Breast Cancer-specific Mortality Research Articles

Prevalence of depressive disorders in breast cancer patients

IntroductionBreast cancer is the most common type of cancer and the leading cause of death from malignant neoplasms in women in Russia and in most countries in the world (Lima et al. EClinicalMedicine 2021; 38 100985). According to an analysis of the incidence and mortality from 36 cancers in 185 countries (Sung et al. CA Cancer J Clin 2021. 3 209-249) in 2020, 2261419 new cases of breast cancer were identified in the world in both sexes, which is accounted for 11.7% of the total cancer incidence. Mortality from breast cancer in 2020 amounted to 684996 cases. Patients with comorbid depression and anxiety disorders experience more severe symptoms, have longer recovery time, use more healthcare resources and have poorer outcome compare to those with cancer alone (Katon et al. Gen Hosp Psychiatry 2007; 2 147-155).ObjectivesAnalytical review of data on the impact of depressive spectrum disorders as comorbid conditions on the survival of breast cancer patients and their quality of life.MethodsThe following databases were searched for publications: PubMed, Embase, CINAHL, PsycINFO, Scopus, Science Citation Index/Social Sciences Citation Index, Cochrane Evidence Based Medicine database. The searches were limited to English language and studies with more than 100 subjects with diagnosed breast cancer where this information was mentioned. The analyzed period is between 1977 and 2018.ResultsThe reported prevalence of depression in breast cancer patients, according to researches, varies 4,5 to 38%. In patients with I-III stage breast cancer depression increased hazards of all-cause mortality by 50% compared to non-depressed patients. Stage-specific analyses demonstrated a 2–2.5 fold increase in breast cancer-specific and all-cause mortality in patients with stage I and II disease (Vodermaier et al. Breast Cancer Res Treat 2014; 2 373-384.). Women with non-metastatic breast cancer who report mild to moderate depressive symptoms in the weeks after surgery have approximately 2.5 times greater risk of death 8–15 years later than women who report little or no depressive symptoms post-surgery (Antoni et al. Gen Hosp Psychiatry 2017; 44 16-21). Depression in advanced cancer not only reduces quality of life but is also an independent predictor of poorer survival (Lloyd-Williams et al. J Affect Disord 2009; 113 127-132.).ConclusionsDepression and anxiety both have adverse effects on recurrence and all-cause mortality in patients with breast cancer. Untreated depression leads to significant increase in incidence and mortality. Depression can debut at any stage of cancer, including the stage of diagnosis. It proves the necessity for affective disorders screening in patients with cancer on the stage of diagnosis. Patients with diagnosed affective disorders should be observed not only by oncologist, but also by a psychotherapist in order to receive the necessary treatment to improve the quality of life and reduce the risk of mortality.Disclosure of InterestNone Declared

Tumor-infiltrating lymphocytes and breast cancer mortality in racially and ethnically diverse participants of the Northern California Breast Cancer Family Registry.

Stromal tumor-infiltrating lymphocyte (sTIL) enrichment in pretreatment breast tumors has been associated with superior response to neoadjuvant treatment and survival. In a population-based cohort, we studied sTIL-survival associations by race and ethnicity. We assessed associations of continuous sTIL scores and sTIL-enriched breast cancers (defined as percent lymphocytic infiltration of tumor stroma or cell nests at cutoffs of 30%, 50%, and 70%) with clinical and epidemiologic characteristics and conducted multivariable survival analyses. Although we identified no difference in sTIL score by race and ethnicity, higher continuous sTIL score was associated with lower breast cancer-specific mortality only among non-Hispanic White and Asian American but not African American and Hispanic women. This finding suggests that complex factors influence treatment response and survival, given that sTIL enrichment was not associated with a survival advantage among women from minoritized groups, who more often experience health disparities. Further study of patient selection for sTIL-guided treatment strategies is warranted.

