Premenopausal Breast Cancer Patients Research Articles

Durable and Drastic Response to the Trastuzumab, Letrozole, Abemaciclib, and Goserelin Combination as First-Line Therapy in HER2-Positive and Hormone Receptor-Positive Metastatic Breast Cancer: A Case Report

Introduction: Chemotherapy combined with anti-human epidermal growth factor receptor 2 (HER2)-targeted therapy is currently a standard treatment for advanced HER2/HR-positive breast cancer (BC), although evidences showed that HR expression compromised effectiveness of the treatment. While cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy is a key therapy for the BC with HR expression, data on the effectiveness and safety of CDK 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic BC are limited. Case Presentation: Here, we report a case of a 46-year-old premenopausal woman diagnosed with stage 4 HER2/HR-positive invasive ductal carcinoma from both right and left breast with hypermetabolic activities in multiple lymph nodes, adrenal, bone, and skin. Interventions: Due to the patient’s refusal to use chemotherapy, she was started on goserelin, abemaciclib, letrozole, and trastuzumab. Outcomes: The patient’s symptoms were relieved with near resolution of the primary breast mass and nearly all of the metastatic sites. Metabolic resolution was observed in bone lesions. The disease was under control for 57 weeks. During the treatment, neutropenia (grade 1–2) and anemia (grade 1) occurred, which spontaneously recovered. Additionally, diarrhea improved after symptomatic treatment. Conclusion: We believe that the combination of trastuzumab, hormone suppression, and abemaciclib is a practicable and effective treatment for HER2-positive and HR-positive metastatic BC in premenopausal patients who cannot tolerate the first-line chemotherapy.

Anticancer-Drug-Related Cardiotoxicity from Adjuvant Goserelin and Tamoxifen Therapy

Background: Breast cancer is a prevalent malignancy with rising incidence globally. Advances in endocrine therapy have improved outcomes for premenopausal women with hormone receptor-positive breast cancer. However, these treatments may induce menopause-like states, potentially elevating cardiovascular risks, including left ventricular (LV) dysfunction. This study aims to evaluate the impact of one year of adjuvant endocrine therapy with goserelin and tamoxifen on LV function in premenopausal breast cancer patients. Methods: The ISACS cardiovascular toxicity (NCT01218776) is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer-drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1 year) and prospectively. The pilot phase focused on the available data on combined goserelin and tamoxifen therapy for breast cancer and its impact on LV disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry was performed assigning 70 patients to combined endocrine therapy (goserelin and tamoxifen). Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary outcome measures were as follows: low LV function in women as defined by a left ventricular ejection fraction (LVEF) < 65% and subclinical LV dysfunction as defined by a 10-percentage point decrease in LVEF. Results: In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3-, 6-, and 12-month follow-up (65.7 ± 2.7% versus 65.3 ± 2.1%, p value = 0.27; 65.5 ± 2.9% versus 65.1 ± 2.5%, p value = 0.34; 65.0 ± 3.2% versus 64.6 ± 3.1%, p value = 0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03 ± 2.5% versus 1.16 ± 2.9%, p value = 0.73). Using IPTW analyses, there were no significant associations between combined therapy and low LV function (risk ratio [RR]: 1.75; 95% CI: 0.71–4.31) or subclinical LV dysfunction (RR: 1.50; 95% CI: 0.35–6.53) compared with controls. Conclusions: One year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size.

Machine learning Nomogram for Predicting endometrial lesions after tamoxifen therapy in breast Cancer patients

