Breast Cancer Research and Treatment最新文献

This commentary appraises Pieniążek et al.'s study on hematologic prognostic markers in sacituzumab govitecan-treated mTNBC, emphasizing residual confounding, absent Trop-2 data, limited modeling flexibility, and incomplete handling of missingness. Methodological refinement and integration of biological, longitudinal, and clinical variables are proposed to enhance prognostic accuracy and translational applicability.

Background: Quality of life (QOL) data for the Brazilian population with breast cancer are scarce. This study aimed to evaluate QOL in Brazilian women with early-stage breast cancer treated with adjuvant endocrine therapy (ET) and to explore its relationship with patients' clinical and social characteristics and type of healthcare insurance.

Methods: We performed a cross-sectional study among women with early-stage estrogen receptor-positive (ER +) invasive carcinoma of the breast in Brazil. Eligible patients who had received locoregional care and had undergone adjuvant ET for more than 6 months were contacted in person during clinic visits. The EORTC QLQ-C30-V3 and QLQ-BR23 scales were used as questionnaires to assess the QOL of patients.

Results: From June 2021 to March 2024, 774 women with ER + early-stage breast cancer from 14 Brazilian institutions were contacted. A total of 347 women (44.8%) were treated at private institutions. The mean age was 56.5 years (SD 11.9). The median duration of ET use was 3.2 years (SD, 2.1). Multivariate regression analysis revealed that treatment at a public institution was a significant predictor of higher nausea and vomiting scores (p = 0.042), pain (p = 0.0008), financial difficulty (p < 0.0001), arm symptoms (p < 0.0001), and breast symptoms (p < 0.0001).

Conclusion: In this cohort, patients treated at public institutions had lower QOL. Younger age (< 60 years), presence of comorbidities, and ovarian suppression associated with ET were key predictors of poor QOL. These findings provide insights for guiding the development of tailored interventions for the Brazilian population.

Purpose: To evaluate and compare patient perceptions of artificial intelligence (AI) use in mammogram interpretation across academic and safety-net healthcare settings.

Methods: We offered a 29-item survey to patients visiting our safety-net (SNH) and academic (ACH) hospital breast imaging clinics between 04/2024-06/2024 and 02/2023-08/2023, respectively. Demographic data was compared between populations using Chi-squared tests. We used ORs (95% CI) to estimate response odds by patient factors. Significant group differences were further analyzed via multivariable regression.

Results: A total of 924 [ACH: 518(56.1%), SNH: 406(43.9%)] surveys were collected. Participants from the ACH were older (≥ 70 years: 20%vs3.1%, p < 0.001), mostly identified as Non-Hispanic White (56%vs7.2%, p < 0.001), had higher income (≥ $100,000: 49%vs3.2%, p < 0.001), higher education (≥ college: 71%vs20%, p < 0.001) and higher self-reported knowledge of AI (68%vs56%, p < 0.001) compared to SNH. Use of AI alone or as a second reader was accepted by 74%, with SNH participants being less likely to accept [OR(95%CI): 0.71(0.53-0.96), p = 0.02]. SNH participants were more likely to request a reading by AI following radiologist-interpreted abnormalities [1.83(1.35-2.49), p < 0.001], rate AI as the same or better than a radiologist at detecting cancer [1.54(1.12-2.15), p = 0.01], and have higher concern regarding data privacy [1.87(1.22-2.93), p = 0.01]. Higher education [1.99(1.33-2.99), p < 0.001] and self-reported AI knowledge [1.98(1.38-2.83), p < 0.001] were associated with higher acceptance of AI use, while Non-Hispanic Black race [0.40(0.25-0.65), p < 0.001] was associated with lower acceptance when controlled for other covariates.

Conclusion: Significant differences exist in patients' views of AI between the demographically distinct academic and safety-net populations. Our study revealed lower educational attainment and Non-Hispanic Black race as independent factors associated with lower acceptance of AI.

Purpose: Decision-making for chemotherapy in early breast cancer (EBC) in OA (older adults: age ≥ 65 years) is complex due to frailty, multimorbidity, and competing risks for mortality. Magnuson (2021) developed a chemotherapy toxicity prediction score, CARG-BC; its external validation can improve generalizability.

Objectives: CARG-BC's ability to predict grade 3 + chemotoxicity in OA with EBC (primary), unplanned healthcare use, and changes to chemotherapy protocol (secondary).

Methods: A single center retrospective cohort study comprising OA with EBC who received (neo) adjuvant chemotherapy from 2013-2023. Clinical, demographic, CARG-BC, and healthcare usage variables were extracted from patient records. Risk groups based on CARG-BC score were compared using T-test (continuous variables) & χ2 test (categorical variables). Toxicity risk based on CARG-BC score was assessed using logistic regression. The predictive ability of the CARG-BC score was evaluated by calculating AUC.

Results: Of 243 patients, the median age was 70 years (range 65-86), 99.6% female, 80.2% with comorbidities, 33.7% with polypharmacy, 28.8% living alone, and 8.2% seen in the geriatric oncology clinic. Over half (53.9%) had grade 3 + toxicities. Healthcare utilization included 19.8% of patients with at least one unplanned clinic visit, 29.6% an emergency care visit, and 14.4% a hospitalization. The median CARG-BC score was 7 (IQR 3, 8) and the CARG-BC AUC was 0.76 (95% Confidence interval [CI] 0.70, 0.82). The odds of grade 3 + toxicity is increased by 1.33 times per CARG-BC point increase.

