Early-stage Breast Cancer Patients Research Articles

Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center.

Breast cancer is a primary cause of cancer-related death among women worldwide. Neoadjuvant chemotherapy (NACT) is a cornerstone treatment for locally advanced, non-metastatic breast cancer. Achieving pathological complete response (pCR) is often used as a surrogate marker for long-term outcomes. This study examines the impact of obesity, defined by a body mass index (BMI) over 30kg/m2, on achieving pCR in patients with early stage breast cancer (eBC) undergoing NACT. A retrospective analysis was conducted on patients with eBC treated with NACT at the University of Tübingen. The primary objective was to assess the impact of obesity on achieving pCR. Logistic regression analysis was used to determine the association between pre-treatment BMI and pCR, adjusting for covariates such as age, tumor stage, grading, and chemotherapy intensity. The study included 325 patients, with 24% classified as obese. While the univariate logistic regression analysis showed no significant impact of obesity on the odds ratio of achieving pCR, the multivariate analysis, accounting for covariates, demonstrated that obese patients had a significantly higher likelihood of achieving pCR. In this retrospective study, obesity significantly affected the likelihood of achieving pCR in patients with eBC cancer undergoing NACT after adjusting for covariates. While obesity is a known risk factor for breast cancer development and progression, its impact on the efficacy of NACT in terms of achieving pCR was positive in our study. These findings contribute to the ongoing debate in the literature, though the retrospective design and potential uncontrolled factors should be considered.

Fat necrosis after accelerated partial breast irradiation or hypofractionated whole breast irradiation: A case-control study.

This study aimed to compare the incidence of fat necrosis after accelerated partial breast irradiation (APBI) vs hypofractionated whole breast irradiation (WBI) in patients with early-stage breast cancer. Data from early-stage breast cancer patients who underwent breast-conserving surgery and adjuvant radiotherapy between 2009 and 2022 were retrospectively collected. Radiation therapy consisted of APBI of 30 Gy in 5 daily fractions (Fx) (delivered in one week, consecutively) to the tumour bed or WBI (42.4 Gy in 16 Fx). Reports on fat necrosis were extracted from yearly mammograms and breast ultrasound imaging. The primary endpoint was the incidence of radiologically detected fat necrosis. A total of 536 patients were included among the APBI and WBI cohorts, with 268 and 268 patients respectively. The three-year Kaplan-Meier actuarial rate of fat necrosis was 32.8% (95% CI: 30.0% - 35.6%) for APBI and 22.3% (95% CI: 19.7% - 24.9%) for WBI patients. Univariate Kaplan-Meier survival analysis revealed a Hazard Ratio of 1.6 [95% CI: 1.1 - 2.2; p = 0.0055] for the fat necrosis rate within the APBI group compared to WBI. Multivariate Cox proportional hazard regression confirmed significant associations between fat necrosis and APBI (HR = 2.2 95% CI: 1.2 - 4.0; p = 0.01). The occurrence of radiologically diagnosed fat necrosis was higher in the APBI group compared to the WBI. Further investigations aiming to identify a lower-dose schedule with comparable efficacy to 30 Gy in 5 Fx but fewer toxicities, particularly for high-risk patients, are warranted.

Higher risk of recurrence in early-stage breast cancer patients with increased levels of ribosomal protein S6

PI3K/AKT/mTOR pathway is implicated in breast cancer progression and recurrence. The identification of PIK3CA and AKT1 mutations and loss of PTEN serve as selection criterion for targeted therapies involving selective inhibitors. However, they do not consistently align with pathway activation, and high-cost determinations limit their routine application. PI3K-downstream epigenetic regulatory mechanisms broaden the alterations that amplify pathway activity and, consequently, sensitivity to selective inhibitors. In this retrospective observational study, conducted within a cohort of early-stage breast cancer patients, we determined phosphorylated ribosomal protein S6 (pS6) at Ser240/244 by immunohistochemistry as an indicator of PI3K pathway activation. Log-Rank test and Cox proportional hazards regression were used to analyze the clinical relevance of pS6, alone and together with clinicopathological variables, regarding recurrence-free survival. ROC curves and the area under the curves were used to evaluate the calibration and discrimination properties of uni- and multivariate models. Our results show that a high percentage of pS6 positive tumor cells was associated with an unfavorable prognosis in a cohort of 129 hormone receptor positive/HER2 negative breast cancer patients (Hazard Ratio = 5.92; Log-Rank p = 9.5e-08; median follow-up = 53 months). When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

Real-World Outcomes with the KEYNOTE-522 Regimen in Early-Stage Triple-Negative Breast Cancer.