Objective Endometrial lesions are a frequent complication following breast cancer, and current diagnostic tools have limitations. This study aims to develop a machine learning-based nomogram model for predicting the early detection of endometrial lesions in patients. The model is designed to assess risk and facilitate individualized treatment strategies for premenopausal breast cancer patients. Method A retrospective study was conducted on 224 patients who underwent diagnostic curettage post-tamoxifen (TAM) therapy between November 2012 and November 2023. These patients exhibited signs of endometrial abnormalities or symptoms such as colporrhagia. Clinical data were collected and analyzed using R software (version 4.3.2) to identify factors influencing the occurrence of endometrial lesions and evaluate their predictive values. Three machine learning methods were employed to develop a risk prediction model, and their performances were compared. The best-performing model was selected to construct a nomogram of endometrial lesions. Internal validation was conducted using the bootstrap method, and the model’s accuracy and fit were assessed using the concordance index (C-index) and calibration curves. Results Independent risk factors for endometrial lesions included ultrasound characteristics, duration of TAM therapy, presence of colporrhagia, and endometrial thickness (P < 0.05). Among the machine learning methods compared, the LASSO regression integrated with a multifactorial logistic regression model demonstrated strong performance, with a concordance index (C-index) of 0.874 and effective calibration (mean absolute error of conformity: 0.014). This model achieved an accuracy of 0.853 and a precision of 0.917, with a training set AUC of 0.874 (95% CI: 0.794–0.831) and a test set AUC of 0.891 (95% CI: 0.777-1.000), closely aligning the predicted risk with the actual observed risk. Conclusion The developed prediction model is effective in evaluating endometrial lesions in premenopausal breast cancer patients. This model offers a theoretical foundation for improving clinical predictions and devising tailored treatment strategies for this patient group.

Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists.

Ovarian function suppression (OFS) has emerged as a crucial adjuvant therapy for premenopausal breast cancer patients. Some patients fail to achieve complete OFS with commonly used OFS drugs. The definition of incomplete OFS remains unclear, and large-scale data on its incidence are lacking. This review provides a comprehensive overview of the definition, occurrence, impact on therapeutic efficacy and corresponding treatment measures for incomplete OFS. We searched PubMed, Embase and Cochrane Library databases in recent twenty years with keywords as "ovarian function escape", "incomplete OFS" and "estrogen breakthrough", and carried out a snowballing of references to important literature. Clinical literature of premenopausal breast cancer patients treated with OFS was screened. The patient characteristics, definition and incidence of incomplete OFS, prognosis, interventions and other information were extracted. A total of 17 studies were included in the analysis, including RCTs, retrospective or prospective cohort studies and case reports. Literature indicates that the incidence of incomplete OFS is around 5-50% when the estradiol (E2) threshold is set as 2.72pg/mL, 10pg/mL, 20pg/mL, or 30pg/mL. Young age, high body mass index (BMI), and no prior chemotherapy were the risk factors for incomplete OFS. The treatment of incomplete OFS included dose adjustments, alternative OFS drugs, or the adoption of other OFS measures. The incomplete OFS rate decreased with the extension of treatment time. It is reasonable to monitor E2 levels to ensure successful OFS in the patients with high risk factors for incomplete OFS or with concurrent use of aromatase inhibitor (AI). Transient incomplete OFS seems to have no impact on prognosis, but sustained incomplete OFS needs personalized adjustment of treatment strategy to ensure complete OFS.

Tinagl1 restores tamoxifen sensitivity and blocks fibronectin-induced EMT by simultaneously blocking the EGFR and β1-integrin/FAK signaling pathways in tamoxifen-resistant breast cancer cells.

Tamoxifen (TAM) is employed to treat premenopausal ER-positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM-resistant MCF-7 breast cancer cells (MCF-7R). We discovered that Tinagl1 plays a pivotal role in countering TAM resistance by inhibiting the EGFR and β1-integrin/focal adhesion kinase (FAK) signaling pathways, both of which are abnormally activated in MCF-7R cells and contribute to the resistance mechanism. Our data showed that the expression level of Tinagl1 in MCF-7R cells was lower compared to their wild-type counterparts, and TAM could further reduce Tinagl1 expression in MCF-7R cells, which was consistent with our microarray results. Moreover, Tinagl1 could restore the sensitivity of MCF-7R cells to TAM and inhibit the motility of MCF-7R cells by regulating epithelial-mesenchymal transition (EMT) in vitro and in vivo experiments. In addition, the level of Tinagl1 in TAM-resistant breast cancer samples was significantly lower than that in their matched primary tumors. Analysis of an online database further indicated that high Tinagl1 expression correlates with better recurrence-free survival (RFS), particularly in patients with ER-positive, HER2-negative breast cancer. Overall, this study positions Tinagl1 not only as a potential prognostic marker but also as a promising therapeutic target.

