Breast Cancer-specific Mortality Research Articles

Breast cancer risk assessment for prescription of menopausal hormone therapy in women with a family history of breast cancer: an epidemiological modelling study.

Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking. To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer. An epidemiological modelling study for women in England using the BOADICEA breast cancer prediction model and data relating to MHT use and breast cancer risk taken from research by the Collaborative Group on Hormonal Factors in Breast Cancer. The risk of developing and dying from breast cancer between the ages of 50 and 80 years was modelled in women with four different breast cancer family history profiles: 'average', 'modest', 'intermediate', and 'strong' by using 1) background risks of breast cancer by age and family history, 2) relative risks for breast cancer associated with MHT use, and 3) 10-year breast cancer-specific net mortality rates. This study modelled use of combined oestrogen-progestogen MHT (cyclical or continuous) and oestrogen-only MHT. For a woman of 'average' family history taking no MHT, the cumulative breast cancer risk (age 50-80 years) is 9.8%, and the risk of dying from the breast cancer is 1.7%. In this model, 5 years' exposure to combined-cyclical MHT (age 50-55 years) was calculated to increase these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative breast cancer risk is 19.6% (age 50-80 years), and the risk of dying from the breast cancer is 3.2%. With 5 years' exposure to MHT (age 50-55 years), this model showed that these risks increase to 22.4% and 3.5%, respectively. In this model, both family history and MHT are associated with increased risk of breast cancer. Estimates of the risks of breast cancer associated with MHT for women with different family histories can be used to support decision making around MHT prescription for women experiencing menopausal symptoms.

Dampak Oforektomi terhadap Kualitas Hidup dan Fungsi Seksual Orang dengan Kanker Payudara

This study aims to identify the impact of orthorectomy on breast cancer patients, especially on their quality of life and sexual function. We conducted a systematic review adhering to PRISMA guidelines, searching articles from PubMed, ProQuest, Embase, and ScienceDirect databases from inception to March 2024. The search terms used were "oophorectomy", "quality of life", "sexual function", and "breast cancer". Results from 8 articles showed that oophorectomy can negatively affect quality of life, especially in physical and psychosocial aspects, and can be associated with sexual dysfunction. Ophorectomy was also associated with significant reductions in all-cause mortality and breast cancer-specific mortality. In conclusion, this study shows about ooforectomy have a significant impact on quality of life and sexual function of women, especially on physical and psychosocial aspects. Although, these impacts do not entirely affect quality of life, Keywords: Oophorectomy, Breast Cancer, Quality of Life, Sexual Dysfunction

Abstract PO2-25-08: Role of social isolation and support on all-cause and breast cancer specific mortality among women with breast cancer: The Western New York Exposures and Breast Cancer (WEB) Study

Abstract Background: Studies of associations of social support with mortality among women diagnosed with breast cancer have been inconclusive. Further, there have been little study of related factors such as marital status, housing, and income, nor of differential impact by treatment received (chemotherapy, radiation, or hormonal therapy). Methods: Women with incident, pathologically confirmed invasive breast cancer, stage I-IV, answered a social support questionnaire data (n=1015) in a population-based study, the Western New York Exposures and Breast Cancer (WEB) Study. Patients were queried regarding the number of their close friends, the number of people with whom they lived with, their income, education, and marital status. Hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality were estimated with Cox proportional hazards models. Associations were also examined within strata of treatment type received. Results: Median follow up time was 18.5 yrs, 449 died of which 279 deaths were from breast cancer. Out of 1015 patients, 98 patients reported 0-1 friends while 917 reported 2 or more friends. The crude association of social isolation, defined as reporting no or one close friend, was significantly associated with higher all-cause mortality with HR 1.57 (95% CI 1.19-2.07) (p=0.0014). Older age (62 yrs vs. 57 yrs), fewer years of education (12.5 yrs vs. 13.5 yrs), longer smoking history (17 pack years vs. 10.7 pack years), higher percentage of non-white population (15.3% vs. 7.52%), lower income (20.7% vs. 7.2%), living alone (45.9% vs. 21.9%), post-menopausal status (83.7% vs. 70.7%), lower receipt of chemotherapy (32.3% vs. 44.8%), higher receipt of hormone replacement therapy (43.9% vs. 37.0%), high blood pressure (53.6% vs. 33.8%), high blood cholesterol (45.8% vs. 34.1%), more likelihood of being divorced/separated, widowed, never married (20.8% v. 12.8%, 19.8% vs. 15.2%, 13.5% vs. 7.8%) were significantly associated with social isolation. After controlling for these variables, there was no association between social isolation and all-cause mortality, HR 1.14 (95% CI, 0.78-1.66). Being widowed (HR 1.53, 95% CI 1.19-1.95), divorced/separated (HR 1.5, 95% CI 1.14-1.99), having lower income (HR 3.58, 95% CI, 1.89-6.77) and lower education (HR 1.07, 95% CI 1.03-1.12) were associated with higher all-cause mortality. In multivariable analyses, only lower income was associated with higher all-cause mortality (HR 2.44, 95% CI 1.16-5.14). There was no association of social isolation, marital status, income, education, or housing with breast cancer specific mortality. There were also no significant associations of marital status, income, social support, or housing with mortality within strata of treatment received. Conclusions: In this population-based study of women who had been diagnosed with breast cancer, social support, measured as the number of friends the breast cancer patient could call on for assistance, was not associated with either all cause or breast cancer mortality. Higher income was associated with lower mortality. Our study focused on social networks; future studies should also analyze emotional domain of social support, that is, perceived social support: feeling encouraged, shared problem-solving etc., which have higher clinical relevance than structural support. Citation Format: Shipra Gandhi, Jing Nie, Archit Patel, Maurizio Trevisan, Kristopher Attwood, Jo L. Freudenheeim. Role of social isolation and support on all-cause and breast cancer specific mortality among women with breast cancer: The Western New York Exposures and Breast Cancer (WEB) 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 PO2-25-08.

