Risk Of Breast Cancer-specific Mortality Research Articles

Racial disparities in health insurance, triple-negative breast cancer diagnosis, tumor stage, treatment and survival in a large nationwide SEER cohort in the United States.

It remains unclear whether there are racial disparities in mortality between women of different races who have the same subtype of breast cancer when tumor stage and size and treatment are controlled for. The present study aimed to investigate whether racial disparities in mortality existed between women of different races who had the same subtype of breast cancer when health insurance, tumor stage and size and treatment were controlled for in a large cohort of women with breast cancer in the United States. This study identified 399,564 women who were diagnosed with incident breast cancer at age ≥20 years between 2010 and 2016 in 17 Surveillance, Epidemiology and End Results (SEER) registries, including 277,319 non-Hispanic white (white), 44,149 non-Hispanic black (black), 34,141 non-Hispanic Asian or Pacific Islander (Asian) and 43,955 Hispanic women. White and Asian women exhibited a lower proportion of triple-negative breast cancer (9.8 and 9.1% respectively) than black (20.8%) and Hispanic women (12.6%). Black women had a significantly higher risk of all-cause mortality compared with white women in only those with triple-negative breast cancer (hazard ratio: 1.39, 95% CI: 1.29-1.51) and those with hormone receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive breast cancer (1.53, 1.48-1.58) after adjusting for confounders. In those with hormone receptor-positive breast cancer, regardless of HER2 receptor status, the risk of all-cause mortality was not statistically different between black and white women, while the risk of breast cancer-specific mortality was significantly higher in all subtypes of breast cancer among black women. There were racial disparities in the presentation of triple-negative breast cancer and in all-cause and breast cancer specific mortality following stratification by triple-negative status and adjusting for tumor stage, size, grade and treatment.

Abstract P2-10-01: Estimating risk of breast cancer-specific mortality (BCSM) and non-BCSM in patients with triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is associated with high risk of distant recurrence and death. At present, our ability to estimate risk of death from causes other than breast cancer is limited. Particularly among elderly patients (pts), who have been historically underrepresented in clinical trials. In pts with TNBC, assessing both risks is important for our treatment recommendations. The aim of this study was to evaluate risk of BCSM and non-BCSM in TNBC by patient (pt) and tumor characteristics. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified women diagnosed with non-metastatic invasive TNBC between 2010-2016. Fine and Gray regression was used to evaluate the association of BCSM with pre-specified variables including pt age, tumor size (T), nodal status (N), and tumor grade, while considering deaths from other causes as competing events. We then estimated cumulative risk of BCSM, non-BCSM and all-cause mortality within subgroups defined by baseline clinical and pathologic variables. We conducted a subset analysis of N0 pts older than 50 years, given that we anticipated this subgroup would have the most clinically useful balance between BCSM and non-BCSM. Results: We included 37,293 pts. Age distribution was: 27.1% <50 years, 51.3% 50-69 years, 15.0% 70-79 years, and 6.6% ≥80 years. Among all pts, 42.4% presented with T2 tumors and 69.5% had N0 disease. In adjusted Fine and Gray regression, risks of BCSM were higher for pts aged >80 years vs 50-69 years (Hazard ratio [HR] 1.62; 95% CI, [1.45 - 1.80]), T4 vs T1a (HR 8.51; 95% CI, [6.20 - 11.68]), N3 vs N0 (HR 6.31; 95% CI, [5.70 - 7.00]) and grade III/IV vs grade I (HR 2.10; 95% CI, [1.44 - 3.07]). The cumulative risk of BCSM in year 0-7 was 10.7% for N0, 27.9% for N1, 46.4% for N2 and 64.0% for N3. In contrast, the cumulative risk of non-BCSM over the same period ranged from 7.5% in N1 to 8.7% in N2. The table shows risks of BCSM, non-BCSM and all-cause mortality among pts with N0 disease by age at diagnosis and tumor size. Pts 50-69 years had an increasing cumulative risk of BCSM by tumor size up to 13.0% in those with T2 tumors, while the risk of non-BCSM ranged from 4.8% to 5.9%. Pts aged 70-79 years with T1a/b, N0 tumors had risks of BCSM that were approximately 60% lower than the risks of non-BCSM. In pts aged ≥80 years, the risk of non-BCSM increased and is significantly higher than BCSM in patients with T1b-T2 disease. Conclusions: The risk of BCSM in TNBC depends on traditional clinicopathologic factors and is in general, much higher than the risk of non-BCSM. However, the high risk of non-BCSM among older pts is substantial which needs to be taken into consideration when making treatment recommendations. An interactive tool to estimate risks of BCSM, non-BCSM and all-cause mortality for TNBC will be presented at the meeting. BCSMnon-BCSMAll-cause mortalityCumulative risk (%) and 95% CICumulative risk (%) and 95% CICumulative risk (%) and 95% CIyears 0-7years 0-7years 0-7Tumor size among age 50-69, N0 onlyT1a2.6 (1.0 - 4.3)5.9 (3.2 - 8.6)8.5 (5.3 - 11.6)T1b3.9 (2.8 - 5.0)4.8 (3.3 - 6.3)8.7 (6.9 - 10.5)T1c8.1 (6.9 - 9.4)4.8 (3.9 - 5.8)13.0 (11.4 - 14.5)T213.0 (11.6 - 14.4)5.5 (4.4 - 6.5)18.5 (16.8 - 20.2)Tumor size among age 70-79, N0 onlyT1a6.1 (0 - 12.7)13.9 (7.0 - 20.9)20.0 (10.2 - 28.7)T1b5.3 (3.0 - 7.7)13.3 (9.0 - 17.7)18.6 (13.7 - 23.3)T1c11.0 (8.7 - 13.4)14.3 (11.4 - 17.2)25.3 (21.7 - 28.8)T221.0 (17.4 - 24.6)17.4 (13.4 - 21.5)38.5 (33.3 - 43.2)Tumor size among age ≥80, N0 onlyT1a6.6 (0 - 19.7)27.0 (11.0 - 43.1)33.7 (11.8 - 50.1)T1b7.1 (2.1 - 12.2)33.2 (23.2 - 43.2)40.3 (28.9 - 49.9)T1c8.4 (5.2 - 11.6)32.7 (26.4 - 39.0)41.1 (34.1 - 47.3)T222.7 (18.1 - 27.3)41.6 (34.2 - 49.1)64.3 (56.0 - 71.1) Citation Format: Jose P Leone, Noah Graham, Julieta Leone, Sara M Tolaney, Bernardo A Leone, Rachel A Freedman, Michael J Hassett, Carlos T Vallejo, Eric P Winer, Nancy U Lin, Nabihah Tayob. Estimating risk of breast cancer-specific mortality (BCSM) and non-BCSM in patients with triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-01.

