Initial Breast Cancer Diagnosis Research Articles

Alzheimer Disease and Related Dementia Following Hormone-Modulating Therapy in Patients With Breast Cancer

Hormone-modulating therapy (HMT) is a widely accepted treatment for hormone receptor-positive breast cancer, although its cognitive effects, including a potential link to Alzheimer disease and related dementias (ADRD), remain understudied. To investigate the association between HMT for breast cancer treatment and risk of developing ADRD in women aged 65 years or older. This cohort study used a comprehensive dataset from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify patients who did and did not receive HMT treatment within 3 years after the initial diagnosis of breast cancer and assessed their risk of developing ADRD in later life. Individuals with a preexisting diagnosis of ADRD or receiving HMT before the diagnosis of breast cancer were excluded. This study was performed from June 2022 through January 2024. Receipt of HMT. Risk of ADRD associated with HMT; associations of risk with age, self-identified race, and HMT type. Risk was measured using hazard ratios (HRs) with 95% CIs and adjusted for potential confounders such as demographic, sociocultural, and clinical variables. Among 18 808 women aged 65 years and older diagnosed with breast cancer between 2007 and 2009 (1266 Black [6.7%], 16 526 White [87.9%], 1016 other [5.4%]), 12 356 (65.7%) received HMT within 3 years after diagnosis, while 6452 (34.3%) did not. The most common age group in both samples was the 75 to 79 years age group (HMT, 2721 women [22.0%]; no HMT, 1469 women [22.8%]), and the majority of women in both groups self-identified as White (HMT, 10 904 women [88.3%]; no HMT, 5622 women [87.1%]). During an average of 12 years of follow-up, 2926 (23.7%) of HMT users and 1802 (27.9%) of non-HMT users developed ADRD. HMT was associated with a 7% lower relative risk of ADRD overall (HR, 0.93; 95% CI, 0.88-0.98; P = .005). The association decreased with age and varied by race. The reduction in ADRD risk associated with HMT was greatest for women aged 65 to 74 years who self-identified as Black (HR, 0.76; 95% CI, 0.62-0.92). This association decreased among women aged 75 years or older (HR, 0.81; 95% CI, 0.67-0.98). Women aged 65 to 74 years who self-identified as White had an 11% relative risk reduction (HR, 0.89; 95% CI, 0.81-0.97), but the association disappeared for women aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races showed no significant association between HMT and ADRD. Age- and race-based associations also varied by HMT type. In this retrospective cohort study, hormone therapy was associated with protection against ADRD in women aged 65 years or older with newly diagnosed breast cancer; the decrease in risk was relatively greater for Black women and women under age 75 years, while the protective effect of HMT diminished with age and varied by race in women. When deciding to use HMT for breast cancer in women aged 65 years or more, clinicians should consider age, self-identified race, and HMT type in treatment decisions.

Survival analysis for patients with metachronous contralateral breast cancer: Insights from a retrospective study.

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors.

The clinical, molecular, and therapeutic implications of time from primary diagnosis to brain metastasis in lung and breast cancer patients

AbstractPurposeLung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM.MethodsWe retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively.ResultsThe median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM.ConclusionsThis single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

Abstract PO5-10-07: Risk factors associated with secondary cancers in AYA patients with breast cancer. A SEER database study

Abstract Background Adolescents and young adults (AYA) diagnosed with breast cancer face unique challenges and have distinct characteristics compared to older patients. While primary breast cancer remains a significant concern, the risk of developing secondary cancers in this population is also of great importance. This study aimed to identify these risk factors by analyzing a large cohort of AYA breast cancer patients using SEER (Surveillance Epidemiology and End Result) Database. Methods Patients were identified from SEER Research Data 17, from 2000 to 2019. Patients aged 18-39 years with breast cancer and at least 1 year of survival were identified. Secondary cancers were then identified and included any disease site. Patient demographic and clinical characteristics were summarized by secondary cancer status using Mann-Whitney U and Fisher’s exact tests. Overall survival from the initial breast cancer diagnosis was summarized by secondary cancer status using standard Kaplan-Meier methods, where the median and 3/5-year rates were estimated with 95% confidence intervals. Comparisons were made using the log-rank test. SAS v9.4 (Cary, NC) was used at a significance level of 0.05. Results A total of 47,912 AYA breast cancer patients were identified, of which 2,886 (6.0%) developed a secondary cancer at least 1 year after the initial breast cancer diagnosis. When comparing patients with and without secondary cancers, we observed significant differences with respect to age at initial breast cancer diagnosis, race, stage, nodal status, surgical procedure, ER status, PR status, Her2 status, and sub-type (Table 1). The analysis of overall survival showed that, from the time of breast cancer diagnosis, there was no statistically significant difference between patients with and without secondary cancers. However, this may be due to an immortal time bias. Breast was the most common site of secondary cancer (67%) followed by gynecological (7%), colorectal (3.7%), skin (3.4%) lung and hematologic (2.7%) Compared to other subtypes, TNBC patients were found to have much shorter time to secondary cancer development of 38 months compared to Her2+ and ER/PR+ (40 and 45 months respectively, P&amp;lt; 0.001). Black and Hispanic individuals were found to have higher rates (7.4% and 6.3%) and earlier development of secondary cancer (76 months and 74 months) as compared to whites and Asians (5.9% and 5%, 88 months and 81 months, P&amp;lt; 0.001 and P&amp;lt; 0.002 respectively). Conclusion This study identified several risk factors associated with the development of secondary cancers in AYA breast cancer patients such as age at initial breast cancer diagnosis, race, stage, nodal status, surgical procedure and sub-type. Higher rates and early development of secondary cancer were observed among TNBC subtype and Black and Hispanic races that calls for further investigation and tailored interventions to improve outcomes in specific patient populations. Table 1 showing significant differences in characteristics AYA breast cancer patients who developed secondary breast cancer compared to those who did not Citation Format: Sheeba Ba Aqeel, Alankrita Taneja, Shipra Gandhi. Risk factors associated with secondary cancers in AYA patients with breast cancer. A SEER database 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 PO5-10-07.