This study aimed to determine if the neoadjuvant (NAT) KEYNOTE-522 regimen was associated with higher rates of pathologic complete response (pCR), corresponding to higher rates of breast conservation therapy (BCT) in early-stage triple-negative breast cancer (TNBC) patients. Stage II-III TNBC patients diagnosed between 2019 and 2022 who underwent NAT were analyzed retrospectively. NAT with KEYNOTE-522 versus control NAT were compared for rates of BCT, axillary node dissection (ALND), pCR, and survival outcomes. The prevalence of immune-related adverse events (irAE) from chemoimmunotherapy was recorded. Of 240 patients identified: 86 received KEYNOTE-522 and 154 received control. The frequency of pCR was significantly higher in KEYNOTE versus the control cohort, 59.3% and 33.1%, respectively (p = 0.001). There was no significant difference in the rate of BCT between the control (33.1%) and the KEYNOTE-522 (32.1%) groups (p = 0.47). Rates of ALND were significantly lower with KEYNOTE-522 (25.6%) as compared with control (39.6%); p = 0.03. The rate of development of grade 2 or higher irAEs was 34.9%. At a median follow-up of 2.4 years, there was no difference in survival outcomes. BRCA1 patients had high rates of pCR regardless of treatment group, KEYNOTE-522: 80.0% (4/5) and control: 75% (9/12), (p = 1). This real-world evidence supports the use of the KEYNOTE-522 regimen in patients with early-stage TNBC given the higher pCR rate and corresponding decrease in the rate of ALND. The majority of patients in both NAT cohorts became BCT eligible, but the rate of BCT did not differ between the two groups.

Risk of type-2-diabetes after breast cancer treatment: a population-based cohort study in Denmark.

Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women. We assembled a population-based cohort of early-stage BC patients aged ≥30 years diagnosed during 1996-2021 in Denmark. We created a comparison cohort of five cancer- and T2D-free women for each BC case, matched six months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D. Among 74,526 BC survivors and 372,630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95%CI = 3.7-3.9) and 3.3% (95%CI = 3.3-3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years=1.20, 95%CI = 1.15-1.25, and aHR15-years=1.09, 95%CI = 1.05-1.12). Adjuvant endocrine therapy (aHR = 1.14; 95%CI = 1.10-1.19), aromatase inhibitors (aHR = 1.25; 95%CI = 1.18-1.32), and less so tamoxifen (aHR = 1.05; 95%CI = 0.99-1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95%CI = 1.03-1.17) and radiation therapy (right-sided aHR = 1.18, 95%CI = 1.09-1.27 and left-sided aHR = 1.24, 95%CI = 1.15-1.33) were associated with increased T2D risk. BC was associated with excess risk of T2D, though of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.

Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

BackgroundMortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for 20 years or more following treatment of the primary tumor. As recurrent breast cancer is typically incurable, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. The importance of this goal is further underscored by emerging evidence suggesting that targeting dormant residual tumor cells in early-stage breast cancer patients may be a means to prevent tumor recurrence and its associated mortality. In this regard, the role of autophagy in dormant tumor cell survival and recurrence remains unresolved, with conflicting reports of both pro-survival/recurrence-promoting and pro-death/recurrence-suppressing effects of autophagy inhibition in dormant tumor cells. Resolving this question has important clinical implications.MethodsWe used genetically engineered mouse models that faithfully recapitulate key features of human breast cancer progression, including minimal residual disease, tumor dormancy, and recurrence. We used genetic and pharmacological approaches to inhibit autophagy, including treatment with chloroquine, genetic knockdown of ATG5 or ATG7, or deletion of BECN and determined their effects on dormant tumor cell survival and recurrence.ResultsWe demonstrate that the survival and recurrence of dormant mammary tumor cells following therapy is dependent upon autophagy. We find that autophagy is induced in vivo following HER2 downregulation and remains activated in dormant residual tumor cells. Using genetic and pharmacological approaches we show that inhibiting autophagy by chloroquine administration, ATG5 or ATG7 knockdown, or deletion of a single allele of the tumor suppressor Beclin 1 is sufficient to inhibit mammary tumor recurrence, and that autophagy inhibition results in the death of dormant mammary tumor cells in vivo.ConclusionsOur findings demonstrate a pro-tumorigenic role for autophagy in tumor dormancy and recurrence following therapy, reveal that dormant tumor cells are uniquely reliant upon autophagy for their survival, and indicate that targeting dormant residual tumor cells by inhibiting autophagy impairs tumor recurrence. These studies identify a pharmacological target for a cellular state that is resistant to commonly used anti-neoplastic agents and suggest autophagy inhibition as an approach to reduce dormant minimal residual disease in order to prevent lethal tumor recurrence.

The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials

BackgroundThis paper aimed to evaluate the effectiveness of incorporating CDK 4/6 inhibitors (CDK4/6i) into ET for the adjuvant treatment of HR + HER2-resected early-stage breast cancer (ESBC) patients, employing meta-analysis. MethodsIn this paper, we compiled randomized clinical trials focusing on CDK4/6i used in the adjuvant treatment of high-risk invasive HR-positive and HER2-ESBC patients. A meta-analysis was performed in line with the PRISMA guidelines. ResultsWe identified four clinical trials that met our inclusion criteria and were published between 2020 and 2024. These trials involved a combined sample size of 17,749 patients diagnosed with breast cancer. The data obtained from the pooled analysis revealed a remarkable beneficial trend in terms of invasive disease-free survival (iDFS) for the use of ET in combination with CDK4/6i compared to the group receiving ET alone (HR = 0.81, 95 % CI: 0.67–0.98, p = 0.03). Of note, CDK4/6 inhibitors demonstrated a notably beneficial effect in both grade 2 (HR = 0.69, 95 % CI: 0.59–0.81, p < 0.001) and grade 3 (HR = 0.76, 95 % CI: 0.65–0.89, p < 0.001). Significant improvements were noted in terms of distant relapse-free survival (dRFS) in the groups treated with abemaciclib and ribociclib (HR = 0.65, 95 % CI: 0.56–0.76, p < 0.001; HR = 0.72, 95 % CI: 0.58–0.89, p = 0.003, respectively). CDK4/6i didn't yield a statistically significant difference in overall survival (OS) (HR = 0.96, 95 % CI: 0.77–1.19, p = 0.69). The use of CDK4/6i with ET was associated with an increased risk of adverse events, particularly anemia and neutropenia, compared with ET alone (OR = 9.12, 95 % CI = 5.04–16.48, p < 0.001). ConclusionThe findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

Comparative long-term oncological outcomes of intraoperative radiotherapy vs. whole-breast irradiation in early breast cancer: a single institute study.

Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breast-conserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings. Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed. A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5cm for BC and 1.2cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030). At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER- patients for IORT.

6550 National Statin Prescription Trends in Patients With Breast Cancer and Diabetes for Primary Cardiovascular Disease Prevention