Abstract P4-02-13: Social isolation promotes mammary cancer recurrence, increases IL6/JAK/STAT3 signaling and causes mitochondrial dysfunction in tamoxifen treated rats, and a traditional herbal mixture reverses all these changes

Abstract BACKGROUND: Social isolation is associated with increased risk and mortality from many diseases, such as breast cancer. Socially isolated breast cancer survivors have a 43% higher risk of recurrence and a 64% higher risk of breast cancer-specific mortality than socially integrated survivors. Since Covid-19 has dramatically increased the incidence of social isolation, it is important to determine if social isolation affects the response to endocrine therapy and/or recurrence after the therapy is completed. Further, since previous studies indicate that social isolation increases circulating inflammatory cytokines, we investigated if an anti-inflammatory herbal mixture Jaeumkanghwa-tang (JEKHT) prevents the adverse effects of social isolation on breast cancer mortality. METHODS: Estrogen receptor positive mammary tumors were initiated with 7,12-dimethylbenz[a]anthracene. When a rat developed a palpable mammary tumor, it was either socially isolated (SI) by housing it singly or a rat was allowed to remain group-housed (GH). Tamoxifen (340ppm via diet) or tamoxifen + JEKHT (500ppm via drinking water) started when the first mammary tumor was detected. Tamoxifen administration ended when a complete response to this therapy had lasted for 9 weeks (corresponds to 5 years in women). Rats which received JEKHT during tamoxifen therapy continued to take it also after tamoxifen therapy ended. RESULTS: During tamoxifen therapy, social isolation non-significantly reduced the rate of complete responses to 21%, from 31% in GH group (p>0.05). After the therapy was completed, SI significantly increased local mammary tumor recurrence (p<0.001; 45% GH vs 75% SI). RNAseq analysis was performed in the mammary glands, since only tamoxifen resistant or recurring mammary tumors were available for analysis. Gene set enrichment analysis (GSEA) of transcriptome showed that the increased recurrence risk in socially isolated rats was associated with an enrichment of IL6/JAK/STAT3 signaling: this result was confirmed in the tumors. In addition, oxidative phosphorylation (OXPHOS) pathway was suppressed: the suppressed genes included those involved in mitochondrial pyruvate transport and conversion of pyruvate to acetyl CoA as well as genes in the TCA cycle and mediating electron transport in mitochondrial complexes I-IV. Despite the reduction in pyruvate transporting and converting genes, lactate levels or lactate dehydrogenase activity were not increased in socially isolated rats, indicating no changes in Warburg effect. Social isolation also increased the expression of inflammatory receptor for advanced glycation end-products (RAGE) (p≤0.05). Consumption of an anti-inflammatory JEKHT inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling and prevented the increased risk of mammary cancer recurrence in socially isolated animals. The percentage of recurrences in the SI rats dropped from 75% without JEKHT to 22% with JEKHT (p<0.001). CONCLUSION: Breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following endocrine therapy using tools that inhibit IL6/JAK/STAT3 inflammatory cytokine signaling and correct disrupted OXPHOS and mitochondrial dysfunction. Citation Format: Fabia Andrade, Lu Jin, Robert Clarke, Imani Wood, MaryAnn Dutton, Chezaray Anjorin, Grace Rubin, Audrey Gao, Surojeet Sengupta, Kevin FitzGerald, Leena Hilakivi-Clarke. Social isolation promotes mammary cancer recurrence, increases IL6/JAK/STAT3 signaling and causes mitochondrial dysfunction in tamoxifen treated rats, and a traditional herbal mixture reverses all these changes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-02-13.

Age and Racial Disparities in the Utilization of Anticancer, Antihypertension, and Anti-diabetes Therapies, and in Mortality in a Large Population-Based Cohort of Older Women with Breast Cancer.

This study examined the receipt of therapies for cancer, hypertension, and diabetes in association with age and racial disparities in mortality among women with breast cancer. This study identified 92,829 women diagnosed with breast cancer at age ≥ 65years in 2007-2015 with follow-up to 2016 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. There were substantial age and racial disparities in the prevalence of hypertension and diabetes, which was higher in women ≥ 75 (86.3% and 32.0%) than younger women 65-74 (72.8% and 29.3%), and the highest in Black women (91.1% and 49.1%), followed by Asian women (80.2% and 40.5%), and White women (77.6 and 27.8%). Black women were significantly less likely to receive chemotherapy (odds ratio: 0.70, 95% CI: 0.64-0.75), radiation therapy (0.87, 0.83-0.92), and hormone therapy (0.80, 0.76-0.85), but significantly more likely to receive antihypertensive (1.26, 1.19-1.33) and antidiabetic (1.19, 1.10-1.28) drugs than White women, after adjusting for sociodemographic and tumor factors. As compared to White women, Black women had a significantly higher risk of all-cause mortality (1.46, 1.41-1.52), but it became insignificant after adjusting for treatment factors (1.01, 0.97-1.06), whereas the adjusted risk of breast cancer-specific mortality remained significantly higher (1.08, 1.01-1.15) in Black women; Asian and other ethnic women had a significantly lower risk of all-cause and breast cancer-specific mortality. There were substantial age and racial disparities in the prevalence of hypertension and diabetes and in the receipt of medications. Black women did not have a significantly higher risk of all-cause mortality but had a significantly higher risk of breast cancer-specific mortality as compared to White women.