Abstract PS18-10: Tumor-Infiltrating Lymphocytes and Breast Cancer Mortality in Racially and Ethnically Diverse Participants of the Northern California Breast Cancer Family Registry

Abstract Purpose: Greater stromal tumor-infiltrating lymphocyte (sTIL) percentage in pre-treatment breast tumor specimens is associated with superior response to neoadjuvant chemotherapy and survival. We hypothesized that sTIL-survival associations vary by race and ethnicity and mediate survival disparities. Patients and Methods: We evaluated pre-treatment percentages of sTILs in deciles for 284 women enrolled in the Northern California Breast Cancer Family Registry and diagnosed with a first primary invasive breast cancer from 1995-2005. We assessed associations of continuous sTIL scores and lymphocyte-predominant breast cancer (LPBC, defined as ≥50% lymphocytic infiltration of tumor stroma or cell nests) with clinical and epidemiologic characteristics using regression analysis and with breast cancer-specific mortality (BCM) and overall mortality (OM) using Cox proportional hazards regression. Results: The cohort was diverse (64% from racially and ethnically minoritized populations) with near-complete (98%) germline BRCA1/2 testing and long-term follow-up (average 16.2 years, range: 1.3-26.7). In multivariable analyses, higher sTIL score was associated with reduced BCM [LPBC versus non-LPBC: HR=0.44 (95% confidence interval 0.20-0.98); and per decile increase in sTIL score: HR=0.80 (0.69-0.93)], with the strongest association in the subset of patients with hormone receptor-negative disease [HR=0.71 (0.57-0.88) and HR=0.37 (0.14-0.94), respectively]. While there was no significant difference in sTIL score between racial and ethnic groups, the continuous sTIL-survival association was statistically significant among non-Hispanic White [HR=0.73 (0.57-0.94)] and Asian American [HR=0.56 (0.35-0.89)] women but was not seen among African American and Hispanic women. Conclusion: We identified novel sTIL-BCM differences by race and ethnicity, with better survival associated with sTIL enrichment among non-Hispanic White and Asian American but not among African American or Hispanic women. Additional studies are needed to determine whether survival and particularly the response to immunotherapy are differentially mediated by immune factors between racial and ethnic groups. Multivariable Cox Proportional Hazards Regression Models of Breast Cancer-Specific and Overall Mortality. Citation Format: Julia Ransohoff, Iain Miller, Jocelym Koo, Vishal Joshi, Allison Kurian, Kimberly Allison, Esther John, Melinda Telli. Tumor-Infiltrating Lymphocytes and Breast Cancer Mortality in Racially and Ethnically Diverse Participants of the Northern California Breast Cancer Family Registry [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 PS18-10.

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received < 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p< 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p< 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p< 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p< 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p< .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [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 PO5-18-02.

Abstract PO2-02-04: The Impact of Statins on Breast Cancer Specific Mortality in a Diverse Patient Population with Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

Abstract Hormone receptor-positive (HR+), HER2 negative (HER2−) breast cancer has a long-term risk of recurrence, compared with other breast cancer subtypes, which ultimately impacts mortality outcomes. Although adjuvant endocrine therapy plays an integral role in risk reduction, disparities persist—with Black women experiencing higher mortality rates compared to White women. Multiple studies have demonstrated that statin use can lead to a reduction in breast cancer mortality, but there is limited information in relation to the impact of statins among diverse patient populations in the United States. To assess whether statin use is associated with an improvement in breast cancer-specific mortality (BCSM), we conducted a large, observational study in women aged 66 and older diagnosed with Stage I–IIIC HR+, HER2- breast cancer between 2013 and 2017. We identified eligible women using the SEER-Medicare database and linked them to the BRIDGE (BReast cancer Investigation of Disparities in GEorgia) cohort, a survivorship cohort of the Georgia Cancer Registry. Patients needed to be continuously enrolled in Medicare Parts A, B, and D in the 12 months following a breast cancer diagnosis. We used Cox proportional hazards models to estimate the impact of statin use within 12 months of diagnosis on BCSM with adjustment for age, stage, and race using multivariable-adjusted hazard ratios (HRs). A total of 2483 participants were identified, and of those, 303 (12.2%) were statin users, 383 (15.4%) were non-Hispanic Black women, and 1564 (63%) resided in census tract with greater than or equal to 10% poverty levels at the time of diagnosis. Distribution of age, stage, and race were similar between statin and non-statin users. Of the statin users, 41/303 (13.5%) were non-Hispanic Black women. The majority of statin users were prescribed lipophilic statins alone (169; 55.8%), and atorvastatin was the most commonly prescribed statin. There was no association between statin use and BCSM (HR 1.09; 95% CI 0.62-1.90) in the multivariable-adjusted model. Although preliminary results suggest that there is no association between statin use and BCSM among women with Stage I–IIIC HR+, HER2− breast cancer, further analyses are planned to explore statin use as a time-varying exposure, which may provide additional insights into the potential relationship between statin use and BCSM. In addition, analyses examining potential heterogeneity by race, tumor and treatment characteristics, and comorbidities are forthcoming. Given the low cost and relative accessibility of statins, we anticipate these findings will inform the clinical management of women with operable breast cancer, increasing parity in outcomes and potentially narrowing race disparities. Citation Format: Ruth Sacks, Maya Bliss, Micah Streiff, Leah Moubadder, Maret Maliniak, Tsion Armidie, Lindsay Collin, Kevin Kalinsky, Lauren McCullough. The Impact of Statins on Breast Cancer Specific Mortality in a Diverse Patient Population with Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer [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 PO2-02-04.