Abstract GS03-02: Mammographic surveillance in early breast cancer patients aged 50 years or over: results of the Mammo-50 non-inferiority trial of annual versus less frequent mammography

Abstract Introduction: Annual surveillance mammograms for an unspecified period, after treatment for early breast cancer, are widely practised in USA and Europe and represent a significant healthcare cost. Current UK guidelines recommend annual mammograms up to 5 years, then reverts to 3 year screening without specified risk stratification. Further evidence is needed to determine the optimum frequency and duration of mammographic surveillance. Methods: A multi-centre, randomised controlled, phase III trial of annual mammography versus 2-yearly for conservation surgery and 3-yearly mammograms for mastectomy patients up to 9 years. Women were eligible if aged 50 years or over at initial diagnosis of breast cancer (invasive or DCIS), and recurrence free 3 years post curative surgery. Primary outcome was breast cancer specific survival (BCSS). Secondary outcomes include recurrence free interval (RFI) and overall survival (OS). BCSS event was defined as deaths from breast cancer and RFI as any locoregional or distant invasive recurrence or new breast primary. 5000 women were needed to detect a 3% absolute non-inferiority (NI) margin for BCSS with 2.5% one-sided alpha and at least 85% power. Analyses were carried out on intention-to-treat basis. Results: 5235 women were randomised between April 2014 and September 2018. 4347 (83%) women were aged 55-75 years, 4203 (80%) had undergone conservation surgery, 4564 (87%) had invasive disease, 1162 (22%) had node positive disease, 4330 (83%) had ER positive tumours and 3812 (73%) were taking hormone therapy at the time of randomisation. Patient characteristics were balanced across arms. With a median of 5.4 years follow-up (interquartile range 4.6-5.9), 319 women have died; 104 of breast cancer (53 on annual arm; 51 on less frequent arm). BCSS at 5 years was 98.2% (95% CI 97.5-98.6%) on annual arm and 98.3% (95% CI 97.7-98.8%) on less frequent arm. Hazard ratio (HR) was 1.04 (95% CI 0.71 -1.54), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p&amp;lt; 0.0001; critical value 2.71) and the 1% margin (NI p=0.02; critical value 1.56). 320 (6%) women had a new invasive breast cancer event (55 loco-regional recurrences, 85 new breast primaries, 139 distant recurrences and 41 with multiple invasive events); 164 on the annual arm compared to 156 on the less frequent arm. Five-year RFI was 94.2% (95% CI 93.2-95.1%) for the annual arm and 94.4% (95% CI 93.4-95.3%) for the less frequent arm; HR= 1.03; (95% CI 0.83-1.28) demonstrating non-inferiority at a 2% margin (NI p=0.006; critical value 1.36). OS at 5 years was 94.9% (95% CI 93.9-95.7%) on the annual arm and 94.3% (95% CI 93.3-95.2%) on the less frequent arm. Hazard ratio (HR) was 1.18 (95% CI 0.94 -1.47), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p=0.003; critical value 1.61) and the 2.5% margin (NI p=0.02; critical value 1.51). A total of 14987 mammograms have been performed on the annual arm and 8047 on the less frequent arm. 1967 (75%) of 2618 women on the annual arm complied with their allocated schedule compared to 1775 (68%) of 2617 women on the less frequent arm. COVID-19 pandemic affected compliance; it is estimated that 345 (7%) women missed mammograms during the pandemic. A sensitivity analysis was performed on the 72% of women who fully complied with their scheduled mammograms as per protocol, and again NI was demonstrated for BCSS, RFI and OS. Conclusions: For patients aged 50 or older and 3 years post diagnosis, Mammo-50 demonstrated that less frequent mammograms were no worse than annual mammograms. These results provide evidence for less frequent mammographic surveillance for this patient population. Citation Format: Janet Dunn, Peter Donnelly, Nada Elbeltagi, Andrea Marshall, Alastair Thompson, Riccardo Audisio, Sarah Pinder, David Cameron, Amy Campbell, Sue Hartup, Lesley Turner, Annie Young, Helen Higgins, Eila Watson, Sophie Gasson, Peter Barrett-Lee, Claire Hulme, Bethany Shinkins, Peter Hall, Andy Evans. Mammographic surveillance in early breast cancer patients aged 50 years or over: results of the Mammo-50 non-inferiority trial of annual versus less frequent mammography [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 GS03-02.