Racial/ethnic disparities in risk of breast cancer mortality by molecular subtype and stage at diagnosis

Previous research has found significant survival disparities between Black and White women among select stages and subtypes of breast cancer, however other racial/ethnic groups have been less well-studied. This study expands on previous research, examining differences in breast cancer-specific mortality across multiple racial and ethnic groups. Women diagnosed with a first primary invasive breast cancer between 2010 and 2016 who were 20-85years of age at diagnosis were identified from 18 Surveillance, Epidemiology, and End Results (SEER) registries. Subtypes were defined by joint hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Cox proportional hazards models for each stage and subtype were fit, with non-Hispanic white women as the reference group. Effect modification by age at diagnosis (< 50, ≥ 50) was found and thus analyses were age-stratified. After multivariable adjustment, younger Black women had greater risks of breast cancer-specific death for all stages of HR+/HER2-, and certain stages of HR+/HER2+ , TN, and HR-/HER2 + breast cancer. Asian/Pacific Islander women generally had a lower hazard of breast cancer-specific death. Older Hispanic White women had a lower hazard of breast cancer-specific death for stages I-III HR + /HER2- and stage II TN breast cancer. These findings demonstrate that different racial/ethnic groups experience different risks of breast cancer-specific mortality by stage and subtype. Efforts to address survival disparities should place additional focus on young Black women, as they experience meaningful disparities in breast cancer-specific mortality.

Antihypertensive medications and risks of recurrence and mortality in luminal, triple-negative, and HER2-overexpressing breast cancer.

Antihypertensives are commonly prescribed medications and their effect on breast cancer recurrence and mortality is not clear, particularly among specific molecular subtypes of breast cancer: luminal, triple-negative (TN), and HER2-overexpressing (H2E). A population-based prospective cohort study of women aged 20-69 diagnosed with a first primary invasive breast cancer between 2004 and 2015 was conducted in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality associated with hypertension and antihypertensives. In this sample of 2,383 luminal, 1,559 TN, and 615 H2E breast cancer patients, overall median age was 52 (interquartile range, 44-60). Hypertension and current use of antihypertensives were associated with increased risks of all-cause mortality in each subtype. Current use of angiotensin-converting enzyme inhibitors was associated with increased risks of both recurrence and breast cancer-specific mortality among luminal patients (HR: 2.5; 95% CI: 1.5, 4.3 and HR: 1.9; 95% CI: 1.2, 3.0, respectively). Among H2E patients, current use of calcium channel blockers was associated with an increased risk of breast cancer-specific mortality (HR: 1.8; 95% CI: 0.6, 5.4). Our findings suggest that some antihypertensive medications may be associated with adverse breast cancer outcomes among women with certain molecular subtypes. Additional studies are needed to confirm these findings.

Abstract 789: Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative

Abstract INTRODUCTION: Benign breast disease (BBD) describes a heterogeneous group of premalignant lesions associated with an increased risk of breast cancer development, especially in those with proliferative BBD with atypia. Whether BBD is associated with higher all-cause mortality is unsettled. Therefore, we examined the association between incident BBD, BBD histotypes and all-cause and breast cancer-specific mortality among WHI participants. METHODS: Included were 68,132 postmenopausal women enrolled in the WHI clinical trials from 1993-1998 at 40 US clinical centres, followed up through March 2019. In these trials, serial mammography was mandated and compliance was high. Cases were participants in the BBD ancillary study (AS)130 with incident BBD confirmed by central pathology review. The comparison group included all other clinical trial participants (intervention and control groups). Cox proportional hazard regression models, stratified by baseline age, clinical trial arms and WHI extension study participation, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality in association with BBD. Analyses were adjusted for age, race/ethnicity, education, income, smoking, BMI, waist circumference, energy intake, alcohol, physical activity, reproductive factors, family history of breast cancer, Gail model score, history of menopausal hormone therapy (MHT) use and history of comorbidities. RESULTS: Compared to women without incident BBD (n=43,439), women with incident BBD (n=3,467) were younger (p&amp;lt;0.001), more likely to have a higher education level (p=0.003), higher income (p&amp;lt;0.001), lower BMI (p=0.003) and waist circumference (p=0.002), a Gail risk score of &amp;gt;1.75 (p&amp;lt;0.001), a family history of breast cancer (p&amp;lt;0.001) and used MHT (p&amp;lt;0.001). There were 737 deaths among the BBD case group and 8,949 deaths among the non-case group. In adjusted analyses, no association was observed between incident BBD and all-cause mortality (HR:0.92, 95%CI: 0.83, 1.01). In adjusted analyses stratified by BBD, compared to women without BBD, no association for all-cause mortality was observed for women with non-proliferative BBD (n=374; HR:0.96; 95%CI: 0.84, 1.09), proliferative BBD without atypia (n=309; HR:0.91, 95%CI: 0.79, 1.05) or proliferative BBD with atypia (n=54; HR:0.72, 95% CI: 0.51, 1.03). In secondary analyses, compared to women without incident BBD, women with incident BBD had a statistically significantly higher breast cancer-specific mortality both for BBD overall and for each BBD histotype. CONCLUSIONS: In postmenopausal women, while a BBD diagnosis was associated with a statistically significant higher risk of breast cancer-specific mortality, irrespective of histotype, a BBD diagnosis was not associated with higher all-cause mortality. Citation Format: Maeve Mullooly, Kathy Pan, Sowmya Vasan, Gretchen L. Gierach, Dorothy S. Lane, Aladdin H. Shadyab, Juhua Luo, Lihong Qi, Kathleen E. Bennett, Thomas E. Rohan, Rowan Chlebowski. Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 789.