Abstract 3425: Genetic predisposition to obesity and survival in women with breast cancer

Abstract Background. Higher body mass index (BMI) is associated with poor survival after breast cancer diagnosis. BMI is a heritable trait. A polygenic risk score (PRS) for BMI has been associated with cardiometabolic traits and found to modify weight loss interventions. Whether BMI genetic scores affect survival in women with breast cancer is unknown. Methods. This analysis was conducted in the Cancer Prevention Study II Nutrition cohort. Women diagnosed with non-metastatic breast cancer between 1992 and 2017 were included in the analysis if they had genotype data. Analyses were restricted to unrelated, postmenopausal women at the time of diagnosis who were of European ancestry (N=3,566). Deaths through 2020 were identified through linkage with the National Death Index. Primary cause of death was based on the International Classification of Disease codes. Pre-diagnosis BMI was self-reported (median 1.3 years from BMI measurement to diagnosis, interquartile range (IQR): 0.6, 1.9). We constructed a PRS using findings from a published meta-analysis of BMI genome wide association studies (GWAS) that included ~700,000 individuals and the PRSice tool.Hazard ratios (HR) and 95% confidence intervals (CI) between the PRS and all-cause mortality were estimated using Cox proportional hazards regression and Fine and Gray models for cause-specific mortality to account for competing risks. Models were adjusted for age and GWAS-specific statistically significant (P<0.05) principal components for population stratification. Mediation was estimated using the mediation R package. Results. The median age at diagnosis was 71.5 years (IQR: 66.3, 76.8). Most women were overweight (33.5%) or obese (18.4%) and were diagnosed with localized stage (63%) and estrogen receptor positive (65%) breast cancer. During a median follow-up of 14.5 years (IQR: 9.7-19.8), there were 1,825 (51.2%) deaths, including 301 breast cancer and 337 cardiovascular disease (CVD) specific deaths. In multivariable models, a 5 Kg/m2 increase in BMI was associated with increased risks of all-cause mortality (HR=1.09, 95% CI: 1.04, 1.15), breast cancer-specific mortality (HR=1.27, 95% CI: 1.13, 1.42), and CVD-specific mortality (HR=1.25, 95% CI: 1.11, 1.41). The PRS was highly predictive of pre-diagnostic BMI (P<0.001). A 1-standard deviation increase in the PRS was associated with statistically increased risk of all-cause mortality (HR=1.06, 95% CI: 1.02, 1.11). Risks of breast cancer (HR=1.07, 95% CI: 0.96, 1.19) or CVD (HR=1.01, 95% CI: 0.90, 1.12) specific mortality did not reach statistical significance. We estimated that 27% of the PRS and all-cause mortality association was mediated by BMI (95% CI: 12%, 91%; P=0.004). Conclusions. Women with breast cancer predisposed to higher BMI were at increased risk of all-cause mortality. A BMI-related PRS may be a useful tool to identify women with breast cancer in need of additional interventions and/or surveillance. Citation Format: Clara Bodelon, Adriana Lori, Mariah Landry, James Hodge, Parichoy Pal Choudhury, Ying Wang, Lauren E. McCullough, Alpa V. Patel, Lauren R. Teras. Genetic predisposition to obesity and survival in women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3425.

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer

It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

Abstract 841: Fine particulate matter exposure during breast cancer treatment among older women associated with increased mortality

