Years Of Tamoxifen Research Articles

Effects of tamoxifen on cognitive function in patients with primary breast cancer.

Tamoxifen may adversely affect cognitive function by interfering with estrogen action in the brain. Despite growing evidence for a relationship between tamoxifen and cognitive problems, findings remain inconclusive. While some tamoxifen-related side effects seem exposure-dependent with concentrations of tamoxifen or its main metabolite, endoxifen, this has never been investigated for cognitive function. We investigated cognitive function after two years of tamoxifen and its association with tamoxifen and endoxifen exposure. 135 women with breast cancer completed the Amsterdam Cognition Scan (ACS), an online neuropsychological test battery, after two years of tamoxifen. Test scores were converted to standardized Z-scores based on a matched 'no-cancer' control group. Tamoxifen and endoxifen concentrations and tamoxifen dose were regressed separately on cognitive functioning. Patients reported mild cognitive complaints and had worse verbal learning, processing speed, executive functioning, and motor functioning compared to matched controls. After correcting for age, mean tamoxifen and endoxifen levels, as well as tamoxifen dose, were associated with worse performance on several cognitive domains. Tamoxifen is adversely associated with objective as well as self-reported cognitive function, which may depend on the level of exposure to tamoxifen and endoxifen. Further research is warranted to confirm this hypothesis.

Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up.

Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.

Racial and Ethnic Disparities in Outcomes After Breast-Conserving Therapy and Endocrine Therapy for DCIS: A Post-Hoc Analysis of the NSABP B-35 Randomized Clinical Trial.

Racial and ethnic disparities in outcomes after treatment for ductal carcinoma in situ (DCIS) are largely unknown. The objective of this study was to examine breast cancer outcomes by race and ethnicity in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 clinical trial. The NSABP B-35 trial randomized postmenopausal women with hormone receptor-positive DCIS treated with breast-conserving therapy to 5 years of tamoxifen or anastrozole. In total, 3104 women were enrolled between 2003 and 2006. For this analysis, patients without complete self-reported race and ethnicity or with immediate trial dropout were excluded. Kaplan-Meier curves and adjusted Cox-proportional hazards models were used for analyses. Of the 3061 women included, 2614 (85.4%) were non-Hispanic white (NHW), 255 (8.3%) were non-Hispanic Black (NHB), 95 (3.1%) were Hispanic, and 96 (3.1%) were Asian or Pacific Islander (API). Endocrine therapy assignment and duration were well balanced between racial and ethnic groups. Median follow-up was 9 years; unadjusted Kaplan-Meier curves did not show any racial differences in disease events. Adjusted Cox-proportional hazards models found API (versus NHW) race to be associated with higher local recurrence [hazard ratio (HzR) 2.45, p = 0.035] and NHB race to be associated with higher distant recurrence (HzR 5.03, p = 0.020) and breast cancer mortality (HzR 3.83, p = 0.046). Despite similar locoregional treatments and standard endocrine therapy in a clinical trial population, racial and ethnic disparities exist in long-term outcomes for hormone-receptor-positive DCIS. These findings suggest that factors outside of access and treatment may impact DCIS outcomes by race and ethnicity.

Association between PIK3CA activating mutations and outcomes in early-stage invasive lobular breast carcinoma treated with adjuvant systemic therapy.

The aim of the study was to evaluate the independent prognostic role of PIK3CA activating mutations and an association between PIK3CA activating mutations and efficacy of adjuvant endocrine therapy (ET) in patients with operable invasive lobular carcinoma (ILC). A single institution study of patients with early-stage ILC treated between 2003 and 2008 was performed. Clinicopathological parameters, systemic therapy exposure and outcomes (distant metastasis-free survival [DMFS] and overall survival [OS]) were collected based on presence or absence of PIK3CA activating mutation in the primary tumor determined using a quantitative polymerase chain reaction (PCR)-based assay. An association between PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival analysis, whereas an association between PIK3CA mutation and ET was analyzed in estrogen receptors (ER) and/or progesterone receptors (PR)-positive group of our patients by the Cox proportional hazards model. Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among 365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associated with differential DMFS and OS (p = 0.36 and p = 0.42, respectively). In patients with PIK3CA mutation each year of tamoxifen (TAM) or aromatase inhibitor (AI) decreased the risk of death by 27% and 21% in comparison to no ET, respectively. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET had a favourable impact on OS. PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC. Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether they received TAM or an AI.