Menopausal Symptom Burden in Premenopausal Breast Cancer Patients: Interaction of Chemotherapy and Ovarian Function Suppression on Tamoxifen Treatment

Menopausal Symptom Burden in Premenopausal Breast Cancer Patients: Interaction of Chemotherapy and Ovarian Function Suppression on Tamoxifen Treatment

Balancing Fertility Preservation and Treatment Efficacy in (Neo)adjuvant Therapy for Adolescent and Young Adult Breast Cancer Patients: a Narrative Review.

Adolescent and young adult (AYA) breast cancer survivors face a significant risk of infertility due to the gonadotoxic effects of (neo)adjuvant therapy, which complicates their ability to conceive post-treatment. While (neo)adjuvant therapy primarily aims to improve recurrence-free and overall survival, fertility preservation strategies should also be considered for young patients. This narrative review explores recent advancements in fertility preservation techniques, such as oocyte, embryo, and ovarian tissue cryopreservation, and evaluates the feasibility of modifying breast cancer (neo)adjuvant therapy to preserve fertility without compromising survival outcomes. Our review highlights that clinical trials with co-primary endpoints of oncological safety and fertility preservation are limited, and substituting standard treatment regimens solely for fertility preservation is currently not recommended. Nevertheless, new clinical studies have emerged that either exclude highly ovarian-toxic agents, such as cyclophosphamide, or omit adjuvant therapy altogether, even if fertility preservation is not their primary endpoint. Unfortunately, many of these trials have not evaluated ovarian toxicity. Notably, since 2020, major oncology organizations, including the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO) have advocated for the routine assessment of ovarian toxicity in all clinical trials. The review underscores the importance of incorporating ovarian toxicity as a standard endpoint in future trials involving premenopausal breast cancer patients to identify treatment regimens that can effectively balance fertility preservation with treatment efficacy.

Comparison of Clinicopathological Features between Premenopausal and Postmenopausal Female Breast Cancer Patients in Kurdistan Region of Iraq: A Retrospective Single Institution Study of 671 Female Patients

Introduction: Breast cancer is the most common cancer in women, and its incidence is increasing annually worldwide. It accounts for 24% of new cancer cases and 15% of cancer deaths in 2018, and according to the GLOBOCAN Cancer Tomorrow prediction tool, incident cases are expected to increase by more than 46% by 2040. Studies carried out thus far have shown that risk factors and histopathological features of breast malignancies may vary among different age groups. Menopausal status is an essential factor influencing clinicopathological characteristics of patients with breast cancer. Prognostic factors are used to estimate how aggressive the tumor may evolve and to decide on a treatment approach. In Iraq, breast cancer is most frequently seen in younger women in their fourth and fifth decades of life, who often show in advanced stages at the time of diagnosis, according to previous surveys. Objectives: The main objective of this study was to assess the clinicopathologic features between premenopausal and postmenopausal breast cancers to provide valuable insights into what may influence the age at diagnosis of breast cancer in the Kurdistan region of Iraq. Methods: This retrospective study included 671 non-metastatic breast cancer patients referred to Zhianawa Cancer Center between January 2015 and December 2017. Disease stage was determined using the American Joint Committee on Cancer and Union for International Cancer Control (UICC) (“Tumour,” “Nodes,” “Metastases”) TNM systems. The patients were divided into premenopausal and postmenopausal groups. The chi-square test was used to evaluate the association between the variables. Results: The mean age of the participants was 47.5 years. The most prevalent age group was 40-49, followed by the age group 50-59. Of the participants, 60.5% were premenopausal, and 39.4% were postmenopausal. Stage IIIA was the most common stage at diagnosis. At the same time, the most minor stage at diagnosis was stage 0. The second most common stage was IIB. There was a strong association between menopausal status with grade (P value 0.001) and LVI (P value 0.01); however, there was a non-significant correlation between menopausal status and stage at diagnosis (P value 0.529). Conclusion: Most patients included in this study had locally advanced disease stages. Menopausal status affected grade and LVI but not stage. Further professional efforts, endorsed by practical policy decisions, are recommended to down stage breast cancer through promoting evidence based protocol guidelines and adopting comprehensive well designed diagnostic, screening and cancer control strategies.