Abstract Background: Fine Particulate Matter (PM2.5) is associated with higher mortality among people with chronic conditions. Breast cancer (BC) survivors may be particularly vulnerable during cancer treatment. We assessed the association between PM2.5 during 9-months following BC diagnosis and all-cause and BC-mortality using policy relevant PM2.5 cut-offs. Methods: Using SEER-Medicare linked with a high-resolution model-based PM2.5 by residential zipcode (2007-2016), we assembled a cohort of women ≥66 years with incident stage I-IV BC. We assessed PM2.5 exposure, categorized as &amp;lt;8 µg/m3 (low), 8-12 µg/m3 (moderate) and &amp;gt;12 µg/m3 (high—above air quality standard), and types of cancer treatments (surgery [SX], chemotherapy [CTX], radiation therapy [RTX]) during a 9-month landmark period. We identified all-cause and BC death within 5 years of diagnosis. We fit multivariable Cox proportional hazard models to assess associations with PM2.5 exposure adjusting for individual-level characteristics (demographics, tumor characteristics, comorbidities), neighborhood SES, SEER state, and long-term PM2.5 exposure. We also evaluated the association between PM2.5 exposure and mortality by treatment types (SX, SX + RTX, SX + CTX, SX + RTX + CTX, and RTX and/or CTX). We used multiple imputation to account for missing variables (race, ER status, HER2 status, grade). Results: Among 72,798 women (mean age 75 years, 83% white, 56% stage I, 32% II, 9.2% III, 2.9% IV), 41%, 32%, 13%, 8.4%, and 5.1% received SX + RTX, SX only, SX + Chemo + RTX, SX + Chemo, and CTX and/or RTX. The mean PM2.5 level was 8.8 µg/m3 [36%, 52% and 11% were exposed to &amp;lt;8, 8-12, and &amp;gt;12, respectively]. We observed 12,163 all-cause and 4,729 BC deaths during follow-up. Compared to those exposed to low levels, higher levels of PM2.5 exposure were associated with increased all-cause mortality for both moderate PM2.5 [HR 1.03 (95%CI:1.00-1.05)] and high PM2.5 [HR 1.09 (95%CI: 1.06-1.14)] but not BC-specific mortality. Among treatment subgroups, PM2.5 was associated with higher all-cause mortality in SX+RTX for moderate [HR 1.24 (95%CI:1.18-1.32)] and high PM2.5 [HR 1.36 (95%CI: 1.25-1.48)] and SX+RTX+CTX for high PM2.5 [HR 1.33 (95%CI: 1.17-1.51)]. There were no association between moderate/high PM2.5 with all-cause mortality in SX only and SX+CTX. Among the SX+RTX subgroup, BC-specific mortality was elevated for both moderate [HR 1.50 (95%CI:1.35-1.66)] and high PM2.5 [HR 1.81 (95%CI: 1.55-2.12)]. Conclusion: Even below EPA regulatory thresholds (PM2.5 &amp;lt;12 µg/m3), we observed increased risk of death in BC survivors who had high PM2.5 exposure during treatment period. The elevated mortality primarily occurred among women who received RTX and was present for all-cause and BC-specific mortality. The potential interaction between RTX and PM2.5 exposure, even after adjusting for tumor subtype and stage, warrants further evaluation. Citation Format: Benjamin Bates, Rachel Nethery, Melanie Rua, Hari Iyer, Elisa Bandera, Soko Setoguchi. Fine particulate matter exposure during breast cancer treatment among older women associated with increased mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 841.

Abstract 2218: Dietary insulinemic potential and survival after breast cancer diagnosis

Abstract Background: Hyperinsulinemia may promote the growth and metastasis of breast cancers by activating the insulin/insulin-like growth factor 1 signaling pathways. Whether the insulinemic potential of the diet contributes to breast cancer prognosis has not been examined previously. Here, we focused on a food-based empirical dietary index for hyperinsulinemia (EDIH), an index previously designed as most predictive of fasting plasma C-peptide. We aimed to investigate whether EDIH (at different time settings) is associated with overall and breast cancer-specific mortality. Methods: For 9,640 women with stage I-III breast cancer from the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII), we calculated the cumulative average EDIH, using repeated measures of post-diagnostic diet from food frequency questionnaires (FFQ). We also considered the pre-diagnostic EDIH score (using the last FFQ reported before diagnosis), the first postdiagnostic EDIH score, as well as a simple updated EDIH score. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. Deaths were ascertained by report from family members or by searching the National Death Index. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: Participants were followed up for a median of 12 years after breast cancer diagnosis. We documented 1,120 deaths due to breast cancer and 2,762 all-cause deaths. Women with higher post-diagnostic EDIH had a 40% higher risk of all-cause mortality (HR for quintile 5 vs. quintile 1 [HRQ5vs.Q1], 1.40; 95% CI, 1.22, 1.61; P-trend&amp;lt;0.0001). EDIH was also associated with a 19% increased risk of breast cancer mortality, although the confidence interval included the null (HRQ5vs.Q1, 1.19; 95% CI, 0.95, 1.48; P-trend=0.17). Findings for overall mortality were similar for EDIH measured at other timings/settings: last pre-diagnosis dietary assessment (HRQ5vs.Q1,1.21; 95% CI, 1.06, 1.39; P-trend&amp;lt;0.0001) and first post-diagnosis dietary assessment (HRQ5vs.Q1,1.23; 95% CI, 1.08, 1.40; P-trend&amp;lt;0.0001). Conclusions: In this large prospective study of breast cancer survivors, higher hyperinsulinemic dietary scores (reflecting higher dietary insulinemic potential) were associated with worse survival outcomes following diagnosis. Thus, dietary recommendations emphasizing the importance of avoiding high insulinemic dietary patterns (i.e., processed meat and red meat) and prioritizing low insulinemic dietary patterns (i.e., coffee, whole fruit and green-leafy vegetables) as components of a healthy diet may improve overall survival. Citation Format: Andrea Romanos-Nanclares, Tengteng Wang, Bernard A. Rosner, Michelle D. Holmes, Wendy Y. Chen, Walter C. Willett, Rulla M. Tamimi, A. Heather Eliassen. Dietary insulinemic potential and survival after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2218.