Abstract PO4-01-11: Ovarian function suppression (OFS) use beyond five years?: Young breast cancer patient preferences

Abstract Background. Breast cancer (BC) is the leading cause of cancer-related death in young women worldwide, and late recurrence of hormone receptor-positive disease plays a substantial role. Adjuvant endocrine therapy with 5 years of ovarian function suppression (OFS) and an aromatase inhibitor or tamoxifen is recommended for many young patients with high risk hormone receptor-positive BC. Data are limited regarding extended endocrine therapy among premenopausal BC survivors, and non-existent to inform treatment decisions regarding extending OFS beyond 5 years. We sought to evaluate young BC survivors’ perceptions and preferences regarding extending OFS beyond 5 years, and consideration of a potential future study to assess the role of extended OFS. Methods. From January-April 2023, email invites were sent to the Young Survival Coalition (YSC) listserv (N=14,291) specifically asking members with a history of invasive BC (≤45 years at diagnosis; stage I-III without metastatic recurrence) receiving OFS injections for adjuvant endocrine treatment to complete a one-time anonymous online survey. The survey was designed to capture information regarding current endocrine therapy use, patient-provider communication regarding extended endocrine therapy including OFS, OFS-related concerns (rating 0-5 [low: 0-1, moderate: 2-3, severe: 4-5]), and interest in a potential future clinical trial utilizing OFS beyond 5 years. Descriptive statistics were utilized to summarize responses, and two-sided Fishers exact tests and chi-square analyses were used for comparisons. Results. A total of 1,030 YSC members completed the survey, and 615 were analyzed due to eligibility and completeness of data. The majority were from the United States (n=579, 94.1%) or Canada (n=8, 1.3%), were non-Hispanic white (n=452, 73.5%), non-Hispanic Black (n=46, 7.5%), or Hispanic (n=43, 7.0%), and had been diagnosed with stage II BC (n=316, 51.4%). The average age at survey was 38.1 years (SD=5.15, range=22-54) and at initial BC diagnosis was 34.6 years (SD=4.96, range=20-49). Most (n=510, 83.0%) were within their first 5 years of OFS treatment while 14.5% (n=89) had already been receiving OFS for more than 5 years. Many respondents (n=344, 55.9%) reported discussing OFS use beyond 5 years with their provider, of whom 39.8% (n=245) reported their provider recommending they continue OFS for more than 5 years. Despite reporting moderate and severe concerns regarding OFS side effects (n=476, 77.4%), inconvenience of injection visits (n=272, 44.2%), and high cost of medication (n=223, 36.3%), most respondents (n=396, 64.4%) would consider continuing OFS beyond 5 years if it would reduce risk of BC recurrence. For nearly half of respondents (n=289, 47.0%) a risk reduction of at least 5% would be required for extended OFS to be worthwhile compared to the remaining 46.3% (n=285) who indicated interest for &amp;lt; 5% risk reduction. When asked hypothetically if they would take part in a clinical trial to determine efficacy of OFS use beyond 5 years, the majority were interested (n=357, 58.0%). Respondents who were interested were less likely to be concerned about the high cost of medication (p=0.003) however they were also less likely to take OFS beyond 5 years if it only led to 1-2% BC risk reduction (p=0.006) compared to those who were not interested. There were no other proportional differences on any other outcome. Conclusion. Many BC survivors and providers are already considering incorporation of OFS beyond 5 years into adjuvant endocrine therapy despite harboring concerns and lack of data. Efforts to determine the efficacy and benefits of extended OFS are necessary given the risk of late recurrence in this population as well as the potential for significant short- and long-term toxicities. The results from this survey study suggest that future clinical trials evaluating potential benefits and risks of long-term OFS use among young BC survivors are needed and likely feasible. Citation Format: Kate Dibble, Tal Sella, Kathryn Ruddy, Craig Snow, Amanda Nixon, Patricia Spears, Karla Ballman, Lisa Carey, Ann Partridge. Ovarian function suppression (OFS) use beyond five years?: Young breast cancer patient preferences [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 PO4-01-11.

