Breast Cancer-specific Survival In Patients Research Articles

Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: a retrospective observational study based on SEER

PurposeMalignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages.MethodsFemale MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan–Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics.Results2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18–45, 46–55, 56–65, and 65–80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18–45 years: OS P = 0.019, BCSS P = 0.016; age group of 46–55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18–45 years: OS P = 0.473, BCSS P = 0.750; age group of 46–55 years: OS P = 0.380, BCSS P = 0.816, age group of 56–65 years: OS P = 0.484, BCSS P = 0.290; age group of 66–80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB.ConclusionThere is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT.

Abstract PO1-28-10: Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy

Abstract Introduction International guidelines recommend chemotherapy for most patients with stage I triple negative breast cancer (TNBC), except for special histological subtypes. However, the absolute benefit of systemic treatment for all stage I TNBC patients is not well known and no tools are yet available to select patients with an excellent prognosis for whom the chemotherapy can be safely omitted. High levels of stromal tumor infiltrating lymphocytes (sTILs) are strongly associated with favorable prognosis in TNBC, however, data solely focusing on patients with stage I TNBC who did not receive chemotherapy are lacking. Methods Patients with pT1N0M0 TNBC diagnosed between 2005 and 2015 not treated with (neo)adjuvant chemotherapy were identified from the nationwide Netherlands Cancer Registry (NCR) and linked to the national pathology database (PALGA). Newly sectioned hematoxylin &amp; eosin (H&amp;E) slides were used for central review of the histology and sTILs scoring following the International TIL working group guidelines (www.tilsinbreastcancer.org). Cause of death was provided by Statistics Netherlands (CBS). Primary endpoint was breast-cancer specific survival (BCSS) at 5-, 10- and 15-years for prespecified sTILs cut-offs of 30%, 50% and 75% sTILs. Results sTILs were evaluated for 1,041 patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. Mean age at diagnosis was 64.4 years [range 26 – 96] and median sTILs value was 5%. Most tumors (91.5%) were invasive ductal adenocarcinomas of no special type (NST) and 6.6% were of histological special types. In 52% of the patients the tumor was &amp;gt;1cm (pT1cN0). Median follow-up was 9.4 years in which 335 patients had died, of whom 107 due to breast cancer. Patients with pT1abN0 tumors had a favorable prognosis compared with patients with a pT1cN0 tumor (HR 0.47, CI 0.32- 0.72). 10-year BCSS in patients with pT1ab was 91.8% and 85.8% in patients with pT1c tumors. In the overall cohort, sTILs-levels of at least 30% were associated with better BCSS compared to sTILs &amp;lt; 30% (HR 0.45, CI 0.26 – 0.77), with 10year-BCSS of 96% and 87%, respectively (table 1). Patients with TNBC of special histological subtype had low sTILs (median 1%). A univariate cox model showed no association between sTILs (continuous) and BCSS in TNBC of special histological subtype (p = 0.56). Next, the prognostic value of sTILs was evaluated separately for pT1ab and pT1c. High sTILs ≥50% were not associated with improved BCSS compared to low sTILs &amp;lt; 50% in patients with pT1ab (HR 1.35, CI 0.65 – 2.82, p = 0.42). In contrast, high sTILs ≥50% showed a strong prognostic importance over low sTILs &amp;lt; 50% (HR 0.27, CI 0.10 – 0.74) in patients with pT1C tumors. We found excellent 10year-BCSS of 95% for patients if sTILs ≥50%, which further increases to 98% with sTILs ≥75% contrasting 10year-BCSS of 83% for patients with sTILs &amp;lt; 30%. Conclusions sTILs-levels provide important prognostic information in patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. The outcome of patients with pT1c TNBC and sTILs ≥50% was excellent, with 10year-BCSS of 95%, and 98% if sTILs &amp;gt;75%. This large registry study provides a foundation for clinical trials in patients with stage I TNBC with high TILs to prospectively confirm their excellent survival without chemotherapy. Citation Format: Veerle Geurts, Sara Balduzzi, Hugo Horlings, Tessa G Steenbruggen, Sabine Siesling, Sylvia Adams, Gabe Sonke, Roberto Salgado, Marleen Kok. Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy [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 PO1-28-10.