Abstract P115: Urban Greenspace and All-Cause, Cardiovascular Disease-Specific, and Breast Cancer-Specific Mortality Among Older Women With Breast Cancer in the United States: Regional Variations Within the Surveillance, Epidemiology, and End Results and Medicare Linked Database

Background: Cardiovascular disease (CVD) and cancer are leading causes of morbidity and mortality in the US. Cancer survivors are at increased risk for adverse CVD outcomes due to multiple factors, including cardiotoxicity. Research suggests that greenspace contributes to better health outcomes, including CVD and breast cancer (BC). Objective: To explore relationships between urban greenspace and all-cause (ACM), CVD-specific (CVDSM), and BC-specific (BCSM) mortality and explore regional differences among older women diagnosed with BC in the US SEER-Medicare database. Methods: The 2011 national landcover database was linked to the 2010 census tracts and the 2010-2017 SEER-Medicare BC cohort. Women were included if they were 66+ years at diagnosis, had invasive BC, enrolled in Medicare Part A and Part B for 12 months before diagnosis, and had a census tract match for greenspace. Independent variable ‘greenspace’ was census tract percent tree canopy quartiles. Outcomes were all-cause, CVD, and BC-specific survival. Censoring was determined by the end of the study date, 12/31/2018. Covariates included age and comorbidity at BC diagnosis, race/ethnicity, dual enrollment in both Medicare and Medicaid eligibility, neighborhood social vulnerability, and tumor stage. Results: Regional variations in association between greenspace and BC survival were observed (Table 1). Greenspace is protective for ACM and BCSM in California, Washington, New Jersey, and Michigan, while no significant associations were observed in Georgia or Louisiana. For CVDSM, greenspace is protective in CA, while no significant differences were observed in Washington, Louisiana, and Michigan. An inverse relationship is observed for CVDSM in Georgia and New Jersey. Discussion: Our findings warrant more studies to investigate why greenspace is protective in some areas (i.e., CA, NJ, MI) or hazardous in other areas (i.e., GA). There is a need to identify critical factors and pathways contributing to these greenspace-survival differences.

Structured screening for sporadic breast cancer

The aim of secondary prevention of breast cancer is to detect the disease at the earliest curable stage and thus to reduce breast cancer-specific mortality. To this end, the nationwide population-based mammography screening program (MSP) was set up in Germany in 2005 in addition to an interdisciplinary prevention project for high-risk groups. Overview of the current state of the MSP, the upcoming age expansion, and potential further developments. Narrative review article with topic-guided literature and data search. Approximately 50% of the 70,500 new cases of breast cancer that occur each year are related to the age group of the MSP. 10years after introduction of the MSP, the incidence of advanced breast cancer stages and breast cancer-related mortality of the screening target group have steadily decreased by about one quarter, while no relevant trends were seen in the neighboring age groups at the population level. The MSP has effectively contributed to areduction of breast cancer mortality. With the expansion of the age groups to 45-75years, more women have access to structured, quality assured screening. With the use of advanced stratifications and diagnostics as well as artificial intelligence, the MSP could be further optimized.

Familial adversity: association with discontinuation of adjuvant hormone therapy and breast cancer prognosis.

Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in breast cancer patients. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer-specific mortality. By cross-linking seven Swedish health registers, we performed a cohort study including all breast cancer patients who initiated adjuvant hormone therapy during 2006-2019 in Sweden (N = 10,701). A group-based multi-trajectory model was used to identify familial adversity groups based on three dimensions: material deprivation, negative family dynamics, and loss or threat of loss. Cox proportional hazard models were used to investigate associations of familial adversity with hormone therapy discontinuation and breast cancer-specific mortality. We identified five distinctive familial adversity groups among the cohort participants. Compared to women with low familial adversity, higher risks to discontinue adjuvant hormone therapy were observed among women with material deprivation (hazard ratio (HR), 1.31; 95% CI, 1.20-1.43), negative family dynamics (HR, 1.16; 95% CI, 1.06-1.28), loss or threat to loss (HR, 1.15; 95% CI, 1.00-1.32), or high familial adversity (HR, 1.53; 95% CI, 1.40-1.68). Furthermore, women with material deprivation (HR, 1.37; 95% CI, 1.05-1.79), negative family dynamics (HR, 1.41; 95% CI, 1.01-1.97), or high adversity (HR, 1.67; 95% CI, 1.26-2.23) were at higher risks of dying from breast cancer. Familial adversity is associated with a higher risk of adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Family-related factors identified in our study may help identify high-risk patients for interventions to prevent treatment discontinuation and subsequently improve breast cancer outcomes.