Abstract PO3-09-06: Role of Obesity-Related Biomarkers on Mortality Among Black Breast Cancer Survivors in the Women’s Circle of Health Followup Study

Abstract Background: Central obesity and higher adiposity have been recently associated with higher all-cause and breast cancer-specific mortality in Black breast cancer survivors participating in the Women’s Circle of Health Followup Study. Adipose tissue is a dynamic organ producing adipocytokines, including leptin, adiponectin, adipsin, resistin, lipocalin-2/NGAL, plasminogen-activator inhibitor type 1 (PAI-1) and CXCL11, TNFα, and IL-6, which modulate inflammatory markers in obesity, including the release of proinflammatory C-reactive protein (CRP). These circulating biomarkers play important roles linking obesity with insulin resistance, hyperinsulinemia, chronic inflammation, and altered immunity, which may impact overall and breast cancer mortality. The goal of this analysis was to determine if circulating adipocytokines and obesity-related biomarkers of systemic inflammation are associated with breast cancer and overall survival in Black breast cancer survivors. Methods: Circulating biomarkers were assayed for 460 Black breast cancer survivors who provided a blood sample 2 years post-diagnosis in the Women’s Circle of Health Followup Study, a population-based cohort of Black breast cancer survivors in New Jersey enrolled within 12 months of diagnosis. Associations between biomarkers (by tertiles) and overall survival were assessed using multivariable Cox regression models. Breast cancer specific survival was assessed based on competing risk analyses using the Fine and Gray subdistribution hazard model. Multivariable models were adjusted for age, body mass index as a measure of overall adiposity, education, menopausal status, stage, grade, subtype, and chemotherapy, hormonal therapy, and radiation treatments received. All tests were two-sided at Analyses were conducted at P=0.05. Results: In multivariable analyses, lipocalin-2, CXCL11, and CRP, biomarkers of adipose tissue inflammation closely related to insulin resistance, were associated with worse overall but not breast cancer specific survival. Compared to women in the lowest tertile of lipocalin-2, women in the highest tertile had a 3-fold increased risk of dying from any cause (T3 vs T1, HR=3.08, 95% CI: 1.29-7.39, p= 0.004) and a ~2-fold increased risk of dying from breast cancer, which was not statistically significant (HR= 1.84, 95% CI: 0.59-5.79, p=0.30). Similarly, women in the highest tertile of CXCL11 were at 2-fold increased risk of dying of any cause (HR: 2.10, 95% CI: 0.96-4.57, p=0.06) but no associations were observed with risk of dying from breast cancer (HR:1.31, 0.42-4.13, p=0.64). Circulating CRP, as a marker of systemic inflammation, was also associated with worse overall survival (T3 vs T1 HR: 2.51, 95% CI: 1.07-5.89, p=0.03), showing a borderline significant association with increased breast cancer specific survival (T3 vs T1 HR: 4.32, 95% CI: 0.87-21.38, p=0.07). No associations with overall or breast cancer specific mortality were observed for any of the other adipocytokines examined. Conclusion: In this population-based cohort study of Black breast cancer survivors, biomarkers associated with adipose tissue related inflammation and insulin resistance were associated with reduced overall survival. Relationships with breast cancer survival were not significant, possibly due to limited sample size. Citation Format: Shipra Gandhi, Chi-Chen Hong, Anthony George, Kristopher Attwood, Bo Quin, Nur Zeinomar, Yong Lin, Christine Ambrosone, Kitaw Demissie, Elisa Bandera. Role of Obesity-Related Biomarkers on Mortality Among Black Breast Cancer Survivors in the Women’s Circle of Health Followup Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-06.

Abstract PO5-25-10: Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways Study

Abstract Background: A subset of breast cancers (BC) typically classified as HER2-negative do express low levels of the protein and can be responsive to targeted therapy trastuzumab-deruxtecan. It is unclear if HER2-low tumors have a biology distinct from that in HER2 negative BC. The goal of this study was to evaluate the clinical and epidemiologic features of tumors with HER2-low expression compared with those classified as HER2-negative in a large population study. Material and methods: The Pathways Study is a prospective multi-ethnic cohort study of women with BC enrolled between 2006-2013 within Kaiser Permanente Northern California (KPNC). Breast biomarker results were extracted from pathology reports and underwent centralized pathology review. HER2-low was defined as 1+ or 2+ (negative by in situ hybridization); HER2-negative was defined as 0+. Other data were collected by self-report or extraction from electronic health records at the KPNC cancer registry, including BC risk factors, tumor characteristics [AJCC stage, ER/PR positive or negative status], treatment modality (chemotherapy, radiation therapy, hormonal therapy, and type of surgery), and survival outcomes [recurrence free survival (RFS), breast cancer specific mortality (BCSM), and overall survival (OS)]. The clinical and epidemiologic variables were tested in association with HER2 status (low/negative) by t-tests. Associations of HER2-low with survival outcomes were calculated by proportional hazards regression. Women were included in this analysis if they had a documented HER2 value that was not classified as HER2-positive. Results: Of the 2,200 eligible cases, 1,295 (57.2%) had tumors that were HER2-low. Hormone receptors (HR) were positive in 1,956 (88.9%) cases. HER2-low expression was observed more often in HR-positive cases than in HR-negative, 1,144 (58.4%) vs. 115 (47.1%), respectively (p=.0005). Patients with HER2-low tumors were less likely than those with HER2-negative BC to have family history: 232 of 1259 (18.6%) vs. 214 of 941 (22.8%), respectively (p=.015). This difference was true for patients with HR-positive tumors but not for HR-negative. HER2-low expression appeared to be more common in Asian patients in the HR-negative group than in patients from any other race or ethnicity group. In the HR-negative group, patients with HER2-low had better OS, BCSM, and RFS (p=.019, .014, and .034, respectively) than those with HER2-negative disease. Multivariable analyses were performed for the HR-negative group and adjusted for age at diagnosis, tumor AJCC stage, and type of treatment. Compared with patients with HER2-negative status, patients with HER2-low tumors had lower risk for OS (hazard ratio=0.48, 95% confidence interval: 0.28 to 0.81, p= .006); for RFS (hazard ratio=0.49, 95% confidence interval: 0.27 to 0.90, p= .021); and for BCSM (hazard ratio=0.36, 95% confidence interval: 0.17 to 0.76, p= .007). In analyses stratified by race and ethnicity and controlled for age at diagnosis, AJCC stage and treatment type, Black patients with HER2-low tumors had lower risk for RFS (hazard ratio=0.44, 95% confidence interval: 0.21 to 0.94, p= .035) compared with patients with HER2-negative tumors. Conclusions: In this large prospective study with well annotated epidemiologic, clinical, and outcome data, we observed some clinical and epidemiologic differences between HER2-low and HER2-negative patients, raising the possibility that HER2-low might be a unique biologic entity. Citation Format: Thaer Khoury, Rochelle Payne Ondracek, Song Yao, Lucas Mendocino, Warren Davis, Angela Omilian, Marilyn Kwan, Janise Roh, Lia D'Addario, Emily Valice, Daniel Fernandez, Isaac Ergas, Christine Ambrosone, Lawrence Kushi. Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways 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 PO5-25-10.