Types of carbohydrate intake and breast cancer survival.

To investigate the associations of different types of carbohydrate intake after breast cancer diagnosis with breast cancer-specific and all-cause mortality. We prospectively assessed post-diagnostic intake of total sugar, added sugar, and natural sugar as well as carbohydrate from different sources, among 8932 women with stage I-III breast cancer that were identified in the Nurses' Health Study from 1980 to 2010 and Nurses' Health Study II from 1991 to 2011. Participants completed a validated food frequency questionnaire every four years after diagnosis and were followed up for death. We prospectively documented 1071 deaths due to breast cancer and 2532 all-cause deaths, over a mean of 11.5years of follow-up. After adjustment for confounding variables, greater post-diagnostic total sugar intake was suggestively associated with greater risk of breast cancer-specific mortality [hazard ratio (HR)Q5vsQ1 = 1.16, 95%confidence interval (CI )= 0.95-1.41; Ptrend = 0.02] and significantly associated with greater risk of all-cause mortality (HRQ5vsQ1 = 1.23, 95% CI = 1.08-1.41; Ptrend = 0.0001). Greater post-diagnostic added sugar intake was significantly associated with greater risk of all-cause mortality (HRQ5vsQ1 = 1.20, 95%CI = 1.06-1.36; Ptrend = 0.001). Post-diagnostic natural sugar (occurring in foods and not added as an ingredient) intake was not associated with mortality risk. Greater post-diagnostic fructose intake was significantly associated with greater risk of breast cancer-specific mortality (HRQ5vsQ1 = 1.34, 95%CI = 1.10-1.64; Ptrend = 0.005) and all-cause mortality (HRQ5vsQ1 = 1.16, 95% CI = 1.02-1.32; Ptrend = 0.01). High post-diagnostic intake of sucrose was associated with higher risk of breast cancer-specific and all-cause mortality. Increased post-diagnostic intake of carbohydrate from fruit juice was significantly associated with higher risk of breast cancer-specific and all-cause mortality and carbohydrate from vegetables was significantly associated with lower risk of all-cause mortality. High post-diagnostic intake of carbohydrate from potatoes was suggestively associated with higher risk of breast cancer-specific mortality and carbohydrate from refined grains was suggestively associated with higher risk of all-cause mortality. We found that higher total sugar intake, especially added sugar, sucrose, and fructose, as well as carbohydrate from fruit juice after a breast cancer diagnosis were associated with poorer prognosis. High post-diagnostic intake of carbohydrate from vegetables was associated with reduced risk of mortality.

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis.

Background: The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial. Objective: To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis. Methods: This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed. Results: This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09–1.32; CCBs: RR = 1.06, 95% CI 1.03–1.08; diuretics: RR = 1.06, 95% CI 1.01–1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01–1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68–0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04–1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer. Conclusion: Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.

Increased risk of breast cancer-specific mortality among cancer survivors who developed breast cancer as a second malignancy

BackgroundCancer survivors who develop breast cancer as a second malignancy (BCa-2) are common. Yet, little is known about the prognosis of BCa-2 compared to first primary breast cancer (BCa-1).MethodsUsing the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 883,881 patients with BCa-1 and 36,313 patients with BCa-2 during 1990–2015. Compared with patients with BCa-1, we calculated hazard ratios (HRs) of breast cancer-specific mortality among patients with BCa-2, using multivariable Cox regression.ResultsDuring the follow-up (median 5.5 years), 114,964 and 3829 breast cancer-specific deaths were identified among BCa-1 and BCa-2 patients, respectively. Patients with BCa-2 had more favorable tumor characteristics and received less intensive treatment e.g., surgery and chemo−/radio-therapy, compared to patients with BCa-1. When adjusting for demographic factors, patients with BCa-2 were at similar risk of breast cancer-specific mortality (HR 1.00, 95% CI 0.97–1.03) compared to patients with BCa-1. However, when additionally controlling for tumor characteristics and treatment modes, BCa-2 patients were at an increased risk of breast cancer-specific mortality (HR 1.11, 95% CI 1.08–1.15). The risk elevation was particularly greater when the first malignancy was lung, bladder, ovarian or blood malignancy (HRs 1.16–1.85), or when the first malignancy was treated with chemotherapy and radiotherapy (HR 1.44, 95% CI 1.28–1.63).ConclusionsOverall, patients with BCa-2 have worse breast cancer-specific survival, compared with their BCa-1 counterparts, although the risk elevation is mild. High-risk subgroups based on first malignancy’s characteristics may be considered for active clinical management.

Factors associated with late risks of breast cancer-specific mortality in the SEER registry

PurposeMost reports describing the risk of late relapse in breast cancer (BC) have been based on selected patients enrolled into clinical trials. We examined population-based long-term risks of BC-specific mortality (BCSM), the risks of BCSM conditional on having survived 5 years, and factors associated with late BCSM.MethodsUsing SEER, we identified women diagnosed with BC (T1-T2, N0-N2, M0) between 1990 and 2005 with known hormone receptor (HR) status. Kaplan–Meier analyses determined cumulative risks of BCSM. We performed Fine and Gray regression stratified by HR status.ResultsWe included 202,080 patients (median follow-up of 14.17 years). Of all BC deaths, the proportion that occurred after 5 years was 65% for HR-positive vs 28% for HR-negative (p < 0.001) BC. In HR-positive BC, the cumulative risks of BCSM during years 5–20 were 9.9%, 21.9%, and 38% for N0, N1, and N2 disease. For HR-negative BC, the risks were 7.9%, 12.2%, and 19.9%, respectively. For T1a/b, N0, HR-positive BC, the risk of BCSM was 6 times lower than the risk of non-BCSM. In N2, HR-positive BC, the risk of BCSM was 43% higher than the risk of non-BCSM. In adjusted Fine and Gray models stratified by HR status, the risks of BCSM conditional on having survived 5 years for both HR-positive and HR-negative depended on T-N status, age, and year of diagnosis. In HR-positive, the risks also depended on race and grade.ConclusionThe risks of BCSM beyond 5 years, although different, remain important for both HR-positive and HR-negative BC. Strategies to prevent early and late recurrences are warranted.