Treatment and Prognosis of Male Breast Cancer: A Multicentric, Retrospective Study Over 11 Years in the Czech Republic.

Male breast cancer (MBC) is a rare, but increasingly common disease, and lacks prospective studies. Collaborative efforts are needed to understand and address MBC, including its prognosis, in different countries. We retrospectively reviewed the clinical, histopathological, and molecular-genetic characteristics, treatments, and survival outcomes of MBC diagnosed between 2007 and 2017 in the Czech Republic. Prognostic factors of overall survival (OS), recurrence-free interval (RFi), and breast cancer-specific mortality (BCSM) were analyzed and indirectly compared to international data. We analyzed 256 patients with MBC (median age 66 years), including 12% with de novo metastatic (M1). Of 201 non-metastatic (M0) patients, 6% were <40 years old, 29% had stage I, 55% were cN0, and 54% underwent genetic testing. Overall, 97% of tumors had estrogen receptor expression ≥10%, 61% had high Ki67 index, 40% were high-grade (G3), and 68% were luminal B-like (HER2-negative). Systemic therapies included endocrine therapy (90%) and chemotherapy (53%). Few (5%) patients discontinued adjuvant endocrine therapy for reasons other than disease relapse or death. Patients treated with aromatase inhibitors alone had significantly shorter RFi (P < .001). OS, RFi, and BCSM were associated with disease stage, T stage, N stage, progesterone receptor expression, grade, and Ki67 index. Median OS reached 122 and 42 months in M0 and de novo M1 patients, respectively. Due to the rarity of MBC, this study highlights important findings from real clinical practice. Although the number of patients with MBC with unfavorable features was higher in this Czech dataset than in international studies, the prognosis remains consistent with real-world evidence.

Does diabetes affect breast cancer survival?

The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rēhita Mate Ūtaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method. The hazard ratio (HR) of breast cancer-specific mortality for women with diabetes compared to women without diabetes was estimated using the Cox proportional hazards model. For women with diabetes, the 5-year and 10-year of cancer-specific survival were 87% (95% CI: 85%-88%) and 79% (95% CI: 76%-81%) compared to 89% (95% CI: 89%-90%) and 84% (95% CI: 83%-85%) for women without diabetes. The HR of cancer-specific mortality for patients with diabetes compared to those without diabetes was 0.99 (95% CI: 0.89-1.11) after adjustment for patient demographics, tumor characteristics, and treatments. Age at cancer diagnosis and cancer stage had the biggest impact on the survival difference between the two groups. When stratified by cancer stage, the cancer-specific mortality between the two groups was similar. While differences in survival have been identified for women with diabetes when compared to women without diabetes, these are attributable to age and the finding that women with diabetes tend to present with more advanced disease at diagnosis. We did not find any difference in survival between the two groups due to differences in treatment.

Mortality Risks Over 20 Years in Men With Stage I to III Hormone Receptor–Positive Breast Cancer

