markers for HR+ BC. We have discovered that the expression and localization of NMT1 are predictive markers for the endocrine therapy response in HR+ BC. The data from many observational studies suggest that after five years of adjuvant endocrine treatment, the likelihood of distant recurrence continues for the subsequent twenty years. We have developed simple immunohistochemical (IHC)-based tests that could become part of routine first line prognostic and predictive tests and have the potential to be incorporated as necessary tests in the panel of BC tests for designing treatment regimens of BC. Methods: Expression patterns of NMT1 were determined using IHC analyses on formalin fixed paraffin embedded primary tumor samples from treatment naïve BC patients. The tumor tissues in duplicates were stained with NMT1 monoclonal/polyclonal antibodies on an autostainer (Leica Bond). Stained slides were scored in a blinded manner to outcomes and scored with an "H" index representing the intensity and percent positive cells within each section. The relationship of UPE was correlated with clinical outcomes of RFS (RFS = endpoint recurrence and/or death due to BC) and OS (OS = endpoint death due to breast cancer). Results: The final cohort was composed of 448 BC cases of primary HR+ tumors from patients who received adjuvant tamoxifen therapy after surgery. UPE2 (defined by > median H score 100) was significantly associated with better clinical outcomes represented by both RFS (HR = 0.70, P = 0.0304, 95% CI 0.510 to 0.97, n = 440) and OS (HR = 0.71, P = 0.0306, 95% CI 0.530 to 0.97, n = 440), whereas UPE4 strongly predicted worse treatment response for both RFS (HR= 1.49, P = 0.0014, 95% CI 1.08 to 2.04, n=440) and OS (HR = 1.54, P = 0.0055, 95% CI = 1.54 to 2.08, n=440). Conclusions: We observed that the expression and localization patterns of NMT1 constitute four unique patterns of expression signatures (UPE:1-4) and serve as prognostic and potentially predictive markers for HR+ BC. This assay provides a novel method to stratify cancers that may better enable endocrine treatment and duration optimization in the adjuvant setting for HR+ breast cancer. Moreover, in distinction to genomic assays, fewer logistic and financial barriers to implementation would exist for the UPE:1-4 IHC assay in resource-poor settings. Citation Format: Danira Jaksic, Amandeep Kaur, Dean Reddick, David David Datzkiw, Shailly Varma Shrivastav, Vijayakrishna Gadi, Leigh Murphy, Anuraag Shrivastav. Novel immunohistochemistry-based predictive and prognostic tests for hormone receptor-positive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5460.

Adherence to endocrine therapy in early breast cancer in relation to Cytochrome P450 2D6 genotype: a comparison between pharmacy dispensation data and medical records

PurposeSuboptimal adherence to adjuvant endocrine treatment (AET) is an important clinical concern. A correlation between CYP2D6 activity and tamoxifen discontinuation has been described. The main aim of this study was to investigate the consistency between pharmacy dispensation data and medical records on adherence to AET.MethodsAdherence was calculated for patients with at least 4.5 years of follow up and was defined as Medical Possession Rate ≥ 80%. Subgroup analyses were performed based on menopausal status, recurrence risk and CYP2D6 activity.ResultsIn 86% of the 1235 included patients the consistency between the two sources of information was within 80–125%. Poor consistency, < 80%, was most frequent in the premenopausal/ high-risk group and CYP2D6 Poor Metabolizers (PMs). Among 899 patients with at least 4.5 years follow up, 72% were adherent to tamoxifen based on pharmacy dispensation data, compared with 77% as reported by medical records. When including patients who switched to aromatase inhibitors after tamoxifen, adherence increased to 82% and 88%, respectively. Adherence did not differ by menopausal status or risk for recurrence. CYP2D6 PMs had poorer adherence (54%) to tamoxifen compared to patients with the highest CYP2D6 activity (83%).ConclusionsThere was a good consistency between medical records and pharmacy dispensing data on the use of AET. Adherence to AET was adequate, especially when including switch to aromatase inhibitors. Surprisingly, CYP2D6 PMs had low adherence to tamoxifen, despite a likely reduced risk of side effects according to previous data.

