Breast Cancer-specific Survival Research Articles

Ki-67 evaluation using deep-learning model-assisted digital image analysis in breast cancer.

To test the efficacy of artificial intelligence (AI)-assisted Ki-67 digital image analysis in invasive breast carcinoma (IBC) with quantitative assessment of AI model performance. This study used 494 cases of Ki-67 slide images of IBC core needle biopsies. The methods were divided into two steps: (i) construction of a deep-learning model (DL); and (ii) DL implementation for Ki-67 analysis. First, a DL tissue classifier model (DL-TC) and a DL nuclear detection model (DL-ND) were constructed using HALO AI DenseNet V2 algorithm with 31,924 annotations in 300 Ki-67 digital slide images. Whether the class predicted by DL-TC in the test set was correct compared with the annotation of ground truth at the pixel level was evaluated. Second, DL-TC- and DL-ND-assisted digital image analysis (DL-DIA) was performed in the other 194 luminal-type cases and correlations with manual counting and clinical outcome were investigated to confirm the accuracy and prognostic potential of DL-DIA. The performance of DL-TC was excellent and invasive carcinoma nests were well segmented from other elements (average precision: 0.851; recall: 0.878; F1-score: 0.858). Ki-67 index data and the number of nuclei from DL-DIA were positively correlated with data from manual counting (ρ = 0.961, and 0.928, respectively). High Ki-67 index (cutoff 20%) cases showed significantly worse recurrence-free survival and breast cancer-specific survival (P = 0.024, and 0.032, respectively). The performances of DL-TC and DL-ND were excellent. DL-DIA demonstrated a high degree of concordance with manual counting of Ki-67 and the results of this approach have prognostic potential.

Prognostic nomograms for young breast cancer: A retrospective study based on the SEER and METABRIC databases.

Young breast cancer (YBC) is a subset of breast cancer that is often more aggressive, but less is known about its prognosis. In this study, we aimed to generate nomograms to predict the overall survival (OS) and breast cancer-specific survival (BCSS) of YBC patients. Data of women diagnosed with YBC between 2010 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated into a training cohort (n = 15,227) and internal validation cohort (n = 6,526) at a 7:3 ratio. With the Cox regression models, significant prognostic factors were identified and used to construct 3-, 5-, and 10-year nomograms of OS and BCSS. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used as an external validation cohort (n = 90). We constructed nomograms incorporating 10 prognostic factors for OS and BCSS. These nomograms demonstrated strong predictive accuracy for OS and BCSS in the training cohort, with C-indexes of 0.806 and 0.813, respectively. The calibration curves verified that the nomograms have good prediction accuracy. Decision curve analysis demonstrated their practical clinical value for predicting YBC patient survival rates. Additionally, we provided dynamic nomograms to improve the operability of the results. The risk stratification ability assessment also showed that the OS and BCSS rates of the low-risk group were significantly better than those of the high-risk group. Here, we generated and validated more comprehensive and accurate OS and BCSS nomograms than models previously developed for YBC. These nomograms can help clinicians evaluate patient prognosis and make clinical decisions.

Mammographic Breast Density at Breast Cancer Diagnosis and Breast Cancer-Specific Survival

Background: Breast density impacts upon breast cancer risk and recurrence, but its influence on breast cancer-specific survival is unclear. This study examines the influence of mammographic breast density (MBD) at diagnosis on breast cancer-specific survival. Methods: The data of 224 patients diagnosed with breast cancer were analyzed. Two area-based MBD measurement tools—AutoDensity and LIBRA—were used to measure MBD via a mammogram of the contralateral breast acquired at the time of diagnosis. These patients were split into two groups based on their percent breast density (PBD): high (PBD ≥ 20%) versus low (PBD < 20%). Breast cancer-specific survival in each of these PBD groups was assessed at a median follow-up of 34 months using Kaplan–Meier analysis and the Cox proportional hazards model. Results: The proportion of women with low PBD who died from breast cancer was significantly higher than that seen with high PBD (p = 0.01). The 5-year breast cancer-specific survival was poorer among women with low PBD than those with high PBD (0.348; 95% CI: 0.13–0.94) vs. 0.87; 95% CI: (0.8–0.96); p < 0.001)]. Women with higher breast density demonstrated longer survival regardless of the method of PBD measurement: LIBRA [log-rank test (Mantel–Cox): 9.4; p = 0.002)]; AutoDensity [log-rank test (Mantel–Cox) 7.6; p = 0.006]. Multivariate analysis also demonstrated that there was a higher risk of breast cancer-related deaths in women with low PBD (adjusted HR: 5.167; 95% CI: 1.974–13.521; p = 0.001). Conclusion: Women with <20% breast density at breast cancer diagnosis demonstrate poor survival regarding the disease. The impact of breast density on survival is not influenced by the method of measurement.