An exploratory study of whether axillary lymph node dissection can be avoided in breast cancer patients with positive lymph nodes.

Breast cancer patients with positive axillary lymph nodes usually require axillary lymph node dissection (ALND), with many postoperative complications, such as lymphedema. For these patients, whether sentinel lymph node biopsy (SLNB) can replace ALND has been a research hotspot in the field of breast cancer. This study developed two risk stratification models for predicting the clinical outcomes of breast cancer patients with positive axillary lymph nodes receiving SLNB alone or ALND to determine which patients could potentially avoid ALND. A total of 21,942 breast cancer patients, including a training set (n=15,362) and a testing set (n=6,580), were enrolled in this study from Surveillance, Epidemiology, and End Results (SEER) between 2000 and 2017. The risk factors associated with breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using multivariate Cox regression analysis and then integrated into nomograms and risk stratification models examined by receiver operating characteristic (ROC) curves and calibration curves. The survival discrepancies were compared between the SLNB and ALND subgroups with different risk scores with Kaplan-Meier plots. In multivariate Cox regression analyses, grade, marital status, T stage, radiotherapy and lymph node metastasis (GMTRL) were independent risk factors in breast cancer patients with both OS and BCSS status in the ALND cohort from the training set. Nomograms have been developed based on these factors to predict 3- and 5-year OS and BCSS in patients with ALND. Calibration curves and ROC curves in both the training and testing sets confirmed the excellent overall predictive performance of the nomograms. Furthermore, we developed two risk stratification models based on OS and BCSS status, revealing that patients with low GMTRL scores might avoid ALND in both OS and BCSS status [OS: hazard ratio (HR) =0.929, 95% confidence interval (CI): 0.841-1.027, P=0.150; BCSS: HR =0.953, 95% CI: 0.831-1.094, P=0.495], but patients with moderate (OS: HR =0.756, 95% CI: 0.666-0.859, P<0.001; BCSS: HR =0.643, 95% CI: 0.537-0.768, P<0.001) and high GMTRL scores could not (OS: HR =0.719, 95% CI: 0.549-0.940, P=0.014; BCSS: HR =0.731, 95% CI: 0.549-0.974, P=0.031). Breast cancer patients with positive nodes could be treated with SLNB alone rather than ALND without affecting prognosis based on GMTRL scores. Patients with high or moderate GMTRL scores benefited greatly from ALND, but not for patients with low GMTRL scores. This study may assist clinicians in tailoring treatments.

Assessment of geriatric and clinical domains for development and validation of a novel nomogram to predict the prognosis of older patients with breast cancer: a real-world retrospective cohort study

BackgroundBreast cancer is a relatively heterogeneous disease in the older population. Survival in older breast cancer patients is not only affected by tumor-related factors, but also by geriatric assessment domains. How tumor clinical factors and geriatric factors specifically affect the survival rate of older patients and how to combine these two factors to predict the risk of death in older patients with breast cancer remain clinical questions to be addressed.MethodWe used the Peking Union Medical College Hospital database to identify older patients (≥65 years) who were newly diagnosed with breast cancer between January 2013 and December 2019. Of the 641 eligible patients, we retrospectively analyzed the clinical and geriatric data of 556 patients who formed our study population. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors and construct a nomogram to predict the 1-, 3-, and 5-year survival rates. The performance of the constructed nomogram was evaluated using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsMultivariate Cox regression analysis revealed seven independent prognostic factors associated with OS in older patients with breast cancer: age, tumor stage, lymph node stage, intrinsic molecular subtype, functional status, comorbidities, and psychological state. Nomogram based on these seven factors yielded excellent performance, with area under the ROC curve (AUROC) of 0.748. Similarly, the nomogram for BCSS had an AUROC of 0.760. Moreover, the calibration curve and DCA revealed good predictive accuracy between the actual and predicted probabilities.ConclusionIndependent prognostic factors for OS and BCSS in older patients with breast cancer in China were determined in our study. A novel nomogram for predicting the 1-, 3-, and 5-year OS and BCSS in this patient population was developed and validated. The nomogram exhibited good accuracy, indicating its potential for clinical decision making and improving outcomes.