Abstract P1-02-04: Real world adjuvant endocrine treatment in premenopausal breast cancer patients compared with the proposed algorithm using the Regan Composite Risk Score

Abstract Background The Regan Composite Risk Score (RCRS) is a web-based prognostic and predictive calculator to guide the use of adjuvant exemestane plus ovarian function suppression (AI + OFS) versus tamoxifen plus ovarian function suppression (TAM + OFS) or tamoxifen alone (TAM) for premenopausal women with hormone receptor-positive HER2-negative early breast cancer (HR+/HER2- EBC). We compared our adjuvant endocrine therapy policy based on the tumor board with the treatment guided by the RCRS during 2 time periods, one before and one after the acquaintance of the Tamoxifen and Exemestane Trial (TEXT) and Suppression and Ovarian Function Trial (SOFT) data. This allowed us to see a possible evolution in therapy policy. Methods A retrospective cohort study of 563 premenopausal patients with HR+/HER2- and HER2+ EBC diagnosed at the University Hospital of Leuven during 2 periods, 2010-2012 (cohort 1) and 2015-2017 (cohort 2), was conducted. For each patient with HER2- EBC, the RCRS was calculated by entering the requested characteristics in the online available tool. The primary outcome was to investigate how frequent our therapy differed from the therapy guided by the RCRS based on the estimated 8-yr distant relapse free interval (DRFI) with an arbitrary cut-off set at 3 %. If the received therapy was ≥ 3 % less efficient in 8-year DRFI compared to the optimal therapy according to RCRS, the patient was considered undertreated. If the received therapy differed by less than 3 % in 8-year DRFI compared to the optimal therapy according to RCRS and yet the most intensive therapy (AI + OFS &amp;gt; TAM + OFS &amp;gt; TAM) was administered, the patient was considered overtreated. In the other cases, the patient was considered to have been treated concordant with the RCRS. Secondarily, nonadherence of the HER2- and HER2+ patients towards the endocrine treatments leading to therapy switch because of intolerance was recorded at 6, 12, 24 and 36 months. Analyses were performed using SAS software and the comparison of both cohorts was performed by the chi-squared test for categorical variables. Results According to the RCRS, 43.2 % (89/206) of the HER2-negative patients of cohort 1 were undertreated compared to 22.1 % (43/194) in cohort 2 (chi- squared test, p-value &amp;lt; 0.001). The number of overtreated patients also differed significantly between the two cohorts (chi-squared test, p-value = 0.003) with 2.9 % (6/206) in the first cohort and 10.3 % (20/194) in the second cohort. Finally, the number of patients treated concordant with the guidance derived from the RCRS was 53.9 % (111/206) in cohort 1 and 67.5 % (131/194) in cohort 2 (chi-squared test, p-value = 0.005). Treatment intolerance and switch was observed in 34.8 %, 16.7 % and 12.4 % of the patients receiving AI + OFS, TAM + OFS or TAM as initial therapy respectively; this was numerically higher for all treatments in cohort 2 vs cohort 1, although the observed difference was only significant for TAM. Conclusion In our center, a recent cohort of premenopausal women was more likely to be treated with the adjuvant endocrine treatment concordant with the guidance derived from the RCRS when using an arbitrary cut-off of 3 % to define a relevant improvement in outcome. Citation Format: Charlotte Berteloot, Patrick Neven, Maja Vangoitsenhoven, Annouschka Laenen, Hans Wildiers, Kevin Punie, Ann Smeets, Ines Nevelsteen, Sileny Han, Thaïs Baert, Hilde Janssen, Eva Oldenburger, Adinda Baten, Patrick Berteloot, Rani Vanhoudt, Anne Deblander, Chantal Remmeriev, Christine Desmedt. Real world adjuvant endocrine treatment in premenopausal breast cancer patients compared with the proposed algorithm using the Regan Composite Risk Score [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 P1-02-04.