IMPACT OF CYP2D6 POLYMORPHISMS IN PREDUCTING OCCURRENCE OF ADVERSE EFFECT TO TAMOXIFEN AND DEVELOPING RECCURENCE IN ER+ BREAST CANCER PATIENETS:

Objectives: Breast cancer is a major public health in Algeria. Tamoxifen has been approved in the treatment of ER+ breast cancer. Some of negative side effects of tamoxifen are frequently a reason for discontinuation of therapy during treatment, which would otherwise be potentially lifesaving. In the current study, we assessed the association between CYP2D6 polymorphisms and tamoxifen efficacy in Algerian population receiving tamoxifen as adjuvant therapy in ER+ breast cancer. Methods: A total of 76 Algerian hormone receptor-positive premenopausal breast cancer patients with adjuvant tamoxifen treatment were investigated (45.36±6.13). DNA genotyping was performed by TaqMan Open Array technology. Tamoxifen and its metabolites levels were measured by ultra-high-performance liquid chromatography (UHPLC) followed by electro spray tandem mass spectrometry (LC-MS/MS). Results: A significant association between the presence of deficit copy of enzyme activity and development of adverse effect after the commencement of tamoxifen therapy. Low plasma endoxifen were observed in patients categorized as (NM/PM), (IM/ IM), (IM/PM) and (PM/PM). Patients with increased plasma endoxifen concentrations were significantly more likely than patients with reduced or null activity to not report recurrences (P&lt;0.05). We realized that the combination genotypes NM/PM, IM/IM, IM/PM, with PM/PM were more strongly associated with disease recurrence and adverse effects than NM carries of CYP2D6*1 allele (P&lt;0.05). Conclusion: Our results affirm that CYP2D6 polymorphism should be considered in predicting the occurrence of adverse effect fatty liver in women treated with tamoxifen. Thus, alternative treatment can be intended and lifestyle modifications can be implemented

7770 Damage of Ovarian Vasculature by Chemotherapies induces Ovarian Dysfunction in Mice

Abstract Disclosure: W. So: None. R. Dong: None. Y. Luan: None. A. Abazarikia: None. S. Kim: None. Background: Chemotherapy demonstrates efficacy to destroying cancer cells; however, it can inadvertently impact normal healthy cells, leading to irreversible side effects, particularly affecting the ovaries in female patients. Female cancer survivors encounter endocrine dysfunction and infertility due to ovarian damage caused by gonadotoxic cancer therapies. The ovary, a vital organ responsible for producing oocytes and endocrine hormones, faces significant challenges following such treatment. A study with premenopausal breast cancer patients reported a significant reduction in ovarian blood flow and volume immediately following chemotherapy. The preservation of ovarian function depends on the ovarian vasculature in supporting the development and maintenance of ovarian follicles. Despite its importance, the relationship between ovarian vasculature and follicle following chemotherapy has not been studied. Results: To investigate the direct impacts of chemotherapy, ovaries from postnatal 5 CD-1 mice were subjected to testing with three chemotherapeutic agents: cisplatin (CDDP), cyclophosphamide (CPA), and doxorubicin (DOXO). The expression of CD31/PECAM-1 (platelet endothelial adhesion molecule) exhibited a significant decrase after 96 hours of culture with 4-HC, an active metabolite of CPA. This reduction implies that ovarian vasculature was also compromised when chemotherapy eliminated immature follicles. In order to evaluate the influence of vascular endothelial growth factor (VEGF) in safeguarding both vasculature and ovarian follicles, ovaries were co-cultured with VEGF165 or VEGF165b in combination with chemotherapy. Interestingly, pre-treatment with VEGF165 before 4-HC led to an increased expression of CD31 in the cortex area, while VEGF165b further diminished CD31 expression compared to treatment with 4-HC alone. Additionally, adolescent CD-1 mice were intraperitoneally injected with CDDP, CPA, or DOXO, and ovaries were harvested one week after injection. Ovaries treated with chemotherapeutic agents exhibited a reduction in ovary weight and decreased CD31 expression compared to control mice. Conclusions: We propose that these chemotherapeutic agents not only induced the loss of ovarian follicles but also affected ovarian vasculature in mice. This suggests a potential decrease in folliculogenesis within the ovary, coupled with the depletion of ovarian reserve, as the delivery of nutrients and oxygen to growing ovarian follicles may be compromised. VEGF165 may play a beneficial role in maintaining ovarian function by safeguarding ovarian vasculature following chemotherapy. Understanding these intricate dynamics is essential for developing strategies to mitigate the negative impact of cancer therapies on reproductive health in female cancer survivors, particularly in preserving endocrine function and reproductive lifespan. Presentation: 6/2/2024

