Premenopausal Breast Cancer Patients Research Articles

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30pg/ml. Patient data was gathered from medical records for this comparison. Of the 264 patients enrolled in this study, 117 were administered 3.6mg of goserelin monthly (goserelin 1M group), 63 received 3.75mg of leuprorelin monthly (leuprorelin 1M group) and 84 were given 11.25mg of leuprorelin every three months (leuprorelin 3M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Abstract PO4-20-06: Impact of iatrogenic menopause on vaginal health and sexuality

Abstract Background Due to the lowering of circulating estrogens symptoms of genitourinary syndrome of menopause (GSM) may arise with premenopausal breast cancer patients who become menopausal due to breast cancer treatment. Clinical signs of GSM are i.a. vaginal dryness, dyspareunia, loss of libido, dysfunction of arousal and/or orgasm: this may negatively impact vaginal health, sexual activity and quality of life. The composition and function of the vaginal microbiome may also change due to changes of gonadal hormones during the menopausal transition. This change may contribute to vaginal discomfort and problems during sexual activity. With this prospective research we aim to uncover the relationship between vaginal health and sexuality, it gives an unique opportunity to investigate the vaginal changes and possible shift of vaginal microbiome when menopause occurs. This is a first in time study where longitudinal samples of the vaginal microbiome in one patient are investigated before and after menopause. The vaginal microbiome might be a future target to treat vaginal discomfort after treatment for breast cancer. Trial design This is a prospective minimal invasive study where participants are asked to undergo a baseline gynecologic examination, again 3 and 6 months after menopause. During this examination we measure vaginal pH, describe vaginal hydration and anatomy (using vaginal-, and vulvar assessment scale (VAS, VuAS)) and sample the vaginal microbiome (analyzed with 16S rRNA gene sequencing and quantitative real-time polymerase chain reaction (qPCR)). At the same time, a blood test is performed (Estradiol, FSH) and participants complete a survey (demographic information, medical history, current well-being using World Health Organisation- Five Well-Being Index (WHO-5), sexual functioning using the Female Sexual Functioning index (FSFI), Female Sexual Dysfunction Scale – revised (FSDS-R) and Short Sexual Functioning scale (SSFS)). Eligibility criteria - Patients (>18 years) with Stage I, IIA, IIB, IIIA, IIIB, IIIC breast cancer - Reproductive age or menopausal transition according to STRAW+10 criteria - Iatrogenic menopause caused by ovarian function suppression (OFS), bilateral salpingo-ovariectomy (BSO) or by starting chemotherapy - Any partner status - Latest cervical cytology is normal - No prior history of hysterectomy - Patients who take oral contraceptives or have a Levonorgestrel- containing IUD can participate. Oral contraceptives should be stopped or the Levonorgestrel-containing IUD should be removed before systemic breast cancer therapy Specific aims To accurately describe what vaginal changes occur during breast cancer treatment To evaluate if the onset of menopause is related to changes in vaginal microbiome To evaluate if there is a relation between the objective vaginal changes and the subjective complaints related to GSM To evaluate if there is a relation between the objective vaginal changes and a possible alteration in sexuality Statistical methods Using multiple comparison procedures in ANOVA (analysis of Variance) model, the clinical findings (VAS, VuAS, pH, composition of microbiome) and validated questionnaires (WHO-5, FSFI, FSDR-r, SSFS) are linked to analyze if vaginal changes are related to changes in sexual wellbeing. The interpretation of the results of this investigation should be interpreted with caution due to the explorative nature of the study. Present accrual/Target accrual 23/60 participants are included (JULY 2023) Citation Format: Nynke Willers, Sileny Han, Patrick Neven, Paul Enzlin, Sarah Lebeer, Sarah Ahannach. Impact of iatrogenic menopause on vaginal health and sexuality [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-06.

