Young Breast Cancer Research Articles

Oxidative stress drives endometrial fibrosis via TGF-β1/MAPK signaling pathway in breast cancer.

Breast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor-derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA-MB-231 in a female BALB/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology invivo and the contribution of co-culture of breast cancer cell and endometrial epithelial cell on this process was examined invitro. Median thickness in endometria was lower in breast cancer patients and tumor-bearing mice compared to controls. A gene signature of uteri in tumor-bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT), and activation of TGF-β and MAPK signaling pathways. In addition, ROS, EMT- and ECM-related protein levels were enhanced in uteri in tumor-bearing mice, as well as in Ishikawa cells which were co-cultured with MDA-MB-231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor-bearing mice via inactivation of the TGF-β1/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF-β1/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients.

Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance.

Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein-RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.

From Real-World Data to Causally Interpretable Models: A Bayesian Network to Predict Cardiovascular Diseases in Adolescents and Young Adults with Breast Cancer.

Background: In the last decades, the increasing number of adolescent and young adult (AYA) survivors of breast cancer (BC) has highlighted the cardiotoxic role of cancer therapies, making cardiovascular diseases (CVDs) among the most frequent, although rare, long-term sequalae. Leveraging innovative artificial intelligence (AI) tools and real-world data (RWD), we aimed to develop a causally interpretable model to identify young BC survivors at risk of developing CVDs. Methods: We designed and trained a Bayesian network (BN), an AI model, making use of expert knowledge and data from population-based (1036 patients) and clinical (339 patient) cohorts of female AYA (i.e., aged 18 to 39 years) 1-year survivors of BC, diagnosed in 2009-2019. The performance achieved by the BN model was validated against standard classification metrics, and two clinical applications were proposed. Results: The model showed a very good classification performance and a clear causal semantic. According to the predictions made by the model, focusing on the 25% of AYA BC survivors at higher risk of developing CVDs, we could identify 81% of the patients who would actually develop it. Moreover, a desktop-based app was implemented to calculate the individual patient's risk. Conclusions: In this study, we developed the first causal model for predicting the CVD risk in AYA survivors of BC, also proposing an innovative AI approach that could be useful for all researchers dealing with RWD. The model could be pivotal for clinicians who aim to plan personalized follow-up strategies for AYA BC survivors.

Prediction model for survival of younger patients with breast cancer using the breast cancer public staging database

Breast cancer (BC) is a major contributor to female mortality worldwide, particularly in young women with aggressive tumors. Despite the need for accurate prognosis in this demographic, existing studies primarily focus on broader age groups, often using the SEER database, which has limitations in variable selection. This study aimed to develop an ML-based model to predict survival outcomes in young BC patients using the BC public staging database. A total of 3,401 patients with BC were included in the study. Patients were categorized as younger (n = 1574) and older (n = 1827). We applied several survival models—Random Survival Forest, Gradient Boosting Survival, Extra Survival Trees (EST), and penalized Cox models (Lasso and ElasticNet)—to compare mortality characteristics. The EST model outperformed others in predicting mortality for both age groups. Older patients exhibited a higher prevalence of comorbidities compared to younger patients. Tumor stage was the primary variable used to train the model for mortality prediction in both groups. COPD was a significant variable only in younger patients with BC. Other variables exhibited varying degrees of consistency in each group. These findings can help identify high-risk young female patients with BC who require aggressive treatment by predicting the risk of mortality.

Prognostic nomograms for young breast cancer: A retrospective study based on the SEER and METABRIC databases.

Young breast cancer (YBC) is a subset of breast cancer that is often more aggressive, but less is known about its prognosis. In this study, we aimed to generate nomograms to predict the overall survival (OS) and breast cancer-specific survival (BCSS) of YBC patients. Data of women diagnosed with YBC between 2010 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated into a training cohort (n = 15,227) and internal validation cohort (n = 6,526) at a 7:3 ratio. With the Cox regression models, significant prognostic factors were identified and used to construct 3-, 5-, and 10-year nomograms of OS and BCSS. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used as an external validation cohort (n = 90). We constructed nomograms incorporating 10 prognostic factors for OS and BCSS. These nomograms demonstrated strong predictive accuracy for OS and BCSS in the training cohort, with C-indexes of 0.806 and 0.813, respectively. The calibration curves verified that the nomograms have good prediction accuracy. Decision curve analysis demonstrated their practical clinical value for predicting YBC patient survival rates. Additionally, we provided dynamic nomograms to improve the operability of the results. The risk stratification ability assessment also showed that the OS and BCSS rates of the low-risk group were significantly better than those of the high-risk group. Here, we generated and validated more comprehensive and accurate OS and BCSS nomograms than models previously developed for YBC. These nomograms can help clinicians evaluate patient prognosis and make clinical decisions.