Associated Factors and Survival Outcomes for Breast Conserving Surgery versus Mastectomy among New Zealand Women with Early-Stage Breast Cancer.

This study aimed to investigate type of loco-regional treatment received, associated treatment factors and mortality outcomes in New Zealand women with early-stage breast cancer who were eligible for breast conserving surgery (BCS). This is a retrospective analysis of prospectively collected data from the Auckland and Waikato Breast Cancer Registers and involves 6972 women who were diagnosed with early-stage primary breast cancer (I-IIIa) between 1 January 2000 and 31 July 2015, were eligible for BCS and had received one of four loco-regional treatments: breast conserving surgery (BCS), BCS followed by radiotherapy (BCS + RT), mastectomy (MTX) or MTX followed by radiotherapy (MTX + RT), as their primary cancer treatment. About 66.1% of women received BCS + RT, 8.4% received BCS only, 21.6% received MTX alone and 3.9% received MTX + RT. Logistic regression analysis was used to identify demographic and clinical factors associated with the receipt of the BCS + RT (standard treatment). Differences in the uptake of BCS + RT were present across patient demographic and clinical factors. BCS + RT was less likely amongst patients who were older (75+ years old), were of Asian ethnicity, resided in impoverished areas or areas within the Auckland region and were treated in a public healthcare facility. Additionally, BCS + RT was less likely among patients diagnosed symptomatically, diagnosed during 2000–2004, had an unknown tumour grade, negative/unknown oestrogen and progesterone receptor status or tumour sizes ≥ 20 mm, ≤50 mm and had nodal involvement. Competing risk regression analysis was undertaken to estimate the breast cancer-specific mortality associated with each of the four loco-regional treatments received. Over a median follow-up of 8.8 years, women who received MTX alone had a higher risk of breast cancer-specific mortality (adjusted hazard ratio: 1.38, 95% confidence interval (CI): 1.05–1.82) compared to women who received BCS + RT. MTX + RT and BCS alone did not have any statistically different risk of mortality when compared to BCS + RT. Further inquiry is needed as to any advantages BCS + RT may have over MTX alternatives.

Twenty-year risks of breast cancer-specific mortality for stage III breast cancer in the surveillance, epidemiology, and end results registry.

We aimed to report the 20-year risk of breast cancer-specific mortality (BCSM), report the risk of BCSM conditional on having survived 5years, and identify factors associated with late deaths in stage III breast cancer. Using Surveillance, Epidemiology, and End Results data, we included women with stage III breast cancer diagnosed from 1990 to 2005. We excluded women with unknown hormone receptor (HR) status, women who did not undergo resection of the primary tumor or axillary nodes, or unknown cause of death. We estimated risks of BCSM using cumulative incidence function and used Fine and Gray regression to identify factors associated with late deaths. Final sample was 36,500 patients with 14years of median follow-up. For each stage subgroup, the risk of BCSM at 20years was significantly higher for HR-negative vs HR-positive tumors (IIIA: 49.8% vs 43.2%, P < 0.0001; IIIB: 60.9% vs 47.6%, P < 0.0001; IIIC: 68.7% vs 63.1%, P < 0.0001). Compared with the risks of non-BCSM, the risks of BCSM at 20years were four times higher in stage IIIC HR-positive disease and seven times higher in stage IIIC HR-negative disease. Risks of BCSM conditional on having survived 5years depended on tumor size, nodal status, race, and tumor grade for HR-positive disease and depended on tumor size, nodal status, and age for HR-negative disease. In stage III breast cancer, the risk of BCSM at 20years is very high and remains important even beyond the first 5years in both HR-positive and HR-negative disease. Late BCSM depends on traditional clinicopathologic factors.

Abstract PS6-13: Population-based tool to estimate residual risks of breast cancer specific mortality (BCSM) and non-BCSM

