Outcomes In Breast Cancer Survivors Research Articles

Incident Myocardial Infarction, Heart Failure, and Oncologic Outcomes in Breast Cancer Survivors

Incident Myocardial Infarction, Heart Failure, and Oncologic Outcomes in Breast Cancer Survivors

Correlation analysis of Ki67 changes with survival outcomes in breast cancer before and after neoadjuvant therapy based on residual cancer Burden grade

PurposeThis study aims to investigate the change of Ki67 value pre- and post-neoadjuvant therapy (NAT) and evaluate its potential value in predicting survival outcomes in different molecular subtypes of breast cancer. MethodsA total of 257 breast cancer patients who underwent NAT at Renmin Hospital of Wuhan University from July 2019 to Sep 2023 were included in this study. The Ki67 index of the patients was re-interpreted by two attending physicians, and the changes of Ki67 value pre- and post-NAT were compared. Chi-square test (χ2) and logistic regression were conducted to examine the correlation between various characteristics and the efficacy of NAT. Disease-free survival (DFS) was calculated using the Kaplan-Meier curve and compared using the log-rank test. ResultsPatients with higher histological grade, negative expression of estrogen receptor (ER) or progesterone receptor (PR), positive expression of human epidermal growth receptor 2 (HER2), higher pretreatment Ki67 index, absence of lymph node metastasis, and those with HER2 positive and triple-negative breast cancer were associated with improved efficacy of NAT. Our study identified that the optimal cut-off value for the changes in Ki67 index pre- and post-NAT related to the effectiveness of NAT was “-88.19 %” in whole chort, which was related to the aforementioned clinical characteristics. Besides, the optimal cut-off values for the luminal, HER2-enriched and triple-negative subtypes were “-91.83 %”, “-46.12 %” and “-81.67 %”, respectively. Survival analysis demonstrated that the changes in Ki67 value were significantly associated with DFS in the HER2-enriched and triple-negative subtype, but not in the luminal subtype. ConclusionsPreoperative clinicopathological features and changes in Ki67 value pre-and post-NAT can contribute to providing patients with a more accurate prognosis.

The prognostic value of skeletal muscle mass and density in breast cancer: a systematic review and meta-analysis.

Aim: The effect of skeletal muscle mass and density on the long-term survival outcome of breast cancer patients is unclear.Materials & methods: Systematically searched all articles in PubMed, Web of science, Springerlink, EMBASEand Wiley databases that studied the association between skeletal muscle and survival outcomes of breast cancer by 25September 2023. The hazard ratios and confidence intervals of the multiple factor analysis results controlling for confounding variables in the study were collected and analyzed using STATA 14.0 software.Results: This meta-analysis included a total of 13 studies, with a median age of 48.2years. Meta results showed that the survival (hazard ratio [HR]: 0.98, 95% CI: 0.89-1.08) and recurrence (HR: 0.96, 95% CI: 0.92-1.00) outcomes of breast cancer patients with sarcopenia were not significantly affected compared with those without sarcopenia. No significant heterogeneity or publication bias was observed in the study.Conclusion: The conclusion that skeletal muscle is regarded as a useful factor that can guide and optimize the prognosis of breast cancer patients is uncertain, or the result is very weak. Considering the impact of research quality and confounding factors, prospective studies are needed in the future to further demonstrate.PROSPERO identifier: CRD42023463480 (www.crd.york.ac.uk/prospero).

Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute.

Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the risk-adapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%-3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice.

Characteristics and Survival Outcomes of Male Breast Cancer in Brazil: A Large Population-Based Study