Abstract PO3-03-02: Effect of Surgery on Breast Cancer-Specific Mortality in Elderly Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer

Abstract Background: The number of elderly patients with breast cancer has been increasing in Japan. Although standard treatment including surgery is desirable if the expected life expectancy is sufficient, not all elderly patients with breast cancer are eligible for surgery due to frailty and comorbidities. Endocrine therapy (ET) alone is an alternative option if surgery is not considered adequate in patients with hormone receptor-positive breast cancer. We evaluated whether ET alone was associated with inferior overall and breast cancer-specific survival compared to standard treatment including surgery in elderly patients. Methods: This study included all patients aged 75 years and over who were diagnosed with non-metastatic primary invasive hormone receptor-positive, HER2-negative breast cancer and treated at Hiraka General Hospital from July 2006 to March 2022. Patients were divided as those who received ET alone (ET alone group) and those who received surgery with other therapies (Surgery group). Survival status as on March 31, 2023 and cause of death were determined. Overall survival and breast cancer-specific survival were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate analysis and multivariate Cox proportional hazards regression model including age, Eastern Cooperative Oncology Group performance status (PS) score, clinical stage, and treatment were used to identify survival-associated factors. Propensity score matching was used to reduce the effect of selection bias on treatment type during survival comparison of the groups. Results: The study cohort comprised 128 patients, including 33 and 95 patients in the ET alone group and Surgery group, respectively. The median ages were 84.6 and 80.4 years in the ET alone group and Surgery group, respectively (p < 0.05). Ten patients (30%) in the ET alone group had poor PS (3 or 4), and no patient in the Surgery group had poor PS (p < 0.01). Also, 24.2%, 54.5%, and 21.2% of the patients in the ET alone group and 48.4%, 43.2%, and 8.4% of the patients in the Surgery group had clinical stage I, II, and III disease at diagnosis, respectively (p < 0.05). Survival status was confirmed in all patients, and the cause of death was confirmed in 52 of the 53 patients who died (98%) during the study period, including 24 and 29 patients in the ET alone group and Surgery group, respectively. Breast cancer was the cause of death in 3 patients (13%) in the ET alone group and 5 patients (17%) in the Surgery group. By univariate analysis, overall survival was significantly better in the Surgery group than in the ET alone group (median, 12.5 vs. 4.1 years; p < 0.0001). Similarly, breast cancer-specific survival was better in the Surgery group than in the ET alone group (p < 0.05). By multivariate Cox proportional hazards regression analysis, age was associated with shorter overall survival time (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.00–1.15; p = 0.04) and surgery was associated with longer overall survival (HR 0.24, 95% CI 0.12–0.47; p < 0.001). Breast cancer-specific survival was associated with age (HR 1.18, 95% CI 1.03–1.36; p = 0.02) and clinical stage (HR 8.89, 95% CI 1.05–75.5; p < 0.05) but not with treatment (HR 0.66, 95% CI 0.73–5.85; p = 0.71). After propensity score matching, overall survival was significantly better in the Surgery group than in the ET alone group (HR 0.26, 95% CI 0.09–0.73; p = 0.01) whereas breast cancer-specific survival was not significantly different between the two groups (HR 0.82, 95% CI 0.08–8.27; p = 0.86). Conclusion: Even in elderly patients, surgery should be considered if sufficient life expectancy is expected. However, most of the deaths were not related to breast cancer in the present study cohort. Therefore, for elderly patients without sufficient life expectancy, endocrine therapy alone would be an appropriate option. Citation Format: Misako Yatsuyanagi, Tomoyuki Shimada, Yuko Takeishi, Yukiko Matsuzaka, Chika ohsawa. Effect of Surgery on Breast Cancer-Specific Mortality in Elderly Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer [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 PO3-03-02.