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

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

409P Biological tumor traits predicting late recurrence in premenopausal breast cancer patients: Insights from the STO-5 trial with 20-year follow-up

409P Biological tumor traits predicting late recurrence in premenopausal breast cancer patients: Insights from the STO-5 trial with 20-year follow-up

330P Randomized phase II study of neoadjuvant chemotherapy with denosumab compared to chemotherapy alone in hormonal receptor-positive, HER2-negative premenopausal breast cancer patients

330P Randomized phase II study of neoadjuvant chemotherapy with denosumab compared to chemotherapy alone in hormonal receptor-positive, HER2-negative premenopausal breast cancer patients

An Overview of Long-Acting GnRH Agonists in Premenopausal Breast Cancer Patients: Survivorship Challenges and Management.

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.

Assessment of Chemotherapy Induced Ovarian Failure Using Serum Anti-Mullerian Hormone in Premenopausal Breast Cancer Patients

Assessment of Chemotherapy Induced Ovarian Failure Using Serum Anti-Mullerian Hormone in Premenopausal Breast Cancer Patients

(116) SUBJECTIVE AND GENITAL SEXUAL RESPONSE IN FEMALE BREAST CANCER SURVIVORS: RESULTS FROM A PSYCHOPHYSIOLOGY STUDY

Abstract Introduction Sexual dysfunction is a prevalent concern affecting more than 70% of female breast cancer survivors, casting a substantial shadow on their quality of life. Beyond the physical impact of cancer and its treatments, the emotional and psychological toll of sexual dysfunction introduces additional challenges, amplifying stress levels and undermining overall well-being. Acknowledging the profound implications of sexual dysfunction in this group and the absence of therapies, there is an urgent need to delve deeper into the intricacies of its manifestations. Objective This study aimed to gather preliminary data on psychophysiological aspects of sexual function in premenopausal breast cancer patients undergoing antihormonal therapy and compare them with a healthy control group. Exploring sexual arousal in breast cancer patients may unveil potential targets for innovative treatment strategies to address sexual dysfunction in this population. Methods Participants were prescreened during a telephone interview. We included 40 premenopausal breast cancer survivors with an age range of 29 to 57 years (M = 43.5, SD = 6.36) on current hormonal treatment and 20 healthy controls with an age range of 22 to 35 (M = 27.55, SD = 3.19). Physiological measures (VPA and HRV), subjective sexual arousal (SSA) and self-reported orgasm were assessed in response to audiovisual stimuli and vibrotactile clitoral stimulation sexual stimuli in breast cancer survivors and healthy controls. Self-reported measures like the Female Sexual Function Index (FSFI), the Sexual Self-Esteem Inventory (SSEI) und the PROMIS29 were incorporated. Data were analyzed using 2-level mixed effect models. Results No significant differences in VPA scores were observed between healthy controls and breast cancer survivors. Both groups exhibited a greater genital response to clitoral vibrator use than to visual stimuli. Group differences emerged in SSA and HRV, with higher SSA and lower HRV being detected. Breast cancer survivors climaxed less frequently than healthy controls and had significantly lower self-reported sexual function. Conclusions Physiological measures of arousal in breast cancer survivors were comparable to healthy controls and only subjective arousal differed. This finding indicates that subjective arousal should be further explored as the focus of intervention and treatment methods for breast cancer patients experiencing sexual dysfunction. Our findings underscore the importance of tailored strategies that resonate with individual narratives, acknowledging the emotional intricacies of post-cancer sexual well-being. This study not only contributes to scientific knowledge but also calls for a compassionate and personalized treatment paradigm, enriching the landscape of survivorship care. Disclosure Yes, this is sponsored by industry/sponsor: WOW Tech GmbH Clarification: No industry support in study design or execution.