Abstract P5-08-12: Lifestyle factors and patient-reported outcome measures using the European Organisation for Research and Treatment of Cancer survivorship questionnaire in early breast cancer patients attending for surveillance imaging

Abstract Background An increasing number of patients survive their early breast cancer (EBC) but may experience longer term impact on their quality of life (QoL) arising from their diagnosis and treatment. Survivors are also at risk of other possibly life-shortening chronic diseases due to concomitant risk factors (smoking, drinking &amp;gt;14 units of alcohol/week, and low exercise levels). Little is known about the lifestyle factors and long-term challenges facing EBC survivors. We report the initial results of a questionnaire (containing patient-reported outcomes measures (PROMS), and lifestyle factor questions) completed by EBC survivors at the Royal Marsden hospital (RMH), UK. Methods We prospectively identified a patient cohort of patients (October 2021 to June 2022) with stage I-III EBC who had completed their curative treatment (endocrine treatment (ET) may be ongoing) and who were attending for their annual surveillance breast imaging at years 1, 2, 4, and &amp;gt;5 years. Patients completed PROMS (using EORTC (European Organisation for Research and Treatment of Cancer) QLQ-SURV100 and -BR23) and questionnaires regarding smoking, alcohol, and exercise levels (via the International Physical Activity Questionnaire (IPAQ)). Patient, clinical, disease and treatment characteristics were recorded and the EORTC and IPAQ questionnaires were analysed according to the EORTC and IPAQ analysis manuals. Results Data are available for 187 women at the time of this analysis (it is anticipated data will be available for 350 at the time of SABCS 2022). Patients were attending for their year 1 (N=66, 35.3%), 2 (N=43, 23%), 4 (N=43), or &amp;gt;5 years (N=35, 18.7%) imaging post-surgery. 62 (86.6%) patients were Eastern Cooperative Oncology Group Performance Status 0-1, and 31 (16.6%) had &amp;gt;2 of other comorbidities. 123 patients (65.8%) were post-, 16 (8.6%) peri-, and 48 (25.7%) premenopausal. 178 (95.2%) underwent primary surgery. Of those patients undergoing surgery, 19 (10.2%) had a mastectomy, and 168 (89.8%) breast conserving surgery. All patients had axillary surgery: 26 (13.9%) axillary dissection, and 158 (84.5%) sentinel lymph node biopsy. 166 patients (88.8%) received adjuvant ET and for most patients (N= 149, 79.7%) this was ongoing at time of analysis. 31.6% (N= 59) had prior exposure to cardiotoxic treatment. Risk groups for other chronic health conditions could be identified: 92 (49.2%) patients had a BMI of &amp;gt;25, 5 (4.2%) were current smokers, and 16 (13.6%) were classified as at-risk drinking. Patients reported that their physical function was affected following their diagnosis and treatment, with 51 (27.3%) having trouble running short distances and 52 (27.8%) taking a long walk carrying a heavy backpack. Nonetheless all patients (N=118 available for IPAQ analysis) had moderate (N=61, 51.7%), or high-level (N= 58, 49.2%) levels of exercise. 85 patients (45.5%) had pain in the past week, and 101 patients (54%) were dissatisfied with the appearance of their body. Most patients (N=152, 81.3%) estimated their overall QoL in the last week as very good (5-7) (scale 1-7, with 7 being excellent). QLQ-BR23 symptom scales were compared between patient groups. Patients who had chemotherapy suffered ongoing from hair loss (52.6% vs 45.2%) than chemo-naïve patients. There were no major differences between groups who received ET and those ET naïve. Conclusions We were able to identify groups of patients at risk for other comorbidities and cancers. We could also highlight groups of EBC survivors with a higher level of QoL concerns. PROMS should be routinely assessed in EBC survivors to better address subgroups at higher risk, inform consultations, and treatment decisions. Citation Format: Jasmin V Waterhouse, Jasmine Pattarukuzhyil Jose, Nikki Snuggs, Annette White, Kate Harper, Marieke van Leeuwen, Alistair Ring. Lifestyle factors and patient-reported outcome measures using the European Organisation for Research and Treatment of Cancer survivorship questionnaire in early breast cancer patients attending for surveillance imaging [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 P5-08-12.