Abstract PO3-01-08: Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study

Abstract Background: Adjuvant endocrine therapy (AET) is commonly used for hormone receptor-positive breast cancer patients. Combining ovarian function suppression (OFS) with tamoxifen improves survival outcomes, but is associated with menopausal symptom-related issues and treatment discontinuation. This study aimed to compare menopausal symptoms between tamoxifen alone and tamoxifen plus OFS over 12 months and identify related factors. Methods: This prospective study included 209 premenopausal breast cancer patients on tamoxifen. Menopausal symptoms were assessed using the Menopausal Rating Scale (MRS) at baseline, 3, 6, and 12 months. Statistical analysis involved linear regression and generalized estimating equations. Results: Of the participants, 27.8% received tamoxifen plus OFS and were younger and more likely to be unmarried. The tamoxifen plus OFS group had lower baseline MRS scores, but higher scores at 6 and 12 months compared to tamoxifen alone. MRS scores increased significantly in both groups, plateauing at 6 months with tamoxifen alone and at 12 months with tamoxifen plus OFS. Factors associated with higher MRS scores at 6 months were baseline MRS scores and addition of OFS. Impact of OFS on MRS scores varied with prior chemotherapy status, being significant in patients without prior chemotherapy. Conclusion: Adding OFS to tamoxifen in premenopausal breast cancer patients was associated with a higher burden of menopausal symptoms compared to tamoxifen alone, particularly in patients who have not undergone prior chemotherapy. Therefore, careful consideration and decision-making regarding this issue are crucial in terms of both treatment outcomes and quality of life. Table 1. Baseline characteristics, Overall and According to adjuvant endocrine therapy, tamoxifen alone versus tamoxifen plus ovarian function suppression (OFS) Table 2. Multivariable linear regression about MRS scores from the baseline to 6 months, and with interaction between addition of OFS and prior chemotherapy effect Table 3. Interaction effect of additional OFS depending on prior chemotherapy; (a) without prior chemotherapy, (b) with prior chemotherapy Citation Format: Youngwon Lee, Jong Won Lee, Sae Byul Lee, Byung Ho Son, Hee Jeong Kim, Beom Seok Ko, Jisun Kim, Il-Yong Chung, Tae-Kyung Yoo. Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-08.

Abstract PO3-12-06: The pilot study for a mobile-based monitoring solution to manage menopausal symptoms of premenopausal breast cancer patients with endocrine therapy

Abstract Background Endocrine therapy (ET) is the most important treatment for hormone receptor (HR)-positive breast cancer (BC) patients. Each of the endocrine medications, such as aromatase inhibitors (AIs), luteinizing hormone-releasing hormone (LHRH) analogs, and selective estrogen receptor modulators, has its own set of side effects, and these might lead to poor drug adherence and eventual discontinuation. There are few systematic monitoring systems for menopausal symptoms of patients on ET. We conducted a prospective, pilot study through the mobile platform-based monitoring solution which contains a questionnaire about menopausal symptoms to assess the feasibility of the solution. Methods We screened and collected data from HR-positive BC patients who underwent surgery at a single institution from May 2022, until recruiting a total of 20 patients. Patients scheduled for postoperative ET at age 50 or younger were included. Preoperatively confirmed metastatic BC patients were excluded. A total of 19 patients were enrolled, excluding one patient who self-discontinued medication. Menopause Rating Scale (MRS) surveys were periodically administered to the patients using a mobile platform-based solution to collect responses during first 3 months of ET. The primary endpoint of this study was the response rate of the patients, and the second endpoint was MRS scores and patient satisfaction. At the time of initial enrollment before the start of ET, MRS was collected using a paper questionnaire. The concordance rate of MRS response using a paper questionnaire and this solution was compared. We also conducted a user evaluation at the end of the third month of ET to determine satisfaction. The data collected from the solution were used by physicians to assist in patient care for clinical use. Results The median age of the cohort was 39 (range 29-47). Six patients were treated with Tamoxifen alone, Tamoxifen with LHRH analog in 12 patients, and AI with LHRH analog in 1 patient. There were 3 (15.8%) of pTis, 13 (68.4%) of pT1, and 3 (15.8%) of pT2, as well as 18 (94.7%) of pN0 and 1 (5.3%) patients of pN1. The total response rate of patients to the solution during the study period was 84.5%. Each symptom has different response rates and MRS scores, from 70.2% for sex-related symptoms to 95.4% for joint pain, and from 1.24 out of 4 for sleep disturbances to 0.45 out of 4 for vaginal dryness. The match rate between mobile and paper surveys was 90.0%. The overall satisfaction score for the solution of patients was 8.06 out of 10, with the highest score (8.79 out of 10) given in terms of using patients’ responses in outpatient appointments with the physician. Conclusion The analysis of MRS using this mobile solution in premenopausal BC patients undergoing postoperative ET is expected to be feasible for clinical use and should be analyzed in a large-scale study in the future. Citation Format: Dong Seung Shin, Jai Min Ryu, Byung Joo Chae, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jonghan Yu. The pilot study for a mobile-based monitoring solution to manage menopausal symptoms of premenopausal breast cancer patients with endocrine therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-06.

Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients

IntroductionPatients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence.MethodsWe included stage I–III premenopausal breast cancer patients diagnosed during 2002–2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns.ResultsWe identified three adherence patterns among 4,353 women—high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers.ConclusionsWomen with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Adjuvant Chemotherapy in Premenopausal Patients With Hormone-Positive Breast Cancer With a Recurrence Score of 16-25: A Retrospective Analysis Using the National Cancer Database.

Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative (HER2-), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database. The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2-. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared. Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]). Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.

Identification of genes and pathways associated with menopausal status in breast cancer patients using two algorithms

BackgroundMenopausal status has a known relationship with the levels of estrogen, progesterone, and other sex hormones, potentially influencing the activity of ER, PR, and many other signaling pathways involved in the initiation and progression of breast cancer. However, the differences between premenopausal and postmenopausal breast cancer patients at the molecular level are unclear.MethodsWe retrieved eight datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) associated with menopausal status in breast cancer patients were identified using the MAMA and LIMMA methods. Based on these validated DEGs, we performed Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks were constructed. We used DrugBank data to investigate which of these validated DEGs are targetable. Survival analysis was performed to explore the influence of these genes on breast cancer patient prognosis.ResultsWe identified 762 DEGs associated with menopausal status in breast cancer patients. PPI network analysis indicated that these genes are primarily involved in pathways such as the cell cycle, oocyte meiosis and progesterone-mediated oocyte maturation pathways. Notably, several genes played roles in multiple signaling pathways and were associated with patient survival. These genes were also observed to be targetable according to the DrugBank database.ConclusionWe identified DEGs associated with menopausal status in breast cancer patients. The association of these genes with several key pathways may promote understanding of the complex characterizations of breast cancer. Our findings offer valuable insights for developing new therapeutic strategies tailored to the menopausal status of breast cancer patients.

Mutational and expressional association of the PIK3CA gene with the risk of breast cancer in the Pakistani population.

PI3K pathway is a very important pathway that is reported to be involved in breast cancer. Mutation ofPI3Kand p110 alpha-catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA) is of high predictive and prognostic values in breast cancer. The purpose of the current study was to screen the hotspot mutations of thePIK3CAgene i.e. rs2677760, rs3806685, rs121913273 & rs121913279 along with expressional analysis ofPI3KandPIK3CAgenes in breast cancer female patients. For mutational analysis, TaqMan assay & Sanger sequencing were performed while for expressional analysis real-time PCR was carried out. Mutant allele C of rs2677760 was observed to be high in postmenopausal patients. The frequency of mutant allele G of rs3806685 was significantly high in breast cancer patients. All diseased and control samples were of wild type for the hotspot rs121913273 and rs121913279 with allele G for rs121913273 and A for rs121913279. Expression of the PI3K was high in breast cancer tissue samples as compared to the adjacent controls. While the expression ofthe thePIK3CAgene was significantly high in premenopausal breast cancer patients. It was concluded that the mutant allele C of rs2677760 might have some sort of association with the menopausal status and it could be used as a diagnostic marker in post-menopausal women if studied further. Mutant allele G of rs3806685 was also found to be associated with breast cancer. While multiallelic rs121913273 and rs121913279 showed a different trend for the studied population. For expressional analysis, PI3Kshowed over-expression in the cases while PIK3CAgene expression was observed to be significantly associated with pre-menopausal status.

Clinical guidelines for managing menopausal symptoms in women with (a history of) breast cancer.

One in eight women will be diagnosed with breast cancer. At the time of diagnosis, 75% of patients are postmenopausal. Many will receive anti-hormone therapy, which often induces menopausal symptoms. Premenopausal breast cancer patients frequently become postmenopausal as a result of the treatment and often experience menopausal symptoms. The increased incidence of breast cancer, combined with longer survival, has led to an increase in the number of women experiencing menopausal symptoms. Therefore, the management of menopausal symptoms in women with a history or current breast cancer is a relevant and common clinical problem. To provide a clinically useful overview of the steps in the management of menopausal symptoms in women with (a history of) breast cancer. A comprehensive literature review was conducted by authors JS and WT using the PubMed and Medline databases. Abstracts were critically appraised and, where appropriate, the full text was analysed. Not applicable. Depending on the condition, either meta-analyses, randomised controlled trials or retrospective cohorts were identified. No evidence was found for some proposed treatments. Menopausal symptoms in women with (a history of) breast cancer require a patient-tailored approach. Shared decision making is paramount and adequate up-to-date knowledge can help the breast cancer specialist to advise and guide patients accordingly. A comprehensive, clinically-based overview of evidence-based treatment options for menopausal symptoms in women with (a history of) breast cancer.

Association of physical weight statuses defined by body mass index (BMI) with molecular subtypes of premenopausal breast cancer: a systematic review and meta-analysis.