Abstract RF02-04: A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with metastatic HER2-positive breast cancer. (JCOG1607 HERB TEA study)

Abstract Background A combination of trastuzumab, pertuzumab, and docetaxel (HPD) is recommended as first-line treatment for patients with HER2-positive metastatic breast cancer. For older patients, it is difficult to maintain a relative dose intensity, which often impairs their quality of life. A new standard treatment option for older patients is required with less toxicity and non-inferior efficacy compared to HPD. Methods The eligibility criteria were as follows: age 65 years and older, HER2-positive metastatic breast cancer, no previous systemic treatment with chemotherapy and anti-HER2 targeted drugs, ECOG PS 0–2 for 65–74 years or 0–1 for 75 years or older, and adequate organ function. Treatment consisted of trastuzumab emtansine (T-DM1) 3.6 mg/kg every 3 weeks or HPD (trastuzumab 8 mg/kg, then 6 mg/kg, pertuzumab 840 mg, then 420 mg/body, and docetaxel 60 mg/m2, could be escalated to 75 mg/m2 if there were no unmanageable toxicity) every 3 weeks after a 1:1 ratio randomization. The trial was designed to achieve 70% power to confirm the non-inferiority of T-DM1 to HPD at a one-sided alpha of 5% with a non-inferiority margin of 1.35 in terms of the hazard ratio (HR) for overall survival (OS) as the primary endpoint. With a median OS of 30 months in both arms, 6.5 years of accrual, and 5 years of follow-up, the planned sample size was 250. Secondary endpoints were progression-free survival (PFS), response rate (RR), adverse events, cumulative breast cancer-specific mortality (BCSM), safety, and deterioration of activities of daily living. (Clinical Trial Information: UMIN000030783). Results In total, 148 patients were enrolled between January 2018 and March 2023. A total of 135 patients were assessed in the preplanned first interim analysis. The median patient age was 72 years (range 65-88) in the T-DM1 arm and 71 (65-84) in the HPD arm. The proportion of estrogen receptor-positive (10%) patients was well balanced between both arms (49.3 and 55.6%, respectively). Of these patients, 64.8% had stage IV disease and 35.2% had recurrent disease. T-DM1 was not non-inferior to HPD (HR 1.487; 99.9% CI, 0.288 to 7.678) in terms of OS. The median PFS was 9.8 months in the T-DM1 arm and 18.4 months in the HPD arm (HR 1.749; 95%CI, 1.124-2.723). Response rates were lower in the T-DM1 arm than that of the HPD arm (52.7% [95% CI, 38.8-66.4] and 76.8% [95% CI, 63.6-87.0], respectively) (p=0.099). BCSM was higher in the T-DM1 arm than that of the HPD arm (HR 1.617; 95% CI, 0.764-3.425). Grade 3 and higher neutropenia were less common in the T-DM1 arm than in the HPD arm (0 vs. 30.4%); however, thrombocytopenia was more common in the T-DM1 arm than in the HPD arm (16.9 vs. 0%). Grade 3 or more non-hematological adverse events were less common and lower in the T-DM1 arm (35.2%) than in the HPD arm (58.6%), including fatigue (5.6% vs. 22.9%), diarrhea (0% vs. 11.4%), appetite loss (8.5% vs. 11.4%), and febrile neutropenia (0% vs. 10.0%), which reduced the quality of life in older patients with HER2-positive metastatic breast cancer. Conclusion T-DM1 was not non-inferior to HPD in terms of OS. However, T-DM1 showed better tolerability in terms of frequency and severity of adverse events. HPD will continue to be the standard of care as the first-line treatment for older patients with HER2-positive metastatic breast cancer. Older patients with breast cancer have heterogeneous health conditions. A subset analysis according to age or geriatric assessment may identify the subpopulation of older patients with HER2-positive metastatic breast cancer for whom T-DM1 is an optional treatment. Citation Format: Akihiko Shimomura, Kenji Tamura, Keita Sasaki, Ryo Sadate, Akihiko Suto, Masataka Sawaki, Naohito Yamamoto, Tomoyuki Yoshiyama, Takako Hayashi, Eriko Tokunaga, Takashi Yamanaka, Chikako Shimizu, Tadahiko Shien, Hiroji Iwata. A phase III study comparing trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with metastatic HER2-positive breast cancer. (JCOG1607 HERB TEA 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 RF02-04.

Abstract PS13-08: Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and women ≥ 65 years account for almost half of BC related mortality. Life expectancy has increased in the US due to improvements in medical care, and therefore the number of older patients with a BC diagnosis is also expected to increase. The population of individuals ≥ 80 years in the US is growing and now comprises more than 9 million. Approximately 15% of BC are human epidermal growth factor receptor 2 amplified (HER2+). The combination of chemotherapy with trastuzumab +/- pertuzumab compared with trastuzumab alone has been shown to be cost-effective in patients 70 years and older but trastuzumab monotherapy could be considered as an option in certain patients. Nevertheless, there is limited guidelines on how to properly care for the geriatric population with HER2+ BC. Methods We conducted a retrospective analysis of data collected from the National Cancer Database (NCDB). NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Women ≥65 years with stage I, II and III HER2+ BC were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy or monoclonal antibodies (no-CT/mAbs), those who received chemotherapy in combination with monoclonal antibodies (CT/mAbs) and those who received monoclonal antibodies alone (mAbs). Using the Logrank P value, we explored the age cut off for which survival rates were not significantly different between treatment groups. Two comparisons were done: no-CT/mAbs vs CT/mAbs and CT/mAbs vs mAbs. The main outcome of this study was all-cause mortality. RESULTS: For the first comparison, a total of 9,924 HER2+ early-stage BC patients were included. Of these, 3,052 (30.8%) received no-CT/mAbs, while 6,872 (69.2%) received CT/mAbs. Kaplan Meier curves comparing mortality by treatment in the whole sample showed that those in the CT/mAbs group had significantly improved survival, compared to the no-CT/mAbs group (Logrank P < 0.001). The 1-year and 3-year survival rates were significantly higher in the CT/mAbs, compared to no-CT/mAbs. Cox proportional regression analysis showed that in the whole sample all-cause mortality was significantly lower among patients in the CT/mAbs group, compared to those in the no-CT/mAbs group (hazard ratio [HR], 0.48; CI: 0.41-0.57). However, the Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to No-CT/mAbs. For the second comparison, a total of 7,457 patients were included. Of these 6,872 (92.2%) receive CT/mAbs and 585 (7.8%) received mAbs. The 1-year and 3-year survival rates were significantly higher in the CT/mAbs compared to the mAbs. The Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to mAbs. Conclusion Chemotherapy in combination with HER2 directed monoclonal antibodies showed a survival benefit in elderly patients, irrespective of age, when compared to no-CT/mAb and mAb alone. These data highlight the importance of individualizing treatment recommendations and not forgoing standard therapy based merely on age. Limitations of the analysis include lack of available information on BC specific mortality. Also, the benefit that we identified could be secondary to selection bias. Additional studies are needed to improve the treatment in elderly patients with HER2+ BC. Table 1. Logrank P values for survival comparison between those who received CT/mAbs and No-CT/mAbs by age cut-off. Citation Format: Ana Sandoval-Leon, Yolcar Chamorro, Muni Rubens, Mukesh Roy, Lauren Carcas, Naomi Dempsey, Manmeet Ahluwalia, Reshma Mahtani. Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis [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 PS13-08.