Abstract Background: The risk of breast cancer death persists for at least 20 years from diagnosis. Most reports describing this risk have been based on selected patients (pts) enrolled into clinical trials. These studies report absolute risks at fixed timepoints (i.e. 10 or 20 years) and do not consider the dynamic changes in risks over time. The aim of this study was to develop a tool to calculate residual risks of BCSM and non-BCSM based on individual pt and tumor characteristics, at any given time after breast cancer diagnosis. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified women diagnosed with non-metastatic invasive breast cancer between 1990-2005, with one primary cancer in their lifetime, and known hormone receptor (HR) status. We estimated the effect of baseline clinical and pathologic variables known to be prognostic, including pt age, HR status, tumor size (T), nodal status (N), and tumor grade, on residual cumulative risks of BCSM and non-BCSM over time. The tool generates the residual death risk (RDR), which is a nonparametric estimate of the cumulative risk of BCSM and non-BCSM by year 20 after any given time from initial diagnosis, among patients defined by baseline clinical and pathologic variables using the method of Gray (1988) implemented in the cmprsk package in R. Results: We included 235,015 pts (median follow-up = 14 years). Among all breast cancer deaths, the proportion occurring after 5 years was 60% for HR+ vs 24% for HR- (p&amp;lt;0.001). The table shows risks of BCSM and non-BCSM by HR and N status. The cumulative risk of BCSM in year 5-20 ranged from 4.2% in HR+ T1a N0 to 50.1% in HR+ N3. Using the RDR tool, a 54 year-old pt, diagnosed 7 years prior with a HR+, T1c, N1, grade 2 breast cancer, has a 16.6% residual cumulative risk of BCSM over the following 13 years, and a residual cumulative risk of non-BCSM over the same period of 4.0%. For a 66 year-old pt, diagnosed 10 years prior with a HR+, T1c, N0, grade 1 breast cancer, her residual cumulative risk of BCSM over the following 10 years is 2.9%, and her residual cumulative risk of non-BCSM over the same period is 10.0%. For a 45 year-old pt, diagnosed 8 years prior with a HR-, T2, N1, grade 3 breast cancer, her residual cumulative risks of BCSM and non-BCSM over the following 12 years are 4.4% and 4.9%, respectively. Conclusions: For HR+ breast cancer, risks of BCSM remain high beyond 5 years from diagnosis. For HR- breast cancer, the risk of BCSM is highest within 5 years from diagnosis; however, risks beyond 5 years are still considerable. The RDR tool provides population-based long-term estimates of cumulative risk of BCSM and non-BCSM over time, based on individual pt and tumor characteristics. BCSMnon-BCSMAll-cause mortality% Event-FreeCumulative risk (%)Cumulative risk (%)Cumulative risk (%)at 5 yat 10 yy 5-20y 0-20y 0-20y 0-20Nodal status by HR status (any T)HR+N097.293.98.610.633.243.8N192.183.920.025.225.550.8N281.566.236.145.621.266.8N367.749.150.163.116.179.2HR-N089.285.47.317.022.739.7N174.268.312.234.317.051.3N257.049.320.053.514.568.0N340.733.526.268.79.378.0Tumor size among N0 onlyHR+T1a99.097.64.25.030.435.4T1b98.997.25.15.934.440.2T1c97.694.38.710.532.943.3HR-T1a97.394.74.97.323.030.3T1b95.191.96.210.527.137.7T1c91.787.97.514.823.037.8 Citation Format: Jose P Leone, Sara M Tolaney, Bernardo A Leone, Rachel A Freedman, Michael J Hassett, Julieta Leone, Carlos T Vallejo, Eric P Winer, Nancy U Lin, Nabihah Tayob. Population-based tool to estimate residual risks of breast cancer specific mortality (BCSM) and non-BCSM [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-13.

Abstract GS2-09: Diabetes risk reduction diet and survival following breast cancer

Abstract Importance: Type 2 diabetes (T2D) is associated with poor breast cancer prognosis. Adherence to a dietary pattern associated with lower T2D risk may improve breast cancer outcomes. Objective: To evaluate the association between adherence to a diabetes risk reduction diet (DRRD) after diagnosis and survival outcomes following breast cancer. Method: We followed 8,320 women diagnosed with stage I-III breast cancer from two large prospective cohort studies, the Nurses’ Health Study (NHS; 1980-2014) and the NHSII (1991-2015). Information on diet and other covariates was repeatedly measured in validated follow-up questionnaires every two to four years. The DRRD adherence score includes 9 dietary components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated:saturated fat ratio; and lower glycemic index of diet, lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red meat. Cumulative average DRRD score was calculated using repeated measures of diet after breast cancer diagnosis. Deaths were reported by family members or via the search of National Death Index, and cause of death was assigned by reviewing death certificates/medical records. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DRRD score and breast cancer-specific and all-cause mortality were estimated using Cox proportional hazards models. Results: During a median of 16 years of follow-up after diagnosis, we ascertained 2,146 deaths, of which 948 were due to breast cancer. In the multivariable-adjusted models, women with higher post-diagnostic DRRD scores had a 17% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR =0.83; 95%CI=0.67-1.02; p-trend=0.03) and 33% lower risk of all-cause mortality (HR =0.67; 95%CI=0.58-0.78; p-trend &amp;lt;0.0001). Associations were slightly attenuated after further adjusting for neighborhood socioeconomic status index (breast cancer mortality: HR =0.86; 95%CI=0.70-1.07; p-trend=0.06; overall mortality: HR =0.69; 95%CI=0.60-0.80; p-trend &amp;lt;0.0001). Compared with women who consistently had lower DRRD score (≤median) before and after diagnosis, those who improved their score from low to high had a significantly lower risk of breast cancer mortality (HR =0.81; 95%CI=0.65-1.00). Conclusion: We found that greater adherence to the DRRD after breast cancer diagnosis was associated with better survival, suggesting dietary modification after diagnosis consistent with T2D prevention may be important to breast cancer survivors. Table 1. Multivariable HRs and 95% CIs for the association between post-diagnostic diabetes risk reduction diet score and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)Quintile 1Quintile 2Quintile 3Quintile 4Quintile 5p-trendMedian (IQR)20 (18-21)24 (23-25)27 (26-28)30 (29-31)34 (33-37)Breast cancer-specific mortalityNo. of events (n=948), 589,953 py207205184176176Model 11 (referent)0.97 (0.80-1.18)0.80 (0.65-0.97)0.79 (0.64-0.96)0.75 (0.61-0.92)0.0008Model 21 (referent)0.88 (0.72-1.07)0.76 (0.62-0.93)0.77 (0.63-0.95)0.83 (0.67-1.02)0.03Model 31 (referent)0.99 (0.81-1.20)0.82 (0.67-1.00)0.85 (0.69-1.04)0.86 (0.70-1.07)0.06All-cause mortalityNo. of events (n=2,146), 589,953 py506447476383334Model 11 (referent)0.83 (0.73-0.94)0.80 (0.71-0.91)0.67 (0.59-0.76)0.57 (0.50-0.65)&amp;lt;.0001Model 21 (referent)0.81 (0.71-0.92)0.87 (0.76-0.98)0.74 (0.65-0.85)0.67 (0.58-0.78)&amp;lt;.0001Model 31 (referent)0.89 (0.78-1.01)0.91 (0.80-1.04)0.78 (0.68-0.90)0.69 (0.60-0.80)&amp;lt;.0001 Table 2. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between changes of diabetes risk reduction diet score before or after diagnosis and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)CharacteristicsHR (95% CI)Breast cancer-specific mortalityCross classified changesNo. of events (n=948), 589,953 pyLow to Low1 (referent)Low to High0.81 (0.65-1.00)High to Low0.97 (0.79-1.19)High to High0.87 (0.74-1.02)All-cause mortalityCross classified changesNo. of events (n=2,306), 589,953 pyLow to Low1 (referent)Low to High0.88 (0.76-1.02)High to Low0.99 (0.87-1.12)High to High0.80 (0.72-0.89) Citation Format: Tengteng Wang, Maryam Farvid, Jae Hee Kang, Michelle Holmes, Bernard Rosner, Rulla Tamimi, Walter Willett, A. Heather Eliassen. Diabetes risk reduction diet and survival following breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-09.