Postoperative Adjuvant Anastrozole for 10 or 5 Years in Patients With Hormone Receptor-Positive Breast Cancer: AERAS, a Randomized Multicenter Open-Label Phase III Trial.

Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on disease-free survival (DFS). This prospective, randomized, multicenter open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients who were disease-free after treatment with either 5 years of anastrozole alone or 2-3 years of tamoxifen followed by 2-3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole for an additional 5 years or stop anastrozole. The primary end point was DFS, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with University Hospital Medical Information Network, Japan (UMIN) clinical trials registry (UMIN000000818). We enrolled 1,697 patients from 117 facilities between November 2007 and November 2012. Follow-up information was available for 1,593 patients (n = 787 in the continue group, n = 806 in the stop group), who were defined as the full analysis set, including 144 patients previously treated with tamoxifen and 259 patients who underwent breast-conserving surgery without irradiation. The 5-year DFS rates were 91% (95% CI, 89 to 93) in the continue group and 86% (95% CI, 83 to 88) in the stop group (hazard ratio, 0.61; 95% CI, 0.46 to 0.82; P < .0010). Notably, extended anastrozole treatment reduced the incidence of local recurrence (continue group, n = 10; stop group, n = 27) and second primary cancers (continue group, n = 27; stop group, n = 52). There was no significant difference in overall or distant DFS. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than those in the stop group, but the incidence of grade ≥3 adverse events was <1% in both groups. Continuing adjuvant anastrozole for an additional 5 years after 5 years of initial treatment with anastrozole or tamoxifen followed by anastrozole was well tolerated and improved DFS. Although no difference in overall survival was observed as in other trials, extended anastrozole therapy could be one treatment choice in postmenopausal patients with hormone receptor-positive breast cancer.

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial

The DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2-3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence. The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design. Between June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n=955) or 6 years (n=957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8-72.3) in the 6-year group (n=827) and 66.0% (95% CI 62.5-69.2) in the 3-year group (n=833) (hazard ratio (HR) 0.86; 95% CI 0.72-1.01; p=0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9-83.5) in the 6-year group and 79.2% (95% CI 76.2-81.9) in the 3-year group (HR 0.93; 95% CI 0.75-1.16; p=0.53). Extended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer. AstraZeneca.

Abstract CC1-2-1: Duration of endocrine therapy

Abstract Patients with hormone-receptor positive, early-stage breast cancer are at considerable risk for late recurrence. Previous randomized clinical trials have shown that extending adjuvant tamoxifen to ten vs. five years improves disease-free survival (and overall survival in one trial). Adding five years of an aromatase inhibitor (AI) after five years of tamoxifen has also been shown to significantly improve disease-free survival in postmenopausal patients. Benefit from extending adjuvant AI therapy beyond five years in patients who have received five years of an AI or tamoxifenàAI has also been recently demonstrated in several clinical trials but the absolute benefit appears small and the ideal duration of the extended therapy is still a topic of debate. Over the past decade, efforts have focused on identifying predictors of risk of late recurrence and predictors of benefit from extended endocrine therapy. Clinicopathologic factors and circulating tumor cells can predict risk of late recurrence but not benefit from extended ET. Several commercially available genomic classifiers can further stratify risk of late recurrence, and some have also been found to predict benefit from extended ET. Their clinical utility for tailoring the use of extended endocrine therapy continues to evolve. Citation Format: Eleftherios (Terry) Mamounas, Kathryn Ruddy. Duration of endocrine therapy [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 CC1-2-1.

Abstract P2-11-11: Computer analysis of nuclear morphology with Multiple Instance Learning Predicts Overall Survival for Node Positive Breast Cancer Patients from SWOG S8814: A Blinded Validation Study

