Breast Cancer-specific Death Research Articles

Association of MammaPrint index and 3-year outcome of patients with HR+HER2- early-stage breast cancer treated with chemotherapy with or without anthracycline.

511 Background: The MammaPrint (MP) risk of distant recurrence signature identifies hormone receptor-positive (HR+), HER2-negative early-stage breast cancer (EBC) patients (pts) with increased or decreased chemosensitivity and chemotherapy (CT) benefit. The MINDACT trial demonstrated excellent outcomes for MP Low Risk tumors without CT, and previous studies show MP High Risk tumors exhibit higher sensitivity and benefit with CT. There remains an unmet clinical need for identifying biomarkers to inform specific regimen planning for pts who qualify for CT. Here, the association of MP index and 3-year (yr) Recurrence-Free Interval (RFI) was evaluated in pts with HR+HER2-, genomically High Risk Luminal B-Type EBC treated with taxane and cyclophosphamide (TC) vs anthracycline + TC (AC-T). Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III breast cancer pts who received MP testing, with or without BluePrint (BP) molecular subtyping, and consented to full transcriptome and clinical data collection. Pts with HR+HER2- MP High Risk and BP Luminal B-Type tumors who received chemotherapy with 3-yr follow-up data (N = 614) were included. High Risk tumors were further classified into High 1 (H1; 0.000 to -0.569) or High 2 (H2; -0.570 to -1.000). Differences in 3-year RFI, defined as time from diagnosis to a local-regional recurrence, distant recurrence, or breast cancer specific death per STEEP 2.0 criteria, between H1 and H2 tumors were evaluated by Kaplan-Meier analysis and log-rank test, stratified by CT regimen. Results: Patients had similar age, menopausal status, race, and lymph node status between H2 vs H1 tumors. H2 tumors were more likely Grade 3, compared to H1 tumors. 86% of tumors were classified as H1 Luminal B-Type (N = 530) and 14% were classified as H2 Luminal B-Type (N = 84). AC-T treated tumors had non-significant differences in 3-yr RFI between H1 Luminal B-Type (95.3% [95% CI, 91.8-98.8]; N = 184) and H2 Luminal B-Type (97.7% [95% CI, 93.4-100.0]; N = 44). In contrast, pts with H2 Luminal B-Type (N = 40) tumors treated with TC demonstrated a significantly worse RFI of 86.4% (95% CI, 74.2-100.0) compared with 97.1% (95% CI, 95.1-99.2) in pts with H1 Luminal B-Type (N = 346) tumors, with an absolute difference of 10.7% (p = 0.0076). Conclusions: These data show that among pts with Luminal B-Type tumors, MP H2 have significantly worse 3-yr RFI than pts with MP H1 tumors when treated with TC. This further supports ongoing research demonstrating the significant benefits of anthracycline-based CT for treating H2 Luminal B-Type tumors. Conversely, MP H1 tumors do not appear to benefit from the addition of anthracycline to CT regimen. These FLEX data add to the growing evidence identifying MammaPrint as a comprehensive genomic signature regarding both prognosis as well as selection of systemic therapy for HR+HER2- EBC pts. Clinical trial information: NCT03053193 .

Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.

10502 Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k, and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]

Abstract PO3-17-09: Outcome after the introduction of personalized treatment for axilla in patients with clinically node-negative early breast cancer