Abstract P2-11-01: Secondary endocrine resistance and high Ki-67 labeling index (≥20%) in patients with low genomic risk identified by 21-gene recurrence score

Abstract Introduction: Although breast cancer with high Ki-67 index are likely to have high genomic risk, some of these might have low genomic risk. In ER+HER2- breast cancer patients with low genomic risk identified by the 21-gene assay, we addressed a clinical significance of Ki-67 index in terms of recurrence-free survival (RFS). Methods: We retrospectively identified 2,295 patients with ER+HER2- breast cancer who underwent the 21-gene assay (Oncotype DX®). High Ki-67 LI was defined as 20% or greater, and low genomic risk was defined by recurrence score (RS) from the assay (&amp;lt; 26). Recurrence after 3 year was regarded as secondary endocrine resistance, which is defined as recurrence while on 2 years of adjuvant endocrine treatment. Results: In all patients, Ki67 index assigned 870 (38%) as the high and 1,425 (62%) as the low groups. Thirty percent (263/870) of the high Ki67 index had high genomic risk, whereas 84/1425 (6%) of the low Ki67 did. Among the patients with low genomic risk who did not receive chemotherapy (n=1,807), high Ki67 index was an independent poor risk factor for recurrence. Furthermore, recurrence after 3 years differed significantly according to Ki-67 index (P=0.003), whereas recurrence within 3 years did not differ (P=0.900). Multivariable analysis demonstrated high Ki67 index as a risk factor for recurrence after 3 years (hazard ratio 3.12; 95% confidence interval, 1.28–7.66). Conclusions: In ER+HER2- breast cancer with low genomic risk identified by 21-gene RS, high Ki67 index is associated with secondary endocrine resistance. Novel approach with CDK4/6 inhibitors is demanded to overcome secondary endocrine resistance in tumors with high Ki67/low genomic profile. Citation Format: Janghee Lee, Hakyoung Kim, Soong June Bae, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn. Secondary endocrine resistance and high Ki-67 labeling index (≥20%) in patients with low genomic risk identified by 21-gene recurrence score [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 P2-11-01.

Abstract P3-11-10: Estrogen receptor reprogramming by HOXB13 and GATA3 in ER-positive breast cancer cells