Abstract Background: Adjuvant chemotherapy is a common treatment for breast cancer patients with aggressive tumors, but imposes severe side effects. Although lymph node involvement is associated with higher likelihood of mortality, a subset of LN+ patients can survive without relapse, even without adjuvant chemotherapy. SWOG-8814 (S8814) was a randomized clinical trial of hormone receptor positive, LN+ post-menopausal women (pathologic stage T1-3N1-2) to compare patient outcome between endocrine therapy alone (tamoxifen), chemotherapy (cyclophosphamide, doxorubicin, and 5-fluorouracil) followed by 5 years of tamoxifen, and chemotherapy with concurrent tamoxifen. In this work, we evaluated the ability of a machine learning approach called multiple instance learning (MIL) to predict long-term overall (OS) and disease-free survival (DFS) in patients from the S8814 clinical trial via analysis of digitized H&amp;E tissue slides. Methods: The training set (St, n=121) consisted of digitized H&amp;E Whole Slide Images (WSIs) of ER+ LN+ patients from ECOG-2197 - a clinical trial to compare patient outcome under chemotherapy with doxorubicin/docetaxel vs. doxorubicin/cyclophosphamide. For each WSI, the nuclei of ten tumor patches (2000 × 2000 pixels) were automatically segmented by a pretrained machine learning algorithm called Convolutional Neural Networks (CNN). The results of the CNN’s segmentations were used to obtain ten corresponding feature vectors of 3963 features relating to nuclear morphology and spatial arrangement. Five top discriminative features (Haralick texture, Delaunay triangulation, orientation entropy, perimeter kurtosis, architecture) were identified by reliefF-MI feature filtering and forward selection on St. A Normalized Set Kernel Support Vector Machine classifier was trained on St to construct a MIL binary classifier (M+), which generates a continuous survival score to predict which patients would have &amp;gt;10-years of DFS and OS. The score cutoff thatmaximized F1 score on St was used to generate binary predictions of patient outcome. Blinded validation of the risk scores on S8814 was performed by SWOG. Results: M+ was significantly prognostic of OS in univariate analysis (HR=0.72, p=0.020, 95% CI= 0.55 – 0.95) on S8814. M+ stratifications remained statistically significant after multivariable analysis controlling for treatment, number of positive lymph nodes, and tumor size (HR = 0.71, p=0.017, 95% CI=0.54-0.94). M+ predictions did not achieve statistical significance for DFS in univariate analysis (HR=0.81, p=0.081, 95% CI 0.64-1.03) nor multivariable analysis (HR=0.81, p=0.080, 95% CI 0.63-1.03). M+ was not predictive of chemotherapy benefit for OS (p=0.88) and DFS (p=0.65). There was no correlation of the generated continuous score with Recurrence Score (r=-0.05), previously shown to be a predictive factor for chemotherapy benefit. Conclusion: Our findings demonstrate that nuclear morphology provides insight into overall survival in ER+ LN+ breast cancer patients. Future work will involve combining the MIL based morphologic predictor with other clinicopathologic factors to improve DFS risk stratification. Funding: Funding NIH/NCI grants U10CA180888, U10CA180819, U24CA196175; and in part by Genomic Health, INC. (now Exact Sciences Corp.) Citation Format: Daniel Shao, William E. Barlow, Haojia Li, Cheng Lu, Kathy S. Albain, James Rae, Daniel F. Hayes, Andrew K. Godwin, Alastair M. Thompson, Anant Madabhushi, Lajos Pusztai. Computer analysis of nuclear morphology with Multiple Instance Learning Predicts Overall Survival for Node Positive Breast Cancer Patients from SWOG S8814: A Blinded Validation Study [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 P2-11-11.

133O Extended adjuvant aromatase inhibition after sequential endocrine therapy: Final results of the phase III DATA trial

The DATA study evaluated the use of different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2-3 years of tamoxifen. Here, we present the final analysis.

Physicians’ acceptance of extended or intermittent adjuvant endocrine therapy (AET): A survey on breast cancer (BC) physicians.

e12515 Background: The results from the GIM4, SALSA, and SOLE trials are potentially practice-changing, but it was unknown whether physicians would accept these trial results and adjust their AET prescriptions for postmenopausal women with BC. Methods: A cross-sectional survey involving 77 BC physicians in China was conducted. The survey questions were developed based on the GIM4, SALSA, and SOLE trial results, as well as referred to the latest NCCN guidelines. Statistical analyses were performed using SPSS version 28.0. Results: Almost half (48%) of the respondents were breast surgeons, 19% were breast specialists, 8% were medical oncologists, and 2% were general surgeons. Forty-five percent of the respondents had a clinical experience of ≥15 years, and the mean ± SD number of BC patients managed annually was 762.10 ± 1,254.50. For pN0, tumor size ≤0.5cm, postmenopausal patients, respondents with ≥15 years of clinical experience were more likely to prescribe a longer duration of AET as compared to those with &lt;15 of clinical experience (p=0.025 and p=0.038 for patients receiving prior 4-5 years of tamoxifen [TAM] and prior 5 years of aromatase inhibitor [AI], respectively). More than half (57.1%) did not agree with the hypothesis that AI resistance can be reversed by intermittent letrozole treatment (the SOLE trial hypothesis), but 50.6% considered intermittent letrozole as an acceptable option, especially for patients with ≤3 positive nodes (79.5%), tumor grade 1 (84.6%), tumor size ≤2cm (82.1%), HER2 negative disease (74.4%). Conclusions: A high proportion of the BC physician respondents would prescribe extended AET with AI beyond 5 years for postmenopausal women with BC, especially for those with higher risk. Intermittent letrozole was considered as an acceptable option for low-risk patients.[Table: see text]