Abstract PS10-22: Breast cancer mortality in women with Her2+ disease treated in a large integrated healthcare system

Abstract BACKGROUND: Women with breast cancer are living longer, including those with risk factors such as having HER2+ tumors or diagnosed at later stages, but a dearth of information exists on patients’ outcomes beyond clinical trials. Thus, we aimed to describe breast-cancer specific mortality risk for women with HER2+ disease in a large community health plan. METHODS: We assembled a cohort of 3777 adult women (&amp;gt;18 years) with HER2+ breast cancer (AJCC TNM Stages I-IV) from a large California health plan, Kaiser Permanente Southern California, from 2009-2017 and followed them through December 2018. Subjects were identified from the health plan’s NCI-SEER affiliated tumor registry. All data elements were captured from the tumor registry and the electronic health records. ER, PR, and HER2 status were assessed by immunohistochemical or FISH techniques. Dates and causes of death were extracted from the inpatient records and state and national death databases. We computed breast cancer-specific mortality rates by exposure to trastuzumab, and by ER, PR, and tumor size. We followed women from the index date up to the date of death or end of study at December 31, 2018, whichever occurred first. Multivariable Cox proportional hazards regression was used to estimated adjusted hazard ratios (HR) and corresponding 95% confidence intervals. RESULTS: Of the 3777 women, the median age at diagnosis was 57 years (range: 22-99 years). The cohort was diverse and included 47% Whites; 12% African American/Blacks; 16% Asian/Pacific Islanders; 24% Hispanics; and 1% of other/mixed backgrounds. Roughly 67% (N=2464) were ER+ and/or PR+. A total of 3170 women (84%) received trastuzumab; N=112 (3%) other chemotherapy only; and N=495 (13%) neither (the majority [85%] had early stage I-II disease). The risk of breast cancer-specific death was 9.3% (351/3777) during a median follow-up of 4.4 years (maximum 10 years). Breast cancer mortality rate was markedly lower in those with trastuzumab (18.32/1,000 PY) therapy than those who did not receive trastuzumab (27.66/1,000 PY), corresponding to a 44% reduced risk (adj HR=0.56, 95% CI: 0.40-0.76) among those who received trastuzumab. Breast cancer mortality rates were higher in women with greater stage; ER-; PR-; tumors &amp;gt;2 cm and with positive lymph nodes. Compared to women diagnosed at Stage I, those with Stage II-III disease were 2.77 times (adj HR=2.77, 95% CI: 1.87-4.10) more likely to die of breast cancer, and this risk was even higher in those diagnosed at Stage IV (adj HR=11.11, 95% CI: 7.02-17.60), after accounting for trastuzumab use; diagnosis age and year; race/ethnicity; geocoded income; ER and PR status; surgery type; other adjuvant therapy (endocrine, radiation, chemotherapy); lymph node status; histology, BMI, Charlson Comorbidity Index. The adjusted breast cancer mortality risk was 37% greater (adj HR=1.37, 95% CI: 0.99-1.90) in those with ER- disease versus ER+, but the result was of borderline statistical significance. In those with tumors&amp;gt;2cm, breast cancer mortality risk was almost 90% greater (adj HR=0.67, 95% CI: 0.49-0.91) versus those with smaller tumors&amp;lt;2cm. CONCLUSION: This population-based study of patients with HER2+ invasive breast cancer confirms that receiving trastuzumab was significantly associated with a 44% reduced risk of breast-cancer mortality. Further, breast cancer mortality risk was greater in those with higher stages, with large tumors (&amp;gt;2 cm) and positive lymph nodes, even after accounting for trastuzumab use. Citation Format: Reina Haque, LieHong Chen, Karen W. Kwan, Nina Oestreicher, Deepa Lalla. Breast cancer mortality in women with Her2+ disease treated in a large integrated healthcare system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-22.

Breast-Conserving Therapy Versus Mastectomy in Young Breast Cancer Patients Concerning Molecular Subtypes: A SEER Population-Based Study

Breast-conserving therapy was once a contraindication in young breast cancer patients (aged ≤40 years). Emerging studies suggest that breast-conserving therapy and mastectomy could achieve similar prognosis in this population. However, the effect of molecular subtype disparity on surgical strategy in these patients remains unclear. Data from 8656 young patients (aged ≤40 years) diagnosed with invasive breast cancer between in 2010 and 2014 were retrospectively reviewed from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards model was used to evaluate subtype-dependent relationships between the surgical method and survival. Of the 8656 patients, 4132 (47.7%) underwent breast-conserving therapy and 4524 (52.3%) underwent mastectomy. The median follow-up period was 30.0 months. Patients in the breast-conserving therapy group demonstrated better overall survival and breast cancer-specific survival than those in the mastectomy group (both p < 0.05). Patients with different molecular subtypes exhibited significant differences in overall survival and breast cancer-specific survival (p < 0.001). Patients with luminal subtypes experienced better overall survival and breast cancer-specific survival than those with the triple-negative subtype. Multivariate analysis revealed that overall mortality risk of the breast-conserving therapy group was lower than that of the mastectomy group among HR(+)HER-2(-) and HR(-)HER-2(-) patients (overall mortality risk of 36.3% [adjusted hazard ratio = 0.637 {95% confidence interval = 0.448–0.905}, p = 0.012] and 36.0% [adjusted hazard ratio = 0.640 {95% confidence interval = 0.455–0.901}, p = 0.010] respectively.) The breast cancer-specific mortality risk was also lower by a percentage similar to that of the overall mortality risk. In the HR(+)HER-2(+) group, the surgical method was an independent prognostic factor for breast cancer-specific survival (adjusted hazard ratio = 0.275 [95% confidence interval = 0.089–0.849], p = 0.025), while there was a trend that patients with breast-conserving therapy had better overall survival than those with mastectomy (p = 0.056). In the HR(-)HER-2(+) group, no significant difference was observed in overall survival and breast cancer-specific survival (p = 0.791 and p = 0.262, respectively). Breast-conserving therapy resulted in significantly better prognosis in patients with luminal and triple-negative subtypes, while no significant difference was observed in patients with the HER-2 enriched subtype. These results may be helpful in informing clinically precise decision-making for surgery in this population.