MiR-17–5p/STAT3/H19: A novel regulatory axis tuning ULBP2 expression in young breast cancer patients

Background and aimUL-16 binding protein 2 (ULBP2) is a highly altered ligand for the activating receptor, NKG2D in breast cancer (BC). However, the mechanism behind its de-regulation in BC patients remains to be explored. The sophisticated crosstalk between miR-17–5p, the lncRNA H19, and STAT3 as a possible upstream regulatory loop for ULBP2 in young BC patients and cell lines remains as an unexplored area. Therefore, this study aimed at unravelling the ncRNA circuit regulating ULBP2 in young BC patients and cell lines. Patients and methodsA total of 30 BC patients were recruited for this study. The expression levels of miR-17–5p, lncRNA H19, and STAT3 were examined in 30 BC tissues compared to their normal counterparts. In addition, the expression signatures of those transcripts were compared in young (<40 years) and old BC (≥40 years) patients. miR-17–5p oligonucleotides, STAT3 and H19 siRNAs were transfected in MDA-MB-231 cells using HiPerfect® Transfection Reagent. miR-17–5p and the transcripts of the target genes quantified using RT-qPCR. Their relative expression was calculated using the 2–ΔΔCT method. ResultsThrough acting as a ceRNA circuit that antagonizes the function of miR-17–5p, H19 prevented the miR-17–5p-induced downregulation of STAT3; this mechanism further contributes to the pathogenesis of BC. Ectopic expression of miR-17–5p in MDA-MB-231 cells displayed its prominent role as an indirect potential activator of NK cells by significantly repressing the expression levels of the oncogenic mediator STAT3 and the oncogenic lncRNA H19 and inducing ULBP2 expression level by 3 folds in TNBC cell lines compared to mock cells. Furthermore, knocking down of STAT3 repressed the lncRNA H19 and increased ULBP2 expression levels, whereas siRNAs against H19 increased the expression levels of ULBP2. ConclusionThis study highlighted the crosstalk between the novel regulatory network composed of miR-17–5p, H19 and STAT3, and their impact on ULBP2 in BC. Moreover, this study underscored the potential role of miR-17–5p in counteracting the immune evasion tactics, particularly the shedding of ULBP2 in young BC patients, through the modulation of the STAT3/H19/ULBP2 regulatory axis. Thus, targeting this novel regulatory network could potentially enhance our understanding and advance the future application of the innate system-mediated immunotherapy in BC.

Healthcare utilization and follow-up care in young adult breast cancer (BC) survivors.