Abstract PO1-09-05: Reversing Rural Disparity Through Increased Access to Breast Care Using Model of Academic-Community Collaboration

Abstract Background: Rural disparity in Breast Cancer (BC) often relates to poor geographic access. We are small county in rural North Carolina with historically poor outcomes, including more advanced stages of BC at presentation, higher mastectomy rates, and higher BC-specific mortality rates than elsewhere. Beginning in 2002 we increased access to care by construction of a 19-bed Critical Access Hospital. With a higher median age population (10 years older), and cancer as the number one cause of death (30% of all deaths), we began to increase access to services with focus on cancer. Two decades later, we still do not provide all aspects of care locally, but through a model of collaboration we have increased access to all aspects of cancer care. Breast Cancer is the most common, and this report details the reversal in disparity seen rurally based on our model of collaboration with both a regional community cancer program and academic cancer program. Methods: We partnered with academic and community cancer centers in nearby counties to increase access to imaging, cancer specialists, radiation therapy and chemotherapy services, and support services for breast care. When we could not provide these services locally, we helped navigate patients to these other facilities to improve access. We invited dedicated breast surgeon from community cancer program to attend clinic weekly in our area. We created virtual breast-specific tumor boards to discuss 100% of cases prospectively, with improved access to pathologists, geneticists, fellowship-trained imaging specialists, breast surgeons and other multi-disciplinary care members (reconstructive surgery, PT/OT, integrative medicine, GYN). We became cancer accredited with both COC and NAPBC. We compare metrics pre/post-improvements. Results: Baseline: 1. Mortality rates: (2002-2006) 5-year BC mortality rates in our region averaged 32.3/100,000 population which was in the top quartile for the state, 30% higher than the state average. 2. Stages at presentation: 47% of BC stages were early (stages 0/1) in our service region compared to 62% elsewhere (NCDB data). Stage IV represented 6% in our region versus 4% elsewhere. 2500 mammograms/year at hospital at baseline. 3. Surgery/Radiation Therapy: Mastectomy rates averaged >50% in region, with correspondingly lower breast conserving rates than elsewhere due to lack of access to breast surgeons and radiation therapy services locally. Closest RT facility 80 miles. 4. Distances to high quality breast care averaged 150 miles. Closest Academic/Community Cancer Program 2-hour drive (one way). Post Collaboration: 1. Mortality rates: (2015-2019), 5-year BC mortality rates in our region averaged 16.3/100,000 population which is in the lowest quartile, 20% lower than the state average. 2. Stages at presentation: 74% of BC stages are early (stages 0/I) in our region versus 68% elsewhere. Stage IV now below parity with 3% locally versus 4% nationally. More than 5100 mammograms/year done currently at local hospital. 3. Surgery/Radiation Therapy: Mastectomy rates average 21%, with partial mastectomy rates of 79% in our area versus 70% elsewhere (NAPBC data) with RT services available locally. 4. Distances to quality breast care average 20 miles, and we are nationally accredited program in breast care as a critical access hospital. Analytic case load is now triple baseline numbers. Conclusion: We reversed the trend in rural disparity in breast cancer outcomes through model of collaboration. We increased screening rates locally, doubling the number of screening/diagnostic exams, increased the percentage of early stage at diagnosis, halved our mastectomy rates, and reduced BC-specific mortality 50% relative to baseline (and now 20% lower than state). We are now at parity with most BC-specific quality metrics reflecting a huge shift in rural disparity, which could only be achieved rurally through collaboration. Reversing Rural Disparity Through Increased Access to Breast Care Using Model of Academic-Community Collaboration This table depicts the changes in our region over time, which have brought us to parity with Breast Care nationally. Citation Format: Charles Shelton, Antonio Ruiz. Reversing Rural Disparity Through Increased Access to Breast Care Using Model of Academic-Community Collaboration [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 PO1-09-05.