The association between overweight/obesity and postmenopausal breast cancer has been proven. However, uncertainty exists regarding the association between physical weight statuses and premenopausal breast cancer subtypes. This study aimed to explore the association of body weight statuses with molecular subtypes of premenopausal breast cancer. A systematic search of Medline, PubMed, Embase, and Web of Science was performed. The Newcastle-Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) Critical Appraisal tools were used to evaluate the quality of the literature. STATA and R software were used to analyze the extracted data. The meta-analysis included 35 observational studies with a total of 41,049 premenopausal breast cancer patients. The study showed that the proportion of underweight patients was 4.8% (95% CI = 3.9-5.8%, P = 0.01), overweight was 29% (95%CI = 27.1-30.9%, P < 0.01), obesity was 17.8% (95% CI = 14.9-21.2%, P < 0.0001), and normal weight was 51.6% (95% CI = 46.7-56.5%, P < 0.0001). The pooled results showed that in comparison to the normal weight group, being physically underweight is related to a 1.44-fold risk (OR = 1.44, 95%CI = 1.28-1.63, P < 0.0001) of HER2 + breast cancer. Overweight is related to a 1.16-fold risk (OR = 1.16, 95%CI = 1.06-1.26, P = 0.002) of TNBC and a 16% lower risk (OR = 0.84, 95%CI = 0.75-0.93, P = 0.001) of ER + breast cancer. When compared to underweight/normal weight populations, both overweight (OR = 0.74, 95%CI = 0.56-0.97, P = 0.032) and obesity (OR = 0.70, 95%CI = 0.50-0.98, P = 0.037) can reduce the risk of ER + PR + breast cancer. In the premenopausal breast cancer population, the distribution of patients' numbers with different weight statuses was significantly distinct among the various breast cancer subtypes. Additionally, the associations between physical weight statuses and the risk of premenopausal breast cancer subtypes are divergent.

Differential distribution of actual and surrogate oncotype DX recurrence scores in breast cancer patients by age, menopausal status, race, and body mass index.

The Oncotype DX Recurrence Score (RS) is a widely used prognostic tool for estrogen receptor-positive breast cancer patients. Multiple surrogate models can predict RS with good accuracy. In this study we aimed to determine whether the RS and two surrogate indices were differentially distributed by age, menopausal status, race, and body mass index (BMI). 516 breast cancer cases treated at a single institution were analyzed. Epidemiologic data, RS, tumor size, grade, and biomarker data were abstracted. Breast Cancer Prognostic Score (BCPS) and modified Magee equation2 were used to calculate surrogate RS. Patients were stratified into different groups based on age, menopausal status, race, BMI, or a combination of strata. Mean and standard deviation were calculated for each group/subgroup. Age below median (< 63) was associated with higher RS, especially in obese and Black patients. RS was also higher in obese and Black patients in the premenopausal subgroup. Black patients had a higher RS compared to White women in the premenopausal and non-obese subgroups. BMI < 30 was associated with higher RS, especially in older, postmenopausal, and Black patients. Some of these observations were replicated by the two surrogate models. The surrogate recurrence scores were higher in the younger age group, in non-obese older/postmenopausal women, and in younger/premenopausal obese individuals. Higher RS was observed in younger and premenopausal breast cancer patients, especially among the Black and obese subgroups, and in non-obese patients, especially among Black and older/postmenopausal women, suggesting more aggressive disease in these subgroups. Some statistical differences could be replicated by both surrogate models, suggesting that they may have utility in breast cancer epidemiology studies that do not have access to Oncotype DX RS or patient outcome data.

The roles of anti-Müllerian hormone in breast cancer.

Anti-Müllerian hormone (AMH) is produced and secreted by granulosa cells of growing follicles, and its main role is to inhibit the recruitment of primordial follicles, reduce the sensitivity of follicles to follicle-stimulating hormone (FSH), and regulate FSH-dependent preantral follicle growth. It has become an effective indicator of ovarian reserve in clinical practice. Research on AMH and its receptors in recent years has led to a better understanding of its role in breast cancer. AMH specifically binds to anti-Müllerian hormone receptor II (AMHRII) to activate downstream pathways and regulate gene transcription. Since AMHRII is expressed in breast cancer cells and triggers apoptosis, AMH/AMHRII may play an important role in the occurrence, treatment, and prognosis of breast cancer, which needs further research. The AMH level is a potent predictor of ovarian function after chemotherapy in premenopausal breast cancer patients older than 35 years, either for ovarian function injury or ovarian function recovery. Moreover, AMHRII has the potential to be a new marker for the molecular typing of breast cancer and a new target for breast cancer treatment, which may be a link in the downstream pathway after TP53 mutation.