AimsThis study evaluated the clinicopathological characteristics, treatment trends, and overall survival (OS) in male breast cancer (BC) in Sao Paulo State of Brazil. Materials and methodsMen diagnosed with invasive breast cancer between January 2000 and June 2020 were identified from Fundação Oncocentro de Sao Paulo database encompasses data pertinent to 46 million residents of the Sao Paulo State of Brazil. Patients were described according to age, education level, clinical stage, treatment modalities, and medical practice. Categorical variables were described as percentages and frequencies. Demographic, treatment factors, and OS were associated using a Cox proportional hazard regression model while accounting for different lengths of participant follow-up. The Kaplan-Meier curves were used to display survival curves. ResultsA total of 907 male BC patients were included. The age distribution at diagnosis was <51 years, 51–70 years, and >70 years in 21.5%, 51.5% and 27.0% of patients, respectively. The proportions of stages I, II, III, and IV were 19.5%, 36.6%, 31.5%, and 12.3%. For each stage I, II, III, and IV, 5- and 10-years OS were 87.9% and 77.8%, 79.9% and 58.9%, 51.6% and 24.5%, 20.0% and 5.6%, respectively. Patients who received postoperative radiotherapy experienced a significant improvement in OS (HR 0.67; 95% CI 0.53–0.84; p < 0.001). In the multivariable analysis adjusted for practice (public or private), education (low or medium/high), age, stage at diagnosis, and treatment modalities, the significant independent predictor for OS was stage at diagnosis. ConclusionMale BC tends to be diagnosed at a more advanced stage and older age at the time of diagnosis. Age and educational level did not influence survival outcomes. Stage at diagnosis and the use of postoperative radiotherapy were factors associated with improved OS.

Menopausal Hormone Therapy in Breast Cancer Survivors.

Menopausal symptoms negatively impact quality of life in breast cancer survivors. The paucity of data on the impact of Menopausal Hormone Therapy (MHT) on oncological outcomes in these patients limits informed clinical discussion. Defining the risk of cancer recurrence with MHT is central to the appraisal of risk/benefit, particularly with low-risk disease (based on genomic profile). The aim of this review is to summarize the current data evaluating MHT in breast cancer patients. A systematic review of the literature was performed to evaluate the impact of MHT on oncological outcomes in breast cancer survivors. Three major databases (PubMed, EMBASE and Medline) were searched. The review included all prospective studies published in English. Four randomized control trials and four non-randomized prospective studies were identified. An increase in breast cancer recurrence with MHT was observed in the early randomized trials whilst no increased risk of recurrence was reported in the observational studies. There remains a need to quantify MHT-related recurrence risk in patients with molecularly favorable disease.

The relationship between tumor budding and survival of patients with breast cancer: A meta-analysis.

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.

Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study

BackgroundHypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited. ObjectivesThe purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients. MethodsWomen with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes. ResultsBC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy (P for interaction = 0.01). ConclusionsWomen with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status.

Land- and water-based aerobic exercise program on health-related outcomes in breast cancer survivors (WaterMama): study protocol for a randomized clinical trial

BackgroundBreast cancer is a prevalent form of cancer among women worldwide, often accompanied by physical and psychological side effects due to the disease and the treatment’s aggressiveness. Regular physical exercise has emerged as a non-pharmacological approach to improve the quality of life of breast cancer survivors. We herein report the protocol of the WaterMama Study, which aims to evaluate the effects of land- or water-based aerobic exercise programs, compared to a health education program, on cancer-related fatigue and other health-related outcomes in breast cancer survivors.MethodsThe WaterMama trial is a randomized, single-blinded, three-arm, parallel, superiority trial. We aim to recruit 48 women ≥ 18 years of age who have completed primary treatment for stage I–III breast cancer. Participants are randomly allocated in a 1:1:1 ratio to 12-week interventions of aerobic exercise training programs either in the aquatic or land environment (two weekly 45-min sessions) plus health education (a weekly 45-min session), or an active-control group receiving health education alone (a weekly 45-min session). The primary outcome is cancer-related fatigue, and the secondary outcomes include cardiorespiratory fitness, muscular performance, muscle morphology, functional capacity, mental health, cognitive function, pain, and quality of life. Outcomes assessments are conducted before and after the 12-week intervention period. The analysis plan will employ an intention-to-treat approach and per protocol criteria.DiscussionOur conceptual hypothesis is that both aerobic exercise programs will positively impact primary and secondary outcomes compared to the health education group alone. Additionally, due to its multi-component nature, we expect the aquatic exercise program promote more significant effects than the land exercise program on cancer-related fatigue, muscular outcomes, and pain.Trial registrationThe study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515

Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis.