Abstract Background : After the results of ACOSOG Z0011 and AMAROS trials were reported, axillary treatment has been promoted to de-escalation. For clinically negative cases of axillary lymph node metastasis (cN0), axillary dissection (Ax) has been the standard treatment when sentinel lymph node (SN) metastasis is positive. In our hospital, for patients with cN0, if SN macro metastasis is positive, Ax or irradiation (RT) is selected after sufficient explanation to the patients. Five years have passed since the introduction of treatment selection for the axilla, we examined treatment outcomes retrospectively. Methods : The subjects were 1376 patients who underwent SN biopsy for primary breast cancer with cN0 at our hospital from October 2004 to December 2018 (median observation period 79 months). Cases who underwent preoperative chemotherapy were excluded. We have introduced the treatment choice system since December 2015, and compared prognosis (local recurrence, distant recurrence and breast cancer specific death) before and after introduction using the log-rank test. Results : There were 947 cases before introduction of treatment choice system (pre group) and 429 cases after introduction (post group). The median observation period for each group was 91 months and 41 months. The maximum observation period post group was 67 months, then we compared the number of events in patients with observation period less than 67 months in pre group. There was no significant difference between two groups (Pre/Post) in terms of age (p=0.52), menopausal status (p=0.90), invasion of primary lesion (p=0.19), biology and SN metastasis status (p=0.41). There were 54 patients (12.6%) in pre group and 135 (14.3%) patients in post group had positive sentinel lymph nodes. In post group, 33 patient (61.1%) were macrometastasis of SN, 28 of whom underwent Ax and 5 underwent RT. Local recurrence was 4 cases (1.7%) in pre group, 9 cases (2.1%) in post group (p=0.84), distant recurrence was 13 cases (5.6%) and 5 cases (1.2%) (p=0.0002), and breast cancer specific death was 8 cases (0.8%) and 1 case (0.2%) (p=0.0003), respectively. Discussion : There was no significant difference in local recurrence rate within 67 months, but were poor prognosis in pre introduction group for distant metastasis and breast cancer specific survival. In the results of this study, there was no significant difference in local recurrence, but the prognosis for distant recurrence and breast cancer-specific death was poor in the before introduction group. The median observation period in the post introduction group was 47 months, and late recurrence of ER-positive breast cancer occurs later. It is necessary to continue the study by extending period and accumulation cases. Conclusion : For cN0 cases, if the case is suitable, we introduced the treatment choice system that allows omitting Ax by performing radiotherapy in SN macrometastasis positive patients. After introduction, there was no increase in the relapse rate after introduction in the short term. Appropriate case selection allowed the safety introduction of individualizes treatment for axilla. Citation Format: Mai Tomiguchi, Kaori Hidaka, Lisa Goto-Yamaguchi, Ayako Kajiwara, Kanako Nishikido, Toko Inao, Yutaka Yamamoto. Outcome after the introduction of personalized treatment for axilla in patients with clinically node-negative early 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 PO3-17-09.

Abstract PO3-03-08: Use of adjuvant Capecitabine after neoadjuvant chemotherapy: A Cohort Study among Elderly Patients with Early-Stage Triple-Negative Breast Cancer