In women with hormone receptor-positive (HR+) breast cancer, the risk of distant recurrence and death persists for at least 20 years from diagnosis. The risk of late mortality in men with HR+ breast cancer has not been reported. To report 20-year risks of breast cancer-specific mortality (BCSM) and non-BCSM in men with stage I to III HR+ breast cancer and identify factors associated with late BCSM. An observational cohort study was conducted of men diagnosed with HR+ breast cancer from 1990 to 2008, using population-based data from the Surveillance, Epidemiology, and End Results program. Men diagnosed with stage I to III HR+ breast cancer were included in the analysis. Cumulative incidence function was used to estimate the outcomes of baseline clinicopathologic variables regarding cumulative risk of BCSM and non-BCSM since diagnosis. Smoothed hazard estimates over time were plotted for BCSM. Fine and Gray multivariable regression evaluated the association of preselected variables with BCSM, conditional on having survived 5 years. BCSM. A total of 2836 men with stage I to III HR+ breast cancer were included, with a median follow-up of 15.41 (IQR, 12.08-18.67) years. Median age at diagnosis was 67 (IQR, 57-76) years. The cumulative 20-year risk of BCSM was 12.4% for stage I, 26.2% for stage II, and 46.0% for stage III. Smoothed annual hazard estimates for BCSM revealed an increase in late hazard rates with each incremental node category, reaching a bimodal distribution in N3 and stage III, with each having peaks in hazard rates at 4 and 11 years. Among patients who survived 5 years from diagnosis, the adjusted BCSM risk was higher for those younger than 50 years vs older than 64 years, those with grade II or III/IV vs grade I tumors, and stage II or III vs stage I disease. The findings of this study suggest that, in men with stage I to III HR+ breast cancer, the risk of BCSM persists for at least 20 years and depends on traditional clinicopathologic factors, such as age, tumor stage, and tumor grade. Among men with higher stages of disease, the kinetics of the BCSM risk appear different from the risk that has been reported in women.

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023. Self-reported bilateral oophorectomy (with or without salpingectomy). All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy. In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

Healthy and Unhealthy Plant-Based Diets and Body Weight in Breast Cancer Survivors: A Narrative Review

Obesity in breast cancer (BC) survivors increase the risk of BC recurrence, second primary BC, BC-specific mortality, and overall mortality. Guidelines for BC survivors encourage healthy lifestyles by promoting healthy diets, engage in physical activity and avoid weight gain to achieve longer survival and improved quality of life. In recent years, there has been a growing interest in the possible beneficial role of plant-based diets in body weight control and in BC risk and prognosis. Plant-based diets can be evaluated using dietary indices which provide a quantitative measure of how closely an individual’s diet aligns with a plant-based dietary pattern. However, there is a need to distinguish plant-based diets in healthy and unhealthy. This approach would address a research gap that often overlooks the quality and specific types of plant foods consumed. The aim of this narrative review is to analyze how a plant-based diet may impact on body weight in BC survivors, synthesizing existing evidence and discussing the potential mechanisms and implications. The findings suggest the importance of considering the quality of plant-based diets, as some may include vegetarian foods with a low nutritional profile which may negatively impact on body weight. This aspect could be crucial in preventing weight gain in women with BC, as body weight is considered a risk factor for poor BC prognosis and reduced survival.

Survival Outcomes in Older Women with Oestrogen-Receptor-Positive Early-Stage Breast Cancer: Primary Endocrine Therapy vs. Surgery by Comorbidity and Frailty Levels.

Primary endocrine therapy (PET) offers non-surgical treatment for older women with early-stage breast cancer who are unsuitable for surgery due to frailty or comorbidity. This research assessed all-cause and breast cancer-specific mortality of PET vs. surgery in older women (≥70 years) with oestrogen-receptor-positive early-stage breast cancer by frailty and comorbidity levels. This study used UK secondary data to analyse older female patients from 2000 to 2016. Patients were censored until 31 May 2019 and grouped by the Charlson comorbidity index (CCI) and hospital frailty risk score (HFRS). Cox regression models compared all-cause and breast cancer-specific mortality between PET and surgery within each group, adjusting for patient preferences and covariates. Sensitivity analyses accounted for competing risks. There were 23,109 patients included. The hazard ratio (HR) comparing PET to surgery for overall survival decreased significantly from 2.1 (95%CI: 2.0, 2.2) to 1.2 (95%CI: 1.1, 1.5) with increasing HFRS and from 2.1 (95%CI: 2.0, 2.2) to 1.4 (95%CI 1.2, 1.7) with rising CCI. However, there was no difference in BCSM for frail older women (HR: 1.2; 0.9, 1.9). There were no differences in competing risk profiles between other causes of death and breast cancer-specific mortality with PET versus surgery, with a subdistribution hazard ratio of 1.1 (0.9, 1.4) for high-level HFRS (p = 0.261) and CCI (p = 0.093). Given limited survival gains from surgery for older patients, PET shows potential as an effective option for frail older women with early-stage breast cancer. Despite surgery outperforming PET, surgery loses its edge as frailty increases, with negligible differences in the very frail.