Tumour innervation is associated with worse patient outcomes in multiple cancers1,2, which suggests that it may regulate metastasis. Here we observed that highly metastatic mouse mammary tumours acquired more innervation than did less-metastatic tumours. This enhanced innervation was driven by expression of the axon-guidance molecule SLIT2 in tumour vasculature. Breast cancer cells induced spontaneous calcium activity in sensory neurons and elicited release of the neuropeptide substance P (SP). Using three-dimensional co-cultures and in vivo models, we found that neuronal SP promoted breast tumour growth, invasion and metastasis. Moreover, patient tumours with elevated SP exhibited enhanced lymph node metastatic spread. SP acted on tumoral tachykinin receptors (TACR1) to drive death of a small population of TACR1high cancer cells. Single-stranded RNAs (ssRNAs) released from dying cells acted on neighbouring tumoural Toll-like receptor 7 (TLR7) to non-canonically activate a prometastatic gene expression program. This SP- and ssRNA-induced Tlr7 gene expression signature was associated with reduced breast cancer survival outcomes. Therapeutic targeting of this neuro-cancer axis with the TACR1 antagonist aprepitant, an approved anti-nausea drug, suppressed breast cancer growth and metastasis in multiple models. Our findings reveal that tumour-induced hyperactivation of sensory neurons regulates multiple aspects of metastatic progression in breast cancer through a therapeutically targetable neuropeptide/extracellular ssRNA sensing axis.

Dietary consumption patterns in breast cancer survivors: Pilot evaluation of diet, supplements and clinical factors

PurposeAdherence to dietary intake guidelines is recommended for optimal nutrition and outcomes in breast cancer survivors. The purpose of this study was to examine dietary quality in a cohort of breast cancer survivors related to current guidelines, guiding further education-based research. MethodsThis exploratory evaluation examined compliance with current dietary guidelines. Data collected included demographics, medical histories and repeated, three-day 24-h dietary recalls. Women with early-stage breast cancer (n = 97) who completed breast cancer treatment between 6 and 24 months were recruited. Descriptive statistics and frequencies were calculated for demographic and lifestyle characteristics, reported fish consumption, body mass index categories, supplement consumption, and adequacy of macronutrient and micronutrient consumption (classified as below, meeting, or exceeding needs). ResultsIn this cohort, 28.9% were classified as overweight and 35% were obese. The mean dietary macronutrient consumption was 44.3% (±8.9%) carbohydrates, 36.6% (±7.3%) fat, and 17.3% (±4.7%) protein. Additionally, 32.3% participants consumed >45 g sugar/d. The mean n-6 to n-3 ratio was 8.0 (±3.3):1. Further, 38% of survivors reported consuming less than 1 serving of fish per week. Participants consumed between 0 and 1.03 servings of fish per day, with an average consumption of 0.16 (±0.26) servings per day and 61.5% (n = 59) consuming 0 servings per day. The mean daily combined dietary and supplement consumption of multiple micronutrients was below the Recommended Daily Allowance for Vitamin D (30%), Calcium (52.6%), Magnesium (42.1%), and Vitamin E (80%). ConclusionBreast cancer survivors 0.5–2 years post-treatment are not meeting recommended nutrition consumption guidelines for a number of nutrients. Findings suggested that nutrition therapy targeting weight loss through reduced sugar, total and saturated fat, while increasing foods rich in omega-3, and ensuring adequate micronutrient consumption would promote better nutritional consumption patterns and improve overall health during survivorship.

Select gene mutations associated with survival outcomes in ER-positive ERBB2-negative early-stage invasive breast cancer: A single-institutional tissue bank study.

The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative early-stage invasive breast cancer (EBC) in a real-world setting is uncertain. Therefore, we aimed to determine the correlation between a 22-gene mutational profile and long-term survival outcomes in patients with ER+/ERBB2- EBC. A total of 73 women diagnosed with ER+/ERBB2- EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse-free survival (RFS) and overall survival (OS). The log-rank test derived p-value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. At follow-up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty-three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85-fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60-5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6-fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31-18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32-27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes. Our single-institution tissue bank study of Taiwanese women with ER+/ERBB2- EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.