Treatment and survival differences between patients with invasive lobular carcinoma versus invasive ductal carcinoma of the breast.

Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared to invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC. We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient. 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced stage disease (stage II, 35% vs. 34%; stage III, 16% vs.11%), and higher rate of hormone receptor-positive disease (97% vs. 81%). Compared to patients with IDC, patients with ILC had better BCSS in the first five years (Hazard ratio [HR]=0.71, p <0.001), but worse BCSS in later years (HR=1.30, p<0.001 in year 6-10; HR=1.75, p<0.001 in year 11-15; HR=2.17, p<0.001 in year 16-20). Patients with ILC survive better in early years but worse in later years compared to patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality. The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC.

Long-term Survival Outcomes in Locally Advanced Breast Cancer after Mastectomy with or without Breast Reconstruction.

There is ongoing debate about the safety of breast reconstruction for patients with locally advanced breast cancer (LABC) who have undergone total mastectomy (TM). More and more LABC patients are undergoing breast reconstruction after TM, but its long-term survival outcomes remain unclear. This study aims to compare the survival outcomes of LABC patients who underwent breast reconstruction after TM with those who did not, based on a large sample. We collected data for all LABC patients who underwent TM with or without breast reconstruction in the Surveillance, Epidemiology, and End Results (SEER) database. We divided patients into two groups: TM group and total mastectomy with reconstruction (TM+R) group. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) analysis was used to eliminate imbalances of baseline data between the in tow groups. Data were analyzed using chi-square tests, Kaplan-Meier methods, and univariate and multivariate cox regression analyses. We identified 39,112 eligible patients (33,169 patients received TM and 5,943 received TM+R), and 8,680 patients were matched after PSM (4,340 patients received TM and 4,340 received TM+R). Patients with middle age, white, married, lived in urban, IIB-IIIA stage, invasive ductal carcinoma (IDC), pathological grade II-III, hormone receptor positive, and undergone chemotherapy were more likely to receive breast reconstruction. After PSM, Kaplan-Meier survival analysis showed better OS and BCSS in the TM+R group versus the TM group (OS:P&lt;0.001; BCSS: P=0.008). Multivariate cox regression analysis showed that TM+R significantly improved OS and BCSS (OS: hazard ratio (HR) 0.73, 95% CI [0.68,0.79], P&lt;0.001; BCSS: 95% CI [0.79,0.94], P=0.001). Subgroup analysis showed that patients with old age, white, and hormone receptor positive had better OS and BCSS by TM+R compared to TM. Breast reconstruction after total mastectomy is associated with better OS and BCSS in patients with LABC.

Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis

Hormone receptor-positive breast cancer (BC) is the most prevalent subtype of BC and is generally correlated with a favorable prognosis. This study aimed to determine the incidence and survival trends among women diagnosed with hormone receptor-positive BC between 1990 and 2019. Female patients with hormone receptor-positive BC for calendar years 1990–2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into six diagnostic groups according to the year of diagnosis. Age-adjusted incidence rates (IRs) were calculated using joinpoint regression. We used the Kaplan–Meier method and multivariate Cox regression analyses to determine the association between diagnostic groups, and overall survival (OS) and BC-specific survival (BCSS). The final analysis included 370,729 women, among whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990 and 1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively. Within the overall cohort, IRs gradually increased from 70 per 100,000 in 1990 to 113 per 100,000 in 2019 (average annual percent change, 1.59%; 95% CI, 1.18–1.99). Multivariate Cox regression analysis revealed that the survival outcomes gradually improved over nearly three decades among hormone receptor-positive BC patients, with a 0.8% and 1.3% decrease in risk for all-cause and BC-specific mortality each year, respectively. Compared to 1990–1994, hormone receptor-positive BC patients diagnosed in 2015–2019 had a 22% lower risk of all-cause death (hazard ratio [HR], 0.78; 95% CI, 0.76–0.81) and a 27% lower risk of BC-specific death (HR, 0.73; 95% CI, 0.70–0.76). The development of treatment strategies within the past three decades, especially endocrine therapy, may contribute to the continuous improvement of clinical outcomes in patients with hormone receptor-positive BC.

Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n=100) and invasive tumours (n=100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68±11.2fibre/µm2) compared to DCIS (p<0.0001). The collagen fibres were thinner (13.78±1.08µm), straighter (0.96±0.006, on a scale of 0-1), more disorganised (95.07°±11.39°) and less aligned (0.20±0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p<0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.

Assessment of Treatment Sequence in Patients With Stage III Breast Cancer

IntroductionStage III breast cancer is defined as locally advanced breast cancer and is treated with curative intent. Historically, overall survival (OS) did not differ based on treatment sequence (neoadjuvant chemotherapy [NAC] followed by surgery versus surgery followed by chemotherapy). Given recent advancements, we examined if treatment sequence may be associated with improved OS in a contemporary cohort of patients with stage III breast cancer. MethodsPatients aged 18-80 years with prognostic stage III breast cancer who received chemotherapy and surgery were selected from the Surveillance, Epidemiology, and End Results database. Patients were stratified by treatment sequence (NAC versus surgery first). Unadjusted OS and breast cancer–specific survival (BCSS) were estimated using the Kaplan–Meier method and compared with log-rank tests. Cox proportional hazards models were used to estimate the association of treatment sequence with OS and BCSS after adjustment for selected covariates. ResultsThe study included 26,573 patients; median follow-up was 62.0 months (95% confidence interval [CI] 61.0-63.0). Patients receiving NAC had a worse OS and BCSS compared to those who underwent surgery first (5-year OS rates 0.66 versus 0.73; 5-year BCSS rates 0.70 versus 0.77; both log-rank P < 0.001). After adjustment for tumor subtype, receipt of NAC (versus surgery first) remained associated with a worse OS (hazard ratio 1.27, 95% CI 1.2-1.34, P < 0.001) and BCSS (hazard ratio 1.35, 95% CI 1.27-1.43, P < 0.001). ConclusionsBased on data from patients treated largely before 2020, undergoing surgery first may be associated with improved survival, even after adjustment for known covariates including tumor subtype. These findings may inform treatment when caring for patients with operable, locally advanced breast cancer.

Trends and efficacy of omitting axillary lymph node dissection in early-stage male breast cancer with limited nodal involvement: A population-based cohort study.

The effectiveness of sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in managing early-stage male breast cancer (MBC) patients with T1-2 tumors and limited lymph node metastasis, all receiving radiotherapy, remains uncertain. This study examines trends and survival outcomes for SLNB and ALND in the United States. We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data from 2010 to 2020 for MBC patients with T1-2 tumors and 1-2 positive lymph nodes undergoing radiotherapy. Patients were classified by nodes removed (SLNB ≤5, ALND ≥10), comparing overall survival (OS) and breast cancer-specific survival (BCSS) between the groups before and after propensity score matching. Of 299 MBC patients analyzed, SLNB usage increased from 18.8% in 2010 to 61.0% in 2020. Multivariable logistic regression highlighted significant associations of SLNB use with diagnosis year, race, surgery type, positive lymph node count, and metastasis size. No significant differences in 5-year OS (77.98% SLNB vs. 85.85% ALND, p = 0.337) or BCSS (91.54% SLNB vs. 94.97% ALND, p = 0.214) were observed. Propensity score matching (96 patients per group) confirmed similar 5-year OS (83.9% for SLNB vs. 82.0% for ALND, p = 0.925) and BCSS (90.1% for SLNB vs. 96.9% for ALND, p = 0.167). SLNB and ALND provide comparable survival outcomes in early-stage MBC patients with limited lymph node metastasis undergoing radiotherapy. The increased utilization of SLNB supports its consideration to reduce surgical morbidity in selected MBC patients despite limited direct evidence.