Abstract Disclosure: A.B. Yang: None. G. Mhango: None. C. Kong: None. J.J. Lin: None. J.P. Wisnivesky: Consulting Fee; Self; Sanofi, Banook, PPD. Grant Recipient; Self; Sanofi, Regeneron Pharmaceuticals, Axella, Arnold Consultants. A. Leiter: None. Background: Cardiovascular disease (CVD) is the leading cause of death in older early-stage breast cancer (BC) survivors. Due to cardiotoxic BC treatments such as chemotherapy and radiation, patients with BC and diabetes (DM) are at increased risk of CVD. In patients with BC and DM, statins decrease CVD mortality. Since 2013, many clinical guidelines broadened statin indications for primary CVD prevention in patients with DM, making &amp;gt;85% of patients eligible. Little is known about statin prescription (Rx) patterns in older BC survivors with DM, a group at high risk of CVD. Hypothesis: We hypothesized that statin Rxs increased over time, but were less likely in BC survivors with more advanced locoregional BC and lower comorbidity burden. Methods: A population-based, retrospective cohort study was conducted using Surveillance, Epidemiology and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting DM who were diagnosed with stage 0-III primary BC between 2008-17. We excluded patients with prior CVD who died &amp;lt;1 year after BC diagnosis. Statin Rx (atorvastatin, pravastatin, rosuvastatin, simvastatin, fluvastatin, lovastatin) was defined as ≥1 statin pharmacy claim &amp;lt;1 year after BC diagnosis. Comorbidity burden was assessed with a modified Charlson Comorbidity Index (CCI). We compared patient demographic and clinical characteristics by statin Rx status using the chi-square test. Using a multivariate logistic regression adjusting for age, race, CCI, BC stage, and diagnosis year, independent predictors of statin Rx were identified. Results: Of 8,423 BC patients with pre-existing DM, 5,698 (68%) had a statin Rx. Statin Rx increased over time (BC diagnosis year 2008-10: 66%, 2011-13: 66%, 2014-15: 69%, 2016-17: 70%; p=0.01) and differed by age (66-69: 66%, 70-74: 70%, 75-79: 69%, ≥80: 65%; p&amp;lt;0.01) and race (White: 68%, Black: 62%, Latinx: 66%, Other: 72%; p&amp;lt;0.01). Statin Rx did not differ by comorbidity burden (CCI 0: 68%, 1-2: 67%, ≥3: 67%; p=0.87) and declined with higher BC stage (0: 73%, I: 70%, II: 65%, III: 63%; p&amp;lt;0.01). In adjusted analyses, more recent BC diagnosis (2016-17 vs. 2008-10: odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.04-1.38), age group (70-74 vs. 66-69: OR: 1.24, 95% CI: 1.09-1.41), race (Black vs. White: OR 0.77, 95% CI: 0.66-0.89) and higher BC stages (II vs. 0: OR: 0.76, 95% CI: 0.58-1.00; III vs. 0: OR: 0.72, 95% CI: 0.54-0.97) remained predictors of statin Rx. Conclusions: In a nationally representative cohort analysis of older early-stage BC patients, statin Rx increased between 2008-17 and varied by age, race, and BC stage. Elucidating gaps in statin Rx can potentially improve guideline-concordant Rx in a group at high risk for CVD and reduce disparities. Presentation: 6/2/2024

Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients

PurposeThe aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients. MethodsA total of 195 eligible early BC cases were tested for genomic risk between 2006 – 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics. ResultsMammaPrint identified 118 (60.5%) patients with genomically Low Risk tumors and 77 (39.5%) patients with genomically High Risk tumors. Age, menopausal status, tumor size, receptor status, and nodal status were comparable between MammaPrint Risk categories. The median follow-up was 8.4 years for DMFS and 9.3 years for OS; 8-year follow-up was reported for both endpoints. The 8-year DMFS was 90.4% (95% CI 84.9 – 95.9) in patients with MammaPrint Low Risk tumors compared to 60.8% (95% CI 49.8 – 71.8) for patients with High Risk tumors. Patients with MammaPrint Low Risk tumors exhibited significantly superior 8-year OS (97.3%; 95% CI 94.4 – 100) compared with MammaPrint High Risk tumors (89.5%; 95% CI 82.6 – 96.4; p = 0.028). Multivariate analyses identified MammaPrint as significantly associated with 8-year DMFS and MammaPrint together with Progesterone Receptor positivity with 8-year OS. ConclusionThe prognostic performance of MammaPrint was demonstrated in early-stage clinically intermediate to high-risk BC patients. Moreover, patients with MammaPrint Low Risk tumors had good outcome regardless of treatment regimen, thus supporting personalized treatment choices.