Profile of breast cancer in patients with Li-Fraumeni syndrome: An institutional experience.

e13042 Background: Li Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome, associated with multisystem cancer predisposition. Considering the rarity of this syndrome, studies are very sparse on survival outcomes of breast cancer with germline TP53 mutation and there exists discrepancy amongst the results. Methods: This retrospective observational study included 17 patients with germline TP53 mutated breast cancer registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st April 2016 to 31st Dec 2023. Among the 577 high-risk breast cancer patients, who underwent germline mutation testing, 231 (40.03%) cases had pathogenic mutation [145(25.12%) were BRCA mutated,15 (2.59%) were TP53 mutated, and the rest were others pathogenic variant]. All the TP53 mutations were crosschecked via the ClinVar mutation database to be classified as pathogenic. Results: The median age of 15 patients was 31 years (23-55) and 12 (80%) cases were premenopausal. All the patients had breast cancer as the index malignancy. The Stage distribution (AJCC-7th edition) Stage I, 1(6.6%); Stage II, 7 (46.6 %); Stage III, 4 (26.6 %); and Stage IV, 3 (20 %). Eight cases (53.3%) were HER2 positive, 4 (26.6%) were hormone receptor-positive, and 3 (20%) were Triple-negative breast carcinoma (TNBC). Ten (10) patients received neoadjuvant chemotherapy and 6 (60%) had a complete pathological response. Eight cases (53.3%) cases had a significant family history with 9 (60%) of them having at least one first-degree relative with cancer and two had more than one first-degree relative with cancer. One patient had a family history of LFS. The most common familial cancer was breast, followed by lung, GI malignancies, brain tumor, and sarcoma. Synchronous breast cancer was seen in 2 patients, synchronous malignancies were seen in 4 cases (one patient: each with lung adenocarcinoma, periampullary carcinoma, carcinoma colon, and synovial sarcoma, along with breast cancer), Four patients (26.6%) had metachronous cancers: lung cancer, ovarian carcinoma, contralateral breast cancer, and high-grade sarcoma respectively. The most common mutations were point mutations ( n = 11, 73.3%) followed by frameshift mutations ( n = 4, 26.6%). The subtypes of point mutations included missense mutations ( n = 9) and nonsense mutations ( n = 2) with the most common aberration being a replacement of arginine with glycine (c.743G&gt;A, p. Arg248Gln) and locus being exon 7. The median disease-free survival was 41 months and progression-free survival was 15 months. Conclusions: The prevalence of TP53 mutation in our breast cancer patients is 2.5%. With standard treatment protocols, the overall survival of LFS-associated breast cancer is similar to the historic cohort of patients without any germline mutation. Active surveillance of the patient and family screening is imperative, for all positive cases.

Prevalence of somatic PIK3CA mutations in hormone receptor-positive metastatic breast cancer: The Indian experience.