Abstract PO3-22-02: Concurrent chemotherapy with adjuvant radiation for patients with high-risk locally advanced breast cancer: safety and outcomes

Abstract Background: Patients with locally advanced breast cancer are at high risk for locoregional and distant recurrence and novel strategies are needed to enhance the efficacy of adjuvant radiation therapy. Selected chemotherapies act synergistically to safely radiosensitize residual disease to radiation therapy and may improve locoregional control when given concurrently. We report our institutional experience using concurrent chemotherapy with adjuvant radiotherapy for high-risk breast cancer patients. Methods: We conducted a retrospective study of breast cancer patients treated definitively with chemotherapy, surgery, and concurrent chemo-radiation (chemo-XRT) in the adjuvant setting between May 2006 and April 2019. The decision to combine chemotherapy with adjuvant conventionally fractionated radiation was based on provider discretion regarding patient’s risk of recurrence. The primary outcome was risk of locoregional recurrence (LRR). Secondary outcomes included disease free survival (DFS), overall survival (OS), and toxicity. The cumulative incidence of local recurrence was estimated with distant recurrence and death as competing risks. DFS and OS was estimated using the Kaplan-Meier method. Results: A total of 42 patients met inclusion criteria; of these 35 (83%) patients were receiving treatment for their initial breast cancer diagnosis and 7 (17%) patients were receiving treatment for a locoregional recurrence. Of the 35 patients treated in the primary setting, the majority had stage III disease (91%). Twenty-nine patients (83%) received neoadjuvant chemotherapy (NAC) all of which had residual disease after NAC and 6 patients (17%) received upfront primary surgery. Overall median total radiation dose was 57 Gy (range 45-68 Gy) with a majority receiving comprehensive regional nodal irradiation (25, 60%). Chemotherapy agents used for chemo-XRT included capecitabine (29, 69%), paclitaxel (8, 19%), and cisplatin (5, 12%). Median follow-up was 5 years after surgery (range: 4 months-16 years). At 5 years, the cumulative risk of LRR was 7% (95% CI: 2-21%). DFS was 47% (95% CI: 34-65%) and OS was 56% (95% CI: 42-74%). Of note, there were multiple exceptional responders, with OS of 51% at 10 years and 45% at 15 years. Chemo-XRT was well tolerated with 7% grade 3 toxicity (dermatitis), no grade 4 toxicity, and no new toxicity signals observed. Conclusions: Concurrent chemo-XRT for breast cancer patients with high risk locally advanced disease was safe and well tolerated. Chemo-XRT showed promise as a method to decrease risk of locoregional recurrence: the studied patient population was at very high risk, but only 7% of patients had a locoregional recurrence at 5 years. Further prospective evaluation of concurrent chemo-XRT is needed. Table 1. Patient characteristics and outcomes (N = 42) XX- XX Citation Format: Lynn Symonds, Sasha Swenson, Macklin Nguyen, Daniel Hippe, Hannah Linden, Jennifer M. Specht, WIlliam Gwin, Janice Kim. Concurrent chemotherapy with adjuvant radiation for patients with high-risk locally advanced breast cancer: safety and outcomes [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 PO3-22-02.

Abstract PO4-16-12: Patient initiated centricity towards improved communication, side effect management and follow-up care by Real World Evidence Survey from patients for patients – Preview of the Breast BRIDGister Platform

Abstract Background Treatment adherence is crucial for outcome improvement. Still up to 50% of patients interrupt e.g. endocrine treatment or other effective treatment choices due to side effects or miscommunication. Reasons may include limited time spent for patient information in daily routine and the intrinsic barriers to frankly tell the truth to the attending physicians. Therefore, a patient initiated survey has been compiled to comprehensively address all clinical, diagnostic and critical aspects of importance for patients by decentral data capture from patients at home via smart devices in a pseudonymized &amp; interactive fashion to refocus on challenges regarding patients needs, fears and wishes to support evidence based statistical analysis of Real World Data. Materials and Methods Establishing a cloud-based IT Platform enabling nationwide, decentral data entry using Climedo clinical trial software tools without the need of any commercial app utilities and therefore obeying GDPR conform standards to create an interconnected online platform integrating 36 interconnected surveys comprising &amp;gt;1.200 singular questions has been set up between 2020 and 2022 based on patients content elaboration &amp; wishes. The questionnaires address all Real World experiences e.g. at initial diagnosis, during primary treatment and all subsequent lines as well as side effect management with complementary medicine and follow up care realities. After 100 patients a preplanned statistical analysis has been performed to evaluate the feasibility of the patient oriented ePRO approach and demonstrate relevance of proof-of-concept results before entering international trial expansion. Descriptive analysis by Excel as well as Correlation analysis; Chi square and Partitioning tests using the SAS JMP® 9.0.0 software were performed. Results Despite in depth complexity &amp;gt; 85% of patients completed the whole survey. Age distribution of the pilot cohort revealed comparably younger patient age (28% between 30-39 years, 40% between 40-49 years, 24% between 50-59 and 10% being above 60 years) and dominance of Triple Negative Patients (~39%) participating the online survey in the pilot cohort. 97% of patients were treated in certified breast centers (50% in larger centers of bigger towns,15% in central clinics, 23% in university sites, 5% in local hospitals and 7% at office based doctors). Interestingly, 25% of patients did not or only partially understand their diagnosis and upcoming treatment. Time spent for communicating initial breast cancer diagnosis was less than 10 minutes for 25% of patients, while 13% did not remember. Exclusively one treatment option was discussed with 86% of patients. 78% have been informed about their initial breast cancer diagnosis in personal meetings, while 21% were informed by phone calls. 37% of patients had been informed about their patient rights. At preplanned interim analysis 38% of patients were lymphnode positive and 6% metastasized at initial diagnosis. 56% of patients were satisfied with their guideline conform follow-up-care, while 42% did pay for additional follow up care on their own. 85% of patients wished to have a risk-adopted, more individualized follow-up care. Conclusion Despite complexity and lengthiness &amp;gt; 85% of patients did complete the survey. There is an apparent need to have more time for initial confrontation with diagnosis and treatment options. Patients are frequently not informed about alternative treatment options as well as patient rights. Patients frequently feel under pressure in their life threatening situation and suffer substantial lack of information as well as appropriate personal communication. Patient centricity should focus on elaborated communication and information systems that support treatment decision acceptance and adherence. Further details analysis will become available in upcoming subanalysis of the Breast BRIDGister platform survey. Citation Format: Cornelia Stuewe, Ralph Wirtz, Christa Gress, Lena Schmidt, Veronika Schweighart, Sebastian Eidt, Claudia Schumacher, Julia Habraschka, Heidi Lehmann, Katrin Schuere. Patient initiated centricity towards improved communication, side effect management and follow-up care by Real World Evidence Survey from patients for patients – Preview of the Breast BRIDGister Platform [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 PO4-16-12.