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.

Longitudinal Trends in Patient-Reported Outcomes in the First Year After Lumpectomy Versus Mastectomy.

It is unclear how patient-reported outcomes (PROs) change longitudinally after breast cancer surgery. We sought to compare trends in PROs among patients who underwent lumpectomy versus mastectomy over the first year after surgery. Newly diagnosed stage 0-III female patients with breast cancer who underwent lumpectomy or mastectomy at an academic breast center between June 2019 and March 2023 were invited to participate in a longitudinal PRO study. Enrolled patients received the BREAST-Q™ module, a validated tool measuring domains, such as satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Scores for each domain were compared between the lumpectomy and mastectomy groups over the first year after surgery. Linear mixed models were used to estimate the change in PRO scores over time. The cohort included 203 who underwent lumpectomy and 144 who underwent mastectomy. Patients who underwent lumpectomy were older, more likely to receive adjuvant radiation and endocrine therapy, and less likely to receive adjuvant chemotherapy. Patients who underwent lumpectomy demonstrated greater increases in scores over time for satisfaction with breasts, psychosocial well-being, and sexual well-being compared with patients who underwent mastectomy, after adjusting for the abovementioned covariates and receipt of reconstruction. The lumpectomy group had a larger decline in physical well-being over time compared with the mastectomy group. Patients who underwent lumpectomy demonstrated greater satisfaction with their breasts, psychosocial well-being, and sexual well-being but worse physical well-being over the first year after surgery compared with patients who underwent mastectomy. These results may help inform early-stage breast cancer patients making decisions about their surgical care.

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study.

A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice. Patients operated for early-stage ER+ breast cancer with disputable chemotherapy indication, had been prospectively included between 2013 and 2015. Oncologists were asked whether they intended to administer adjuvant chemotherapy before deployment of the 70-GS test. Information on adjuvant systemic treatment and oncological outcome was obtained through active follow-up by data managers of the Netherlands Cancer Registry. The primary endpoint of this study was distant metastasis-free survival (DMFS) according to the genomic risk. Exploratory analyses were done to evaluate DMFS in relation to the oncologists' pre-test advice. After a median follow-up of 7 years, distant metastases were diagnosed in 23 of the 606 patients (3.8%) and 36 (5.9%) patients had died. The DMFS rate for the 357 70-GS genomic low-risk patients was 94.2% (95% CI 91.2-96.2) and 89.1% for the 249 genomic high-risk patients (95% CI 84.3-92.4). Of the low-risk patients 3% had received chemotherapy compared to 80% of the high-risk patients. For the subgroups based on the pre-test oncologists' advice (no chemotherapy/chemotherapy/unsure) there were no clinically relevant differences in DMFS (89.8, 93.2 and 92.0%, respectively), while comparable proportions of patients had received chemotherapy. In patients with early-stage ER+ breast cancer with a disputable chemotherapy indication it is sensible to deploy the 70-GS to better select patients for adjuvant chemotherapy.

Knowledge-map and research trends of circulating tumor cells in breast cancer: a scientometric analysis

Assessing circulating tumor cells (CTCs) in early-stage breast cancer patients can help identify relapse risk for timely interventions. Molecular analysis of CTCs can reveal vulnerabilities for personalized treatment options in metastatic breast cancer. This study aims to summarize CTCs in breast cancer research understanding and evaluate research trends. Extracted from the Web of Science Core Collection, publications on CTCs in breast cancer studies spanning from January 1, 2008, to December 21, 2023, were included. Co-authorships, references, and keywords were analyzed using Bibliometrix R packages and VOSviewer software. References and keywords burst detection were conducted with CiteSpace, and BICOMB was utilized to generate high-frequency keyword layouts. Biclustering analysis of the binary co-keyword matrix was performed using gCLUTO. 1747 articles focusing on CTCs in breast cancer were identified. The USA and the University of Texas MD Anderson Cancer Center demonstrated the highest productivity at the national and institutional levels, respectively. The journal “CANCERS” had the highest publication outputs on this subject. Pantel K emerged as the foremost author with the highest publication and co-citation counts. Analysis of co-keywords unveiled five prominent research areas concerning CTCs in breast cancer. The prognostic and predictive roles of CTCs in breast cancer have substantial implications for clinical practice. Nevertheless, precise assessment of CTCs, encompassing its quantities and attributes through advanced technologies, and its role in detecting minimal residual disease in breast cancer, continue to pose notable challenges. In conclusion, recent advancements and trends in CTCs research in breast cancer are examined through scientometric analysis in this study. The results provide valuable insights for the formulation of novel approaches in CTCs research, emphasizing the current research frontiers.