Measuring Ovarian Escape in Premenopausal Estrogen Receptor-Positive Breast Cancer Patients on Ovarian Suppression Therapy at Suez Canal University Hospital, Ismailia, Egypt

Measuring Ovarian Escape in Premenopausal Estrogen Receptor-Positive Breast Cancer Patients on Ovarian Suppression Therapy at Suez Canal University Hospital, Ismailia, Egypt

Effect of astragalus polysaccharides (PG2) treatment of adjuvant chemotherapy-induced fatigue in premenopausal patients with breast cancer.

537 Background: Fatigue is one of the most common symptoms of breast cancer (BC) patients who are receiving adjuvant chemotherapy. Astragalus Polysaccharides (PG2) had been proved to relieve cancer-related fatigue in advanced BC patients. The aim of this study is to evaluate the efficacy of PG2 as a complementary treatment among stage II/III BC patients with adjuvant chemotherapy of epirubicin-cyclophosphamide(EC) regimen in reduction of chemotherapy-induced toxicity and encouraging compliance with chemotherapy. Methods: This double blind, multicenter, phase II trial randomized stage II/III BC patients who would receive adjuvant EC at least 4 cycles to either PG2 500 mg or placebo on day1, 3, 8 every 21 days as the combination. Changes in chemotherapy-related fatigue score (CRFS) was evaluated by the Brief Fatigue Inventory-Taiwanese Form and incidence of Grade 3/4 neutropenia were the primary endpoints. Results: A total of 66 eligible patients were enrolled and equally randomized to PG2 and placebo groups, 30 cases in each group completed this trial. In general, there was no significant difference in the mean change of CRFS and fatigue intensity between the groups. But the CRFS and fatigue intensity in premenopausal-PG2 group were less aggravated after 4 cycles of EC than that of postmenopausal-placebo group. Persisted significance difference in CRFSs from cycle 1 day 5 (PG2: 0.6; Placebo: 1.9, P = 0.023) to cycle 4 day 15 (PG2: -0.3; Placebo: 0.7, P = 0.002). In all population, a lower proportion of patients suffered from grade 3/4 neutropenia from cycle 1 to cycle 4 were observed in the PG2 group compared to the placebo group (78.8% vs. 87.9% in intent-to-treat population). Conclusions: PG2 combined with adjuvant EC significantly improved adjuvant EC-induced fatigue in premenopausal BC patients. PG2 assists these patients with maintaining normal daily life and job activities, also less need of family support during chemotherapy. Furthermore, patients treated with PG2 might have better compliance to complete the whole course of adjuvant chemotherapy. Clinical trial information: NCT03314805 .

Efficacy of ovarian function suppression of 3-monthly versus monthly GnRH agonist as endocrine therapy for premenopausal breast cancer patients.

527 Background: The combined analysis of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials have shown significant survival benefit of adding ovarian function suppression (OFS) with GnRH agonists (GnRHa) to aromatase inhibitors (AI) versus tamoxifen in high-risk premenopausal patients (pts) with estrogen receptor (ER)-positive breast cancer (BC). In both studies, GnRHa was administered every 4 weeks. However, the efficacy of 3-monthly GnRHa plus AI has not been well studied. We conducted a retrospective study designed to assess the efficacy of OFS with 3-montlhy compared with monthly goserelin, associated with AI, in premenopausal pts with ER-positive BC. Methods: Medical records of premenopausal pts with ER-positive BC who received OFS with 10.8mg 3-montlhy goserelin plus AI or 3.6mg monthly goserelin plus AI, between June/2013 and January/2023 were reviewed. Patient characteristics, such as age, body mass index (BMI) and prior chemotherapy were analyzed. Estradiol (E2) levels were measured by gas chromatography tandem mass spectrometry. Pts with at least one E2 level above 2.72 pg/ml were considered to have ineffective OFS. Analysis of E2 measurements was divided into periods: &lt; 3, 3 to 6, 6 to 9, 9 to 12, 12 to 18, 18 to 24 and &gt; 24 months. E2 levels greater than 2.72 pg/ml were evaluated at each timepoint. Results: A total of 88 pts were included. 27 (30.7%) received monthly goserelin and 61 (69.3%) 3-monthly goserelin. Patient characteristics were well balanced between the groups. Relevant demographic data are shown in table. For E2 analysis, 20 (22.7%) pts had at least one measurement greater than 2.72 pg/ml, 11 (40.7%) in the monthly group and 9 (14.8%) in the 3-monthly group (p = 0.007). The percentages of E2 measurements ≥ 2.72 pg/ml, in each time period, were 0%, 40%, 12.5%, 16.7%, 33.3%, 50% and 50% in monthly group versus 8%, 4.2%, 10%, 14.3%, 4.8%, 8.3% and 5.6%, in 3-monthly group, respectively. Conclusions: Our study demonstrated that more pts who underwent 3-monthly goserelin had E2 levels below the defined threshold of 2.72 pg/ml compared with monthly goserelin, when associated with AI, with statistical significance. These findings suggest that 3-monthly goserelin may result in better efficacy in OFS when comparing with monthly and provide greater convenience for pts. [Table: see text]