e13047 Background: The phosphatidylinositol 3-kinase (PI3K) inhibitors have been found to improve survival outcomes in hormone receptor-positive metastatic breast cancer (MBC) and are FDA-approved in this setting after progression on hormonal therapy. However, real-world data from India on the prevalence of PIK3CA mutations is scarce. Methods: This is a retrospective study including patients with hormone receptor-positive breast cancer registered at our center between January 2017- and December 2023 who developed metastatic disease on follow-up after getting appropriate treatment (adjuvant /neoadjuvant) as per institutional protocol. The PIK3CA mutation testing was done on the biopsy specimen. FDA-approved therascreen PIL3CA RGQ PCR kit from Qiagen was used and the assay is a real-time qualitative PCR test for the detection of 11 mutations phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene (Exon 7: C420R; Exon 9: E542K, E545A, E545D [1635G&gt;T only], E545G, E545K, Q546E, Q546R; and Exon 20: H1047L, H1047R, H1047Y) using genomic DNA (gDNA) extracted from formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue. The clinical demographics of patients with PIK3CA mutations were extracted from the hospital database and represented descriptively. Results: A total of 80 consecutive patients with hormone-positive breast cancer at relapse were screened and 26 were found to have PIK3CA mutations (32.5%) of which 24 were female (92.3%). The median age of patients with mutated PIK3CA cases was 50 years (range: 31 to 72 years). The clinical stage of disease at presentation was: stage II in 11.5%, IIIA in 23.1%, and IIIB in 65.4% of cases. The median time of relapse was 21 months from diagnosis (range: 10 to 42 months). The disease sites at relapse were multiple in 23 patients (88.46%) [including central nervous system (CNS) relapse in 3 patients) and CNS (brain) only in 3 patients (11.54%). The mutations detected included H1047R (3140A&gt;G at exon 20) in 8 cases, E545K (1633 G&gt;A at exon 9) in 5 cases, Q546R (1637 A&gt;G at exon 9) in 4 cases, E542K (1624 G&gt;A at exon7) in 3 cases and synchronous mutations (E542K/E545K at Exon 7) in 3 cases and (H1047R/H1047L at exon 20 ) in 3 cases. Only eight patients received alpelisib with fulvestrant due to financial constraints. Conclusions: This is the first Indian study that describes the prevalence of PIK3CA mutations in hormone-positive breast cancer at relapse. Around one-third of patients harbor this mutation and 23.1% of cases have CNS involvement at relapse. The most common PIK3CA mutation detected was H1047R (exon 20) followed by E545K (exon 9).

Racial disparities in presentation and survival for lobular breast cancer.

1596 Background: We characterized differences in presentation and survival, and identified predictors of survival, among women of varying race with lobular breast cancer. We also assessed if these trends were unique to ILC by comparing with invasive ductal carcinoma (IDC) and mixed invasive ductal-lobular carcinoma (IDLC). Methods: Using the SEER database, we performed a population-based retrospective cohort study of women diagnosed with ILC, IDC, and IDLC between 1998 and 2019. We collected race, age, marital status, and income. Clinical data included grade, size, laterality, clinical stage, receptor status, surgery type, chemotherapy, radiation, and breast-cancer-specific survival (BCSS). Differences between racial groups were assessed using Chi-square tests or one-way ANOVA. To identify predictors of survival, Cox-proportional hazard models were constructed. Statistical analyses were performed using SAS and P values &lt; 0.05 were considered significant. Results: 38,769 women with ILC were identified, including 32,857 White, 2398 Black, 2352 Asian, and 1162 women of other race. Black women presented with higher-grade, advanced clinical stage, ER+ disease, N2-3 stage, and lower rates of unilateral/bilateral mastectomy than White women. Black women were more likely to not undergo surgery (7.13%), compared with White (4.25%) and Asian (4.04%) women ( P = .0001). Asian women were younger, had more ER-/PR- ILC, and received more chemotherapy. The five-year BCSS rates in Black, White, Asian, and women of other race were 91.5%, 94.2%, 93.7%, and 95.7%, respectively ( P&lt; .0001). Predictors of worse survival include Black race (HR 1.32, P &lt; .0001), ER-/PR- (HR 2.18, P&lt; .0001), ER+/PR- (HR 1.52, P&lt; .0001), and no surgery (HR 4.19, P &lt; .0001). Radiotherapy was associated with improved survival (HR 0.82, P &lt; .0001), while chemotherapy did not affect survival (HR 1.1, P= 0.0504). In comparing across breast cancer subtypes, Black women similarly present with higher grade tumors, advanced clinical stage, ER+ disease, and had higher rates of surgery omission in IDC and IDLC. However, ER-/PR- subtype was notably higher in ILC among Asian women compared with IDC, whereas Black women have higher rates of ER+/PR+ and ER-/PR- ILC. Black women had the lowest five-year BCSS rates across all breast cancer subtypes. Predictors of worse survival in IDC and IDLC include Black race and negative hormone receptor status, while radiation therapy was associated with improved survival. Conclusions: There are differences in clinical presentation of invasive lobular breast cancer according to race.Black women had more advanced disease, while Asian women were younger. Across all subtypes, overall survival for Black women at 5 years was worse compared to other racial groups. Our data provides insight into the complex interactions of race, clinical characteristics, and survival outcomes in lobular breast cancer, with implications for screening considerations.