Effectiveness of post-mastectomy adjuvant chemotherapy for the treatment of patients with prognostic stage IB breast cancer: A SEER-based study.

Adjuvant chemotherapy (AC) is an important, effective treatment for breast cancer. This study evaluates the effectiveness of post-mastectomy AC in treating patients with prognostic stage IB breast cancer. We conducted a retrospective cohort-based study using Surveillance, Epidemiology, and End-Results database. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated using the Kaplan-Meier method. Multivariate Cox risk models were used to identify the impact of AC. Stratified analysis was performed according to molecular subtypes, anatomic stages, and other risk factors to evaluate the effect of AC on survival. 28,825 women diagnosed with prognostic stage IB breast cancer were included. The 5-year OS was significantly higher in AC group than in non-adjuvant chemotherapy (NAC) group (P<0.0001); however, the 5-year BCSS in AC group was significantly lower than in NAC group (P=0.039). Multivariate analysis revealed that AC was a favorable prognostic factor for OS (P<0.001), but not BCSS (P=0.407). AC was not an independent prognostic factor for BCSS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR[+]/HER2[-]) subtype or pT1a-1b/N0-1 stage with HER2 overexpression (HER2[+]) subtype, regardless of whether HR was positive or negative (P>0.05). Meanwhile, AC is not an independent prognostic factor for OS and BCSS in patients with lymph node micrometastases. Our study demonstrates that patients with prognostic stage IB do not fully benefit from AC. Individualized treatment management is required for patients with pT1a-1b/N0-1 tumors, lymph node micrometastases, or HR(+)/HER2(-) subtypes.

Comparison of breast-conserving surgery without radiotherapy and mastectomy in the treatment of elderly patients with early breast cancer: A PSM and SEER database study.

At present, there is no research on which surgical method can lead to a better prognosis in elderly patients with early breast cancer. The purpose of this study was to establish a nomogram to predict the survival outcome of elderly patients with early breast cancer and to compare the prognosis of the breast-conserving surgery (BCS) group who did not receive postoperative radiotherapy and the mastectomy group through risk stratification. This study included patients with early breast cancer aged ≥70 years from the Surveillance, Epidemiology, and End Results database (n = 20,520). The group was randomly divided into a development cohort (n = 14,363) and a validation cohort (n = 6157) according to a ratio of 7:3. Risk factors affecting overall survival (OS) and breast-cancer-specific survival (BCSS) were analyzed using univariate and multivariate Cox regression. Present results were obtained by constructing nomograms and risk stratifications. Nomograms were evaluated by the concordance index and calibration curve. Kaplan-Meier curves were established based on BCSS and analyzed using the log-rank test. Multivariate Cox regression results showed that age, race, pathological grade, T and N stages, and progesterone receptor (PR) status were independent risk factors for OS and BCSS in the BCS group and mastectomy group. Subsequently, they were incorporated into nomograms to predict 3- and 5-year OS and BCSS in patients after BCS and mastectomy. The concordance index was between 0.704 and 0.832, and the nomograms also showed good calibration. The results of risk stratification showed that there was no survival difference between the BCS group and the mastectomy group in the low-risk and high-risk groups. In the middle-risk group, BCS improved the BCSS of patients to a certain extent. This study constructed a well-performing nomogram and risk stratification model to assess the survival benefit of BCS without postoperative radiotherapy in elderly patients with early breast cancer. The results of the study can help clinicians analyze the prognosis of patients and the benefits of surgical methods individually.

A retrospective comparative cohort study of SEER database analysis of the prognostic value of breast-conserving surgery and mastectomy in patients with multifocal multicenter breast cancer.