Abstract Background: The Breast Cancer Index (BCI) is a gene expression-based signature comprising two functional biomarker panels. The Molecular Grade Index (MGI) is composed of five genes that measure tumor proliferation. BCI (H/I) is a ratio of the HOXB13 and IL17BR genes and measures estrogen signaling. Integration of MGI and BCI (H/I) provides a single prognostic score that quantifies the risk of both late (5-10 years) and overall (0-10 years) distant recurrence. BCI (H/I) has been validated to predict benefit from extended endocrine therapy across multiple adjuvant endocrine treatment backgrounds in several prospective-retrospective studies. Hormone receptor responses are dependent on genome-wide hormone receptor binding patterns. In hormone-dependent cancers, nuclear receptor binding patterns are frequently reprogrammed by other transcription factors. The homeobox transcription factor HOXB13 has previously been shown to reprogram genome-wide binding of the androgen receptor (AR) during prostate cancer tumorigenesis, where it colocalizes with FOXA1 at reprogrammed AR binding sites. Similarly, the transcription factor GATA3 was found to mediate enhancer accessibility at regulatory regions involved in estrogen receptor (ER)-mediated transcription. We have shown previously that HOXB13 overexpression reprograms and expands the ER binding pattern in breast cancer cells. In this study, we have further characterized the role of HOXB13 in reprograming the ER cistrome and evaluated potential interactions with GATA3. Methods: HOXB13 was expressed in MCF-7 and T47D cells by electroporating HOXB13 mRNA or eGFP mRNA as control. Cells were harvested after 18 hours and analyzed by western blot and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) using antibodies against ER, HOXB13, FOXA1, GATA3 and histone H3K27ac. Chromatin accessibility was assessed by ATAC-seq. After aligning reads with Bowtie2, peak calling, data integration and motif enrichment analysis was performed using HOMER v4.10. Results: ChIP-seq analysis of T47D cells expressing HOXB13 confirmed previous results in MCF-7 cells, where binding of HOXB13 to a significant number of genomic binding sites induced changes in binding of ER, FOXA1 and GATA3 compared to control cells. Integrative analysis of ATAC-seq and ChIP-seq data revealed that HOXB13-induced reprogramming results in open chromatin that frequently exhibits increased acetylation of histone H3K27, a hallmark of transcriptional activation. While both increased chromatin accessibility and H3K27 acetylation were associated with HOX and AP-1 motif enrichment of the underlying DNA sequences, newly open chromatin was specifically co-enriched for motifs for pioneering factors such as FOXA1 and GRHL1. Conclusion: This study lends further support to a model of HOXB13-mediated reprogramming of the ER cistrome in breast cancer. Motif analysis of HOXB13-induced chromatin opening suggests interactions with other pioneer transcription factors including FOXA1 and GRHL1, while HOXB13-induced transcriptional activation is associated with motifs for activating factors such as AP-1. These results will be expanded to inducible cell lines to further characterize the effects of HOXB13 expression on ER binding and function. Citation Format: Kai Treuner, Camila De Arruda Saldanha, Sven Heinz. Estrogen receptor reprogramming by HOXB13 and GATA3 in ER-positive breast cancer cells [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 P3-11-10.

Abstract P4-07-05: Real world data of adjuvant endocrine therapy for breast cancer in very young women. A Chilean 20-year experience

Abstract BACKGROUND: Breast cancer (BC) is the most common cancer diagnosed in premenopausal women with an increasing incidence for age 35 or less. Although proportionally less frequent, hormone receptor (HR)–positive BC still remains the main subtype for this group, but given tumor characteristics and suboptimal adjuvant endocrine therapy (ET), present inferior long-term outcomes when compared to HR-positive BC in older women. Both Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) have helped to optimize ET strategies for premenopausal women, identifying which patients benefit from ovarian function suppression (OFS). In Chile, we have scarce data on very young BC patients and limited access to proper OFS treatment specially in our public health system. Thus we aim to characterize a cohort of very young women regarding treatment strategies and survival, plus as an exploratory analysis evaluate Regan Score in our cohort. METHODS We conducted a retrospective population-cohort study involving women under 36 years of age, with early HR-positive/human epidermal growth factor receptor 2 (HER2)–negative BC, treated both at a community hospital and at an academic private hospital between 2001 and 2021. We did a descriptive analysis including stage distribution and treatment strategies (chemotherapy (CT), ET of choice and OFS use). We evaluated prognosis for the entire population. Survival analysis was carried out using the Kaplan-Meier method. RESULTS A total of 143 patients were included. Median age at diagnosis was 33 (19 - 36); 15.4% percent of patients were diagnosed in stage I, 51.4% stage II and 30.1% stage III. Eighty six percent received CT, 35.0% neoadjuvant. Ninety three percent received endocrine adjuvant treatment: 81.2% TAM alone, 6.8% TAM/OFS and 10.5% IA/OFS. Regarding OFS strategies only 38.5% received gonadotropin-releasing hormone (GnRH) agonists while the rest were oophorectomized. Regan median composite score was 2.77 (2.61 - 2.93) for the entire cohort. Rising to 2.95 (2.79 - 3.11) for patients treated with CT plus ET compared to 1.91 (1.55 - 2.27) for those treated with ET exclusively (p=0.0001). Patients that received TAM alone had a median Regan Score of 2.72 (0.77-4) compared to 3.14 (2.07-4.0) for patients that had OFS added (p=0.04). With a median follow-up of 59 months, 5-year Disease Free Survival (DFS), Distant DFS and Overall Survival (OS) for the entire cohort were 63.5%, 66.9% and 88.7%, respectively. CONCLUSION. To our knowledge this is one of the largest cohorts considering very young women BC in Latinamerica. We confirm their elevated overall risk with markedly higher Regan scores compared to SOFT and TEXT populations for both CT and ET exclusively treated patients. Due to access difficulties very few patients received OFS and when used, surgical oophorectomy was the main strategy of choice, with all the potential long term consequences it conveys. Thus OFS use was restricted to very high risk women, meaning that a large group of only TAM users were undertreated according to nowadays standards. This could explain the elevated recurrence risk observed in our population when compared to other under 35 years of age cohorts. Table 1. Cohort characteristics Table 2. Regan risk score Citation Format: Ana Heredia, Benjamin Walbaum, Francisco Acevedo, Cesar Sánchez. Real world data of adjuvant endocrine therapy for breast cancer in very young women. A Chilean 20-year experience [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 P4-07-05.