Outcomes for breast cancer survivors with metastatic disease in a physical activity program for medically underserved cancer survivors.

This study examined the effectiveness and feasibility of the Active Living After Cancer (ALAC) program for metastatic breast cancer (MBC) survivors. ALAC is a 12-session community-based program to help cancer survivors improve their physical functioning and quality of life through increased physical activity. ALAC participants with MBC (stage IV) were compared to survivors with early-stage breast cancer (stages I and II). The International Physical Activity Questionnaire, Godin Leisure-Time Physical Activity, 30-second sit-to-stand test, and PROMIS Global Health were administered at baseline and follow-up. Program satisfaction and retention were assessed at week 12. Repeated-measures mixed models were used to compare changes in outcomes between survivors with early-stage breast cancer and MBC. A total of 585 women (59.3 y ± 10.6), most of whom were Hispanic (54%) or non-Hispanic Black (22%), were included (early stage, n = 538; MBC, n = 47). After the ALAC program, a significant increase in physical activity (P < 0.001), improved physical and mental health T-scores (P < 0.001), and more sit-to-stand repetitions (P < 0.001) were observed for both survivors with early-stage breast cancer and MBC. Women with MBC showed significantly lower physical health (P = 0.037) and physical function (P = 0.010) compared to early-stage at baseline. The ALAC program increased physical activity and improved health-related quality of life and physical function among breast cancer survivors with both early-stage and metastatic disease. This study emphasizes the importance of incorporating physical activity interventions like the ALAC program into the comprehensive care of cancer survivors, including those with metastatic disease.

Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study

BackgroundExperimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates.MethodsA retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information.ResultsA total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7–62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90–0.95 and HR 0.93, 95% CI 0.91–0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7–62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90–0.96 and HR 0.93, 95% CI 0.90–0.96).ConclusionsHigher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Effect of young age (below 40 years) on oncologic outcomes in Lebanese patients with breast cancer: a matched cohort study

BackgroundDeveloping countries have a significantly higher incidence of breast cancer in patients younger than 40 years as compared to developed countries. This study aimed to examine if young age at diagnosis is an independent prognostic factor for worse survival outcomes in breast cancer as well as the effect of age on Disease-free survival (DFS) and local recurrence free survival (LRFS) after adjusting for various tumor characteristics, local and systemic treatments.MethodsThis is a secondary analysis of prospective cohort of patients from two existing databases. We identified patients with breast cancer aged 40 years or less and we matched them to those older than 40 years. We also matched based on stage and molecular subtypes. In cohort 1, we matched at a ratio of 1:1, while in cohort 2 we matched at a ratio of 1:3.ResultsIn cohort 1, Disease-free survival (DFS) at 5 years was significantly shorter for those younger than 40 years (75.6% and 92.7% respectively; p < 0.03). On multivariate analysis, only chemotherapy was found to be significant, while age was not found to be an independent predictor of prognosis. Local recurrence free survival at 5 years was similar between both age categories. Only hormonal therapy is a significant predictor for LRFS at 5 years. In the second cohort, DFS and LRFS at 3 years were similar between those younger and those older than 40 years. On multivariate analysis, no factor including age was found to be an independent predictor of prognosis.ConclusionData in the literature is controversial on the effect of young age on breast cancer prognosis. Our findings could not demonstrate that age is an independent prognostic factor in our population. There is a need for outcomes from larger, prospective series that have longer follow-ups and more data from our region.