Treatment pattern of early-stage premenopausal breast cancer patients with low Oncotype DX score: Single center experience.

e12510 Background: The predictive value of Oncotype DX in early-stage node negative breast cancer had been previously well established. As per TAILORx, patients with a low Oncotype DX Recurrence Score RS (0–25) did not benefit from chemotherapy. Premenopausal patients are a crucial subgroup for which recommendations based on Oncotype DX are imprecise. Those with Oncotype DX RS 16-25 are thought to have a small benefit from chemotherapy. Our goal was to study the treatment pattern for this group of patients managed at our institution. Methods: We conducted a retrospective analysis to assess premenopausal patients with early-stage breast cancer who had Oncotype DX testing done. All eligible patients were compared based on whether chemotherapy was given or not. The primary endpoint evaluated was the rate of local recurrence. Univariate comparisons were assessed using t-tests or ANOVA for continuous variable &amp; chi-square for categorical variable. Results: A total of 506 patients younger than 50 years diagnosed between 01/2018 and 12/2020 who had an Oncotype DX available were identified. Of these, 344 were White, 137 were Black and 23 identified as another race. The average age of patients was 42.7 ± 5.5 years. Patients treated with chemotherapy were found to be on average younger than those who did not receive chemotherapy (42 years old vs 43.6 years old, P &lt; 0.0001). The average tumor size for patients who got chemotherapy was 3.26 cm compared to an average size of 2.78 cm for patients who avoided chemotherapy. 72.1% of patients with stage 2 disease had received chemotherapy compared to 38.1 % of patient with stage 1. There were 462 patients with RS &lt; 16, 28 patients with RS 16-25, and 16 patients with RS &gt; 25 as illustrated. Patients were followed from a range of 1.8 months to 30.7 months. There were 6 patients who had local recurrences identified, all of which had RS scores &lt; 16. Conclusions: In our study, 91.3% had RS &lt; 16 and generally should have avoided chemotherapy, however 35% of these patients continued to receive chemotherapy. Only 5.5% of our population had RS 16-25, a quarter of which (n = 7) received chemotherapy. Of those 7 patients, 3 had positive lymph node disease. None of these patients had disease recurrence to date. Patients with RS &gt;25 made up 3.2% of the population and would generally benefit from chemotherapy, however 12.5% of these patients did not end up receiving it. Using Oncotype DX in early-stage breast cancer helps avoid chemotherapy safely in majority of patients. [Table: see text]

Evaluation of PAM50 intrinsic subtypes and risk of recurrence (ROR) scores in premenopausal women with early-stage HR+ breast cancer: A secondary analysis of the SOFT trial.

504 Background: The landmark Suppression of Ovarian Function Trial (SOFT) in premenopausal breast cancer patients revealed that the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with either tamoxifen (T+OFS) or exemestane (E+OFS) reduces the risk of recurrence compared with adjuvant tamoxifen alone. There are no biomarkers to aid decision-making about intensification of endocrine therapy with OFS. The purpose of this study is to assess the prognostic and predictive ability of PAM50 intrinsic subtypes and ROR scores in premenopausal women with HR+/HER2- breast cancer in the SOFT trial. Methods: Gene expression analyses were performed via the NanoString Breast Cancer 360 assay on RNA isolated from FFPE tumor samples from the SOFT trial that were HR+/HER2- (n=1245/3047). PAM50 subtype and ROR score were determined centrally by NanoString Technologies (Seattle, WA, USA), blinded to clinical characteristics, treatment and outcome. Median follow-up was 12 years. Primary endpoint in this study was distant recurrence-free interval (DRFI). Secondary endpoints were breast cancer-free interval (BCFI) and disease-free survival (DFS). Kaplan-Meier analysis and Cox proportional hazards regression models, stratified by prior chemotherapy and lymph node status, were used to evaluate the predictive performance of PAM50 intrinsic subtypes and ROR categories (low vs intermediate vs high), and secondarily ROR score as a continuous variable. We also investigated differences between very young (&lt;40yrs) vs young (&gt;40yrs) women. Results: Tumor samples from 1084/1245 (87%) patients successfully completed PAM50 testing and are included in this analysis. Patient characteristics in this cohort were similar to the entire SOFT trial population. Intrinsic subtype and ROR category distribution is described below. Subtype distribution significantly differed between very young vs young premenopausal women, with fewer luminal A and more luminal B and non-luminal tumors seen in the very young (p&lt;0.001). The ROR score distribution also differed significantly: in node-negative patients there were significantly more ROR-high scores amongst very young compared to young women (36% vs 14%, p&lt;0.001). Conclusion: Breast cancer diagnosed in very young women has aggressive disease biology. Prognostic and predictive analyses of both intrinsic subtypes and the ROR score are ongoing and will be presented at the meeting. Clinical trial information: NCT00066690 . [Table: see text]