Estrogen therapy after breast cancer diagnosis and breast cancer mortality risk

PurposeThe safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case–control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment.MethodsIn a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls.ResultsNo statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use.ConclusionsThe study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.

Impact of clinicopathological factors on extended endocrine therapy decision making in estrogen receptor-positive breast cancer.

In our study, we aim to analyze the impact of clinicopathological factors on the recommendation of extended endocrine therapy (EET) in patients with ER+ breast cancer and to retrospectively validate the value of CTS5 in EET decision making. The retrospective analysis was performed in patients with ER+ breast cancer who have finished 4.5-5 years of adjuvant endocrine therapy and undergone MDT discussion from October 2017 to November 2019. Multivariate logistic regression was used to identify the independent factors for treatment recommendation. CTS5 was calculated for retrospective validation of the EET decision making. Two hundred thirty-five patients were received; 4.5-5 years of adjuvant endocrine therapy were included in the study. Multivariate analysis suggested that age (OR 0.460, 95% CI 0.219-0.965, p = 0.04), pN (OR 39.350, 95% CI 9.831-157.341, P < 0.001), and receipt of chemotherapy (OR 3.478, 95% CI 1.336-9.055, p = 0.011) were independent predictors for the recommendation of EET. In the previously selective estrogen receptor modulator (SERM)-treated subgroup, pN and receipt of chemotherapy were independent predictors for the recommendation of EET. In the previously AI-treated subgroup, age, pN, and receipt of chemotherapy were independent predictors. Adverse events did not affect the recommendation in patients previously treated with adjuvant endocrine treatment nor in the previously SERM or AI-treated subgroups. CTS5 (OR 21.887, 95% CI 2.846-168.309, p = 0.003) remained an independent predictor for the recommendation of EET. Our study indicated that age, lymph nodal status, and receipt of chemotherapy were independent predictors for the recommendation of EET. The application of the CTS5 on EET decision making might be valuable among ER+ breast cancer patients.

Compliance to adjuvant endocrine therapy and survival in breast cancer patients.