Abstract PO5-07-07: The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk

Abstract Introduction: The amount and degree of the fibroglandular tissue (FGT) enhancement on breast MRI, known as background parenchymal enhancement (BPE), is an emerging marker of breast cancer risk. Higher qualitative and quantitative BPE levels have been shown to correlate with both future risk of initial breast cancer diagnosis and breast cancer recurrence after treatment. Furthermore, adjuvant and preventative therapies such as radiation and endocrine therapy have been shown to lower BPE in many women, potentially serving as a marker of treatment efficacy. However, the biological basis of BPE remains unclear and elucidation of this mechanism could identify novel targeted prevention strategies. The goal of this study was to assess the association of BPE levels with markers of inflammation, vascularity, proliferation, and estrogen sensitivity in a cohort of high-risk women. Materials and Methods: In this IRB-approved retrospective study, we identified asymptomatic high-risk women who underwent at least one dynamic contrast-enhanced (DCE) breast MRI within one year of prophylactic bilateral mastectomy. Qualitative BPE assessments were obtained from clinical reports. Quantitative BPE measures were obtained using in-house semi-automated software: whole breast FGT was first segmented on pre-contrast images, percent enhancement (PE) was calculated for each voxel as (S1-S0)/S0 × 100%, where S0 and S1 are pre- and early post-contrast signal intensity, respectively, and quantitative BPE was then defined as the mean PE of the FGT. Additionally, the BPE volume ratio was calculated as the fraction of FGT that had a PE &amp;gt;50%. Histopathology markers of inflammation (COX-2), vascularity (VEGF), proliferation (Ki-67), and estrogen receptor status (ER) were prospectively measured on archived mastectomy specimens of each breast. BPE metrics were correlated with histopathological markers using Spearman’s rank correlation, with and without adjustment by menopausal status of the patient. All tests were based on generalized estimating equations models to account for the non-independence of the two breasts per patient. A p-value &amp;lt; 0.05 was considered significant. Results: We identified 56 women (median age: 39; range: 26-63 years) for this study, of which 39% were post-menopausal (N=22). Distribution of qualitative BPE levels were 41% minimal (N=23), 29% mild (N=16), 18% moderate (N=10), and 12% marked (N=7). Qualitative BPE and quantitative BPE markers were moderately positively correlated (r=0.37-0.54, p&amp;lt; 0.01). Table 1 lists the correlations between BPE metrics and histopathology markers. After adjusting for menopausal status, qualitative BPE was positively associated with ER (r=0.27, p=0.02) and VEGF (r=0.24, p&amp;lt; 0.01; r=0.21, p=0.02 adjusted). Quantitative BPE and BPE volume ratio were both positively correlated with VEGF (p&amp;lt; 0.04) and negatively correlated with COX2 (p&amp;lt; 0.05). No significant associations were observed between BPE and Ki-67. Discussion: Our study suggests that increased BPE on MRI positively correlates with increased vascularity and higher estrogen receptor expression but not inflammation or proliferation within normal breast tissue in high-risk women. These findings, along with established associations between BPE and cancer risk, could be useful to select and assess efficacy of targeted preventative treatments. Table. Spearman rank correlations between BPE metrics and histopathological markers. Citation Format: Pegah Khoshpouri, Anum Kazerouni, Sana Parsian, Daniel Hippe, Olivia Walsh, Lisa Koch, Savannah Partridge, Habib Rahbar. The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk [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 PO5-07-07.

Metastatic Breast Cancer: Prolonging Life in Routine Oncology Care.