363 Background: The incidence of BC in young adults is increasing; given their extended survivorship, characterizing healthcare utilization and adherence to surveillance guidelines can inform unmet health needs and gaps in care. Methods: The multi-center Young Women’s BC Cohort Study enrolled 1302 women ≤40 yrs with newly diagnosed (dx) BC from 2006-2016. Participants completed surveys every 6 mos for 3 yrs post-dx, then annually. The current analysis includes patients with Stage 0-III BC without recurrence who completed the 7-yr survey assessing survivorship care, including types of providers visited, BC surveillance, and other health maintenance practices. Multivariate logistic regression evaluated factors (clinical, demographics, concern about recurrence) associated with 1) full transition to a primary care provider (PCP) for follow-up; adherence to 2) mammography (among women who had a unilateral mastectomy or lumpectomy) and 3) bone density scans (among current hormonal therapy [HT] users), per ASCO/ACS guidelines. Results: Of 660 women with Stage 0-III BC, median age at dx was 37 (range: 17-40); 89% identified as White, 5%, Asian, 3%, Black, 3% as other/multiracial, and 4%, Hispanic. Most had received chemotherapy (75%) and radiation (61%) and 35% reported current HT; 12% had a BRCA1/2 mutation. For cancer-related follow-up, 57% reported seeing an oncology provider only, 12%, PCP only, and 29% saw a PCP + oncology provider. Among women with remaining breast(s) (n=348), 90% reported a mammogram in the last year. Adherence to other health maintenance practices varied: 68% reported having had a flu shot, 76% a pap test/pelvic exam, and 56% cholesterol screening within the last 2 yrs. Among current HT users (n=210), 46% reported a bone density scan within the last 2 yrs. In multivariate analyses assessing the odds of seeing a PCP only (vs. oncology + PCP), having stage 0 vs I disease (OR 2.74 95% CI 1.01-6.80) was associated with higher odds while any HT use (OR .31 95% CI .16-.58) and concern about recurrence (OR .23 95% CI .12-.47) were associated with lower odds. The table includes factors significantly associated with non-adherence to mammography and bone density scans. Conclusions: At 7-years post-dx, most young survivors participating in a cohort study receive cancer follow-up care from an oncology provider and have not fully transitioned their care to a PCP. Adherence to recommendations related to bone health among HT users was suboptimal. Additional research to identify barriers/facilitators to receipt of guideline-concordant follow-up care at the patient, provider, and systems levels may inform strategies to optimize survivorship in young BC survivors. Multivariable analysis: factors associated with non-adherence. MammogramOR 95% CI Bone density scanOR 95% CI Her2+ .38, .15 -.98 NS BRCA1/2 + 8.36, 1.38-50.47 .17, .05 -.62 Chemotherapy NS .22, .06 -.78 Unilateral mastectomy vs lumpectomy 6.64, 2.69-16.34 NS

Breastfeeding experiences among young breast cancer survivors: A survey study.

Following breast cancer (BC), many young women are interested in future childbearing and some may wish to breastfeed. However, limited information is available regarding their lactation experiences. Participants in the Young Women's Breast Cancer Study, a multicenter, prospective cohort study of women ≤40 years diagnosed with stage 0-III BC between 2006-2016 and who reported one or more live births following diagnosis, were surveyed about pregnancy and breastfeeding after BC treatment, including reasons for attempting and stopping breastfeeding, satisfaction, and supports. Of 143 eligible women sent a survey, 115 responded and 94 were included in the analytic cohort. Breastfeeding was attempted by 55% of women (52 of 94). Among those who had not attempted, 93% noted prior bilateral mastectomies (39 of 42). Among those who attempted breastfeeding, 69% had undergone lumpectomy and radiotherapy (36 of 52), 83% of whom reported no milk production from their treated breast (30 of 36). Most (65%, 34 of 52) were at least somewhat satisfied with their ability to breastfeed. Reasons for stopping breastfeeding included: having completed the planned duration (36%, 19 of 52); to start/resume endocrine therapy (21%, 11 of 52); and to resume breast imaging (8%, 4 of 52). Approximately half (27 of 55) of women who had not undergone bilateral mastectomies recalled receiving specific information about breastfeeding after BC, mostly from the oncology team (59%, 16 of 27), online resources (48%, 13 of 27), or a lactation consultant (44%, 12 of 27). Most young BC survivors who attempted to breastfeed were able to and were satisfied with the experience, despite challenges. Specific resources to support BC survivors who wish to breastfeed are needed.

ThP2.2 - Breast cancer in the very young

Abstract Aims A small proportion of breast cancer (BC) affects women under 35 years old: very young breast cancer (VYBC). We conducted a retrospective cohort study of VYBC treated by our breast unit with the aim of adding to the existing, limited literature. Methods All patients treated between January 2012 and July 2023 were included. Case notes, MDT outcomes, operative findings and histology reports were cross-referenced. The primary outcome assessed was overall survival. Other factors investigated were parity, genetics, treatment plans and some, specific, psychosocial concerns. Results There were 95 women with VYBC in this 11-year study period. The median age at diagnosis was 32 years, and median length of follow-up was 5 years. 81% of the cohort had early BC, and 28% of carcinomas were triple negative. Overall survival was 87%. 16% of women either presented with or developed distant metastases, with a survival rate of less than 27% in this group. BC recurrence affected 21% of women. Surgery was performed in 94% of patients, with 64% having at least a unilateral mastectomy. Ahead of treatment, fertility concerns were expressed by at least 45% of women. 85% of the cohort were genetically tested, revealing a genetic mutation in 20% of these patients. Conclusions This study demonstrates the outcomes of VYBC within our breast unit, which are comparable to published reports. It also highlights unique, psychosocial challenges faced by these women. Long term follow-up of this group is recommended.

Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features.

Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-relatedAURKA-associated biological processes. Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts < 50 years at breast cancer diagnosis (n = 368) were investigated for differentially expressed genes and enriched gene sets in AURKA mRNA high tumors stratified by age. Differentially expressed genes and gene sets were investigated using network analyses and g:Profiler. High Aurora kinase A protein expression associated with aggressive clinico-pathologic features, a basal-like subtype, and high risk of recurrence score. These patterns were confirmed using mRNA data. High AURKA gene expression demonstrated independent prognostic value when adjusted for traditional clinico-pathologic features and molecular subtypes. Notably, high AURKA expression significantly associated with reduced disease-specific survival within patients below 50 years, also within the luminal A subtype. Tumors of high AURKA expression showed gene expression patterns reflecting increased DNA damage activation and higher BRCAness score. Our findings indicate higher AURKA expression in young breast cancer, and associations between high Aurora-A/AURKA and aggressive tumor features, including higher tumor cell proliferation, and shorter survival, in the young. Our findings point to AURKA as a marker for increased DNA damage and DNA repair deficiency and suggest AURKA as a biomarker of clinical relevance in young breast cancer.

Mediators of a Mindfulness-Based Intervention for Younger Breast Cancer Survivors: Effects on Depressive Symptoms.

Depression is associated with poor outcomes in breast cancer patients, with higher prevalence among younger women. Although mindfulness-based interventions (MBIs) have demonstrated therapeutic effects, the mechanisms of intervention effects are poorly understood. We investigated whether rumination, self-kindness, intrusive thoughts about cancer, cancer-related worry, or a sense of meaning and peace mediated the intervention effects of an MBI, Mindful Awareness Practices (MAPs), on depressive symptoms. Additionally, we explored the same variables as mediators of a psychoeducation program, Survivorship Education (SE). Women diagnosed with stage 0-III breast cancer at age <50 years were randomized to 6 weeks of MAPs ( n = 85), SE ( n = 81), or wait-list control (WLC; n = 81). During preintervention, postintervention, and 6-month follow-up (FU), we assessed depressive symptoms, rumination, self-kindness, intrusive thoughts, worry, and meaning and peace. MAPs and SE significantly reduced depressive symptoms at postintervention, and reductions remained through 6-month FU for MAPs. Models revealed that reductions in rumination ( β = -0.68, 95% confidence interval [CI] = -1.64 to -0.07) and intrusive thoughts ( β = 1.17, 95% CI = -2.17 to -0.37) and improvements in self-kindness ( β = -1.09, 95% CI = -2.37 to -0.28) and meaning and peace ( β = -1.09, 95% CI = -3.16 to -0.56) mediated MAPs' effects at all time points. Reductions in worry ( β = -1.34, 95% CI = -2.47 to -0.45]) mediated effects at postintervention only. Worry and intrusive thoughts mediated SE effects at postintervention and 6-month FU, respectively. Findings identified depression-relevant mediators of MAPs' effects, expanding the understanding of MBI mechanisms. Results highlight pathways that could be leveraged to optimize intervention outcomes. ClinicalTrials.gov identifier: NCT03025139 .

Use of tamoxifene-controlled ovarian hyperstimulation for fertility preservation before breast cancer treatment: A prospective cohort study with a 5-year follow-up

PurposeFertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. MethodsThis multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. ResultsNinety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. ConclusionTamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

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

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

Fertility among young breast cancer survivors attempting pregnancy: A prospective, multicentre cohort study.