The prognosis of multifocal multicentric breast cancer (MIBC) was related to many factors, and there are different recommendations for surgical approaches. We compare the effects of breast-conserving surgery (BCS) and mastectomy on the survival of multifocal multicenter breast cancer female patients. A total of 38,164 female patients with pathologically confirmed multifocal multicenter invasive breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were extracted, and the effects of different factors on the survival of these patients were retrospectively analyzed. The patients were divided into a BCS group and a mastectomy group, and the differences of breast cancer-specific survival (BCSS) and overall survival (OS) were compared between the 2 groups. Of the 38,164 patients included in the analysis, 14,533 (38.08%) underwent BCS and 23,631 (61.92%) underwent mastectomy. Multivariate analysis showed that age, grading, staging, number of lesions, radiotherapy, and BCS would affect the independent factors of BCSS and OS in patients. The median follow-up time was 108 months [interquartile range (IQR): 64-162 months). Multifactorial Cox proportional model analysis of prognostic risk showed that BCS reduced BCSS in patients older than 70 years [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.2-1.53; P<0.001], stage I and II, positive hormone receptor (HR), all 2-3 lesions, no radiotherapy (HR: 1.46; 95% CI: 1.33-1.6; P<0.001) and no chemotherapy (HR: 1.42; 95% CI: 1.28-1.57; P<0.001); BCS also reduced OS in patients over 40 years of age, stages I, II, and IIIC, all molecular subtypes, all HR-positive or negative, 2-3 lesions, and no radiotherapy (HR: 1.38; 95% CI: 1.31-1.46; P<0.001) and no chemotherapy (HR: 1.36; 95% CI: 1.29-1.44; P<0.001) patients. Multivariate Cox regression showed that BCS is an adverse factor for BCSS [adjusted HR 1.2 (1.11-1.3), P<0.001] and OS [adjusted HR 1.24 (1.19-1.3), P<0.001]. In early, good prognosis, treatment-sensitive patients, there is no survival advantage for BCS and more BCSS and OS benefit for mastectomy patients.

Prognostic effect of radiotherapy in breast cancer patients underwent immediate reconstruction after mastectomy.

It is still unclear whether radiotherapy affects the long-term survival of breast cancer (BC) patients after immediate breast reconstruction (IBR). This study aims to evaluate the actual prognostic impact of radiotherapy on BC patients undergoing IBR, and to construct survival prediction models to predict the survival benefit of radiotherapy. Data on eligible BC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Competing risk models were used to assess breast cause-specific death (BCSD) and non-breast cancer cause-specific death (NBCSD). Kaplan-Meier curve, Cox risk regression model and forest map were used to evaluate and demonstrate overall survival (OS) and breast cancer-specific survival (BCSS). Survival prediction nomograms were used to predict OS and BCSS probabilities. A total of 22,218 patients were selected, 24.9% received radiotherapy and 75.1% were without radiotherapy. Competing risk models showed that whether BCSD or NBCSD, the cumulative long-term risk of death in the radiotherapy group was higher than that in the non-radiotherapy group. The Kaplan-Meier curve showed that patients with different lymph node metastasis had different radiotherapy benefits. Multivariate stratified analysis showed that radiotherapy after autologous reconstruction was associated with poor BCSS in patients with stage N0, and radiotherapy after autologous reconstruction and combined reconstruction improved OS and BCSS in patients with stage N3. The C-indexes of nomogram (between 0.778 and 0.847) and calibration curves showed the good prediction ability of survival prediction model. Radiotherapy can improve OS and BCSS in N3 stage BC patients undergoing immediate autologous reconstruction after mastectomy. The practical nomograms can be used to predict OS and BCSS of patients with or without radiotherapy, which is helpful for individualized treatment.

Effect of postmastectomy radiotherapy on T1-2N1M0 triple-negative breast cancer.

The effect of postmastectomy radiotherapy (PMRT) on T1-2N1M0 triple-negative breast cancers (TNBC) remains unclear. The population-based study aimed to investigate the survival outcomes of T1-2N1M0 TNBC patients who underwent PMRT or not. We selected 1743 patients with T1-2N1M0 TNBC who underwent mastectomy between 2010 and 2015 through the Surveillance, Epidemiology and End Results (SEER) database. After propensity score matching (PSM), the PMRT and no-PMRT groups consisted of 586 matched patients, respectively. The Kaplan-Meier method was applied to calculate breast cancer-specific survival (BCSS) and cox proportional hazard model was used to determine the prognostic factors of T1-2N1M0 TNBC. The 5-year BCSS for the PMRT and no-PMRT groups was 79.1% and 74.7%, respectively. Analysis showed that in patients with three nodes positive, radiotherapy could significantly improve BCSS (HR = 0.396, 95% CI = 0.175-0.900, P = 0.027), but it brought no significant advantage in BCSS in patients with one or two nodes positive (HR = 1.061, 95% CI = 0.725-1.552, P = 0.761; HR = 0.657, 95% CI = 0.405-1.065, P = 0.088). In addition, PMRT improves the BCSS in TNBC patients with T2 tumor concomitant with three positive lymph nodes (HR = 0.343, 95% CI = 0.132-0.890, P = 0.028). TNBC patients with T2 tumor concomitant with three positive lymph nodes can benefit from PMRT.

