Breast Cancer Research and Treatment最新文献

Purpose: Postpartum breast cancers (PPBC) have a worse prognosis than other breast cancers, but the impact of timing postpartum (PP) and concurrent breastfeeding (BF) on diagnostic patterns and outcomes remains unclear.

Methods: We analyzed 161 PPBC patients diagnosed from 2002 to 2014, hypothesizing that diagnosis < 2 years PP (vs 2-5 years) and concurrent BF (vs not BF) at diagnosis would be associated with delayed diagnosis. We compared 2-year PP patients (N = 60) and 2-5 year PP patients (N = 101), and subsequently, patients who were (n = 36) and were not (n = 24) BF at diagnosis among the 2-year PP group with respect to clinicopathologic characteristics, breastfeeding details, diagnostic patterns, and disease outcomes. Differences were evaluated using chi-square and Mann-Whitney tests. Kaplan-Meier analysis assessed overall survival (OS) and distant disease-free survival (DDFS).

Results: Median follow-up was 54 months. Patients in the 2-year PP group were more likely to be BF at diagnosis (60% vs 7%, p < 0.001), and have their symptoms attributed to lactational change (37 vs 9%, p < 0.001). They were also diagnosed at a higher stage (43 vs 24% Stage III/IV, p = 0.01), had worse 5-year OS (79% vs 97%, p < 0.001), and DDFS (74% vs 93%, p = 0.003) compared to 2-5 year PP patients. Among 2-year PP patients, patients BF at diagnosis were more likely to be diagnosed with mastitis preceding diagnosis (31% vs 4%, p = 0.03), more often had their symptoms attributed to lactational change (58% vs 4%), trended toward higher stage at diagnosis (53 vs 29% Stage III/IV, p = 0.1), had significantly worse 5-year DDFS (62% vs 91%, p = 0.032), and trended toward worse OS (74% vs 86%, p = 0.08) compared to those not BF.

Conclusions: Our findings suggest that early PPBC and BF at diagnosis are associated with diagnostic delay and higher stage at diagnosis, which may have implications for prognosis.

Purpose: Randomized clinical trials have shown no benefit from adding anthracyclines to neoadjuvant treatment for HER2-positive breast cancer; however, the efficacy in inflammatory breast cancer (IBC) is unknown. Here we compared pathologic response rates for preoperative regimens with or without anthracyclines in HER2-positive primary IBC.

Methods: We retrospectively reviewed patients diagnosed with HER2-positive primary IBC in 2014-2021 who received neoadjuvant therapy and modified radical mastectomy at MD Anderson Cancer Center, IBC Network institutions and Dana-Farber Cancer Institute. The primary outcome was a pathological complete response (pCR) rate. Secondary outcomes included time to local or regional recurrence (TLRR), event-free survival (EFS), and overall survival (OS). Univariate and multivariable analyses were performed with adjustments for clinically relevant covariates.

Results: Of the 101 patients included, 39 received docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and 62 (docetaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) received THP-AC regimen. Median follow-up time was 3.02 years. The pCR rates did not differ by regimen type (48.7% TCHP vs. 53.2% THP-AC, p = 0.659). Multivariable logistic regression adjusted for age and estrogen receptor positivity showed no association between pCR or regimen. The multivariable Cox model showed that the patients who received THP-AC had longer TLRR (hazard ratio [HR] 0.279, 95% CI 0.102-0.765, p = 0.0131) and EFS (HR 0.462, 95% CI 0.228-0.936, p = 0.032), with no difference in OS.

Conclusion: These findings indicate that an anthracycline-containing neoadjuvant regimen is not associated with pCR, but may prolong disease control in patients with HER2-positive IBC. Further investigation of the optimal neoadjuvant regimen for such tumors is warranted.

Purpose: Cancer registries rarely track breast cancer relapse due to the resource-intensive nature of manual chart review. To address this gap, we developed natural language processing (NLP) models to automate the identification of breast cancer relapse in pathology reports.

Methods: We collected pathology reports from patients diagnosed with breast cancer between January 1, 2005, and December 31, 2014, in British Columbia, Canada, and manually annotated each for the presence or absence of local, regional, distant, and any breast cancer relapses. With these reports, we fine-tuned large language models to classify pathology reports.