BackgroundData on compliance to adjuvant endocrine treatment (ET) is mainly reported from prospective clinical trials or from smaller retrospective cohorts without correlation to outcome. AimsTo determine compliance to adjuvant ET and the impact on survival in a population-based series of patients with early breast cancer (BC) advised ET. Patients and methods1090 consecutive patients with hormone receptor positive (HR+) stage I-III BC diagnosed from 1 January 1997 to 31 December 2003 from one health care region of Sweden were included. Data on tumour, type of ET, compliance, reason for termination and outcome were collected. Statistical analyses were calculated with patients in three groups. Results72 patients were excluded leaving 1018 patients with a HR+ stage I to III BC for analyses. The most common ET was tamoxifen (n = 751, 73.8%). At the last follow up (31 Dec 2019) with a median follow-up of 18 years (interquartile range 16–22) 228 (22.4%) patients had a relapse. 71.1% of the included patients were compliant to endocrine therapy. Older patients ≥74 years had lower compliance, 61% compared with 75% in the other age groups (≤50 years and 51–73 years) (p < 0001), other parameters including type of ET were not associated with compliance. Low compliance remained as an independent risk factor in multivariate analyses for lower relapse-free survival, HR=1.83, 95% Confidence Interval (CI) 1.52–2.19, p < 0.001 and for time to BC death, HR=2.69, 95%CI 1.82–3.98, p < 0.001. ConclusionsPatients compliant to adjuvant ET have an improved survival.

Investigation of The Effect of Adjuvant Endocrine Treatment on Depression, Sleep Quality and Sexual Function in Hormone Receptor-Positive Early-Stage Breast Cancer

Investigation of The Effect of Adjuvant Endocrine Treatment on Depression, Sleep Quality and Sexual Function in Hormone Receptor-Positive Early-Stage Breast Cancer

The positive predictive value of using fsh and Inhibin-B serum levels to diagnose gonadotropin insufficiency in bilateral cryptorchid boys is high

Despite early surgery, many boys with bilateral cryptorchidism at surgery have a reduced number of germ cells per tubular cross-section (G/T) in testicular biopsies and/or low inhibin-B with no elevated follicle-stimulating hormone (FSH) as expected based on a normal gonadotropin feed-back mechanism. Such boys have a high risk of later infertility because of insufficient gonadotropin stimulation and may benefit from adjuvant hormonal treatment. Testicular biopsies are not always wanted or accepted. The study aim was to investigate the value of a low inhibin-B and normal FSH to identify patients that might benefit from adjuvant hormonal treatment avoiding the need for testicular biopsy. A series of boys with cryptorchidism were evaluated with serum levels of inhibin-B and FSH in relation to G/T in testicular biopsies, which were compared to previously published age-matched normal control values. A total of 365 boys who underwent bilateral orchidopexy between 0.4 and 7.8 (median: 2) years of age were included. Twenty-seven (7%) patients had increased FSH and low G/T, whereas 11 of these also had low inhibin-B indicating hypergonadotropic hypogonadism. Moreover, 85 (23%) patients between 0.75 and 7.5 (median: 2) years of age had both low G/T (median: 0.3) and low inhibin-B (median: 56pg/ml) but normal FSH (median: 0.6 U/l) indicating a gonadotropin insufficiency. Three patients with normal FSH and low inhibin B had normal G/T. Our study shows that if surgeons prefer to avoid testicular biopsies and only wish to rely on hormonal parameters (low inhibin-B and normal FSH) in order to diagnose a gonadotropin insufficiency as the cause of hypogonadism, they will identify only about 30% of such cases and overlook about 70% of patients sharing the same endocrinopathy. In addition, if surgeons treat patients for gonadotropin insufficiency only based on low inhibin-B and normal FSH they will solely treat patients with gonadotropin insufficiency and would not overtreat patients. Adjuvant hormonal treatment was indicated by a gonadotropin insufficiency discerned in 23% of boys with bilateral cryptorchidism. Without histology, the clinicians are left with more difficult clinical judgments to identify patients for adjuvant hormonal treatment. The positive predictive value of low inhibin-B and normal FSH corroborated by low G/T was 0.97 (85/85+3), but the sensitivity was low (0.30).

Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests.

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice.