A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis

BackgroundBreast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments. Patients and methodsA total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram. ResultsNomograms were constructed for the breast NEC and breast IDC groups after PSM. The C–index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818–0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone. ConclusionsWe established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.

Survival Outcomes After Breast-Conserving Therapy Compared With Mastectomy for Patients With Early-Stage Invasive Micropapillary Carcinoma of the Breast: A SEER Population-Based Study.

BackgroundInvasive micropapillary breast carcinoma (IMPC) is a relatively rare pathological type of invasive breast cancer. Little is currently known on the efficacy and safety of breast-conserving treatment (BCT, lumpectomy plus postsurgical radiation) compared with mastectomy in women diagnosed with early-stage IMPC. Accordingly, we sought to investigate the long-term prognostic differences between BCT and mastectomy in patients with T1-3N0-3M0 invasive micropapillary breast carcinoma using data from the Surveillance, Epidemiology, and End Results (SEER) database.Materials and MethodsWe retrospectively analyzed 1,203 female patients diagnosed with early-stage IMPC between 2004 and 2015 from the SEER database. The impact of different surgical approaches on patient prognosis was assessed by the Kaplan-Meier method and Cox proportional risk models.ResultsA total of 609 and 594 patients underwent mastectomy and BCT, respectively. Compared with patients who underwent a mastectomy, patients in the BCT group were older and had lower tumor diameters, lower rates of lymph nodes metastasis, and higher rates of ER receptor positivity and PR receptor positivity (p < 0.05). Kaplan-Meier plots showed that the overall survival (OS) and breast cancer-specific survival (BCSS) were higher in the BCT group than in the mastectomy group. In subgroup analysis, patients with T2 stage in the BCT group had better OS than the mastectomy group. Multivariate analysis showed no statistical difference in OS and BCSS for patients in the mastectomy group compared with the BCT group (hazard ratio (HR) = 0.727; 95% confidence interval (95% CI) 0.369–1.432, p = 0.357; HR = 0.762; 95% CI 0.302–1.923, p = 0.565; respectively). During the multivariate analysis and stratifying for the T stage, a better OS was found for patients with T2 stage in the BCT group than the mastectomy group (HR = 0.333, 95% CI: 0.149–0.741, p = 0.007). There was no significant difference in OS for patients with T1 and T3 stages between the BCT and mastectomy groups (p > 0.05).ConclusionIn women with early-stage IMPC, BCT was at least equivalent to mastectomy in terms of survival outcomes. When both procedures are feasible, BCT should be recommended as the standard surgical treatment, especially for patients with T2 disease.

Using Inflammatory Blood Markers as Useful Prognostic Factors in Patients Undergoing Neo-Adjuvant Therapy for Stage II-III Breast Cancer