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022. A total of 1610 patients with a median age of 63 years (23-100) were evaluated. In all, 82.9% had hormone-receptor-positive disease, and 23.8% were HER2-positive. Evaluation in time cohorts by initial MBC diagnosis date showed a continuous prolongation of median OS from 31.6 months (0.5-237.3+) (1995-2000) to 48.4 months (0.4-61.1+) (2018-2022) (p = 0.003). Univariable analyses showed a significant dependence on the time cohort of diagnosis, metastatic status at initial diagnosis, age at metastasis, hormone and HER2 status, general condition, metastasis localization, and the number of affected organs. A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years.

Abstract 3474: Racial disparities in receipt of surveillance mammography after breast cancer diagnosis

Abstract Background: The 5-year survival rate for breast cancer (BC) stands at an estimated 91%, with approximately 3.8 million BC survivors in the U.S. This large population of breast cancer survivors remains at risk of loco-regional recurrence, with variations noted across racial groups. White survivors face a locoregional breast cancer recurrence rate of 1.8%, whereas Black, Asian, and Hispanic survivors experience higher rates of 3.9%, 3.6%, and 3.1%, respectively. Notably, Black BC survivors with recurrent breast cancer exhibit a median survival time of 1.8 years compared with 3.6 years observed for White BC survivors. Current recommendations from the U.S. Preventative Services Task Force and the American College of Radiology advocate for surveillance through annual mammography and routine clinical visits following breast-conserving surgery and lumpectomies. However, there are gaps in the data available regarding disparities in the utilization of surveillance mammography by race/ethnicity. Thus, the goal of this study is to estimate race/ethnic disparities in surveillance mammography utilization and its impact on survival among breast cancer survivors at a large comprehensive cancer center. Methods: A retrospective cohort study of female breast cancer survivors ≥19 years diagnosed and/or treated at the Duke Cancer Institute (DCI) between 2014 and 2022 was conducted. Data was abstracted on patient socio-demographics, cancer type (invasive ductal and ductal in situ carcinomas) and utilization of surveillance mammography within 2-5 years post initial breast cancer diagnosis. Chi-squared testing will be used to analyze rates of mammography surveillance receipt among different races presenting with BC at DCI. Kaplan-Meier estimates will be used for analysis on survival. Results: A total of 10,904 women with a mean age of 43.7 years were included in the study. The study cohort is comprised of 69% non-Hispanic (NH) White, 24% NH Black, 2.2% Hispanic, 0.5% NH Native American, 1% NH other, and 3.2% NH Asian women. There were 1,791 cases of ductal in situ carcinomas and 9,113 invasive ductal carcinoma cases. NH Black women had the lowest 5-year relative survival rate (81.5%) of all represented racial groups: NH White 89.1%, Hispanic 95.3%, NH Native 87.8%, Asian 97.9%, and NH Other 88.0%. Ongoing analysis will be completed to estimate disparities in the use of post-treatment surveillance mammography amongst breast cancer survivors. Conclusions: This study will inform efforts to increase post-treatment surveillance and improve adherence to survivorship guidelines with the ultimate goal of reducing mortality disparities among breast cancer survivors. Citation Format: Jasmine G. Wilkerson, Frances Wang, Yadurshini Raveendran, Tomi Akinyemiju. Racial disparities in receipt of surveillance mammography after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3474.

Survival Analysis of Male Patients with Brain Metastases at Initial Breast Cancer Diagnosis over the Last Decade.

Breast cancer in men represents approximately 1% of all breast cancer diagnoses. Among all patients with breast cancer, approximately 30% will develop brain metastases. Over the past decade, there have been multiple advances in the treatment of metastatic breast cancer; however, long-term outcomes of this presentation in male patients are lacking. We evaluated male patients with de novo stage IV breast cancer using the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Overall survival (OS) was estimated using the Kaplan-Meier method and differences between groups were compared using log rank tests. In total, 22 male patients with brain metastases at initial breast cancer diagnosis were included. Patients with HR-positive/HER2-negative tumors had the longest OS (median 13 months). Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.

Survival analysis of patients with brain metastases at initial breast cancer diagnosis over the last decade.

There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.

Gastric metastasis from breast cancer: five cases and a single-institutional review.

Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.

Bidirectional association between breast cancer and meningioma: a systematic review and meta-analysis.

An association between breast cancer and meningioma has been suggested in cohort studies. We aimed to perform a systematic review and meta-analysis to determine whether there is an association between initial breast cancer and subsequent meningioma diagnosis and vice versa. A systematic literature search was performed on Medline, Embase, Scopus and Google scholar from inception up to April 2023. A meta-analysis of selected studies was performed using Review Manager 5.4. There were eight studies included in the systematic review. Seven had reported Standardized Incidence Ratio (SIR) for female patients and were suitable for the meta-analysis. Only one study reported SIR for male patients. For the association between initial breast cancer and subsequent meningioma, in 795 000 female patients with follow-up ranging from 7 to 13 years, the SIR was 1.27 (95% CI: 1.20-1.34, P-value <0.00001). For the association between initial meningioma and subsequent breast cancer, in 28 000 female patients with follow-up ranging from 6 to 15 years, the SIR was 1.32 (95% CI: 1.21-1.45, P-value <0.00001). There were low heterogeneity and no significant publication bias. There was a small but significant association between initial breast cancer and subsequent meningioma as well as initial meningioma and subsequent breast cancer in female patients. The potential underlying mechanisms and risk factors were unclear from current literature and would be a potential area for future research.