Surgical treatments for older breast cancer patients: A systematic review and meta-analysis of real-world evidence

BackgroundOlder patients with breast cancer are often underrepresented in clinical trials, leading to a lack of evidence-based guidelines for surgical treatment in this cohort. Consequently, synthesizing real-world data is crucial for determining the optimal surgical management of geriatric patients with breast cancer. MethodsA comprehensive search was conducted of the PubMed, Embase, and Cochrane Library databases. The review included clinical studies evaluating treatments in patients aged ≥65 years with breast cancer. Comparisons were made between primary surgical treatment and endocrine therapy alone, breast-conserving surgery without radiotherapy versus mastectomy, sentinel lymph node biopsy versus omission of sentinel lymph node biopsy, and surgery plus axillary lymph node dissection versus omission of axillary lymph node dissection. ResultsA total of 44 studies were analyzed. Surgery significantly increased overall survival, breast cancer–specific survival, and recurrence-free survival compared with endocrine therapy alone. Pooled estimates revealed that mastectomy yielded significantly better prognoses than breast-conserving surgery without radiotherapy in terms of both overall survival and breast cancer–specific survival. Omitting sentinel lymph node biopsy and axillary lymph node dissection did not significantly reduce overall survival. ConclusionsFor older patients with breast cancer, primary surgical treatment significantly enhances survival and regional control compared with endocrine therapy alone without compromising quality of life. Frail patients with nonmetastatic breast cancer who are unwilling to undergo radiotherapy benefit from mastectomy, with no notable psychosocial decline compared with breast-conserving surgery alone. Sentinel lymph node biopsy omission does not increase recurrence rates or mortality, and avoiding axillary lymph node dissection may be viable for node-positive older patients due to its comparable survival outcomes.

Developing machine learning models for personalized treatment strategies in early breast cancer patients undergoing neoadjuvant systemic therapy based on SEER database

This study aimed to compare the long-term outcomes of breast-conserving surgery plus radiotherapy (BCS + RT) and mastectomy in early breast cancer (EBC) patients who received neoadjuvant systemic therapy (NST), and sought to construct and authenticate a machine learning algorithm that could assist healthcare professionals in formulating personalized treatment strategies for this patient population. We analyzed data from the Surveillance, Epidemiology, and End Results database on EBC patients undergoing BCS + RT or mastectomy post-NST (2010–2018). Employing propensity score matching (PSM) to minimize potential biases, we compared breast cancer-specific survival (BCSS) and overall survival (OS) between the two surgical groups. Additionally, we trained and validated six machine learning survival models and developed a cloud-based recommendation system for surgical treatment based on the optimal model. Among the 13,958 patients, 9028 (64.7%) underwent BCS + RT and 4930 (35.3%) underwent mastectomy. After PSM, there were 3715 patients in each group. Compared to mastectomy, BCS + RT significantly improved BCSS (p < 0.001) and OS (p < 0.001). Prognostic variables associated with BCSS were utilized to develop machine learning models. In both the training and validation cohorts, the random survival forest (RSF) model demonstrated superior predictive performance (0.847 and 0.795), not only outperforming other machine learning models, including Rpart (0.725 and 0.707), Xgboost (0.762 and 0.727), Glmboost (0.748 and 0.788), Survctree (0.764 and 0.766), and Survsvm (0.777 and 0.790), but also outperforming the classical COX model (0.749 and 0.782). Lastly, a web-based prediction tool was built to facilitate clinical application [https://jhren.shinyapps.io/shinyapp1]. After adjusting other confounders, BCS + RT was associated with improved outcomes in patients with EBC after NST, compared to those who underwent mastectomy. Moreover, the RSF model, a reliable tool, can predict long-term outcomes for patients, providing valuable guidance for operative methods and postoperative follow-up.

Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive breast cancer: A Surveillance, Epidemiology, and End Results population‐based study

AbstractBackgroundPersistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking.MethodsData on patients with T1cN0M0‐stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well‐balanced cohorts for the NAT and AT groups. Kaplan–Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer–specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT.ResultsAfter PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35–0.77; p &lt; .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37–0.98; p = .041). A logistic regression model revealed that White race and hormone receptor–negative status independently predicted pCR.ConclusionsFor patients with T1cN0M0‐stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Abstract A058: Investigating the role of race/ethnicity on the association between neighborhood deprivation and breast cancer outcomes among Kentucky breast cancer patients years 2010-2022

Abstract Background: Despite advances in medical knowledge and treatment, disparities in breast cancer outcomes persist along demographic and socioeconomic lines. To quantify these disparities, the Area Deprivation Index (ADI) emerges as a powerful metric. It offers insights into the interplay between neighborhood socioeconomic status and breast cancer outcomes by encompassing factors pertaining to income, education, employment, and housing quality. There have been limited studies to examine the role of race and neighborhood disadvantage on specific breast cancer outcomes. Kentucky also faces a unique burden as it has the third highest breast cancer mortality rate in the United States. This study aims to examine the association between neighborhood socioeconomic disadvantage, and breast cancer outcomes including receipt of surgical treatment, radiation therapy, chemotherapy, and breast cancer-specific survival. While also examining how any associations are modified by race and ethnicity among Kentucky breast cancer patients. Methods: We conducted a retrospective cohort analysis using data from the Kentucky Cancer Registry (KCR) among breast cancer patients diagnosed between 2010 and 2017 with follow-up data through December 31, 2022. The KCR dataset was then linked with census tract data to examine ADI. We conducted consecutive multilevel logistic regression for binary outcomes and Cox Proportional hazard models using SAS (version 9.4, SAS Institute, Inc., Cary, North Carolina, USA) for time-to-event of breast cancer survival. Results: Women in the most disadvantaged quartile (4th quartile) were more likely to be Non-Hispanic Black (NH-Black), Appalachian residents, current tobacco users, divorced and using government insurance. Compared to women in the least disadvantaged neighborhoods (1st quartile) women living in the most disadvantaged neighborhoods (4th quartile) were 50% more likely to die from breast cancer (HR: 1.50, 95 CI: 1.28-1.76). Women in the most disadvantaged neighborhoods (4th quartile) were also more likely to be diagnosed at later stages (aOR:1.26, 95 CI:1.13-1.42). These associations were all observed after adjusting for age, race, tobacco use, marital status, insurance status, family history, and residence in Appalachia. Conclusions: Women living in areas of greater disadvantage had significantly increased odds of late-stage diagnosis and risk of breast cancer death regardless of race suggesting that neighborhood-level factors contribute to breast cancer disparities. Our findings underscore the need for neighborhood-level interventions to improve cancer outcomes. Citation Format: Breyanna E. Walker, Elinita Pollard, Justin Moore, Sydney Howard, Pamela Hull, Kathleen O'Connor, Samantha Jones, Lovoria Williams, Adebola Adegboyega, Veronica Jones, Eric Durban, Xiaoqin Wang, Wendi Owen. Investigating the role of race/ethnicity on the association between neighborhood deprivation and breast cancer outcomes among Kentucky breast cancer patients years 2010-2022 [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A058.

Abstract A004: Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients

Abstract PREDICT Breast v3 is the latest version of a prognostic tool designed to predict the treatment responses for early invasive breast cancer patients. It was developed using data from approximately 35,000 women diagnosed between 2000 and 2018 in the United Kingdom. However, its performance in the United States (US) population is unknown. This study aims to validate PREDICT Breast v3 using the newly released Surveillance, Epidemiology, and End Results (SEER) outcome data for US breast cancer patients and to address potential health disparities. We selected over 860,000 female patients diagnosed with primary breast cancer between 2000 and 2021 and followed for at least 5 years from the SEER database. The model’s performance was measured by calibration and discrimination; comparing predicted and observed 5-, 10- and 15-year breast cancer-specific survival outcomes and determining discrimination through the area under the receiver-operator curves (AUC). PREDICT Breast v3 demonstrated good calibration and discrimination for both short- and long-term up breast cancer-specific mortality in US populations. The predicted 10-year breast cancer-specific mortality differed from observed by 11% in ER-positive and 6 % in ER-negative patients. The AUCs for 15-year breast cancer-specific mortality were 0.81 for ER-positive patients and 0.76 for ER-negative patients. When stratified by race and ethnicity, the model showed strong performance in Non-Hispanic Asians ER-positive patients, despite being originally developed based on the UK population. These results are consistent with previous validations in Malaysia, Japan, and other Asian countries for PREDICT Breast v2. However, the model poorly estimated the number of deaths in Non-Hispanic Black individuals for both ER-positive and ER-negative. In conclusion, this study marks the first validation of PREDICT Breast v3 in the US and demonstrates that it is a reliable and generalizable tool, capable of providing longer term follow-up time up to 15 years for a wide and diverse population. Citation Format: Yi-Wen Hsiao, Paul Pharaoh, Pei-Chen Peng. Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A004.