PAM50 subtyping and ROR score add long-term prognostic information in premenopausal breast cancer patients

PAM50 intrinsic subtyping and risk of recurrence (ROR) score are approved for risk profiling in postmenopausal women. We aimed to examine their long-term prognostic value in terms of breast cancer-free interval (BCFi) and overall survival (OS) (n = 437) in premenopausal women randomised to 2 years of tamoxifen versus no systemic treatment irrespective of hormone-receptor status. Intrinsic subtyping added independent prognostic information in patients with oestrogen receptor-positive/human epidermal growth factor 2-negative tumours for BCFi and OS after maximum follow-up (overall P-value 0.02 and 0.006, respectively) and those with high versus low ROR had worse prognosis (maximum follow-up: hazard ratio (HR)BCFi: 1.70, P = 0.04). The prognostic information by ROR was similar regarding OS and in multivariable analysis. These results support that PAM50 subtyping and ROR score provide long-term prognostic information in premenopausal women. Moreover, tamoxifen reduced the incidence of breast cancer events only in patients with Luminal APAM50 tumours (0–10 years: HRBCFi(Luminal A): 0.41, HRBCFi(Luminal B): 1.19, Pinteraction = 0.02).Trial registration: This trial is registered in the ISRCTN database, trial ID: ISRCTN12474687.

Abstract PD13-10: Extended adjuvant endocrine therapy in a longitudinal cohort of young breast cancer survivors

Abstract Background: Extended adjuvant endocrine therapy (eET) beyond the first 5 years of ET improves long-term outcomes in breast cancer survivors. For women who remain premenopausal, evidence for benefit has only been demonstrated to date for 5 years of additional tamoxifen, after an initial 5 years of tamoxifen (from ATLAS, aTTom). There are no data available for eET among premenopausal women treated with initial adjuvant aromatase inhibition (AI) and ovarian functions suppression (OFS). Thus, there is uncertainty regarding the optimal eET regimen for young breast cancer survivors. Methods: The Young Women’s Breast Cancer Study (YWS) is a multicenter prospective cohort of women age ≤40 years newly diagnosed with breast cancer between 2006-2016. Women with stage I-III hormone receptor positive breast cancer, ≥6 years post-diagnosis without breast cancer recurrence were considered candidates for eET. Use of eET was elicited on surveys completed at 6, 7 and/or 8 years post-diagnosis, censoring for recurrence or death. Those completing ≥1 survey were eligible for analysis. Patient characteristics were compared by Chi-square test between eET users and non-users, and logistic regression applied to identify factors associated with eET use. Results: Of 667 potential eET candidates, 73.9% (493/667) returned ≥1 survey between year 6-8 and were eligible for analysis. Compared to those without a year 6-8 survey, the analytic cohort tended to be more non-Hispanic white (86.0% v. 77.6%), more financially comfortable (53.9% v. 39.5%) and more likely to have children pre-diagnosis (59.6% v. 41.4%); age and disease characteristics were similar. Overall, 59.6% (294/493) reported any eET use, with use declining over time from 56.9% (265/466) to 51.4% (219/426) to 46.8% (162/346) at years 6, 7 and 8 post-diagnosis, respectively. Among eET users (n=294), tamoxifen monotherapy was the most common approach (76.9%, 226/294), followed by AI monotherapy (22.1%, 65/294, presumably women who transitioned into menopause), AI-OFS (7.1%, 21/294) and tamoxifen-OFS (3.1%, 9/294). Women diagnosed after 2012 were as likely to receive eET as those diagnosed 2006-2011 (59.4%, 117/197 v. 59.8%, 177/296 p=0.928), however eET more often included AI, with or without OFS (41.0% v. 18.6%, p&amp;lt;0.001), or OFS (17.9% v. 7.3%, p=0.005) in later years. In multivariable analysis, increasing age (per year odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.15, p&amp;lt;0.001), higher stage (II v. I: OR: 2.85, 95% CI: 1.81-4.48, p&amp;lt;0.001; III v. I: OR: 3.73, 95% CI: 1.87-7.42, p&amp;lt;0.001) and receipt of chemotherapy (OR: 3.50, 95% CI: 2.08-5.91, p&amp;lt;0.001) were independently significantly associated with any eET use, while women not of white non-Hispanic race/ethnicity were less likely to report eET use (OR: 0.49, 95% CI: 0.28-0.87, p=0.014). Rates of pregnancy in years 1-5 did not differ between eET users and non-users (10.0%, 29/291 v. 8.7%, 17/195, p=0.645) Conclusion: The majority of eligible young breast cancer survivors in the YWS have received eET despite limited data regarding its utility in this population. Heterogeneity exists regarding strategies utilized, and while some factors associated with eET use appear to reflect appropriate risk-based care, such as stage and receipt of chemotherapy, others, including age and race, suggest disparate uptake. Clinical studies are needed in order to determine the optimal approach to eET for young women with a history of early stage hormone receptor-positive breast cancer who remain premenopausal following 5 years of ET. Ensuring risk and preference-based uptake of eET should be a priority. Citation Format: Tal Sella, Yue Zheng, Shoshana M Rosenberg, Kathryn J Ruddy, Shari I Gelber, Rulla M Tamimi, Jeffrey M Peppercorn, Lidia Schapira, Virgina F Borges, Steven E Come, Lisa A Carey, Eric P Winer, Ann H Partridge. Extended adjuvant endocrine therapy in a longitudinal cohort of young breast cancer survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD13-10.