Half of most frequently mutated genes in breast cancer are expressed differentially between premenopausal and postmenopausal breast cancer patients

Breast cancer has distinct causes and molecular characteristics at premenopausal and postmenopausal ages. The age-standardized incidence rate for postmenopausal breast cancer is more than 10 times higher than in premenopausal breast cancer. Here, we showed that the expression of 10 out of 20 most frequently mutated genes in breast cancer (namely, PIK3CA, CDH1, MUC16, PTEN, FAT3, FAT1, SPEN, ARID1A, LRP1B and RUNX1) is higher in premenopausal women with breast cancer than in postmenopausal women with breast cancer. The most significant differences in the expression in terms of menopause status were observed for RUNX1 and FAT1. Furthermore, we found that the majority of these 10 genes also show ER (estrogen receptor) or PR (progesterone receptor) status-dependent expression in both premenopausal and postmenopausal breast cancer patients. Unlike what we observed in the case of ER or PR status, the expression of most of these genes does not change depending on HER2 (human epidermal growth factor receptor 2) status in both premenopausal and postmenopausal breast cancer patients. Combined, our analysis suggests that menopause status might influence the expression of most frequently mutated genes in breast cancer, and that the most of these genes whose expression differ between pre- and post-menopausal women with breast cancer also show ER or PR status-dependent expression in women with breast cancer.

Different dosage forms of gonadotropin-releasing hormone agonist with endocrine therapy in premenopausal hormone receptor-positive breast cancer.

Despite the wide use of a 3-month gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a 1-month GnRH agonist regimen when combined with selective estrogen receptor modulators or aromatase inhibitors, especially in younger patients. This retrospective cohort study included 1109 premenopausal hormone receptor-positive breast cancer patients treated with GnRH agonist plus selective estrogen receptor modulator or aromatase inhibitor. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1-month or 3-month GnRH agonist in cohorts and different subgroups was analyzed. Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1-month and 3-month groups achieved more than 90% E2 inhibition within 24 months (94.53% vs 92.84%, with a 95% confidence interval for the difference ranging from -4.78% to 1.41%), confirming the noninferiority of 3-month GnRH agonist. Both 1-month and 3-month GnRH agonist rapidly and consistently reduced E2 levels. Of the patients, 60 (6.3%) experienced incomplete ovarian function suppression, with similar rates in the 1-month and 3-month groups (5.5% vs 7.2%). Incomplete ovarian function suppression mainly occurred within the first 12 months, with age younger than 40 years and no prior chemotherapy being the risk factors. Similar disease-free survival and overall survival were found in the 1-month and 3-month groups and in patients with complete and incomplete ovarian function suppression (P > .05). The ovarian function suppression with 3-month GnRH agonist was not inferior to that with 1-month GnRH agonist, regardless of age or combination with a selective estrogen receptor modulator or an aromatase inhibitor.

Prognostic value of Oncotype recurrence score (RS) and Mammaprint (MP) in premenopausal patients with hormone positive (HR+) breast cancer (BC) with low genomic risk, stratified by race: A study of the National Cancer Database (NCDB).