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome.

Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry. In addition, PTK7 mRNA expression in the METABRIC (n = 1980) and the TCGA breast cancer cohorts (n = 1082) was evaluated. Associations between PTK7 expression and clinicopathological criteria and patient outcome were determined. No association between PTK7 protein expression and breast cancer-specific survival was observed; however, PTK7 mRNA expression in the METABRIC cohort was associated with breast cancer-specific survival (p < 0.001). PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.

21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer.

To assess the predictive value of the 21-gene recurrence score (RS) on the survival outcomes of postoperative radiotherapy (PORT) in elderly patients with T1N0 luminal breast cancer after breast-conserving surgery. We retrospectively included patients aged ≥ 70years and diagnosed with T1N0 luminal BC between 2004 and 2015 using the data from the Surveillance, Epidemiology, and End Results. The RS groups were categorized using the TAILORx criteria as follows: low risk (RS < 11) (LR), intermediate risk (RS 11-25) (IR), and high risk (RS > 25) (HR). Kaplan-Meier analysis, propensity score matching (PSM), and Cox proportional hazards analysis were used for statistical analysis. We included 5901 patients in the analysis. Of the patients, 4492 (76.1%) underwent PORT, while 1409 (23.9%) did not receive PORT. There were 1588 (26.9%), 3613 (61.2%), and 700 (12.0%) patients classified as LR, IR, and HR, respectively. There were 1182 (74.4%), 2773 (76.8%), and 537 (76.7%) patients in the LR, IR, and HR groups receiving PORT, respectively (P = 0.182). A total of 1353 pairs of patients were completely matched using PSM. PORT was independently associated with better overall survival (OS) (P < 0.001) and breast cancer-specific survival (BCSS) (P = 0.015) in the entire cohort. The sensitivity analyses showed that the receipt of PORT was not associated with OS (P = 0.887) and BCSS (P = 0.861) in the LR group. However, the receipt of PORT was associated with OS (P < 0.001) and BCSS in the IRHR group (P = 0.026). Our study highlights the possible role of the 21-gene RS in predicting the survival outcomes of PORT following BCS in elderly patients with T1N0 luminal breast cancer.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Is Oncoplastic Surgery Safe in High-Risk Breast Cancer Phenotypes?

Oncoplastic surgery (OPS) has increased in popularity over the recent years. It is a form of breast conservation surgery allowing for larger partial mastectomy (PM) resections followed by either volume displacement or volume replacement reconstruction techniques. However, there is a lack of evidence on the effectiveness and safety of OPS with radiotherapy (OPS + RT) in high-risk breast cancer phenotypes, such as triple negative breast cancer (TNBC) and HER2 positive (HER2+) patients. Our aim was to compare the breast cancer-specific survival (BCSS) and postoperative surgical complications in OPS + RT compared to PM alone with radiation (PM + RT) and total mastectomy (MTX) without radiotherapy (MTX-RT). Patient data were analyzed from the Surveillance, Epidemiology, and End Results (SEER) cancer registries from January 1, 2012 to December 31, 2020. Patients were stratified according to the type of surgery. Cox regression analysis was performed to assess prognostic factors of BCSS. A total of 24 621 patients with high-risk breast cancer phenotypes were identified, 180 underwent OPS + RT; 13 402, PM + RT; and 11 039 MTX-RT. OPS + RT was more frequently performed in younger (mean age of 65.53 years, SD: 9.29, p < 0.001), non-Hispanic White (90.5% vs. 77.7% vs. 76.3%) and single women (17.9% vs. 12.1% vs. 13.3%). MTX-RT was usually performed in patients with high histological grade, TNBC, and higher stages. Overall complication rates were higher in the MTX-RT, compared to OPS + RT and PM + RT, 2%, 1.1%, and 0.7%, respectively, p < 0.001. Rates of hematoma and surgical site infections were higher in the MTX-RT group. With a median follow-up of 46 months, OPS + RT had better BCSS rates at 5 years compared to PM + RT and MTX-RT (97.1% vs. 94.7% vs. 89.8%, p < 0.001). MTX-RT was found to be an independent prognostic factor of worse BCSS compared to OPS + RT (hazard ratio [HR] = 2.584; 95% confidence interval [CI]: 1.005-7.171), while PM + RT had no difference compared to OPS + RT (HR = 1.670, 95% CI: 0.624-4.469). OPS is a safe breast surgical option in patients with HER2+ and TNBC. Patients with high-risk phenotypes who underwent OPS + RT and have similar BCSS and complication rates compared to standard breast surgical options. As such, OPS should be considered as an option whenever breast conservation surgery is being discussed.