A systematic review on the techniques, long-term outcomes, and complications of partial breast irradiation after breast-conserving surgery for early-stage breast cancer.

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk assessment tool with the Methodological Index for Non-Randomized Studies (MINORS), and the research information were analyzed using data analysis software. Clinical studies were collected from the earliest available date until September 2023. Fifty-one studies were included, with a total sample size of 7708. The results of network meta-analysis (NMA) showed that ISBT can lower the local recurrence (SUCRA: 73.8%). In terms of reducing distant metastasis, 3DCRT may be the best choice (SUCRA: 52.5%). And IORT has the highest 5-year overall survival (SUCRA: 90%). Furthermore, ISBT also has the advantages of lowest risk with fat necrosis (SUCRA: 72.5%), infection (SUCRA: 78.3%) and breast pain (SUCRA: 86.2%). BBT may be the optimal solution for fibrosis (SUCRA: 76.9%) and hyperpigmentation (SUCRA: 66.7%). 3DCRT has lower incidence of telangiectasia (SUCRA: 56.7%) and better cosmetic result (SUCRA: 85%). Postoperative PBI treatment using ISBT after breast-conserving surgery in patients with early-stage breast cancer may be a more valuable choice based on the treatment efficacy and is associated with fewer late side-effects. Large-scale, prospective, long-term studies are warranted to clarify the role of different PBI techniques in selected patients.

Mainstream Germline Genetic Testing with Expanded Eligibility for Early Breast Cancer Patients in a Large Integrated Health System.

This study evaluated a new mainstream genetic testing pathway for hereditary cancer, with expanded eligibility for early-stage breast cancer patients. The study compared multigene panel (62 genes) germline testing uptake and results for breast cancer patients at 4 pilot sites (n = 502 patients) and 10 non-pilot sites (n = 1792 patients) within Kaiser Permanente Northern California from December 2020, to June 2021. At the pilot sites, breast care coordinators (BCCs) offered and consented patients for testing, with eligibility expanded to include all patients age 65 years or younger. At the non-pilot sites, eligible patients were referred to genetics for pre-test counseling, ordering, and follow-up evaluation with the standard guideline that included all patients age 45 years or younger. Demographic and disease characteristics were similar at the pilot and non-pilot sites. At the pilot verses non-pilot sites, a higher percentage of patients was tested overall (61.6% vs 31.7%) and across all age groups. The median time from breast biopsy to test result also was reduced (22 vs 33 days, respectively). A higher percentage of patients at the pilot sites was identified as having a pathogenic/likely pathogenic variant (PV/LPV) in a breast cancer-related gene (3.6% vs 1.6%). Although the percentage of total patients tested was nearly twofold higher at the pilot sites than at the non-pilot sites, the percentage of total patients seen by genetics was estimated to be similar (33.7% vs 31.7%). Mainstream genetic testing of breast cancer patients facilitated by BCCs makes it feasible for a large health care system to expand germline genetic testing to early breast cancer patients age 65 years or younger.

HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Non-irradiated area of intraoperative radiotherapy with electron technique: outcomes and pattern of failure in early-stage breast cancer from a single-center, registry study

IntroductionIntraoperative radiotherapy (IORT) with electrons has revealed to have higher rates of ipsilateral breast tumor recurrence (IBTR) than external beam radiotherapy in updated large-scale, randomized controlled trials in 2021. This study details the oncological outcomes of IORT with electron beams using our strict IORT policies. We have found new and important observations regarding the location of recurrence.Methods and materialsThis is a single institution registry of early-stage breast cancer patients who underwent lumpectomy and electron beam IORT with appropriate cone size. All patients met our pre-excision requirements. The primary endpoint was 5-year IBTR rate, with secondary endpoints being 5-year locoregional failure rate, 5-year distant metastasis rate, 5-year overall survival and, importantly, the failure patterns.ResultsBetween January 2011 and December 2022, 124 patients were recruited. The median follow-up was 6.7 years. The 5-year IBTR rate was 1.87% (95% CI 0.47–7.29%), which is much lower than the ELIOT trial and comparable with other accelerated partial breast irradiation (APBI) techniques. The 5-year locoregional failure rate was 3.68% (95% CI 1.40–9.52%), and the 5-year distant metastasis rate was 0.88% (95% CI 0.13–6.12%), while the 5-year overall survival rate was 97.52% (95% CI 92.44–99.19%). Six patients experienced IBTR. All recurrences were in surgical area, occurring superficial to the tumor bed and within 1 cm of the skin dermis. This failure pattern is very unique and might be explained by our hypothesis of the non-irradiated area beneath the skin.ConclusionsIORT with electron beams with strict patient selection criteria and strict large cone size is still an acceptable treatment for select patients with early-stage breast cancer. However, our new findings support extreme caution in the non-irradiated area beneath the skin around the tumor cavity. Given the constraints of our sample size, these findings should be interpreted cautiously and warrant further investigation in larger, more comprehensive studies.

Omission of sentinel lymph node biopsy in patients with clinically axillary lymph node-negative early breast cancer (OMSLNB): protocol for a prospective, non-inferiority, single-arm, phase II clinical trial in China

IntroductionSentinel lymph node biopsy (SLNB) is a standard procedure for patients with clinically assessed negative axillary lymph nodes (cN0) during early-stage breast cancer (EBC). However, the majority of EBC patients...

Association between pembrolizumab-related thyroid adverse events and outcomes in early-stage triple-negative breast cancer patients.

Pembrolizumab-related thyroid dysfunction has been associated with better outcomes in metastatic cancer patients. This study aims to examine the outcomes (pathological complete response (pCR) and event-free survival (EFS)) in early-stage triple-negative breast cancer (TNBC) patients receiving preoperative therapy who developed pembrolizumab-related thyroid dysfunction. Patients were divided into four groups based on the occurrence or not of pembrolizumab-related thyroid dysfunction (group A and D, respectively) and, in case of pre-existing thyroid disorder, based on the need for levothyroxine start/adjustment or not (group B and C, respectively). pCR and EFS in groups A, B, and C were compared to the ones in group D. Sixty-four early-stage TNBC patients were included, and the median follow-up was 16.5 months (IQR 12.0-23.8). Multiple patterns of thyroid irAEs were observed (overt hypothyroidism in 56.3%, subclinical thyrotoxicosis in 28.1%, overt thyrotoxicosis and subclinical hypothyroidism in 21.9%, and 21.9% of patients). No statistical difference was found in pCR (chi-square test, P = 0.611) comparing groups A, B, and C to group D. The median EFS in groups A, B, and C and in group D were 16.5 (IQR 12.0-24.0) and 16.0 (IQR 12.0-22.3) months, respectively (log-rank test, P = 0.671). The percentage of patients obtaining pCR was 85.7% in patients developing pembrolizumab-related overt thyrotoxicosis and 42.1% in remaining patients (chi-square test, P = 0.036). The EFS was 16.0 months (IQR 12.0-25.0) in patients developing pembrolizumab-related overt thyrotoxicosis and 16.0 months (IQR 12.0-23.5) in the remaining patients (log-rank test, P = 0.494). In conclusion, multiple patterns of pembrolizumab-related thyroid dysfunction occur in early-stage TNBC. Patients developing pembrolizumab-related overt thyrotoxicosis are more likely to achieve pCR.