1518 Background: Despite high interest among young women diagnosed with breast cancer (BC) in future fertility, prior research has been hampered by short follow-up and lack of prospective assessment of pregnancy attempts. We sought to describe fertility outcomes among young women participating in a prospective cohort who reported pregnancy attempt post-BC diagnosis. Methods: Women with stage 0-III BC in the Young Women's Breast Cancer Study (YWS, NCT01468246), a multicenter, prospective cohort of women diagnosed at age ≤40 from 2006-2016 who reported attempting pregnancy post-diagnosis were included. Those with prior hysterectomy, bilateral oophorectomy, or metastatic disease at diagnosis were excluded. Data on attempting pregnancy and fertility outcomes were obtained from serial surveys. Multivariable logistic regression with stepwise model selection was used to identify factors associated with pregnancy and live birth. Results: Among 1213 eligible participants, 197 reported any attempt of pregnancy (16%) over a median follow-up of 11 years (range: 3-17). Among attempters, median age at diagnosis was 32 years (range: 17-40); 74% were non-Hispanic White; 41% had stage I, 35% stage II, 10% stage III, and 14% stage 0 BC; 76% had HR+ disease; 68% received chemotherapy; 57% received endocrine therapy within one year post-diagnosis; 13% were BRCA1/2 pathogenic variant (PV) carriers; 51% reported financial comfort at baseline; 51% were nulligravida and 72% nulliparous at diagnosis; 28% had undergone fertility preservation consisting of egg/embryo freezing at diagnosis; 15% reported a history of infertility before BC diagnosis. Most (73%) reported ≥1 pregnancy after diagnosis and 65% reported ≥1 live birth. Median time from diagnosis to first pregnancy was 48 months (range: 6-125). In the multivariable model, greater age at diagnosis (odds ratio [OR] 0.82 per year increase, 95% CI 0.74-0.90, P&lt;0.0001) was negatively associated with pregnancy, while financial comfort at baseline (OR 2.04, 95% CI 1.01-4.12, P=0.047) was predictive of pregnancy. For live births, greater age at diagnosis was negatively associated (OR 0.82 per year increase, CI 95% 0.76-0.90, P&lt;0.0001) while having undergone fertility preservation at diagnosis was predictive (OR 2.78, 95% CI 1.29-6.00, P=0.009). History of infertility, nulliparity at diagnosis, tumor characteristics, cancer treatment, race, ethnicity, and BRCA1/2 PV status were not associated with either outcome. Conclusions: This is the first prospective study with greater than 10 years of follow-up to report fertility outcomes in young BC survivors accounting for attempting pregnancy. The majority achieved a pregnancy and most reported a live birth. Our findings can be incorporated into the counseling of young BC patients and survivors, and highlight the need for accessibility of fertility preservation services for this population. Clinical trial information: NCT01468246 .

Trends of demographic and clinical traits of young patients with breast cancer from the National Cancer Database: Disproportionate effect on underrepresented underserved populations.

e13715 Background: Over the past decade, there has been increasing incidence of young patients diagnosed with cancer. Despite these developments, there is still uncertainty surrounding the factors and patterns contributing to the rising incidence in young age. This study aims to explore the demographic and clinical characteristics of young breast cancer (YBC) patients. Methods: We obtained characteristics and survival data from 206,156 of young patients (≤ 40 years of age) diagnosed with breast cancer between 2005 and 2019 in the National Cancer Database (NCDB). The demographic and clinical data were subdivided the patients into two comparison groups based on year of diagnosis with 10 years interval (2005-2009, Old vs. 2015-2019, New group). The z-score test was employed to measure the changes in the 2 groups. Cox proportional hazards model was used to explore the variables influencing overall survival (OS). Results: Overall, the absolute number of YBC patients have been increasing every year. The comparison between Old (55397 pt) and New groups (67930 pt) showed increase in Hispanic (4,575 (8.3%) vs 6,720 (9.9%), p &lt;0.0001), Black (8,695 (15.7%) vs 11,156 (16.4%), p=0.0005), Asian (2,592 (4.7%) vs 4,512 (6.6%), p&lt;0.0001), and other minority populations. Non-Hispanic White showed no change (p=0.1902). Additionally, there was a reduction in the proportion of patients with private insurance (43,940 (79.3%) vs 51,104 (75.2%), p&lt;0.0001) and an increase in patients with Medicaid (5,893 (10.6%) vs 10,694 (15.7%), p&lt;0.0001). Interestingly, there was a significant increase in hormone positive disease (35,142 (63.4%) vs 49,409 (72.7%), p&lt;0.0001), while no change in hormone negative disease. In New group, the influence of race is evident in the observed variations in OS (Table). Finally, patients with Medicaid or without insurance exhibited a diminished OS compared to those with private insurance, and a lower median income was associated with a negative impact on OS. Conclusions: For YBC patients, the proportion of underrepresented and underserved population is increasing. There is an increasing rate of hormone positive disease. This can cause substantial personal and societal implications, such as family planning and early menopause. Therefore, awareness of these at-risk populations is important for early identification of breast cancer and mitigation of poorer outcomes. [Table: see text]