Abstract Background: The use of capecitabine in the adjuvant setting in patients with residual disease after neoadjuvant chemotherapy has been incorporated into practice based on the results of the CREATE-X trial. We evaluate utilization patterns of adjuvant capecitabine use, its association with outcomes, and subsequent hospitalizations and emergency room (ER) visits among elderly patients with early-stage triple-negative breast cancer (TNBC). Methods: We identified patients aged ≥66, diagnosed with early-stage TNBC between 2010 and 2017 in the SEER and Texas Cancer Registry (TCR)-linked Medicare databases. All patients were treated with neoadjuvant chemotherapy for localized or regional-stage disease. All patients had continuous enrollment in Medicare Parts A & B without a Health Maintenance Organization enrollment 12 months before cancer diagnosis and 12 months after cancer diagnosis. Chemotherapy administration was identified using HCPCS codes from outpatient and physician’s carrier claims. We analyzed the patterns of capecitabine use, its association with survival outcomes, and the frequency of ER visits and hospitalizations during treatment (between the first capecitabine claim and 30 days after the last claim for capecitabine). Descriptive statistics were used. Primary analyses included logistic regression, Kaplan-Meier estimates, and Cox regression models with propensity score adjustments. This study adhered to the STROBE guidelines for cohort studies. Results: 1,239 patients with localized or regional TNBC treated with neoadjuvant chemotherapy were included (median 72 years). Of them, 96 (7.7%) were prescribed adjuvant capecitabine. Treatment with capecitabine was associated with recent year of diagnosis, regional disease, and residing in non-metropolitan areas. Specifically, the use of capecitabine increased from 1% in 2010 to 10% in 2016 and 21% in 2017. The median duration of capecitabine treatment was 4 cycles. In multivariable logistic regression analyses, older age was associated with decreased odds of receiving ≥4 cycles of capecitabine (OR=0.25; 95% CI: 0.11–0.60; p =0.002). Among capecitabine users, 3-year OS was 46% and 78% for patients who received 1-3 and ≥4cycles of capecitabine, respectively (p< 0.001). The 3-year estimate of BCSS was 43% and 85% respectively (p< 0.001). After multivariable adjustment for comorbidity score, stage, and propensity score, receiving ≥4 cycles of capecitabine was associated with decreased risk of death (HR=0.29; 95%CI 0.13–0.63, p=0.002) and breast cancer-specific death (HR=0.15; 95%CI: 0.05–0.51, p=0.002) compared to receiving 1-3 cycles. Twenty-seven (28%) patients had ER/hospitalization during capecitabine treatment; median time from initial capecitabine claim to ER/hospitalization was 24 days (IQ 13-39). The median number of capecitabine cycles was 3 (IQR 2-5) and 5 (IQR 3-8) for those with and without ER/hospitalization (p=0.02). The most common diagnosis codes associated with ER/hospitalization included pleural effusion, GI symptoms, pneumonia, and acute kidney failure. A higher comorbidity score at diagnosis was associated with an increased risk of ER/hospitalization (HR=2.76; 95%CI 1.05-7.28, p=0.04). Conclusion: We demonstrate an increasing trend in capecitabine utilization among elderly patients with early-stage TNBC. Although the limited sample size hindered a conclusive analysis, more cycles of capecitabine were associated with improved survival outcomes. Notably, a significant proportion of patients undergoing capecitabine treatment experienced ER/hospitalizations. These findings contribute valuable information on the risks and benefits of capecitabine treatment, aiding evidence-based decision-making to prevent serious complications. Citation Format: Marija Sullivan, Xiudong Lei, Catalina Malinowski, Sharon Giordano, Marianna Chavez. Use of adjuvant Capecitabine after neoadjuvant chemotherapy: A Cohort Study among Elderly Patients with Early-Stage Triple-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 PO3-03-08.

Abstract PO1-02-14: Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort

Abstract Background Compared to middle-aged women, older women have a higher risk of breast cancer death. Whether the increased risk of breast cancer death is present in all subgroups of older adults with breast cancer, or negligible in the subgroups receiving adequate surgical and oncological treatment, has been debated. We studied long-term prognosis by age and subtype, adjusting for stage, treatment, socioeconomic status and comorbidity, clarifying which subgroups of older patients that are at increased risk of breast cancer death. Methods In a nation-wide cohort of 45,949 women aged ≥60 years at diagnosis of breast cancer 1997-2014, we estimated crude probabilities of breast cancer death and from other causes using competing risk methods. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI. Results In this large population-based cohort study of older women with breast cancer, we found an increasing risk of breast cancer death with increasing age at diagnosis, both at 5- and 10-year follow up. The strong association between age and breast cancer death was found for all breast cancer subtypes, being most prominent in Her2-positive breast cancer. The age effect was also significant in Luminal A breast cancer where treatment opportunities are not necessarily affected by age. High-risk tumors were equally common in all age groups above 60 years. In multivariable analysis, stage, subtype, grade and treatment were important explanatory variables to the age-related differences in survival, while comorbidity and socioeconomic status contributed minorly. After adjustments, older age remained an independent risk factor for both overall and breast cancer survival. Older women with triple-negative (60-79 years) or Her2-positive (60-84 years) tumors had a 5-year risk of breast cancer death exceeding the risk of death by other causes. Conclusions Older women had a significantly higher risk of breast cancer death irrespective of breast cancer subtype, also in Luminal A disease where treatment opportunities are not necessarily affected by age. Table 3. Crude probabilities of breast cancer specific death and death by other cause (competing cause of death) at 5, 10 and 15 years. Table 4. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) Table 5. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) by age at diagnosis and subtype. Citation Format: Amelia Chiorescu, Anna L V Johansson, Antonis Valachis, Alexios Matikas, Jan Frisell, Lars Holmberg, Irma Fredriksson. Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort [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 PO1-02-14.