Association of vitamin C intake with breast cancer risk and mortality: a meta-analysis of observational studies.

The association between vitamin C intake and breast cancer is unclear. This meta-analysis aimed to precisely assess the association of vitamin C intake with breast cancer risk and mortality. We searched the PubMed, Embase, and Web of Science databases up to June 2020 and found 69 studies relevant to breast cancer risk (54 studies) and survival (15 studies). Relative risks and 95% confidence intervals were calculated using the random-effects models. Pooled results suggested that the highest versus lowest vitamin C intake was significantly associated with a lower risk of breast cancer incidence (Relative Risk = 0.86; 95% confidence interval, 0.81–0.92). Dietary vitamin C but not supplements was found to reduce breast cancer risk (Relative Risk = 0.89; 95% confidence interval, 0.82–0.96). For the highest versus lowest vitamin C intake, the pooled hazard risk for breast cancer-specific mortality was 0.78 (95% confidence interval, 0.69–0.88), totality mortality was 0.82 (95% confidence interval, 0.74–0.91), and recurrence was 0.81 (95% confidence interval, 0.67–0.99). Our analysis suggests that higher vitamin C intake is significantly associated with reduced breast cancer incidence and mortality. However, the intake of vitamin C supplements has no significant effect on breast cancer prevention.

The Prognostic Impact of Age at Diagnosis Upon Breast Cancer of Different Immunohistochemical Subtypes: A Surveillance, Epidemiology, and End Results (SEER) Population-Based Analysis.

Background and Objectives: The influence of age at diagnosis of breast cancer upon the prognosis of patients with different immunohistochemical (IHC)-defined subtypes is still incompletely defined. Our study aimed at examining the association of age at diagnosis and risk of breast cancer-specific mortality (BCSM).Methods: 172,179 eligible breast cancer patients were obtained for our study cohort using the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Patients were classified into four IHC-defined subtypes according to their ER, PgR, and HER2 status. Kaplan–Meier plots were used to describe BCSM among patients in different age groups. A Cox proportional hazards model was used for multivariate analysis. A multivariable fractional polynomial model within the Cox proportional hazards model was used to evaluate the relationship between age at diagnosis and the risk of BCSM.Results: For the whole cohort, the median follow-up time was 43 months. Patients younger than 40 years and those older than 79 years presented with the worst BCSM (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.03–1.23, and HR 3.52, 95% CI 3.23–3.83, respectively, p < 0.01, with age 40–49 years as the reference). The log hazard ratios of hormone receptor (HoR)(+)/HER2(–) patients formed a quadratic relationship between age at diagnosis and BCSM, but not in the other three subtypes of breast cancer. In the HoR(+)/HER2(–) subtype, patients younger than 40 years had worse BCSM than those aged at 40–49 years (HR 1.26, 95% CI 1.10–1.45, and p < 0.01).Conclusions: Women diagnosed with HoR(+)/HER2(–) breast cancer younger than 40 years or older than 79 years of age suffer higher rates of cancer-specific mortality. Young age at diagnosis may be particularly prognostic in HoR(+)/HER2(–) breast cancer.

Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer.

Cutoffs of the 21-gene recurrence score (RS), a commonly used genomic assay for hormone receptor-positive breast cancer, have been updated. Little is known about racial/ethnic differences in RS results, RS-guided chemotherapy use, and outcomes on updated cutoff (RS ≥ 31 defined as high-risk) in the real-world setting. A total of 81,937 women [75.0% whites, 7.7% blacks, 8.3% Asian American/Pacific Islanders (AAPIs), and 9.0% Hispanics] diagnosed with hormone receptor-positive breast cancer between 2004 and 2015, who received the 21-gene assay, were identified from the Surveillance, Epidemiology, and End Results. Logistic regressions estimated the race-associated odds ratios (ORs) of RS and chemotherapy use. Cox regressions estimated the race-associated hazard ratios (HRs) of breast cancer-specific and all-cause mortality. Compared with white women, black women were more likely to have RS-defined high-risk tumors (adjusted OR [aOR] 1.29; 95% CI 1.16-1.42). In high RS, blacks had lower odds of chemotherapy use (aOR 0.76; 95% CI 0.62-0.94) than whites, particularly among women ≥ 65years (aOR 0.51; 95% CI 0.35-0.76), while AAPI and Hispanic women had no variation in chemotherapy use compared with whites in high RS. Black women had a higher risk of breast cancer-specific mortality (HR 1.37; 95% CI 1.12-1.67) and all-cause mortality compared with white women after adjusting for demographic and pathological factors, county-level socioeconomic deprivation, treatments and RS; AAPIs had lower mortality and Hispanics had similar mortality. Black women were more likely to have a high-risk RS tumor and less likely to receive chemotherapy in the group of high RS, especially those ≥ 65years. Further studies are needed to identify barriers to chemotherapy in black patients with high RS scores.