Modeling of Aquila Optimizer with Hybrid ResNet-DenseNet enabled Breast Cancer Classification on Histopathological Images

Breast cancer (BC) is the most common cancer amongst women that threatens the health of women, initial diagnosis of BC becomes essential. Though there were several means to diagnose BC, the standard way is pathological analysis. Precise diagnosis of BC necessitates experienced histopathologists and needs more effort and time for completing this task. Recently, machine learning (ML) was successfully implemented in text classification, image recognition, and object recognition. With the emergence of computer aided diagnoses (CAD) technology, ML was effectively implemented for BC diagnosis. Histopathological image classification depends on deep learning (DL), particularly convolution neural network (CNN), which frequently needs a large amount of labelled training models, whereas the labelled data was hard to obtain. This study develops an Aquila Optimizer(AO) with Hybrid ResNet-DenseNet Enabled Breast Cancer Classification on Histopathological Images (AOHRD-BC2HI). The proposed AOHRD-BC2HI technique inspects the histopathological images for the diagnosis of breast cancer. To accomplish this, the presented AOHRD-BC2HI technique uses hybridization of Resnet with Densenet (HRD) model for feature extraction. Moreover, the HRD method can be enforced for feature extracting procedure in which the DenseNet (feature value memory by concatenation) and ResNet (refinement of feature value by addition) were interpreted. For BC detection and classification, the DSAE model is utilized. The AO algorithm is exploited to improve the detection performance of DSAE model. The experimental validation of the presented AOHRD-BC2HI approach is tested using benchmark dataset and the results are investigated under distinct measures.Also the proposed model achieved the accuracy of 96%. The comparative result reports the improved performance of the presented AOHRD-BC2HI technique over other recent methods.

Characteristics and post-metastasis survival of recurrent metastatic breast cancer over time – An Australian population-based record linkage study, 2001–2016

AimTo assess population-level characteristics and post-metastasis survival of people with recurrent metastatic breast cancer (rMBC) during a period when new publicly-subsidised adjuvant and metastatic systemic therapies became available. MethodsRecord linkage study of females in NSW Cancer Registry (NSWCR) diagnosed with non-metastatic breast cancer (BC) in 2001–2002 (C1) and 2006–2007 (C2). We identified first rMBC from NSWCR, administrative hospital records, dispensed medicines and radiotherapy services (2001–2016). We used death registrations to estimate cumulative incidence of BC death. ResultsThe analysis included 2267 women with rMBC (C1:1210, C2:1057). Compared to C1, C2 had access to adjuvant HER2-targeted therapy and were more likely to have received adjuvant chemotherapy (C1:38%, C2:47%) and aromatase inhibitors (C1:52%, C2:73%, of those dispensed endocrine therapy). Five-year probability of BC death was 65% (95%CI:62–68%) in C1 and 63% (95%CI:60–66%) in C2. Regional disease (T4 or N + ) at initial BC diagnosis (C1:62%, C2:68%), and age ≥ 70 years at first metastasis (C1:27%, C2:31%) were more common in C2 and had poorer prognosis. Five-year probability of BC death was lower in C2 than C1 for treatment-defined HER2-positive BC (C1:72% 95%CI:63–79%; C2:52% 95%CI 45–60%) and those dispensed chemotherapy alone (C1:76% 95%CI:69–82, C2:67% 95%CI:59–74%, p = 0.01), but not treatment-defined hormone receptor-positive HER2-negative BC (C1:60% 95%CI 56–63%, C2:64% 95%CI 60–68%). ConclusionsDespite less favourable prognostic characteristics in C2, BC-related survival following rMBC was similar between the two cohorts; and improved for women with HER2-positive tumours. These findings support the real-world benefits of newer treatments for rMBC.

Abstract 16797: The Role of Adiposity on Microvascular Dysfunction and Arterial Stiffness in Patients With New Onset Breast Cancer