Abstract PS13-07: Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and is the leading cause of new cancer diagnosis among women in the United States. Although the median age of diagnosis is 63 years (yrs.), over a third of patients diagnosed, and about half of BC mortality in Western societies are in patients over 70 yrs. old. Overall, outcomes for early-stage BC have improved. Despite the lower incidence of triple negative BC (TNBC) (12%-15%) the 5-year survival is 8% to 16% lower than in hormone receptor-positive BC. With the improved life expectancy in the US and the increased incidence of BC as patients age, it is of vital importance to know how to treat BC in the elderly. Unfortunately, optimal management of BC among the elderly has not been adequately studied due to underrepresentation in clinical trials. Furthermore, there is limited information of the potential toxicity and real benefit of chemotherapy in older patients. Methods This is a retrospective analysis of data collected from the National Cancer Database (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, during the years 2004 to 2019. All women ≥65yrs with early stage TNBC (stages I-III) were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy (No-CT), those who received chemotherapy (CT), and those who received chemotherapy and immunotherapy (CTIO). After adjusting for multiple variables including race, insurance, Charleson-Deyo score, stage at diagnosis, and receipt of loco-regional therapy, using the log rank P value, the age cutoff over which the survival rates were not significantly different between two treatment groups (No-CT and CT/CTIO) was identified. The main outcome of this study was all-cause mortality Results A total of 11,416 women with TNBC were included in the analysis. Of these, 4105 (36.0%) received No-CT, while 7311 (64.0%) received CT/CTIO. Log rank P values showed that above 81 years, there was no survival benefit between No-CT and CT/CTIO. A further analysis categorized patients into two groups – those between 65-80yrs and those ≥81 yrs. old. Cox proportional regression analysis showed that among patients between 65-80 yrs. all-cause mortality was significantly lower among patients in the CT/CTIO group compared to those in the No-CT group (hazard ratio [HR], 0.52; CI: 0.45-0.60). However, among patients ≥81yrs old, there was no significant difference in all-cause mortality between the treatment groups (hazard ratio [HR], 0.84; CI: 0.67-1.05). Conclusions: Among patients who were >81yrs old with early-stage TNBC, those who received treatment with CT/CTIO did not have an overall survival benefit as compared to those who received No-CT. Limitations of this study includes the small number of patients >81yr old who received chemotherapy which could explain why we were not able to identify a statistically significant benefit of CT/CTIO. Another limitation is that we were not able to assess breast cancer specific mortality. However, this analysis highlights the importance of individualizing treatment recommendations in older patients, who may not garner the same benefit of treatment as younger patients. Additional studies are required to clarify contributing factors and to help optimize the management of geriatric patients with TNBC. Table 1. Patient characteristics based on treatment. Citation Format: Yolcar Chamorro, Muni Rubens, Mukesh Roy, Naomi Dempsey, Reshma Mahtani, Manmeet Ahluwalia, Lauren Carcas, Ana Sandoval-Leon. Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis [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 PS13-07.

Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases

Abstract Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (>50 years old, 87.1% vs 73.6%, p < 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p < 0.001; grade Ⅲ 37.8% vs 28.3%, p < 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p < 0.001, stage Ⅲ 17.5% vs 10.5%, p < 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p < 0.001). Patients were divided into 0-5 year and >5 year cohorts based on whether they had a BCSS event within 5 years. In the >5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients. Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [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 PO1-08-05.

Abstract 161: Myocardial Infarction Accelerates Melanoma Tumor Progression

Adult survivors of cancer are at increased risk of cardiovascular disease (CVD). Indeed, while CVD emerges as the second leading cause of death in recovering cancer patients, cross-disease communication remains poorly understood. We previously demonstrated that myocardial infarction (MI) accelerates breast cancer tumor growth and cancer-specific mortality in mice and humans. However, whether MI alters tumor growth of other cancer types and impacts metastasis is not known. To assess these gaps, we examined the effect of acute MI, induced by ligation of the left anterior descending (LAD) coronary artery, in syngeneic C57BL6 mouse models of primary and metastatic melanoma. Compared to sham surgery, LAD ligation resulted in a two-fold increase in tumor growth in both the B16 and YUMM melanoma models. Notably, tumor burden significantly correlated with the size of the infarct, suggesting a direct relationship between injury signal activation and disease progression. Analysis of the intratumoral immune cell landscape by flow cytometry revealed an enrichment of immunosuppressive CD4 + FoxP3 + T regulatory cells after MI, and systemic depletion of FoxP3 + cells attenuated MI-induced tumor growth. Finally, histological analysis and magnetic resonance imaging revealed an increase in the number and size of metastatic foci in the liver after MI compared to sham. Our data suggest that MI dampens antitumor immunity and reorganizes the tumor microenvironment to exacerbate tumor progression via infiltration of immunosuppressive FoxP3 + T cells. Collectively, these findings of deleterious cross-disease communication underscore the importance of implementing strategies that mitigate CVD risk in cancer patients.

Red Blood Cell Polyunsaturated Fatty Acids and Mortality Following Breast Cancer.

Intake of polyunsaturated fatty acids (PUFA) may affect mortality following breast cancer; however, epidemiological studies have relied on the self-reported assessment of PUFA intake. Herein, we examined the associations between red blood cell (RBC) PUFAs and mortality. This nested case-control study included 1,104 women from the Women's Healthy Eating and Living study, a multistate randomized controlled trial. Cases (n = 290) comprised women who died from 1995 to 2006. Matched controls (n = 814) comprised women who were alive at the end of follow-up. PUFAs were measured in baseline RBC samples and included four ω-3 and seven ω-6 PUFAs. We examined each PUFA individually and principal components factor analysis (PCFA)-derived scores in association with all-cause mortality (ACM) and breast cancer-specific mortality (BCM) using conditional logistic regression to estimate ORs and 95% confidence intervals (CIs). In fully adjusted models, ACM ORs were elevated among women with PUFAs above the median (>median) versus at the median or below (≤median) for α-linolenic acid (ALA; OR = 1.63, 95% CI, 1.18-2.24) and linolenic acid (LA; OR = 1.56, 95% CI, 1.16-2.09). BCM ORs were elevated for ALA (OR = 1.83, 95% CI, 1.27-2.63), LA (OR = 1.70, 95% CI, 1.23-2.37), and γ-linolenic acid (GLA; OR = 1.50, 95% CI, 1.04-2.16). PCFA Factor 1 (arachidonic acid-adrenic acid-docosapentaenoic acid) scores above the median (vs. ≤median) were associated with lower odds of ACM (OR = 0.71, 95% CI, 0.52-0.97) and BCM (OR = 0.69, 95% CI, 0.49-0.97). PCFA Factor 4 (ALA/GLA) scores above the median (vs. ≤median) were associated with increased odds of BCM (OR = 1.47, 95% CI, 1.04-2.09). RBC ALA, LA, and GLA may be prognostic indicators among breast cancer survivors. These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors.