551 Background: It is hypothesized that in African American (AA) women, RS has a lower prognostic accuracy. We evaluated this with a large population based national database. Methods: The 2021 NCDB PUF was used to include premenopausal female BC patients aged 18-50 years. Inclusion criteria were N0, M0 patients with any T stage, RS ≤ 15 or MP low risk, estrogen or progesterone receptor+ and HER2-. Patients were stratified by their recorded race (Caucasians vs AA). Univariate analysis was used to study the distribution. Kaplan-Meier (KM) and multivariate (MV) propensity score (PS) weighted Cox model were used to compare survival between the cohorts. Results: 27523 patients had an RS≤15 [Caucasian-25227(91.66%) AA-2296(8.34%)] and 4818 had MP low [Caucasian-4393(91.18%) AA-425(8.82%)]. &gt;99% had regional lymph node surgery and &gt;90% of the patients did not get chemotherapy. &gt;70% of the patients were T1. Majority did get hormonal therapy (HT) [RS≤15 Caucasian-92.97% AA-91.81%, MP low- Caucasian-92.42% AA-89.65%]. On analyzing grade, AA had more poorly differentiated tumors [RS≤15 Caucasian-6.18% AA-9.46% p=&lt;0.001 MP low- Caucasian-9.1% AA-16.02% p=&lt;0.001]. KM survival estimates for RS≤15 at 5 years [Caucasian-99.3(99.2,99.5) %, AA-98.8(98.0,99.3) %] were similar and 10 years [Caucasian-97.5(97.0,97.9) %, AA-94.6(91.6,96.6)] showed a small difference. For MP low, the survival at 5 years [Caucasian- 99.0(98.6,99.3) %, AA-98.9(97.0,99.6) %] and 10 years [Caucasian- 97.0(95.9,97.8) %, AA-95.8(91.0,98.1) %] were almost equal. Adjusted Hazard Ratio estimate for Caucasian vs AA for RS≤15 did not reach significance overall [0.802 (95% CI 0.47-1.37)] nor when stratified by grade, histology, or T stage. Conclusions: Through our analysis, we show that there was no major difference in overall survival between Caucasians and AA among low genomic risk, premenopausal, hormone positive, N0 BC patients. There was a 2.9% difference between the racial groups at 10 years, but this was not seen in the adjusted analysis. The results show that genomic scores like RS and MP retain their prognostic utility even in the low-risk spectrum in both Caucasians and AAs. These results differ from other database studies, where the utility of these tools in the low-risk AA groups were questionable. Confounding associated with retrospective studies could be contributing to this and the predictive ability of genomic scores in varied racial groups needs to be analyzed in prospective models.

Neoadjuvant dalpiciclib, exemestane, and goserelin in premenopausal women with HR-positive, HER2-negative breast cancer: A prospective, multicenter, randomized two-group, non-controlled phase 2 clinical trial.

TPS625 Background: The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy has significantly improved progression-free survival and overall survival in patients with HR-positive, HER2-negative advanced breast cancer (BC), revolutionizing the treatment landscape. However, previous CDK4/6i neoadjuvant studies have predominantly focused on postmenopausal populations, leaving a gap in preoperative treatment for early HR-positive, HER2-negative premenopausal BC patients. Therefore, the present trial is conducted to investigate the efficacy of dalpiciclib, exemestane and goserelin as neoadjuvant therapy in premenopausal women with HR-positive, HER2-negative BC. Methods: This is a multicenter, randomized two-group, non-controlled phase 2 clinical trial. Key eligibility criteria include: Patients aged 18 years or older with no prior treatment, an ECOG performance status of 0-1, at least 1 measurable lesion, and clinical stage II-III HR-positive, HER2-negative premenopausal invasive BC. Initially, all enrolled patients will receive two cycles of treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC). Subsequently, patients with complete response (CR) or partial response (PR) will receive an additional four cycles of TAC, whereas patients with progressive disease (PD) will undergo surgery or treatment options decided upon by the investigators. Those with stable disease (SD) will be randomly assigned 1:1 to either an experimental group receiving 16 weeks of dalpiciclib, exemestane, and goserelin (dalpiciclib: 125 mg daily for 21 days followed by 7 days off, exemestane: 25 mg daily for 28 days, goserelin: 3.6 mg every 28 days) or a standard chemotherapy group receiving four more cycles of TAC. Treatment response is assessed according to RECIST 1.1 criteria. Surgery will be performed after completion of the planned neoadjuvant treatment, followed by radiation therapy and systemic treatment according to local guidelines or the investigators' choices. The study's primary endpoint is the objective response rate (ORR) of the experimental group. Secondary endpoints include the ORR, residual cancer burden, preoperative endocrine prognostic index, event-free survival, and safety of both. Using Simon's two-stage optimal design and assuming a 40% response rate as desirable in the experimental group, at least 13 responses among a total of 43 patients were required to meet the primary endpoint. The trial will be terminated if fewer than 3 patients respond in the first stage. Considering an 80% SD rate post two neoadjuvant TAC cycles and a 10% attrition, the sample size was ultimately set at 119. The trial is actively recruiting. Clinical trial information: NCT06009627 .