<h3>Purpose/Objective(s)</h3> The prognostic value of inflammatory blood markers (IBMs) in breast cancer patients have been an area of growing interest. Most of the studies took parameters from one defined point, usually the pretreatment ones. Current study aims to investigate the potential prognostic significance of IBMs among patients with stage II-III breast cancer receiving neo-adjuvant therapy (NAT). <h3>Materials/Methods</h3> Patients with stage II-III breast cancer who received NAT and postoperative radiotherapy (RT) at a single institute from Jan 2009 to Dec 2016 were retrospectively reviewed. The neutrophil, lymphocyte, platelet and monocyte count were collected at different stages of treatment, after NAT but before surgery, before and after RT, respectively. LMR and SII was calculated for each patient. The breast cancer specific survival (BCSS) and locoregional recurrence free survival (LRRFS) were defined from the date of the start of RT until last follow up. Univariate and multivariate Cox regression analysis was performed to identify independent predictors for BCSS and LRRFS. Model performance was evaluated by the concordance index (c-index). <h3>Results</h3> In total, 205 patients were enrolled. After a median follow-up of 65 months, 19 BCSS events were identified. The optimal cutoff value of SII and LMR after NAT but before surgery by receiver operating characteristic curve were 467.76 × 10⁹ (AUC = 0.63) and 1.57 (AUC = 0.65). The five-year BCSS of the group with lower LMR (LMR≤1.57) and higher LMR (LMR > 1.57) were 74.2% and 93.7%, respectively (P = 0.001). The 5-year risk of BCSS in patients with high SII value (SII > 467.76 × 10⁹) and low SII value (SII≤467.76 × 10⁹) were 81.5% vs 96.4%, respectively, <i>P</i> = 0.003. The multivariate analysis found that in addition to the traditional prognostic factors including hormone receptor, ypT, ypN stage and lymphovascular invasion, both post-NAT LMR (HR = 0.28, 95% CI = 0.10-0.81, <i>P</i> = 0.02) and SII (HR = 4.06, 95% CI = 1.37-12.00, <i>P</i> = 0.01) were independent predictors for BCSS. The C-index of the multivariate model of Neo-Bioscore for BCSS was 0.71(95% CI = 0.83-0.59), which was improved to 0.80((95% CI = 0.94-0.67) by adding LMR and SII. The prognosis of pre-RT and post-RT SII on LRRFS was analyzed in124 patients. The optimal cutoff value of SII before and after RT were 412.2 × 10⁹ (AUC = 0.71) and 571.48 × 10⁹ (AUC = 0.69) respectively. Patients with pre-RT SII > 412.2 × 10⁹ or post-RT SII > 571.48 × 10⁹ had a higher rate of locoregional failure (<i>P</i> = 0.02 and <i>P</i> = 0.01). After adjusting for cT, cN stage and age, post-RT SII remained predictive of locoregional failure (HR = 10.22, 95% CI = 1.25-83.45, <i>P</i> = 0.03). <h3>Conclusion</h3> IBMs after NAT was useful prognostic factor for stage II-III breast cancer patients. Adding LMR and SII to Neo-Bioscore can further stratify the prognosis of BCSS. High level of SII after RT had a negative impact on local-regional control, whether it reflects preclinical studies of post-RT inflammation-mediated tumor recurrence needs further study.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer

BackgroundTo develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer.MethodsThirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group.ResultsFollowing independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination.ConclusionsThe nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BackgroundWe aim to assess the value of locoregional treatment (LRT) including breast‐conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer.MethodsPatients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan‐Meier analysis, log‐rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis.ResultsA total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer‐specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5‐year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5‐year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5‐year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis.ConclusionsPostoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non‐inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.

Adjuvant chemotherapy and survival in women aged 70 years and older with triple-negative breast cancer: a Swedish population-based propensity score-matched analysis