YTHDF2 favors protumoral macrophage polarization and implies poor survival outcomes in triple negative breast cancer

Patients with triple-negative breast cancer (TNBC) frequently experience resistance to chemotherapy, leading to recurrence. The approach of optimizing anti-tumoral immunological effect is promising in overcoming such resistance, given the heterogeneity and lack of biomarkers in TNBC. In this study, we focused on YTHDF2, an N6-methyladenosine (m6A) RNA-reader protein, in macrophages, one of the most abundant intra-tumoral immune cells. Using single-cell sequencing and exvivo experiments, we discovered that YTHDF2 significantly promotes pro-tumoral phenotype polarization of macrophages and is closely associated with down-regulated antigen-presentation signaling to other immune cells in TNBC. The invitro deprivation of YTHDF2 favors anti-tumoral effect. Expressions of multiple transcription factors, especially SPI1, were consistently observed in YTHDF2-high macrophages, providing potential therapeutic targets for new strategies. In conclusion, YTHDF2 in macrophages appears to promote pro-tumoral effects while suppressing immune activity, indicating the treatment targeting YTHDF2 or its transcription factors could be a promising strategy for chemoresistant TNBC.

Abstract PO1-03-07: Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level

Abstract Background: Pathological complete response (pCR) has been used as a primary endpoint in neoadjuvant clinical trials for non-metastatic breast cancer and as a surrogate endpoint for long-term survival outcomes. The U.S. Food and Drug Administration (FDA) accepted pCR as a surrogate endpoint for the approval of new drugs in the neoadjuvant setting in high-risk early-stage breast cancer. However, though the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) pooled analysis in 2014 showed that at the patient level achieving pCR was associated with longer overall survival (OS) and event-free survival (EFS), at the trial-level the association between high pCR rate and better OS and EFS outcomes was weak (coefficient of difference [R2]; 0.03 and 0.24, respectively) among all subtypes of breast cancer. A recent study reported that this association at the trial-level was similarly weak among Human Epidermal Growth Factor Receptor-2 (HER-2) positive breast cancer (R2; 0.02 and 0.23, respectively). However, the potential surrogacy of pCR rate for OS and EFS in triple-negative breast cancer (TNBC) in the neoadjuvant setting has not been well studied in a comprehensive manner. Moreover, because of significant advances in systemic treatment strategies in TNBC over the past decade including a combination of immune checkpoint inhibitors (ICIs) with conventional cytotoxic agents, the trial-level surrogacy needs to be reassessed in recently published neoadjuvant clinical trials for TNBC. Our primary objective is to assess the association between pCR rate and survival outcomes in neoadjuvant clinical trials for TNBC by collecting data from articles published after the CTNeoBC article in 2014. Methods: We performed a systematic literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed, Cochrane Library, and Web of Science databases. Articles published between January 1, 2014, and March 31, 2023, were searched. We included only randomized control trials of neoadjuvant treatments for clinical stage I-III TNBC that compared two or more regimens followed by curative intent breast surgery. The selected trials had data for odds ratio (OR) for pCR and hazard ratios (HRs) either for OS or for EFS or disease-free survival (DFS). We excluded trials including estrogen receptor positive, progesterone receptor-positive, or HER-2 positive diseases, and those without data enough to obtain ORs for pCR, HRs for OS, EFS, or DFS. Unpublished data as a full article was also excluded. If EFS could not be obtained from the articles, DFS was used in place of EFS. Two independent investigators (TY and TF) searched and extracted data. Any disagreement was resolved by discussion with the third author (ZZ). A linear regression model on a logarithmic scale weighted by the sample size of each trial was performed and the R2 was used to assess the trial-level association between OR for pCR and HRs for OS or EFS. Results: We identified eight trials with a total of 2,926 patients. Three of the eight trials used ICIs in the intervention arm. One trial did not provide OS data and was not included in the OS analysis. In four trials, EFS was not available and DFS was used for EFS analysis. The R2 was 0.191 (95% confidence interval [CI], 0.165 to 0.218) for OS and 0.193 (95% CI, 0.167 to 0.219) for EFS. Conclusions: Similarly to the previous reports, our findings suggest that the surrogacy of the pCR rate for OS and EFS in recent neoadjuvant clinical trials for TNBC is weak. At this moment, there is no strong evidence to support using pCR as a surrogate for long-term survival outcomes in neoadjuvant clinical trials for TNBC. Citation Format: Toru Yoshino, Zao Zhang, Ryota Sato, Stanley Lipkowitz, Takeo Fujii. Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level [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 PO1-03-07.