Survival following adjuvant trastuzumab-based treatment among older patients with HER2-positive early invasive breast cancer: A national population-based cohort study using routine data

BackgroundRandomised controlled trials (RCTs) reported adjuvant trastuzumab-based treatment improved overall survival (OS) among patients with HER2-positive early invasive breast cancer (EIBC). Few RCTs included older patients or those with comorbidity/frailty. This study aimed to determine whether the effect of adjuvant trastuzumab-based treatment on survival outcomes varies by patient age and fitness, using national data from routine care. MethodsWomen (50+ years) newly-diagnosed with HER2-positive EIBC between 2014 and 2019 were identified from England Cancer Registry data. Registration records were linked to Systemic Anti-Cancer Therapy data for treatment details and ONS death register for mortality details. A propensity score analysis employing the inverse probability of treatment weighting method was used to balance the patient variables across treatment groups. Cox models were used to evaluate whether the effect of treatment on OS was associated with patient age and fitness; competing risks regression models were used for breast cancer-specific survival (BCSS). Results5238 women initiated adjuvant trastuzumab-based treatment. Median follow-up was 56.7 months. Comparison with 3421 women who did not receive adjuvant trastuzumab highlighted differences at diagnosis in relation to age, fitness, grade, nodal involvement, surgery type and use of radiotherapy. Weighted survival analysis found trastuzumab was associated with improved OS (hazard ratio HR 0.56, 95 %CI: 0.45–0.70) and improved BCSS (subHR 0.62, 95 %CI: 0.47–0.82). We found no evidence of a difference in effect by age or patient fitness for either outcome. ConclusionIn this national dataset, adjuvant trastuzumab was associated with improvements in survival, with an OS effect size similar to RCT evidence. The effect size was not found to vary by patient age or fitness. Chronological age and fitness alone should not be barriers to receipt of effective adjuvant targeted treatment.

Management of Ipsilateral Breast Tumor Recurrence Following Breast Conservation Surgery for Ductal Carcinoma In Situ: A Data-Poor Zone.

Breast conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS), but neither randomized trials nor guidelines address management of ipsilateral breast tumor recurrence (IBTR) after BCS for DCIS. We identified women treated with BCS for DCIS who developed IBTR as a first event. Between those treated with mastectomy versus re-BCS, we compare the clinicopathologic characteristics, the use of adjuvant radiotherapy (RT) both upfront ("primary RT") and post IBTR ("secondary RT"), of tamoxifen, the rate of third events (local, regional, distant), and both breast cancer specific (BCSS) and overall survival (OS). Of 3001 women treated with BCS for DCIS (1978-2010), 383 developed an IBTR as a first event (1983-2023) and were treated by mastectomy (51%) versus re-BCS (49%). Compared with re-BCS, mastectomy patients at initial treatment were higher grade (74% versus 59%, p = 0.004), with more frequent primary RT (61% versus 21%, p < 0.001). Third local events were more frequent for re-BCS than mastectomy (16% versus 3%, p = 0.001), but there were no differences in breast cancer specific or overall survival. For isolated IBTR following BCS for DCIS and treated by mastectomy versus re-BCS (1) mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, (2) re- recurrence was more frequent with re-BCS, and (3) BCSS and OS were comparable. Our data suggest a wider role for re-BCS and further study of the relationship between secondary RT and the rate of third breast events.