Results: The corpus contained 1,888 pathology reports from a cohort of 993 breast cancer patients. Of these reports, 673 (35.6%) described local, 296 (15.7%) regional, and 654 (34.6%) distant relapses. In addition, 1,510 (80.0%) described at least one of any relapse type. The median time from diagnosis to first relapse was 7.3 years (range 0.2-18.2). All models demonstrated excellent performance. The local-relapse model performed particularly well, with > 93% accuracy, sensitivity, specificity, and 0.98 area under the receiver operating characteristic curve (AUC) score.

Conclusion: We developed NLP models to detect breast cancer relapses from pathology reports with excellent accuracy, sensitivity, specificity, and AUC. NLP may facilitate more efficient and accurate collection of breast cancer outcomes data from clinical reports.

Purpose: An important goal of routinely scheduled physical examination in the post-treatment surveillance of patients with early breast cancer (EBC) is to allow for earlier detection of potentially curable recurrences. We present an updated analysis of recurrence detection, and its potential for curative management, at a single-centre survivorship program that follows ASCO recommendations.

Methods: Patients with EBC referred to the Wellness Beyond Cancer Program who had breast cancer recurrence between February 2013 and June 2023 were reviewed. Descriptive analyses were used to present patient and disease characteristics stratified by type of recurrence and mode of cancer detection.

Results: Of 389 first recurrences, 250 were distant (64.3%), 75 local (19.3%), and 64 (16.5%) contralateral new breast primaries. Distant recurrences were primarily detected via patient-reported symptoms (220/250, 88.0%). 42.7% (32/75) of ipsilateral breast recurrences were detected by patients and 53.3% (40/75) by routine imaging. Contralateral breast primaries were primarily detected by routine imaging 71.9% (46/64) and patient-reported symptoms 25.0% (16/64). 2.1% (8/389) recurrences were detected by healthcare providers, 3 were coincidental intraoperative findings and 1.3% (5/389) were detected by healthcare providers at routinely scheduled follow-up visits. Of the 5 recurrences detected at routinely scheduled follow-up visits, only 0.3% (1/389) was potentially curable.

Conclusion: Despite following ASCO guidelines, potentially curable recurrences are rarely detected by healthcare providers at routinely scheduled follow-up appointments. Our data suggests that approximately 87,670 follow-up visits were required for healthcare providers to detect one curable recurrence. Updated evidence-based guidelines are required to optimise the post-treatment surveillance procedures.

Purpose: In 2016, the Society of Surgical Oncology and Choosing Wisely Campaign recommended against sentinel lymph node biopsy (SLNB) in women > 70 years with early-stage, hormone receptor-positive (ER/PR +) breast cancer, citing limited clinical benefit. Despite earlier evidence supporting de-implementation, SLNB rates remained high. We aimed to evaluate patient, tumor, facility, and unmeasured contextual factors associated with SLNB de-implementation using a national cohort.

Methods: We queried the National Cancer Database (NCDB) for women > 70 years diagnosed with early-stage ER/PR + and HER2-negative breast cancer between 2012 and 2019. A mixed effects logistic regression model assessed associations between SLNB non-utilization and patient, tumor, and facility-level characteristics. Interaction terms between year and facility breast surgery volume quartiles were included to examine trends over time. Reference Effect Measures (REM) were used to estimate the contribution of unmeasured contextual effects relative to measured covariates.

Results: Among eligible patients, SLNB use declined from 86.7% in 2012 to 81.0% in 2019. SLNB use was significantly associated with age, insurance, urbanization, distance to facility, education, income, tumor size, lymphovascular invasion, treatment type, facility region, program type, and surgical volume. Academic programs had the highest adjusted odds of SLNB non-utilization (AOR 1.62; 95%CI: 1.29-2.02), while facilities in the South had the lowest (AOR 0.53; 95%CI: 0.45-0.63). High-volume centers de-implemented more rapidly post-2016, with 24% higher odds of SLNB non-utilization per year. REM analysis identified patient age and unmeasured contextual effects as the predominant drivers of de-implementation.

Conclusion: SLNB use in older women is influenced by multi-level factors, with patient age and unmeasured contextual effects driving de-implementation-though progress remain slow and limited in the United States.

Purpose: This study aimed to systematically assess the efficacy of cardioprotective agents in preventing anthracycline-induced cardiotoxicity in patients with breast cancer using a comprehensive network meta-analysis (NMA).