Comparison of clinicopathological and prognostic features of breast cancer patients younger than 40 years and older than 65 years

PurposeThis study aims to compare the clinicopathological and prognostic features of women aged 40 years and younger and 65 years and older with breast cancer.MethodsBetween January 2011 and December 2021, 136 female cases aged 40 years and younger and 223 female cases aged 65 and over were identified among all cases (1395 cases) registered as breast cancer in the file archives of Afyonkarahisar Health Sciences University Faculty of Medicine, Department of Medical Oncology for the study. A Chi-square (× 2) test was used for categorical variables, and an independent sample t-test for continuous variables. Log-rank test and Kaplan–Meier plots were used for survival analysis. For the statistical evaluation, p < 0.05 was considered significant.ResultsBoth overall survival (p < 0.01) and breast cancer-specific survival (BCSS) (p = 0.01) were significantly worse in the older group. BCSS were significantly worse in the older group in Luminal B (HER2−) (p = 0.013) and HR− HER2+ (p = 0.015) subtypes detected. In multivariate Cox regression analysis, only the presence of metastases at diagnosis or follow-up (p < 0.001) and ECOG PS 2–3 status (p = 0.001) were associated with an increased risk of breast cancer-specific death.ConclusionTo our knowledge, no study directly compares these two groups. In our study, similar to many studies, more aggressive tumor features were found in young patients, but unlike many studies, mortality was found to be significantly higher in older patients. The presence of metastasis and poor ECOG PS were found to be the most influential factors in breast cancer-specific death risk.

Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.

Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT). Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model. The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05). For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.

Abstract B136: Hypertension, anti-hypertensive drug use, and breast cancer survival among Black women

Abstract Introduction: In the United States (US), Black women are 59% more likely to have hypertension than White women. US Black women are also 40% more likely to die from breast cancer when compared to US White women, yet the associations between hypertension, use of anti-hypertensive medications, and breast cancer survival are not well-established in this population. Methods: The prospective Black Women’s Health Study includes 1,757 women with invasive breast cancer diagnosed at stages 1, 2 or 3. Data on physician-diagnosed hypertension and use of anti-hypertensive medications (i.e., angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, beta blockers, and diuretics) are collected every two years. We used Cox proportional hazards models adjusted for age and stage at breast cancer diagnosis to estimate hazard ratios (HR) and 95% confidence intervals for associations of untreated and treated hypertension around the time of breast cancer diagnosis with breast cancer survival. Results: The HR for breast cancer mortality was 1.60 (1.10, 2.34) for women with untreated hypertension relative to women without hypertension. The association was especially strong among Stage 2/3 cases (HR=1.89 [1.25, 2.87]) and estrogen receptor negative cases (HR=1.96 [1.11, 3.48]). Women with treated hypertension did not have a higher risk of breast cancer-specific death relative to women without hypertension (HR=0.96 [0.73, 1.27]), although there was some evidence of variation by type of anti-hypertensive used. HRs were 0.86 (0.54, 1.37), 1.04 (0.68, 1.57), 1.26 (0.85, 1.87), and 1.25 (0.85, 1.86) for hypertensive women who used ARBs, ACE inhibitors, beta blockers, and diuretics, respectively. Conclusions: Among Black women with hypertension, breast cancer-specific survival is better if the hypertension is treated. Data from our study and others suggest that treatment with ARBs or ACE inhibitors may be especially beneficial when a key concern is breast cancer-specific survival. Citation Format: Mollie E. Barnard, Nuo N. Xu, Dennis Jones, Julie R. Palmer. Hypertension, anti-hypertensive drug use, and breast cancer survival among Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B136.

Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.

Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC. Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD). Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC. All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. To estimate overdiagnosis associated with breast cancer screening among older women by age. Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. Women 70 years and older who had been recently screened. Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. National Cancer Institute.