(550) Sexual Arousal in Premenopausal Breast Cancer Patients on Antihormonal Treatment

Abstract Introduction Breast Cancer is the most common cancer in women and is associated with a severe impairment of general life quality, body-related self-esteem and sexual function and satisfaction. Sexual satisfaction has been shown to have a significant impact on general health and well-being. Nevertheless, research aiming at understanding sexual function in breast cancer patients is very scarce, no vaginal plethysmography data measuring vaginal blood flow on breast cancer patients currently exists. A better understanding of the interplay of the physiological sexual response and subjective sexual arousal in breast cancer survivors could help develop new strategies for treating this specific target group and contributing to improve their health and life quality. Objective The aim of this study is to collect preliminary data on psychophysiological aspects of the sex.al function of premenopausal breast cancer patients on antihormonal therapy and compare them with healthy controls. Specifically, we hypothesized that (1) genital arousal following visual stimuli is less in breast cancer patients than in healthy controls, (2) genital arousal following tactile stimuli is the same in breast cancer patients and healthy controls, (3) genital arousal following tactile stimuli is greater than following visual stimuli in both breast cancer patients and healthy controls. Serum sex hormone levels and self-reported sexual function are analyzed as moderators. Methods Breast cancer survivors (n=60) treated with antihormonal therapy for breast cancer, who are in complete remission for at least one year and healthy controls (n=20), undergo vaginal plethysmography while sexual stimuli (visual, tactile, visual + tactile) are presented. Subjective arousal and genital arousal are recorded continuously. Hormone serum levels, self-reported sexual function, sexual self-esteem, and quality of life measures are analyzed as potential moderators. Results Intraindividual differences (subjective and genital arousal) and interindividual differences (breast cancer patients, healthy controls) are analyzed based on a 2-level mixed effect models for each outcome variable. Pearson correlations are calculated to assess the relationships between subjective arousal and genital arousal for each group. Conclusions This study is the first to provide data on genital and subjective arousal in premenopausal women with breast cancer on antihormonal treatment compared to healthy controls and explore the data in connection with serum hormone levels. Overall, it will give a further insight in sexual function of breast cancer survivors to reveal targets to improve sexual function in this target group. Disclosure Yes, this is sponsored by industry/sponsor: WOW Tech™ Group. Clarification Industry funding only - investigator initiated and executed study.

Altered resting-state hippocampal functional connectivity in breast cancer survivors with chemotherapy-induced amenorrhea.

Amenorrhea induced decrease of hormones is associated with cognitive impairment. This study aimed to evaluate hippocampal functional connectivity patterns in chemotherapy-induced amenorrhea (CIA) breast cancer (BC) patients, to evaluate the relationship between the functional connectivity features and hormone levels. Neuropsychological test, functional magnetic resonance imaging, and assessment of hormone levels were conducted in 21 premenopausal BC patients before chemotherapy (t0 ) and 1 week after completing chemotherapy (t1 ). Twenty matched healthy controls (HC) were also included and underwent the same assessments at similar time intervals. Mixed effect analysis and paired t-test were used to compare differences in brain functional connectivity. Voxel-based paired t-tests revealed increased functional connectivity of the right and left hippocampus with the left fusiform gyrus, inferior and middle temporal gyrus, inferior occipital gyrus, left lingual gyrus, and parahippocampal gyrus after chemotherapy (p<.001) in CIA patients. Repeated measures analysis revealed significant group-by-time interactions in the left hippocampus with the bilateral fusiform gyrus, right parahippocampal gyrus, left inferior temporal gyrus, and left inferior occipital gyrus (p<.001). Premenopausal BC patients had no significant differences in cognitive function compared with HC at baseline. However, the CIA patients had high levels of self-rating depression scale, self-rating anxiety scale, total cholesterol, and triglycerides. Further, the CIA patients showed significant differences in hormone and fasting plasma glucose levels and cognitive performances between t0 and t1 (p<.05). Functional connectivity changes between the left hippocampus and the left inferior occipital gyrus was negatively correlated with E2 and luteinizing hormone changes (p<.05). The CIA patients had cognitive dysfunction mainly in memory and visual mobility. Chemotherapy may affect hippocampal-posterior cortical circuit which mediates visual processing in CIA patients. Moreover, E2 may be involved in this process.