Methods: This study included patients with breast cancer undergoing anthracycline-based chemotherapy. Randomized controlled trials (RCTs) published before March 2020 were identified through systematic searches in MEDLINE, Cochrane CENTRAL, Web of Science, and CINAHL. The primary outcome was left ventricular ejection fraction (LVEF), assessed using cardiac magnetic resonance imaging, multigated radionuclide angiography, or echocardiography. The NMA integrated direct and indirect comparisons to estimate the relative effectiveness of pharmacological interventions.

Results: The systematic review included 31 RCTs with 3,228 participants, whereas the NMA synthesized 25 effect sizes from 15 RCTs. Mineralocorticoid receptor antagonists (MRAs) [standardized mean difference (SMD): -1.78, 95% confidence interval (CI): -2.81 to -0.75] and trimetazidine (SMD: -1.12, 95%CI: -2.32 to -0.09) exhibited the most substantial cardioprotective effects. Dexrazoxane (SMD: -0.53, 95%CI: -1.90 to -0.02) and β-blockers (SMD: -0.34, 95%CI: -0.70 to 0.02) showed potential benefits, albeit with greater uncertainty. Direct comparisons showed that dexrazoxane was more effective than β-blockers (SMD: -1.25, 95%CI: -2.22 to -0.48), with mineralocorticoid receptor antagonists (MRAs) outperforming both. Despite heterogeneity and potential publication bias, mineralocorticoid receptor antagonists (MRAs) and trimetazidine consistently ranked as the most effective interventions. LVEF findings confirmed the cardioprotective benefits of β-blockers, ARBs, ACE inhibitors, and dexrazoxane.

Conclusions: RCT evidence suggested that cardioprotective drugs effectively mitigate anthracycline-induced LVEF decline. However, the lack of direct head-to-head trials limits definitive conclusions on comparative efficacy, warranting trials in patients with lower baseline LVEF to optimize cardioprotective strategies.

Purpose: Benign breast disease (BBD), particularly with proliferative changes, is a risk factor for breast cancer (BC) development in average risk women. There is a paucity of data on high-risk, BRCA1 and BRCA2 pathogenic variants (PVs) carriers.

Methods: Female BRCA1 and BRCA2 PV carriers treated at the Meirav Clinic, Sheba Medical Center between May 2011 and December 2024 were eligible. Data on in-hospital breast biopsies were retrieved following an ethically approved protocol. Statistical analyses included χ² test (categorical variables) Mann-Whitney U test (continuous variables) and logistic regression for multivariate analysis.

Results: Overall, 1466 women (849 BRCA1 PV carriers) were monitored over 10,113 women/years. A total of 1453 biopsies were carried out in 454 participants (range 1-8 biopsies), with the majority (76.3%) benign and 242 (16.6%) malignant. Rates of BC in women undergoing at least two benign biopsies were correlated with the number of biopsies, being an older BRCA1 PV carrier, whereas having been diagnosed with fibroadenoma-seems not to increase BC risk.

Conclusions: In Israeli BRCA PV carriers, the number of biopsies, BRCA1 PV carriership were associated with an increased risk for developing BC, whereas fibroadenoma does not increase that risk. It is imperative to validate these preliminary observations.

Purpose: The use of neoadjuvant chemotherapy (NAC) in cT1N0 patients with triple-negative (TN) or HER2-positive (HER2+) breast cancer has been controversial. It is unclear whether NAC or upfront surgery minimizes axillary dissection (ALND) risk in the contemporary cT1N0 TN/HER2+ patient population.

Methods: Consecutive cT1N0 TN/HER2+ patients who received NAC or underwent upfront surgery at our institution between 01/2020-12/2022 were examined. ALND was indicated for any positive sentinel nodes (+SLNs) after NAC, ≥ 3 positive SLNs after upfront surgery, or 1-2 positive SLNs after upfront mastectomy not requiring radiotherapy (RT). Clinicopathologic features, nodal burden, and ALND rates were compared between NAC versus upfront surgery cohorts.