Effect of dietary patterns on the prognosis of breast cancer patients

Breast cancer (BC) is a serious threat to women's health. Higher BC risk is allegedly related to personal lifestyle like diet. However, it is still unclear how dietary quality affect BC survivors. This meta-analyse aimed to figure out it. The highest and lowest categories of healthy and unhealthy dietary patterns were compared by using the random-effects meta-analyses, which combined relative risks (RRs) and 95% confidence intervals (CIs) that were multivariable-adjusted. 11 eligible articles, including two RCTs, three case-control studies, and six cohort studies, were found and included in this paper after they met the inclusion criteria. According to the pooled analyses, when compared to the lowest group, women with the highest quality healthy diet (highest quintile/quartile/tertile) had 24% lower risk of overall death(random effects (RR = 0.76; 95%CI = 0.67-0.86), 16% lower risk of BC specific death (random effects (RR = 0.84; 95%CI = 0.75-0.94), 28% lower risk of No-BC death (random effects (RR = 0.72; 95%CI = 0.63-0.83),and 4% higher risk of recurrence (random effects (RR = 1.04; 95%CI = 0.97-1.12). According to our meta-analysis, consuming a high-quality healthy diet was linked to a lower risk of all-cause death. The results could have significant effects on encouraging the use of daily dietary treatment regimen to benefit breast cancer patients. To achieve better long-term survival and better quality of life for BC patients, definitively establishing effective interventions will necessarily require further researches.

Prognostic value and mode selection of locoregional treatment in Stage-IV breast cancer patients.

This study aimed to assess the actual prognostic significance of different locoregional treatment (LRT) (surgery and radiotherapy) modalities for stage-IV breast cancer (BC) patients and construct a competing risk nomogram to make precise predictions of the breast cancer-specific death (BCSD) risk among LRT recipients. A total of 9279 eligible stage-IV BC patients from the Surveillance Epidemiology and End Results (SEER) database were included in this study. Initially, we evaluated the impact of LRT on survival both before and after the propensity score matching (PSM). Then, we used the Cox hazard proportional model and competing risk model to identify the independent prognostic factors for LRT recipients. Based on the screened variables, a comprehensive nomogram was established. Kaplan-Meier curves demonstrated that LRT significantly prolonged overall survival (OS) and breast cancer-specific survival (BCSS) (P < 0.001). In addition, patients treated with surgery combined with postoperative radiotherapy (PORT) possessed the optimal survival (P < 0.001). Regardless of the surgical modalities, primary tumor resection combined with radiotherapy could ameliorate the prognosis (P < 0.05). Subgroup analysis showed that in patients with T2-T4 stage, PORT had a survival benefit compared with those undergoing surgery combined with preoperative radiotherapy (PRRT) and surgery only. Based on the screened independent prognostic factors, we established a comprehensive nomogram to forecast BCSD in 1year, 2years and 3years, which showed robust predictive ability. PORT was associated with a lower BCSD in stage-IV BC patients. The practical nomogram could provide a precise prediction of BCSD for LRT recipients, which was meaningful for patients' individualized management.

Trends in breast cancer death by stage at diagnoses in 2000-2018.