Identifying determinants of adherence to adjuvant endocrine therapy following breast cancer: A systematic review of reviews.

In oestrogen-receptor positive breast cancer, daily oral adjuvant endocrine therapy (ET) for at least 5 years significantly reduces risks of recurrence and breast cancer-specific mortality. However, many women are poorly adherent to ET. Development of effective adherence support requires comprehensive understanding of influences on adherence. We undertook an umbrella review to identify determinants of ET adherence. We searched PubMed, Embase, CINAHL, PsycINFO, Cochrane and PROSPERO (inception to 08/2022) to identify systematic reviews on factors influencing ET adherence. Abstracted determinants were mapped to the World Health Organization's dimensions of adherence. Reviews were quality appraised and overlap assessed. Of 5732 citations screened, 17 reviews were eligible (9 quantitative primary studies; 4 qualitative primary studies; 4 qualitative or quantitative studies) including 215 primary papers. All five WHO dimensions influenced ET non-adherence: The most consistently identified non-adherence determinants were patient-related factors (e.g. lower perceived ET necessity, more treatment concerns, perceptions of ET 'cons' vs. 'pros'). Healthcare system/healthcare professional-related factors (e.g. perceived lower quality health professional interaction/relationship) were also important and, to a somewhat lesser extent, socio-economic factors (e.g. lower levels of social/economic/material support). Evidence was more mixed for medication-related and condition-related factors, but several may be relevant (e.g. experiencing side-effects, cost). Potentially modifiable factors are more influential than non-modifiable/fixed factors (e.g. patient characteristics). The evidence-base on ET adherence determinants is extensive. Future empirical studies should focus on less well-researched areas and settings. The determinants themselves are numerous and complex in indicating that adherence support should be multifaceted, addressing multiple determinants.

Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Additionally, obese and postmenopausal women are at higher risk of all-cause and breast cancer-specific mortality compared with non-obese women with breast cancer. In this context, increased levels of estrogens, excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, adipocyte-derived adipokines, hypercholesterolemia, and excessive oxidative stress contribute to the development of breast cancer in obese women. Genetic evaluation is an integral part of diagnosis and treatment for patients with breast cancer. Despite trimodality therapy, the four-year cumulative incidence of regional recurrence is significantly higher. Axillary lymph nodes as well as primary lesions have diagnostic, prognostic, and therapeutic significance for the management of breast cancer. In clinical setting, because of the obese population primary lesions and enlarged lymph nodes could be less palpable, the diagnosis may be challenging due to misinterpretation of physical findings. Thereby, a nomogram has been created as the "Breast Imaging Reporting and Data System" (BI-RADS) to increase agreement and decision-making consistency between mammography and ultrasonography (USG) experts. Additionally, the "breast density classification system," "artificial intelligence risk scores," ligand-targeted receptor probes," "digital breast tomosynthesis," "diffusion-weighted imaging," "18F-fluoro-2-deoxy-D-glucose positron emission tomography," and "dynamic contrast-enhanced magnetic resonance imaging (MRI)" are important techniques for the earlier detection of breast cancers and to reduce false-positive results. A high concordance between estrogen receptor (ER) and progesterone receptor (PR) status evaluated in preoperative percutaneous core needle biopsy and surgical specimens is demonstrated. Breast cancer surgery has become increasingly conservative; however, mastectomy may be combined with any axillary procedures, such as sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection whenever is required. As a rule, SLNB-guided axillary dissection in breast cancer patients who have clinically axillary lymph node-positive to node-negative conversion following neoadjuvant chemotherapy is recommended, because lymphedema is the most debilitating complication after any axillary surgery. There is no clear consensus on the optimal treatment of occult breast cancer, which is much discussed today. Similarly, the current trend in metastatic breast cancer is that the main palliative treatment option is systemic therapy.