INTRODUCTION: Increased adiposity is a risk factor for both cardiovascular disease (CVD) and cancer. Microvascular endothelial dysfunction and arterial stiffness are independent risk factors for CVD and can accelerate vascular aging. Whether or not adiposity plays a role in vascular aging over time in patients with new-onset breast cancer (BC) has yet to be elucidated. Hypothesis: Adiposity impacts microvascular dysfunction and arterial stiffness differently in women undergoing therapy for recent BC diagnoses. Methods: Two lean (L; BMI &lt; 25 kg/m 2 ) and four overweight and obese (Ow/Ob; BMI &gt; 25 kg/m 2 ) women diagnosed with BC within the last 3 months participated in the study. Using laser Doppler imaging, microvascular endothelial function was assessed with three protocols: 1) cutaneous post-occlusion reactive hyperemia (PORH), 2) local thermal heating (LTH), and 3) iontophoresis of acetylcholine. Arterial stiffness was assessed using pulse wave velocity (PWV) and pulse wave analysis (PWA). Assessments were made at baseline and at 3 and 6 months following enrollment. Data are reported as means ± SE. Results: No differences in age, height, blood pressure, or total cholesterol (all p &gt;0.05) were observed between L and Ow/Ob groups. Microvascular function and arterial stiffness were similar at baseline between groups. There was a greater decrease in LTH responses from baseline to 6 months post-baseline in Ow/Ob women (Δ-48±4 PU; p =0.001) compared to L women (Δ-16±13 PU; p =0.125). Similar responses in both groups were noted for PORH ( p =0.886) and iontophoresis ( p =0.784). PWV was similar from baseline to 6 months post-baseline in both groups; however, the PWA tended to increase over time in Ow/Ob women (Δ2.5±4.7) and decrease in L women (Δ-3.0±5.0). CONCLUSION: Ow/Ob women have a greater rate of decline in LTH responses compared with L women, whereas similar responses between L and OW/OB women were observed over time for PORH and iontophoresis. In addition, central aortic stiffness increased in Ow/Ob women and decreased in L women, while no change in PWV was observed. These findings suggest that adiposity may impact vascular beds differently over time following the initial diagnosis of breast cancer.

Endocrine therapy initiation among women diagnosed with ductal carcinoma in situ breast cancer from 2001-2016.

487 Background: Endocrine therapy (ET) initiation in people within 1 year of diagnosis of estrogen-receptor-positive (ER+) ductal carcinoma in situ (DCIS) has ranged from 21-45% in prior studies; however, these studies did not evaluate initiation post-2011 and may not reflect current patterns of use. ET use following ER+ DCIS diagnosis can reduce the relative risks of recurrence and contralateral breast cancer by 30-50%. We evaluated ET initiation over time and by demographic, tumor, and treatment characteristics in the Kaiser Permanente Breast Cancer Survivors Study between 2001-2016. Methods: We included people aged 20+ years diagnosed with unilateral DCIS with at least 1 year of cancer-free follow-up from three U.S. integrated health systems. We excluded people with ER-negative disease, no surgery, and those who received chemotherapy or unknown radiation therapy. ET dispensings (tamoxifen and aromatase inhibitors) were extracted from electronic pharmacy records within 1 year of a person’s initial DCIS breast cancer diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated relative rates (RRs) of ET use (vs none) over time and by demographic, tumor, and other treatment characteristics. Results: Among 1,782 pre- and postmenopausal people, 577 (32%) initiated ET within 1 year of diagnosis. From 2001-2016, ET use did not change over time (34% vs 36%), tamoxifen use declined slightly (34% vs 29%), and aromatase inhibitor use increased slightly (0% vs 7%). People were less likely to initiate ET if they were ≥65 years, Black, had borderline or unknown ER status, were not tested for ER, had breast conserving surgery (BCS) without radiation, or had a unilateral mastectomy. Conclusions: Only one-third of people with DCIS diagnosed in a community healthcare setting and potentially eligible for ET, initiated treatment within 1 year of their diagnosis. Previous studies have shown long-term benefits of ET use in people with DCIS; however, we saw no increase in use over time. Concerns about side-effects, overdiagnosis and overtreatment of DCIS, and confusion about treatment guidelines may explain relatively low ET initiation.[Table: see text]

Latent pathway-based Bayesian models to identify intervenable factors of racial disparities in breast cancer stage at diagnosis.

We built Bayesian Network (BN) models to explain roles of different patient-specific factors affecting racial differences in breast cancer stage at diagnosis, and to identify healthcare related factors that can be intervened to reduce racial health disparities. We studied women age 67-74 with initial diagnosis of breast cancer during 2006-2014 in the National Cancer Institute's SEER-Medicare dataset. Our models included four measured variables (tumor grade, hormone receptor status, screening utilization and biopsy delay) expressed through two latent pathways-a tumor biology path, and health-care access/utilization path. We used various Bayesian model assessment tools to evaluate these two latent pathways as well as each of the four measured variables in explaining racial disparities in stage-at-diagnosis. Among 3,010 Black non-Hispanic (NH) and 30,310 White NH breast cancer patients, respectively 70.2% vs 76.9% were initially diagnosed at local stage, 25.3% vs 20.3% with regional stage, and 4.56% vs 2.80% with distant stage-at-diagnosis. Overall, BN performed approximately 4.7 times better than Classification And Regression Tree (CART) (Breiman L, Friedman JH, Stone CJ, Olshen RA. Classification and regression trees. CRC press; 1984) in predicting stage-at-diagnosis. The utilization of screening mammography is the most prominent contributor to the accuracy of the BN model. Hormone receptor (HR) status and tumor grade are useful for explaining racial disparity in stage-at diagnosis, while log-delay in biopsy impeded good prediction. Mammography utilization had a significant effect on racial differences in breast cancer stage-at-diagnosis, while tumor biology factors had less impact. Biopsy delay also aided in predicting local and regional stages-at-diagnosis for Black NH women but not for white NH women.