Ethnic disparities in breast cancer patterns in Brazil: examining findings from population-based registries.

To investigate breast cancer (BC) incidence and mortality rates among specific racial groups in Brazil. BC incidence was evaluated from 2010 to 2015, using Brazilian Population-Based Cancer Registries, incorporating crude ratios and annual average percentage change (AAPC). Clinical and sociodemographic data from 2000 to 2019 were obtained from Hospital-Based Cancer Registries. Mortality data from 2000 to 2020 were sourced from the National Mortality Information System, comparing White women and Black women. Across 13 Brazilian registries, 70,896 new BC cases were reported from 2010 to 2015. The median BC incidence rate was notably higher for White women (101.3 per 100,000) compared to Black women (59.7 per 100,000). In the general population, non-significant decrease in annual BC incidence was observed (AAPC = - 1.2; p = 0.474). Black women were more likely to live in underdeveloped areas, have lower education levels, live without a partner, and have higher alcohol consumption as compared to White women. A higher proportion of Black women received advanced-stage diagnoses (60.1% versus 50.6%, p < 0.001). BC-related mortality analysis showed 271,002 recorded deaths, with significant increase in BC-specific mortality rates in both racial groups. Black women displayed an AAPC of 2.3% (p < 0.001), while White women demonstrated a moderately elevated AAPC of 0.6% (p < 0.001). This study underscores the need for targeted policies to address disparities in access to early detection and proper treatment, particularly for Black women in underprivileged regions, aiming to improve the survival rates of Brazilian women grappling with BC.

Higher disease burden and lower utilization in Mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. A total of 34878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11-4 776.42) vs. $2227.35 (686.65-5929.59), P <0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15-33.89) vs. 27.78 (95% CI: 26.77-28.83) per 1000, P =0.036] and BC-specific mortality [18.78 (95% CI: 16.64-21.13) vs. 15.22 (95% CI: 14.47-16.00) per 1000, P =0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09-1.34); P <0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14-1.49); P <0.001]. The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Abstract SY34-02: Age-related and organ-specific host mosaicism as a driver of dormant cancer cell awakening

Abstract Most BC patients succumb to metastatic relapse years to decades following primary tumor resection due to reactivation of dormant disseminated cancer cells (DCCs). Improved BC patient survival has led to metastatic relapse manifesting in an older patient population. This population carries somatic mosaicism in many organs including bone marrow. Age-specific somatic mutations (e.g., DNMT3A, ASXL1, TET2) in hematopoietic stem and progenitor cells (HSPCs) results in CH, which is associated with increased inflammatory myeloid cells and risk of leukemia and intriguingly with BC-specific mortality. In this presentation I will discuss new data from a team effort to test the hypothesis that CH myeloid cells could shape target organs niches that harbor dormant DCCs to be pro-metastatic. This hypothesis has been explored in clinical trials data where the presence of CH in ER+ and HER2+ metastatic BC patient cohorts (MSK-IMPACT) was associated with the response to first line CDK4/6i/endocrine therapy or taxol/herceptin/pertuzumab, respectively. We also tested whether CH can accelerate dormant DCC awakening in a murine model of CH carrying mutations in DNMT3A (KO or point mutation) and HER2+ mammary cancer. We propose our work may provide unprecedented insights into how a traceable age-related-mosaicism in the bone marrow (CH) may shape distant organs to be drive metastatic relapse. Citation Format: Julio A. Aguirre-Ghiso, Michael Papanicolaou, Pablo Sánchez Vela, Julie Yang, Anton Safonov, Jacqueline Tao, Sebastia Franch Exposito, Vera Tiedje, Erica Dalla, Luis E. Valencia Salazar, Nicole Barth, Merve Sahin, Kevin Chen, Jinae Park, Matthew Wereski, Aishwarya Krishnan, Anthony Martinez Benitez, Ryan Ptashkin, Mark E. Robson, Elisa de Stanchina, Lior Z. Braunstein, Ahmet Zehir, Elizabeth Comen, Larry Norton, Michael Berger, Richard Koche, Pedram Razavi, Ross Levine. Age-related and organ-specific host mosaicism as a driver of dormant cancer cell awakening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr SY34-02.

356 The Effect of Regional Anesthesia on Breast Cancer Recurrence

OBJECTIVES/GOALS: To determine the impact of regional anesthesia (RA) on rates of breast cancer recurrence, breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use among patients who received regional anesthesia during primary breast cancer surgery. METHODS/STUDY POPULATION: Study population: Patients who underwent primary breast cancer surgery at Emory University and among a national patient cohort. Methods: This is a retrospective analysis of patients who underwent primary breast cancer surgery. Invasive breast cancer specific survival &amp; breast cancer-specific survival will be estimated using Kaplan-Meier method and compared among patient groups. Cox proportional hazards will be utilized to estimate the unadjusted &amp; adjusted risk of breast cancer recurrence and breast cancer-specific mortality between the two groups. RESULTS/ANTICIPATED RESULTS: We will present on our work comparing rates of breast cancer recurrence among patients who received regional anesthesia compared to patients who did not. DISCUSSION/SIGNIFICANCE: This study aims to establish the effect of regional anesthesia on breast cancer recurrence,breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use following primary breast cancer surgery.