Influence of postdiagnostic aspirin use on clinical outcomes of women with breast cancer: a meta-analysis

ABSTRACT We examined the association between postdiagnostic aspirin use and recurrence and disease-specific mortality among women with breast cancer in a meta-analysis. The PubMed, Embase, and Web of Science databases were searched to identify observational studies with longitudinal follow-ups according to the aim of the meta-analysis. Combining the results was achieved using a random-effects model that included inter-study heterogeneity. Fifteen cohort studies with 131,636 women with breast cancer were included. Based on a meta-analysis, women who took aspirin after being diagnosed with breast cancer had a lower risk of breast cancer recurrence (adjusted risk ratio [RR]: 0.77, 95 percent confidence interval [CI]: 0.63 to 0.95, P = .02; I2 = 72 percent) and breast cancer specific mortality (adjusted RR: 0.73, 95 percent CI: 0.60 to 0.90, P = .004; I2 = 80 percent) than those who did not use aspirin. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluations scoring system showed moderate certainty for both the outcomes because significant inconsistency was observed. In conclusion, aspirin use after diagnosis might be associated with reduced recurrence and disease-specific mortality in women with breast cancer.

Association of molecular subtypes and treatment with survival in invasive micropapillary breast cancer: an analysis of the Surveillance, Epidemiology, and End Results database.

This study aims to examine the features, treatments, and survival of invasive micropapillary carcinoma (IMPC) according to different molecular subtypes. In this cohort study, data between 2010 and 2018 were retrospectively reviewed from the Surveillance, Epidemiology, and End Results database. Molecular subtypes were categorized into four varieties: hormone receptor (HR)+/HER2- (Luminal A), HR+/HER2+ (Luminal B), HR-/HER2- [triple-negative (TN)], and HR-/HER2+ (HER2 enriched). In this study, 1,180 IMPC patients were included, with 99 patients (8.39%) of the 1,180 patients having an overall mortality, and 53 patients (53.54%) of the 99 patients having a breast cancer-specific mortality. The follow-up duration was 40.00 (18.50, 61.00) months. TN molecular subtype was associated with worse OS and BCSS in IMPC patients. Treatment of chemotherapy, radiation, and combination therapy were associated with better survival in HR+/HER2+ molecular subtype and HR+/HER2- molecular subtype. However, in HR-/HER2- molecular subtype, treatment of chemotherapy was associated with a poor BCSS, and treatment of radiation was not associated with OS and BCSS. Surgery treatment was not associated with survival in HR+/HER2+ molecular subtype and HR+/HER2- molecular subtype. However, surgery treatment of mastectomy was associated with better OS in HR-/HER2- molecular subtype (P < 0.05). The prognosis of IMPC was significantly influenced by different molecular subtypes. Chemotherapy and radiotherapy are beneficial in HR+/HER2+ and HR+/HER2- patients. However, they should be used with caution in HR-/HER2- (TN) patients.

Post-diagnosis weight trajectories and mortality among women with breast cancer

Weight gain after breast cancer diagnosis is associated with adverse health outcomes. Yet, few studies have characterized post-diagnosis weight change in the modern treatment era or populations most at risk for weight changes. Among women diagnosed with stages I–III breast cancer in the Smilow Care Network (2013–2019; N = 5441), we abstracted demographic and clinical characteristics from electronic health records and survival data from tumor registries. We assessed if baseline characteristics modified weight trajectories with nonlinear multilevel mixed-effect models. We evaluated body mass index (BMI) at diagnosis and weight change 1-year post-diagnosis in relation to all-cause and breast cancer-specific mortality with Cox proportional hazard models. Women had 34.4 ± 25.5 weight measurements over 3.2 ± 1.8 years of follow-up. Weight gain was associated with ER/PR−, HER2+ tumors, BMI ≤ 18.5 kg/m2, and age ≤ 45 years (+4.90 kg (standard error [SE] = 0.59), +3.24 kg (SE = 0.34), and +1.75 kg (SE = 0.10), respectively). Weight loss was associated with BMI ≥ 35 kg/m2 and age ≥ 70 years (−4.50 kg (SE = 0.08) and −4.34 kg (SE = 0.08), respectively). Large weight loss (≥10%), moderate weight loss (5–10%), and moderate weight gain (5–10%) 1-year after diagnosis were associated with higher all-cause mortality (hazard ratio [HR] = 2.93, 95% confidence interval [CI] = 2.28–3.75, HR = 1.32, 95% CI = 1.02–1.70 and HR = 1.39, 95% CI = 1.04–1.85, respectively). BMI ≥ 35 kg/m2 or BMI ≤ 18.5 kg/m2 at diagnosis were also associated with higher all-cause mortality. Weight change after a breast cancer diagnosis differed by demographic and clinical characteristics highlighting subgroups at-risk for weight change during a 5-year period post-diagnosis. Monitoring and interventions for weight management early in clinical care are important.