Acupuncture for cancer symptoms: Clinical application and longitudinal impact.

e23191 Background: Evidence for acupuncture (ACUP) in cancer care is inconsistent. ACUP is variously used for multiple symptoms, e.g. anxiety, chemotherapy-related peripheral neuropathy, dyspnea, hot flashes, insomnia, and pain. Approximately 500 unique patients are treated for ACUP annually in our Section of Integrative Oncology. Our objective was to evaluate ACUP’s clinical application and longitudinal impact on symptoms severity. Methods: This was a retrospective analysis of those treated in a group ACUP session. Symptoms were rated before each session on a severity numeric rating scale (0-10). Clinical improvement was defined as a 2-point decrease from baseline (T1). We report symptoms from baseline to the fourth sessions (T1-T4). Counts are presented as percentages and numbers summarized by mean (standard deviation; SD) or median (interquartile range; IQR). Groups were compared statistically as appropriate. Results: 2239 consecutive patients were treated between 2015-2022. Mean (SD) age was 57 (±12); 83% were female; 57% breast primary site, 9% hematologic, 9% gastrointestinal, 8% gynecologic, 4% lung, 3% prostate, and 9% other malignancies. Symptoms treated were pain (61%), insomnia (48%), fatigue (44%), neuropathy (41%), anxiety (37%), hot flashes (37%), and other symptoms (17%). 68% presented with multiple symptoms. They received a median (IQR) of 4 (2-6) sessions and 7 (7-14) days apart. At T1 symptom severity scores, median (IQR), were anxiety 5(2-7), fatigue 5(3-7), hot flashes 6(4-8), insomnia 6(4-8), neuropathy 5(3-8), and pain 5(3-7); Table1. By T2, improvement was observed in patients, N (%), with hot flashes 476 (66%), anxiety 434 (62%), fatigue 464 (56%), insomnia 407 (55%), neuropathy 441 (55%), and pain 563 (50%). Symptom severity improvement was statistically significant by T2 and by T3 clinically relevant; Table 1. By T4, about 60% were still on ACUP treatment. Multiple ACUP sessions ( &gt; 1) were associated with older age and higher symptom burden, and fewer sessions with more severe T1 anxiety and fatigue. Fewer males were treated, yet symptoms improved like in females. Conclusions: Symptoms were of moderate severity at referral. In this large consecutive sample (N = 2239) of mostly younger breast cancer women, group ACUP was associated with broad based symptom benefit. Repeated ACUP treatments were important for clinical improvement. Males and females benefited equally however fewer males were referred. Several confounders need to be considered interpreting these results. [Table: see text]

An overview of psychological analysis of patients with breast cancer undergoing total mastectomy and breast conservation surgery and its impact on objectified body consciousness at a tertiary care cancer centre.