e18855 Background: Approximately 40-45,000, women die from breast cancer each year, most of which are due to metastatic recurrence of stage I-III cancers. Stage I and II cancers are considered highly curable, but they also include most patients. The goal of this analysis is to examine the contribution of stage I, II, III, and IV disease to annual breast cancer-specific death and assess time trends. Methods: Data from patients diagnosed with stage I-IV breast cancer between 1975-2018 (N = 1,545,502) were obtained from The Surveillance, Epidemiology, and End Results (SEER) Program. After filtering for the female sex, one primary site only, surgery performed, known AJCC stage &gt; 0, and survival data available we included N = 1,018,331 patients. We estimated the year of breast cancer-specific death (BCSD) by adding time to BCSD to a year of diagnosis for each patient. We summarized the proportion of BCSD by stage at diagnosis in each year between 2000 and 2017. All temporal trends were assessed by fitting the linear model with interactions between stage and year, then running the ANOVA to test model coefficient significance. For each year of diagnosis, Kaplan-Meier curves were fitted to patient data grouped by stage, and 5-year survival was estimated. Results: The study population included 24% ER-, 73% ER+ (the rest unknown) cancers; 35% HER2-, 6% HER2+ (the rest unknown); 24% were &lt; 50 and 76% &gt; 50 years of age; 60% received adjuvant chemotherapy. Over time, the frequency of stage I cancers increased from 49% in 2000 to 54% by 2017 (slope = 0.37 [95% CI: 0.32; 0.42]), and stage II and III decreased from 35.2% to 34.9% (slope = - 0.09 [-0.15; -0.04]) and from 14% to 10% (slope = -0.23 [-0.29; -0.18]), respectively. Five-year breast cancer-specific survivals remained stable for stage I cancers and increased significantly for stage II (slope = 0.002 [0.001;0.003]), stage III (slope = 0.006 [0.005;0.007]) and IV cancers (slope = 0.011 [0.010; 0.012]). The contribution of stage I cancers to annual breast cancer death increased and reached 23% in 2017, while death from stage III disease decreased to 30%. Since 2003, &gt; 50% of breast cancer deaths are from stage I-II cancers. Conclusions: The prevalence of stage I breast cancers increased in the past 20 years, and despite excellent overall prognosis, stage I-II cancers account for over 60% of all BCSD. To substantially reduce breast cancer death, we need to better identify the minority of Stage I-II patients who remain at risk for recurrence and death. [Table: see text]

2-[18F]FDG-PET/CT is a better predictor of survival than conventional CT: a prospective study of response monitoring in metastatic breast cancer

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities.Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www.ClinicalTrials.gov.

Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study

PurposeStatins are the most widely prescribed cholesterol lowering medications and have been associated with both improved and unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of statins and breast cancer outcomes (death and recurrence) in a large, representative sample of New Zealand (NZ) women with breast cancer.MethodsWomen diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic statin use.ResultsOf the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63–0.86). The association was attenuated when considering a subgroup of ‘new’ statin users (HR: 0.91; 0.69–1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77; 0.63–0.94), postmenopausal women (HR: 0.74; 0.63–0.88), and in women with advanced stage disease (HR: 0.65; 0.49–0.84).ConclusionIn this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.

Research on the Effects of Chemotherapy on Survival Outcomes for Older Patients with Primary Triple-Negative Breast Cancer after Surgery: A Propensity Score Matching and Competing Risk Analysis of the SEER Database

Background: The population of older women (≥70 years old) with triple-negative breast cancer (TNBC) is increasing, but there are few prognostic studies for these patients. In the study, we explored the effects of chemotherapy on breast cancer-specific death (BCSD) and other cause-specific death (OCSD) in older patients with TNBC. Methods: In accordance with the inclusion and exclusion criteria, we extracted primary TNBC older patients (≥70 years old) from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. We used propensity score matching (PSM), cumulative incidence function (CIF) and multivariate Fine and Gray competitive risk analyses to explore the effects of chemotherapy on survival for older patients with primary TNBC after surgery. Results: After one-to-one matched PSM analysis, we identified 2478 primary TNBC patients (≥70 years old) finally. CIF analysis showed that the 3-year, 5-year and 8-year mortalities were 15.34%, 20.30% and 23.73% for BCSD, and 7.36%, 13.20% and 23.02% for OCSD. The survival analysis showed that patients who received chemotherapy had a better overall survival than those who did not received chemotherapy (hazard ratio 0.72, 95% confidence interval 0.63–0.82, p &lt; 0.001). There was no difference in BCSD between older patients with chemotherapy and no chemotherapy. The OCSD rate for patients with chemotherapy was lower than that of those with no chemotherapy (Gray’s test, p &lt; 0.001). Diseases of heart were the most common cause of death in elderly patients with TNBC. After multivariate Fine and Gray competitive risk, age in diagnosis, race black, tumor grade, T status, N status and receiving radiotherapy were proven to be independent predictive factors of BCSD. Meanwhile, age in diagnosis, radiotherapy status, and chemotherapy status were proven to be independent predictive factors of OCSD. Conclusions: For older patients (≥70 years old) with TNBC, chemotherapy improved overall patient survival by reducing the rates of OCSD, but not by reducing the rates of BCSD. The impact of non-cancer causes of death on the prognosis of older cancer patients should not be ignored.