Results: Among 506 patients, 43% (N = 218) were TN and 57% (N = 288) were HER2+; 9% (N = 47) received NAC before surgery; 68%( N = 343) underwent upfront breast-conserving surgery (BCS); 23% (N = 116) underwent upfront mastectomy. Axillary ultrasound was performed in 23% of patients who received NAC versus 26% of patients who underwent upfront BCS versus 33% of patients who underwent upfront mastectomy. ALND was performed in 6.4% (N = 3) of patients with any positive SLN after NAC, 1.7% (N = 6) who underwent upfront BCS, and 1.7% (N = 2) who underwent upfront mastectomy with ≥ 3 positive SLNs or 1-2 positive SLNs not meeting RT criteria (p = 0.13). No factors were associated with ALND, including T stage, upfront versus NAC approach, or tumor subtype.

Conclusion: Nodal disease burden is low among cT1N0 TN/HER2+ patients even in the absence of routine axillary ultrasound. ALND was performed in < 2% of patients with cT1N0 TN/HER2+ disease who had upfront surgery, and adjuvant systemic therapy was de-escalated among many pathologically node-negative patients following surgery.

Purpose: Several patients undergoing aromatase inhibitors (AIs) for breast cancer (BC) report cognitive difficulties, although studies on the cognitive effects have yielded mixed findings. This prospective study aimed to investigate the impact on cognitive function of adjuvant AIs and the changes over time.

Methods: Patients with diagnosis of early-stage BC, eligible for adjuvant AIs endocrine therapy, underwent comprehensive neuropsychological assessments for the evaluation of several cognitive domains before and after 12 months of therapy. Participants were stratified according to menopausal status, type of surgery, and prior chemotherapy.

Results: Eighty-three subjects were enrolled and, among these, 77 patients underwent neuropsychological assessments. At baseline, post-menopausal subjects (71%) performed significantly worse than pre-menopausal subjects in tests assessing executive functions. Subjects who received chemotherapy were younger, but showed poorer episodic memory performance compared to those chemotherapy-naïve. After 12 months, although most patients (66.1%) reported cognitive difficulties, the neuropsychological performance did not show significant deterioration. Notably, differences in verbal episodic memory between subjects treated with or without chemotherapy persisted over time.

Conclusion: This study suggests that the cognitive difficulties reported by BC patients who underwent AIs may be more influenced by prior chemotherapy rather than from the direct cognitive effects of AIs, highlighting the persistent cognitive consequences of chemotherapy. These findings emphasize the need for further research to better understand the interplay between chemotherapy, AIs, and cognitive function and the relevance of cognitive assessments.

Purpose: The Fasting-Mimicking Diet (FMD) has emerged as a promising approach for mitigating the side effects and enhancing the efficacy of chemotherapy in cancer patients, while it is still challenging to implement FMD in clinical setting due the concern of nutritional supplements. This study is aimed to evaluate the feasibility of a recipe-based FMD among breast cancer (BC) patients, and assessing its effects on metabolic health and body composition.

Methods: This is a single-arm, pilot clinical trial involving BC patients undergoing chemotherapy. Participants were required to adhere to the FMD recipes for four days prior to and on the day of each chemotherapy cycle, which provided 34-54% of the normal caloric intake, with a total of three cycles needed for the study. FMD-related adverse events, body composition, and serum samples were monitored.

Results: A total of 30 participants were enrolled, and 27 of them completed 3 cycles of the FMD. The incidence of grade III or worse FMD-related adverse effects was 5.95% (5/84). A decline in IGF-1 compared to baseline was observed to be statistically significant at the end of the first FMD (B =  - 23.29, p = 0.001) and second FMD (B =  - 16.20, p = 0.023), but no statistical difference at the end of the third FMD (B =  - 8.372, p = 0.327). After 3 FMD cycles and a 21-day washout, BC patients experienced a statistically significant reduction in body mass (- 2.04kg, 95% CI - 2.86, - 1.21 kg; p < 0.001), fat mass (- 1.88kg, 95% CI - 2.72, - 1.05 kg, p < 0.001), visceral fat area (- 14.78%, 95% CI - 21.13, - 8.43%, p < 0.001) and waist circumference (- 4.01,95% CI - 6.18, - 1.83, p < 0.001), while muscle mass remained stable (- 0.05 kg, 95% CI - 0.36, 0.27 kg; p = 0.270).

Conclusion: The recipe-based FMD program is well-tolerated by BC patients. It is proved to be safe, with few or no fasting-related adverse effects and an acceptable magnitude of weight loss. Additionally, it is effective in reducing IGF1, indirectly correlating to insulin resistance and inflammation that could enhance efficacy of anticancer therapies.