e12537 Background: Breast cancer is the most common cancer among females, and surgery plays a central role in its treatment. Surgical treatments may have a negative psychological impact on women’s mental health regarding their body image. The purpose of this study was to compare the psychological health insights pertaining to objectified body consciousness scores before and after the surgery and also to observe whether these scores were comparable across the surgery types. Methods: This retrospective qualitative study included 706 breast carcinoma patients who underwent either Breast Conservation Surgery or Total Mastectomy at Manipal Cancer Centre, between the years 2020-2021. A validated questionnaire of Objectified Body Consciousness was used to obtain responses at diagnosis and at 6 months postsurgery and final scores were calculated for both instances. Two sample t- tests/analysis of variance and Chi-square tests were used to compare continuous and categorical variables respectively. Results: Out of total 706 breast cancer patients, 402 patients underwent Breast Conservation Surgery and 304 underwent Total Mastectomy procedure. A statistically significant change was seen in the mean Objectified Body Consciousness Score (14.22±15.44) for all patients when compared pre-operatively (72.72±11.38) and postoperatively (60.15±17.58). This change was higher in the Total Mastectomy group (29.38±11.53). Also, statistically significant rise in scores was seen with increasing age. There was a statistically significant difference between BCS and Total Mastectomy groups with respect to the distribution of age group, marital status, types of cancer, stage and grade of cancer, NACT administration and postoperative mean objectified body consciousness scores of patients (p-value &lt;0.05). Conclusions: We could affirmatively conclude in our study that younger breast cancer patients and all patients who underwent a total mastectomy, had more psychological apprehension with the body image post-surgery, signifying these groups should be encouraged by healthcare professionals to reach out for counselling at the earliest. Knowing the pre-operative Objectified Body Consciousness scores and the type of surgery the patient is going to undergo, will help us to streamline categorical psycho-educational programs for each group and personalise our healthcare professionals to encourage women to reach out to social support groups and directed counselling at the earliest. This will help women adapt to their transformed life and be mentally prepared for the changes that are expected post-surgery.

Age-Related Clusters and Favorable Immune Phenotypes in Young Breast Cancer Patients

Breast cancer (BC) patients aged <40 years at diagnosis experience aggressive disease and poorer survival compared with women diagnosed with BC at 40 to 49 years, but the age-related biology is described to little extent. Here, we explored transcriptional alterations in BC to gain better understanding of age-related tumor biology. We studied a subset of the Bergen in-house cohort (n = 127; age range, 26-49 years) and used the NanoString Breast Cancer 360 expression panel on formalin-fixed paraffin-embedded BC tissue, and publicly available global BC messenger RNA expression data (n = 204; age range, 22-49 years), to explore differentially expressed genes between the young (age <40 years) and older (age 40-49 years) patients. Unsupervised hierarchical clustering was applied to identify gene expression–based patient clusters. We applied established computational approaches to define the PAM50 subtypes, risk of recurrence scores (ROR), and risk groups and to infer the proportions of 22 immune cell types from bulk gene expression profiles of patients aged <50 years at BC diagnosis. Differentially expressed genes and gene sets were investigated using OncoEnrichR and g:Profiler to describe functional profiles and pathway enrichment. We identified 4 age-related patient clusters presenting distinct characteristics of PAM50 subtypes and ROR profiles, which demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the known molecular subtypes. Our findings showed better survival than expected in the basal-enriched cluster 2 and in triple-negative and basal-like BC. Deconvolution analyses of immunophenotypes indicated higher levels of M0 and M1 macrophages than M2 macrophages in subsets of young BC. Our approach identifies age-based patient clusters with distinct clinicopathologic profiles, to a large extent overlapping with the PAM50 subtypes, although with independent prognostic values in multivariate survival analyses. The patient clusters provided new insight in the immune cell distribution across tumor subtypes, potentially contributing to survival differences between the clusters and the molecular subtypes and indicating age-related mechanisms improving outcome. Our study confirms the applicability of ROR as a valid prognosticator also in a young BC cohort.

Breast cancer and the steadily increasing maternal age: are they colliding?