Phase 2 data on a new treatment for hot flushes in women with breast cancer

Bothersome vasomotor symptoms (ie, hot flashes or flushes and night sweats) are common after breast cancer, sometimes aggravated by chemotherapy-induced premature menopause or adjuvant endocrine treatments. Consequently, there is a long history of clinical trials testing a variety of centrally acting agents, including selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, gabapentin, and others,1,2 to manage vasomotor symptoms when menopausal oestrogen therapy (transdermal or oral oestrogens) is contraindicated.

Extended adjuvant endocrine therapy for women with hormone receptor-positive early breast cancer: A meta-analysis with trial sequential analysis of randomized controlled trials.

The aim of the current study is to explore the association between extended adjuvant endocrine treatment and prognosis of women with hormone receptor-positive (HR+) early breast cancer. Databases including PubMed, Web of Science, Embase and the Cochrane Library databases were electronically searched to identify randomized controlled trials (RCTs) that reported extended endocrine therapy for women with HR+ early breast cancer. The retrieval time was limited from inception to September 2022. Two reviewers independently screened literature, extracted data, and assessed risk bias of included studies. Meta-analysis was performed by using R software Version 4.1.2 and STATA Version 12.0. A total of 15 RCTs involving 29497 cases were included. The overall analysis showed that compared with the control, extended adjuvant endocrine therapy increased disease-free survival (DFS) (HR=0.814, 95% CI: 0.720-0.922, 95% PI: 0.556-1.194), overall survival (OS) (HR=0.885, 95% CI: 0.822-0.953, 95% PI: 0.771-1.035), relapse-free survival (RFS) (HR=0.833, 95% CI: 0.747-0.927, 95% PI: 0.575-1.159), distant metastatic-free survival (DMFS) (HR=0.824, 95% CI: 0.694-0.979, 95% PI: 0.300-2.089) and reduced new breast cancer cumulative incidence (NBCCI) (HR=0.484, 95% CI: 0.403-0.583, 95% PI: 0.359-0.654). For adverse events, extended adjuvant endocrine treatment was associated with a significantly higher risk of bone fracture (RR=1.446, 95% CI: 1.208-1.730, 95% PI: 1.154-1.854) and osteoporosis (RR=1.377, 95% CI: 1.018-1.862, 95% PI: 0.347-5.456). Our study showed that extended adjuvant endocrine therapy increased DFS, OS, RFS, DMFS, the incidence of bone fracture and osteoporosis, and reduced NBCCI. https://www.crd.york.ac.uk/prospero, identifier (CRD42022351295).

Extended adjuvant endocrine treatment for premenopausal women: A Delphi approach to guide clinical practice.

The use of an aromatase inhibitor (AI) in combination with ovarian function suppression (OFS) has become the mainstay of adjuvant endocrine therapy in high-risk premenopausal patients with hormone receptor-positive breast cancer. Although five years of such therapy effectively reduces recurrence rates, a substantial risk of late recurrence remains in this setting. Multiple trials have shown that extending AI treatment beyond five years could offer further protection. However, as these studies comprised only postmenopausal patients, no direct evidence currently exists to inform about the potential benefits and/or side effects of extended AI + OFS therapies in premenopausal women. Given these grey areas, we conducted a Delphi survey to report on the opinion of experts in breast cancer treatment and summarize a consensus on the discussed topics. A total of 44 items were identified, all centred around two main themes: 1) defining reliable prognostic factors to pinpoint premenopausal patients eligible for endocrine therapy extension; 2) designing how such therapy should optimally be administered in terms of treatment combinations and duration based on patients' menopausal status. Each item was separately discussed and anonymously voted by 12 experts representing oncological institutes spread across Italy. The consensus threshold was reached in 36 out of 44 items (82%). Herein, we discuss the levels of agreement/disagreement achieved by each item in relation to the current body of literature. In the absence of randomized trials to guide the tailoring of extended AI treatment in premenopausal women, conclusions from our study provide a framework to assist routine clinical practice.