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with poor survival, in which adjuvant systemic treatments are limited to chemotherapy. Due to competing mortality risks and comorbidities, older patients with TNBC are often undertreated with adjuvant chemotherapy, and clinical trials on this problem are scarce, despite a growing patient population. This study aimed to assess outcomes for patients aged 70 years and older with TNBC with or without chemotherapy in a national population-based registry, to provide information that can assist in treatment decisions for these patients. In this population-based registry study, data on all patients aged 70 years and older diagnosed with primary early TNBC (larger than 5 mm in diameter and without distant metastasis) and surgically treated between Jan 1, 2009, and Dec 31, 2016, were retrieved from the Swedish National Breast Cancer Register, the Swedish Patient Register, and the Swedish Cause of Death Register. Patients with incomplete data (on oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status, surgical procedure in the breast, or information about chemotherapy) were excluded. A propensity score-matched (PSM) model was used to examine the outcomes of adjuvant chemotherapy on 5-year breast cancer-specific survival (BCSS) and 5-year overall survival (OS), adjusted for age, tumour size, tumour grade, nodal status, and comorbidities. Of 1130 women eligible for analysis, 368 (32·6%) received adjuvant chemotherapy, 45 (4·0%) received neoadjuvant treatment, and 717 (63·5%) did not receive chemotherapy. 5-year BCSS was significantly improved in patients who received adjuvant chemotherapy (85% [95% CI 81-89]) compared with patients who did not receive chemotherapy (68% [64-72]; p<0·0001). A similar benefit was observed in 5-year OS (79% [95% CI 75-84] vs 49% [45-53]; p<0·0001). In our PSM analysis, 5-year BCSS in patients treated with adjuvant chemotherapy was 83% (95% CI 78-89), versus 73% (67-80; p=0·014) in patients not treated with chemotherapy. 5-year OS in patients treated with adjuvant chemotherapy was 75% (95% CI 69-82), versus 63% (57-71; p=0·029) in patients who did not receive chemotherapy. In this PSM registry analysis of surgically treated female patients aged 70 years and older with TNBC without distant metastasis, we identified a significant benefit both in 5-year BCSS and 5-year OS with adjuvant chemotherapy versus no chemotherapy, which persisted when adjusting for age and comorbidities. These results underline the importance of considering adjuvant chemotherapy in older patients. Knut and Alice Wallenberg Foundation, Assar Gabrielsson Foundation.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

BackgroundThe value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population.MethodsPatients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups.ResultsOf the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191).ConclusionsRadiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC.

Predicting Survival Benefit of Sparing Sentinel Lymph Node Biopsy in Low-Risk Elderly Patients With Early Breast Cancer: A Population-Based Analysis.

Objective: The application of sentinel lymph node biopsy (SLNB) in elderly patients with early breast cancer remains somewhat controversial. This study aimed to establish individualized nomograms to predict survival outcomes of elderly patients with and without SLNB and find out which patients could avoid SLNB.Methods: A total of 39,962 ≥70-year-old patients diagnosed with T1–T2 breast cancer in 2010–2015 were included from the Surveillance, Epidemiology, and End Results (SEER) program and were divided into the training set (n = 29,971) and the validation set (n = 9,991). Axillary surgery was not specified in the SEER database, and we defined removing one to five lymph nodes as SLNB. Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Multivariate Cox analysis was utilized to identify risk factors for overall survival (OS) and breast-cancer-specific survival (BCSS). Nomograms and a risk stratification model were constructed.Results: In the training set, patients with SLNB had better OS (adjusted HR 0.57, P < 0.001) and BCSS (adjusted HR 0.55, P < 0.001) than patients without SLNB. Multivariate COX analysis identified age, marital status, grade, subtype, T stage, and radiation as independent risk factors for OS and BCSS in both SLNB and non-SLNB groups (all P < 0.05). They were subsequently incorporated to establish nomograms to predict 3- and 5-year OS and BCSS for patients with or without SLNB. The concordance index ranged from 0.687 to 0.820, and calibration curves in the internal set and external set all demonstrated sufficient accuracies and good predictive capabilities. Further, we generated a risk stratification model which indicated that SLNB improved OS and BCSS in high-risk group (OS: HR 0.49, P < 0.001; BCSS: HR 0.54, P < 0.001), but not in the low-risk group (all P > 0.05).Conclusion: Well-validated nomograms and a risk stratification model were constructed to evaluate survival benefit from SLNB in elderly patients with early-stage breast cancer. SLNB was important for patients in the high-risk group but could be omitted in the low-risk group without sacrificing survival. This study could assist clinicians and elderly patients to weigh the risk–benefit of SLNB and make individualized decisions. We look forward to more powerful evidence from prospective trials.