BackgroundPregnancy-related cancers are mostly breast cancers, and their incidence is likely to increase as a result of the modern trend of delaying childbearing. In particular, advanced maternal age increases breast cancer risk, and younger breast cancer patients are more likely to die and metastasize. This study compared a population with a high incidence of delayed childbearing with another population with a lower mean age at childbirth in order to determine whether breast cancer diagnosis and childbearing age overlap.MethodsWe retrospectively analyzed multiple data sources. The Surveillance, Epidemiology, and End Results (SEER) program, the United States National Center for Health Statistics as part of the National Vital Statistics System, the United Nations Population Division, the GLOBOCAN Cancer Observatory, the CLIO-INFRA project database, the Human Fertility Database, and anonymized local data were used.ResultsAs women’s age at delivery increased, the convergence between their age distribution at breast cancer diagnosis and childbearing increased. In addition, the overlap between the two age distributions increased by more than 200% as the average age at delivery increased from 27 to 35 years.ConclusionsAs women’s average childbearing age has progressively risen, pregnancy and breast cancer age distributions have significantly overlapped. This finding emphasizes the need for increased awareness and educational efforts to inform women about the potential consequences of delayed childbearing. By providing comprehensive information and support, women can make more informed decisions about their reproductive health and cancer prevention strategies.

Abstract PO2-12-01: Five-year quality of life (QOL) trajectories among young breast cancer (BC) survivors

Abstract Background: Young BC survivors are at risk for impaired QOL in part due to issues that are unique to their life stage. We sought to characterize trajectories of QOL in the 5 years following diagnosis among young BC survivors as well as evaluate patient and clinical characteristics associated with poorer or deteriorating QOL trajectories over time. Methods: Women diagnosed with stage I-III BC at age ≤40 enrolled in the Young Women’s BC Study, a prospective cohort in North America, who completed ≥2 study surveys through 5 years of post-diagnosis follow-up. QOL was evaluated with the Cancer Rehabilitation Evaluation System (CARES) physical, psychosocial, and sexual subscale scores. Demographic, treatment, and clinical characteristics were ascertained through surveys and chart review. Longitudinal trajectories for each CARES subscale were defined using group-based trajectory modeling; associations between patient/clinical characteristics and trajectory group membership were estimated for each subscale using multivariable multinomial logistic regression. Results: Among 900 women, median age at diagnosis was 36 (range: 17-40) 89% were white, 2% Black, and 4% Hispanic. At baseline, 73% were partnered, 61% parous and 49% perceived themselves as financially comfortable. Most had hormone-receptor positive (74%), HER2-negative (70%) BC, and most received chemotherapy (82%); 36% underwent mastectomy with radiation. Physical and psychosocial scores each clustered into 4 trajectories, with &amp;gt;75% of participants clustering in groups reflecting excellent or good QOL that was stable over time and few (6% for physical and 4% for psychosocial) clustering into groups that reflected poorer QOL at baseline that did not improve over time. Sexual health trajectories were more variable, clustering into 5 trajectories, with over half of participants clustered into groups reflecting good (35%) or excellent (20%) QOL that remained relatively stable over time, 22% clustered into a trajectory that was poor at baseline but moderately improved over follow-up, 13% in a group that reflected deteriorating from moderate-to-poor QOL and 11% in a group with poor QOL at baseline that did not improve over time. In multivariable regression analyses (Table), factors associated with clustering in a poorer trajectory (vs. clustering in an excellent trajectory), in multiple QOL domains included baseline financial discomfort (associated with poorer QOL across all 3 domains), mastectomy+radiation (vs. lumpectomy, associated with poorer QOL across all 3 domains); chemotherapy receipt (associated with poorer physical and sexual health trajectories); and baseline BMI &amp;gt;25 (vs. 18.5-24.9, associated with poorer physical and poorer/deteriorating sexual health trajectories). Conclusions: Young BC survivors follow distinct QOL trajectories in survivorship. While most will not experience substantial QOL impairment through the first 5 years following diagnosis, a substantial minority report persistently poor or deteriorating QOL. The association between more extensive local therapy and poorer physical/psychosocial/sexual health trajectories underscores the importance of communicating the potential for negative QOL outcomes when women are making surgical decisions. Additionally, the pervasive impact of financial wellbeing on multiple QOL domains supports the potential value of systematic screening for and addressing of financial distress to prevent or mitigate financial toxicity in survivorship Factors associated with clustering in poorer/deteriorating (vs. excellent) QOL trajectories *Reference trajectory=excellent QOL Citation Format: Tal Sella, Zheng Yue, Kathryn Ruddy, Shari Gelber, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Steven Come, Eric Winer, Ann Partridge, Shoshana Rosenberg. Five-year quality of life (QOL) trajectories among young breast cancer (BC) survivors [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 PO2-12-01.