Abstract P3-03-19: Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients

Abstract Background: triple-negative breast cancer (TNBC) is associated with hereditary and environmental risk factors plus an overall worse prognosis compared to other Breast Cancer (BC) subtypes. While TNBC risk factors, prevalence, clinical characteristics and prognosis may vary throughout different populations, limited data on Latin American patients forces clinical decisions to be based predominantly on data coming from non-Hispanic women. To obtain local epidemiological information, regarding risk factors and clinical outcomes, we analysed the largest Chilean BC registry. Methods: we conducted a retrospective population-cohort study involving females with any stage TNBC, treated at a community hospital (mid-low income) and at an academic private hospital (high income), between the years 2010 and 2021. Risk factors, reason for consultation, clinical and pathological characteristics and prognosis were separately analysed for both TNBC and non-TNBC subgroups. Univariate and multivariate analyses were performed to identify prognostic factors for survival on TNBC patients. Results: From 5,806 patients, 647 (11.2%) were identified as TNBC. Compared to non-TNBC patients, women were younger (median age 55.2 vs. 57.2, p=0.0001), with 15.8% of TNBC patients having been diagnosed before the age of 40 compared to 9.6% in non-TNBC (p= 0.0001). TNBC had a significantly lower screen-detected cancer rate (14.5% vs. 31.6% p= 0.0001) and worse stage at diagnosis. No differences were seen between patients seen at a community hospital and private centre, for both TNBC rate and stage. Other risk factors such as parity, age at first gestation, menarche, hormone therapy replacement and obesity showed no significant differences between TNBC and no-TNBC patients (table 1). With a median follow up of 57 months, 5-year overall survival (OS) and BC specific death were significantly shorter for TNBC compared to non-TNBC (76.4% vs 88.1% and 78.9% vs 91.2%, respectively; p=0.0001) (table 2). In the multivariate analysis, TN subtype (HR=2.3, p=0.0001), stage (HR=2.05 for stage II vs stage I, HR=7.04 for stage III vs. stage I, p=0.0001), lower income (HR= 1.64, p=0.0001), and non-screened detected BC (HR=1.32, p=0.03) were all associated with worse overall survival (table 3). Conclusion: This is the first study focusing on TNBC characteristics in Chilean BC patients and to our knowledge, the largest performed in a Latin American population. We identified a lower proportion of TNBC patients when compared with data reported from other LA groups and worldwide, a very low screen detected cancer rate and as expected significantly lower TNBC survival rate compared to non-TNBC women. While TNBC patients were younger compared to the non-TNBC group, this age difference was marginal compared to other reported studies. Community hospital patients (with mid-low income) were associated with lower survival rates for both all-cause mortality and BC specific survival, regardless of a similar stage distribution at diagnosis. Reflecting an underlying interaction between social and biological factors that needs to be addressed. Table 1. Patient characteristics: Triple-negative versus noN-triple negative breast cancer BMI: Body mass index; FH: Family history * Difference is statistically significant. Table 2. Survival comparison in triple-negative versus non-triple negative breast cancer * Difference is statistically significant. Table 3. Cox Regression Multivariate analysis * Difference is statistically significant. Citation Format: Benjamin Walbaum, FRANCISCO ACEVEDO, Catherine Bauerle, Mauricio Camus, Manuel Manzor, Raul Martinez, Paulina Veglia, Marisel Navarro, Constanza Guerra, Francisco Dominguez, Tomas Merino, Lidia Medina, CÉSAR SÁNCHEZ. Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-19.

The impact of age on outcomes of breast cancer in different hormone receptor and HER2 groups.