Abstract P2-03-11: Differential Long-Term Benefit from Adjuvant Tamoxifen Therapy in Estrogen Receptor (ER)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Premenopausal and Postmenopausal Breast Cancer Patients

Abstract Background: Tamoxifen is a standard endocrine therapy for both pre- and postmenopausal ER-positive breast cancer patients. Patients with ER-positive disease have a long-term risk of distant recurrence, thus, long-term follow-up studies are essential to understand true treatment benefit. Clinically used tumor characteristics are prognostic 5-10 years after primary diagnosis, however, whether these characteristics are predictive of long-term tamoxifen benefit is largely unexplored. Therefore, we aimed to determine the long-term tamoxifen therapy benefit by the clinically used tumor characteristics in pre- vs postmenopausal patients in the Stockholm tamoxifen (STO)-trials with 20-years complete follow-up. Methods: Secondary analysis of 1242 ER-positive/HER2-negative patients from the STO-trials, randomized to at least 2 years of 40 mg tamoxifen vs no endocrine therapy (control). Premenopausal lymph node-positive patients were allocated to chemotherapy as standard of care and postmenopausal high-risk patients were further randomized to chemotherapy vs radiotherapy. Tumor immunohistochemical analysis was recently conducted. Complete 20-year follow-up was obtained from Swedish high-quality registries. Long-term distant recurrence-free interval (DRFI) was assessed by multivariable Cox proportional hazard regression and time-varying analysis using flexible parametric modelling. Results: Premenopausal patients showed significantly improved long-term DRFI from tamoxifen vs control if they were lymph node-negative (Hazard Ratio [HR]=0.46; 95% CI, 0.24-0.87), PR-positive (HR=0.61; 95% CI, 0.41-0.91), or of genomic low risk (HR=0.47; 95% CI, 0.26-0.85), see Table. In postmenopausal patients, significantly improved long-term DRFI from tamoxifen vs control was seen for all good prognosis tumor characteristics, i.e. small tumor size (pT≤20mm: HR=0.55; 95% CI, 0.39-0.77), tumor grade 1-2 (HR=0.55; 95% CI, 0.41-0.73), lymph node-negative (HR=0.44; 95% CI, 0.30-0.64), PR-positive (HR=0.60; 95% CI, 0.44-0.80), Ki-67-low (&amp;lt; 15%: HR=0.51; 95% CI, 0.38-0.68), and genomic low risk (HR=0.53; 95% CI, 0.37-0.74), see Table. Also, postmenopausal patients with large tumor size (pT&amp;gt;20mm: HR=0.64; 95% CI, 0.44-0.94) and PR-negative tumors (HR=0.51; 95% CI, 0.32-0.81) showed significant long-term tamoxifen benefit. Time-varying analysis in premenopausal patients indicated that tamoxifen therapy benefit diminished over time. Significant tamoxifen benefit until year 5, 10, and 15 after primary diagnosis was observed for PR-positive, lymph node-negative, and genomic low-risk patients, respectively. Postmenopausal patients had a significant long-term tamoxifen benefit if they had tumors of small or large tumor size, tumor grade 1-2, lymph node-negative status, PR-positive status, low Ki-67 levels, or genomic low risk. Conclusions: This study suggests a differential long-term tamoxifen therapy benefit in pre- vs postmenopausal patients. Clinically defined low-risk postmenopausal patients have long-term tamoxifen benefit, whereas the benefit is absent or diminish over time for premenopausal patients. Improved long-term prognostic and endocrine therapy predictive markers in premenopausal breast cancer patients with poor prognosis and long life-expectancy is needed, which could involve molecular tools. Long-term tamoxifen benefit in premenopausal and postmenopausal breast cancer patients by the clinically used tumor characteristics. Table Multivariable Cox proportional hazard regression analysis of 20-year distant recurrence-free interval (DRFI) for patients with ER-positive/HER2-negative tumors, comparing patients randomized to tamoxifen vs patients randomized to no endocrine therapy (control). Adjusted for age, randomization year, tumor size, tumor grade, lymph node status, PR status, Ki-67 status, chemotherapy, radiotherapy, and type of surgery. Citation Format: Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Christina Yau, Christopher C. Benz, Laura J. Esserman, Laura Van’t Veer, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Linda S. Lindström. Differential Long-Term Benefit from Adjuvant Tamoxifen Therapy in Estrogen Receptor (ER)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Premenopausal and Postmenopausal Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-11.