Werner Syndrome Protein Expression in Breast Cancer

IntroductionWerner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), which is characterized by premature aging and cancer predisposition. Malignancies that are commonly linked to WS are thyroid carcinoma, melanoma, breast cancer, meningioma, and soft tissue and bone sarcomas. Currently, the clinicopathologic significance of WRN in breast cancer is largely unknown. Patients and MethodsWe investigated the clinicopathologic and prognostic significance of WRN protein expression in a cohort of clinically annotated series of sporadic (n = 1650) and BRCA-mutated (n = 75) invasive breast cancers. We correlated WRN protein expression to clinicopathologic characteristics, DNA repair protein expression, and survival outcomes. ResultsThere is strong evidence of association between low nuclear and cytoplasmic WRN co-expression and low levels of KU70/KU80, DNA-PK, DNA Pol-B, CKD18, cytoplasmic RECQL4, and nuclear BLM protein expression (adjusted P-values < .05). Tumors with low nuclear or cytoplasmic WRN expression have worse overall breast cancer-specific survival (BCSS) (adjusted P-values < .05). In topoisomerase I overexpressed tumors, low WRN nuclear expression was associated with poor BCSS (P-value < .05). In BRCA-mutated tumors, low WRN cytoplasmic expression conferred shortest BCSS (P < .05). ConclusionsLow WRN protein expression is associated with poor BCSS in patients with breast cancer. This can be used to optimize the risk stratification for personalized treatment.

Early progression of breast cancer during neoadjuvant chemotherapy may predict poorer prognoses

Background: In Finland, breast cancers treated with neoadjuvant chemotherapy (NACT) are usually locally advanced and/or have an inflammatory phenotype. We evaluated early NACT responses in breast tumours and lymph nodes and their correlation with survival.Material and methods: We collected a retrospective dataset of 145 patients with very high-risk but non-metastasised breast cancers that were treated with NACT in a Finnish University Hospital between September 2013 and January 2019. The patients underwent magnetic resonance imaging (MRI) scans before beginning NACT and after every second NACT cycle thereafter.Results: The total pathological complete response rate was only 10.7% and breast cancer-specific survival (BCSS) at 24 months was 93.0%. The 2-year breast cancer-specific survival (BCSS) rate was 93.0%, but this varied from 86.5% for the triple-negative subtype to 100.0% for the luminal A-like subtype. Enlargement of the malignant axillary lymph nodes during the first two NACT cycles was associated with poor BCSS rates in HER2-negative patients (p = .00003 in the univariate analysis; hazard ratio = 26.3; 95% confidence interval = 2.66–259.6; p = .005 in the multivariate analysis). Furthermore, progression in the combined diameters of the breast tumours and axillary lymph nodes during the period between a patient’s pre-treatment MRI and her MRI after two NACT cycles was also correlated with worse BCSS rates in both univariate and multivariate analyses.Conclusions: An early MRI assessment after two NACT cycles, specifically of the tumour’s axillary lymph nodes, has the potential to predict short-term BCSS in patients with locally advanced HER2-negative breast cancers.

Individualized Prediction of Survival Benefit From Locoregional Surgical Treatment for Patients With Metastatic Breast Cancer.

Objective: Recently, performing locoregional surgical treatment still remains debatable in patients with metastatic breast cancer (MBC). Current study aimed to develop prognostic nomograms for predicting the long-term survival in MBC patients with or without surgical intervention, thereby assisting clinicians in making individualized choice.Methods: The training set included 5173 patients who were diagnosed with MBC in 2010–2013 from the Surveillance, Epidemiology, and End Results Program, while the validation set comprised 2924 patients diagnosed in 2014–2015. Multivariant Cox hazard model was applied to determine the independent risk factors for overall survival (OS) and breast cancer specific survival (BCSS). Then, individualized pre- and postoperative nomograms for predicting 1- or 3-year survival probabilities were constructed accordingly. Internal and external validations were conducted to determine the accuracy of these nomograms by calculating concordance index (C-index) and plotting calibration curves.Results: The survival analysis indicated that surgical management conferred improved OS and BCSS in patients with metastatic breast cancer. Age, T stage, grade, distant metastatic site, ER, PR and HER2 status, radiation, and chemotherapy were independent risk factors for OS and BCSS both in surgery and non-surgery group. All these factors were subsequently incorporated into the nomogram which showed acceptable predictive capabilities with C-index range of 0.65–0.80 both in training set and external validation set. In addition, a preoperative nomogram incorporating variables capable of being determined before surgery was also built with C-index above 0.70 both in training and validation set.Conclusion: Surgical management in patients with metastatic breast cancer suggests a potential survival advantage. In addition, these well-validated pre- and postoperative nomograms may provide a useful tool to assist clinicians in treatment decision-making and in evaluating patients' long term prognosis.