Abstract P2-10-07: Prediction of menstruation recovery timing in premenopausal breast cancer patients taking tamoxifen after chemotherapy: An ASTRRA substudy

Abstract Introduction Addition of ovarian function suppression to conventional endocrine therapy alone in premenopausal women provides a survival benefit with moderate to high risk hormone-receptor positive breast cancer, especially who received chemotherapy Prediction of menstruation recovery after chemotherapy is important for deciding subsequent endocrine treatment and addressing fertility issues. Methods In the adding OFS after chemotherapy trial (ASTRRA), patients who resumed ovarian function up to 2 years after chemotherapy were randomized to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. With these 1383 patients, we developed a model that predicts when patients recover menstruation within 3 years after chemotherapy using several variables including age, BMI, chemotherapy regimen and duration, serum E2 and FSH level. Results A total of 1017 patients data were used to develop prediction model and 366 patients data were used for external validation. In development group, 546 (53.6%) patients resumed menstruation during follow up period of 5 years. In multivariable analysis, younger age and AC based regimen without taxane were strong predictive factor for menstruation recovery. However predictive value of chemotherapy regimen was not constant over time. Therefore, we conducted another model with patients (n= 624) who did not recover menstruation within one year. In this patient group, predictive factors for menstruation recovery was age and serum E2 level at 6 months after chemotherapy. We also conducted a simplified scoring system to estimate change of recovery by using risk factors mentioned above. Conclusion Younger age is an important persisting factor predicting menstrual recovery after chemotherapy. Although chemotherapy regimen predicts shor-term menstrual recovery, over time, patient factors have more predictive influence on recovery. Recovery of serum E2 level would be important to predict subsequent menstruation recovery. Citation Format: Young Joo Lee, Woo C Noh, Seok J Nam, Byeong-Woo Park, Eun S Lee, Seock A Im, Yong S Jung, Jung H Yoon, Sung S Kang, Kyong H Park, Soo-Jung Lee, Min H Lee, Joon Jeong, Sung Y Kim, Hyun-Ah Kim, Se-Hwan Han, Wonshik Han, Min H Hur, Seonok Kim, Sei-hyun Ahn, Hee J Kim. Prediction of menstruation recovery timing in premenopausal breast cancer patients taking tamoxifen after chemotherapy: An ASTRRA substudy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-07.

Role of Exemestane in the Treatment of Estrogen-Receptor-Positive Breast Cancer: A Narrative Review of Recent Evidence.

Breast cancer (BC) is the most common type of cancer diagnosed among women worldwide with an estimated 2.3 million new cases every year. Almost two-thirds of all patients with BC have estrogen receptor-positive (ER+) tumors. In this review, the clinical evidence of exemestane in different treatment settings in ER+ BC is presented and summarized. A search strategy with the keywords "breast cancer [MeSH Terms]" AND "exemestane [Title/Abstract]" was devised and a search was performed in PubMed. The efficacy of exemestane in different treatment settings has been established by numerous clinical studies. Exemestane is recommended as an adjuvant treatment in postmenopausal women previously treated with tamoxifen in trials comparing 5years of tamoxifen with 2-3years of tamoxifen combined with 2-3years of exemestane, which proved that treatment with exemestane provided better survival outcomes. Similarly, exemestane could be considered as a safe treatment option for neoadjuvant treatment, prevention of chemotherapy, and treatment of advanced BC either alone or in combination with other targeted therapy drugs in both pre- and postmenopausal women. Exemestane could be considered as a reasonable therapeutic option in the treatment of ER+ BC at any stage in pre- and postmenopausal women.

Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer: A pragmatic, multicenter, and prospective clinical trial in China.

This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive (ER+) early breast cancer in China. Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy. The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer, appearance of a second primary or contralateral breast cancer, or death due to any cause. Other endpoints included the proportion of patients experiencing each event, incidence rate per annum, relationships between human epidermal growth factor receptor 2 status and time to event, and relationship between disease history variables and time to event. Overall, 558 patients were included in the full analysis set: 397 (71.1%) completed the study, 20 experienced an event, and 141 discontinued [47 owing to an adverse event (AE); 37 no longer willing to participate]. Median duration of treatment was 29.5 (range, 0.1-57.7) months. Median time to event was not reached. Event-free survival probability at 36 months was 91.4% (95% CI, 87.7%-95.1%). The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years (20/565). Multivariate analysis showed an association between tumor, lymph node, and metastasis stage at initial diagnosis and time to event [hazard ratio: 1.532 (95% CI, 1.129-2.080); P=0.006]. Most AEs were grade 1 or 2 in severity, with arthralgia (7.7%) being the most common treatment-related AE. This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+ breast cancer previously treated with adjuvant tamoxifen for 2-3 years. No new safety signals were identified in the Chinese population.

Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions.

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor-positive, human epidermal growth factor receptor 2-negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.

Survival outcome and treatment tolerability for postmenopausal females with early stage hormone receptor positive breast cancer treated with different adjuvant hormonal lines (TAM vs. AI vs. switching strategy) for 5 years

Abstract Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.

Optimal adjuvant endocrine therapy for breast cancer.

Adjuvant endocrine therapy is the principal systemic treatment for non-metastatic hormone receptor-positive breast cancer. Incorporation of an aromatase inhibitor is superior to tamoxifen alone for postmenopausal women.1 Guidelines recommend aromatase inhibitor either upfront or as part of an early switch strategy after 2–3 years of tamoxifen.2 Recommendations on extended adjuvant endocrine therapy after 5 years are evolving. A randomised trial3 of extended adjuvant tamoxifen showed a survival benefit, but results from trials2,4,5 evaluating extended aromatase inhibitor therapy have been mixed and the optimal duration or type of endocrine therapy remains uncertain.

Treatment of male breast cancer: meta-analysis of real-world evidence.

Breast cancer is rare in men and managed by extrapolating from breast cancer in women. The clinicopathological features of male breast cancer, however, differ from those of female breast cancer. Because clinical trials are rare, the synthesis of real-world data is one method of integrating sufficient evidence on the optimal treatment for this patient population. PubMed, Embase, and Cochrane Library databases were searched. Clinical studies were included if they evaluated the treatments of interest in male breast cancer; these evaluations included breast-conserving surgery (BCS) versus mastectomy, postmastectomy radiation therapy versus no radiation, the accuracy of sentinel lymph node biopsy (SLNB), and a comparison of various endocrine therapies. Forty studies were retrieved. The pooled estimate of overall survival (OS) revealed no difference between BCS and mastectomy groups. Postmastectomy radiation to the chest wall significantly increased OS relative to no postmastectomy radiation (hazard ratio (HR) 0.67, 95 per cent confidence interval 0.54 to 0.84). The pooled estimates of identification and false-negative rates of SLNB were 97.4 and 7.4 per cent respectively. Tamoxifen treatment was associated with significantly increased OS compared with no tamoxifen intake (HR 0.62, 0.41 to 0.95). Identification and false-negative rates for SLNB were comparable to those in female breast cancer. Breast-conserving surgery can be effective and safe; postmastectomy radiation to the chest wall and 5-year tamoxifen treatment improves survival.

118O Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: A randomised, phase III trial of the Gruppo Italiano Mammella

The benefit of extended adjuvant therapy with aromatase inhibitors (AIs) in postmenopausal hormone-receptor positive breast cancer patients treated with tamoxifen for 2-3 years followed by an AI for 2-3 years is still controversial. We aimed to determine whether, after 2-3 years of tamoxifen, 5 years of letrozole is more effective than the standard duration of 2-3 years.