The aim of the current study was to explore the association between age and outcomes in breast cancer. Patients during 2010-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and breast cancer-specific death (BCSD) were taken as endpoints. The restrict cubic spline graph (RCS) was used to explore the relationship between age and outcomes in patients, and the cumulative incidence of BCSD and non-BCSD was calculated using the Gray method. Age-specific gene expression profiles were studied using RNA sequence data from the Cancer Genome Atlas (TCGA) database to explore whether there were young age-related gene or gene sets. A total of 142,755 patients with breast cancer were included. The hazard ratio (HR) of OS for Patients with stage I-III breast cancer was roughly stable before 53 years old and increased significantly after that, and the HR of BCSD for these patients showed a U-shaped distribution when plotted against age, with patients younger than 50 years and patients older than 70 years experiencing the worst survival. Further stratified analysis according to molecular subtype revealed that the U-shaped distribution of the HR of BCSD with was only found in the Hormone receptor-positive/HER2-negative (HoR+/HER2-) subgroup. The cumulative incidence plots showed that young age was associated with worse BCSD in the breast cancer patients with stage I-III and HoR+/HER2- subgroup. In stage IV breast cancer, there was a linearity of the relationship between poor OS and increasing age. We failed to find any differentially expressed age-specific genes between 20-40 years and 41-60 years groups in 258 patients with stage I-III and HoR+/HER2- subtype. Young age could predict worse BCSD of patient with stage I-III and HoR+/HER2- breast cancer. The escalating therapy was recommended to young age breast cancer with stage I-III and HoR+/HER2- subtype.

Superior survival for breast-conserving therapy over mastectomy in patients with breast cancer: A population-based SEER database analysis across 30 years.

It has been believed that breast-conserving therapy (lumpectomy plus adjuvant radiation, Lum + RT) and mastectomy without radiation (Mast + NoRT) have equivalent survival outcomes. However, there is a need to re-evaluate the role of lumpectomy plus adjuvant radiation due to changed breast cancer management over time. This study aimed to conduct a population-based study that compare long-term oncologic survival outcomes after Lum + RT vs Mast + NoRT. The Surveillance, Epidemiology and End Results database was used to identify female breast cancer patients with a primary localized breast cancer diagnosis from 1988 to 2018. The standardized incidence/mortality ratio (SIR/SMR) for breast cancer recurrence (BCR) and breast cancer-specific death (BSD) was estimated by the SEER*Stat program. Cumulative incidences of BCR and BSD were assessed using Gray's method. We evaluated the effects of Lum + RT vs. Mast + NoRT on breast cancer recurrence-free survival (BRFS) and breast cancer-specific survival (BCSS). Fine-Gray competing risk model analyses, propensity score-adjusted Kaplan-Meier analyses and Cox proportional hazards model analyses were applied. A total of 205,788 women were included in the study. Patients who underwent Lum + RT had higher SIR of BCR (4.14 [95% confidence interval, CI: 3.94-4.34] vs. 1.11 [95% CI: 1.07-1.14]) and lower SMR (9.89 [95% CI: 9.71-10.08] vs. 17.07 [95% CI: 16.82-17.33]) than patients who underwent Mast + NoRT. Lum + RT was associated with higher competing risk of BCR (adjusted hazard ratio [HR]: 1.996, 95% CI: 1.925-2.069, p < 0.001) and lower competing risk of BSD when compared to Mast + RT (adjusted HR: 0.584, 95% CI: 0.572-0.597, p < 0.001). Multivariate Cox regression analysis revealed similar results (adjusted HR after PSW for BRFS: 1.792, 95% CI 1.716-1.871, p < 0.001; adjusted HR after PSW for BCSS: 0.706, 95% CI 0.688-0.725, p < 0.001). These findings persisted in the sensitivity and subgroup analyses. The present study further confirmed superior long-term survival with lumpectomy plus adjuvant radiation over mastectomy independent of patient characteristics including age, race, time period, historic subtype, tumor size, historic grade and stage, indicating that this benefit may result from the treatment itself.

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study

BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality. MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses. ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant. ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.