Conclusion: The CARG-BC model retained good discrimination for grade ≥ 3 chemotoxicity and should be used in shared-decision-making with OA.

Purpose: In breast cancer, a low skeletal muscle index (SMI) and prognostic nutritional index (PNI) negatively affect patient outcomes. However, the prognostic implications of changes in these values in patients with metastatic breast cancer (MBC) remain unclear. We evaluated the association between baseline levels and changes in SMI and PNI during eribulin treatment and patient outcomes.

Methods: We retrospectively analyzed 67 patients with MBC treated with eribulin. SMI and PNI were assessed at baseline (pre-SMI, and pre-PNI) and at disease progression; changes from baseline were calculated. Patient outcomes were compared according to baseline status and direction of change.

Results: SMI and PNI were not significantly correlated (p = 0.26, R = 0.02). High pre-SMI and high pre-PNI were associated with significantly improved overall survival (OS) (SMI; hazard ratio [HR] = 0.54, p = 0.04, PNI; HR = 0.33, p < 0.001). Patients with SMI gain during eribulin had longer OS than those with stable SMI or loss (HR = 0.48, p = 0.04), whereas PNI increase was not significantly associated with OS (HR = 0.74, p = 0.32).

Conclusion: Baseline SMI and PNI provide complementary prognostic information in patients with MBC receiving eribulin. Furthermore, on-treatment SMI gain, but not PNI increase, was associated with improved survival. Monitoring and enhancing skeletal muscle mass may improve outcomes, highlighting the importance of integrating supportive care strategies during chemotherapy.

Purpose: This study aimed to evaluate the prognostic significance of baseline laboratory parameters and inflammatory indices in patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) in the second line and beyond, potentially aiding personalized patient management.

Methods: This retrospective cohort study analyzed data from 83 female patients with mTNBC who initiated SG therapy at four Polish oncology centers between August 2021 and September 2024. Hematological parameters-white blood cell count (WBC), hemoglobin (Hb), platelets (Plt) and inflammatory indices-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were assessed at baseline and before each dose of first four SG cycles. Median progression-free survival (mPFS) and overall survival (mOS) were estimated, and, as the primary objectives, associations between baseline laboratory variables and survival outcomes were assessed using multivariate Cox regression models (α = 0.05). Secondary objectives included assessing their associations with patient and disease characteristics, prior treatment lines, and adverse events (AEs), which were classified using the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE), version 5.0.

Results: The mPFS was 4.07 months (95% CI 3.05-6.18), while the mOS was 8.01 months (95% CI 6.05-9.75). Lower baseline Hb was significantly associated with shorter PFS (HR = 0.82, p = 0.03) but not OS. Elevated baseline NLR predicted worse OS (HR = 1.18, p = 0.03), while PLR and SII lacked prognostic significance. Changes in blood parameters within initial four SG cycles showed no significant correlations with survival outcomes. Furthermore, baseline hematological markers and inflammatory indices showed no significant association with clinical characteristics, prior therapy lines, tumor burden, or the occurrence and severity of AEs.

Conclusions: Baseline Hb and NLR were identified as independent prognostic biomarkers in patients with mTNBC receiving SG treatment, predicting PFS and OS, respectively. Other inflammatory indices (PLR, SII) did not demonstrate prognostic relevance. Prospective validation in larger cohorts is essential to confirm these findings and potentially guide personalized treatment strategies.

Purpose: Our goal is to leverage publicly available whole transcriptome and genome-wide CRISPR-Cas9 screen data to identify and prioritize novel breast cancer therapeutic targets.

Methods: We used DepMap dependency scores > 0.5 to identify genes that are potential therapeutic targets in 48 breast cancer cell lines. We removed genes that were pan-essential or were not expressed in TCGA breast cancer cohort. Genes were prioritized based on druggability using the Drug-Gene Interaction Database. Targets were defined separately for ER+, HER2+, and TNBC. A broader list of genes with dependency score > 0.25 were used to assess the associations between dependency scores and mutations and copy number variations (CNV) to identify potential synthetic lethal relationships and to map survival critical genes into biological pathways.

Results: 66, 53, and 29 genes were prioritized as targets in ER+, HER2+, and TNBC, respectively. These included known actionable targets and many novel targets. ER+ included FOXA1, GATA3, LDB1, TRPS1, NAMPT, WDR26, and ZNF217; HER2+ cancers included STX4, HECTD1, and TBL1XR1; and TNBC included GFPT1 and GPX4. Synthetic lethal associations revealed 5 and 19 significant associations between potential survival critical genes and mutations in HER2+ and TNBC, respectively. For example, PIK3CA mutation increased dependency on NDUFS3 in HER2+ cancers, and CNTRL mutation increased dependency on electron transport chain (ETC) genes in TNBC. 329, 747, and 622 CNVs showed synthetic lethal association in ER+, HER2+, and TNBC, respectively.

Conclusion: We provide a genome-wide drug target prioritization list for breast cancer derived from integrated large-scale omics data.

Background: The management of high-risk breast lesions is controversial. There is a lack of long-term follow-up studies to evaluate clinical management decisions.

Methods: We included 267 consecutive high-risk breast lesions with pathology-radiology concordance that were prospectively recommended for surgery or follow-up at a multidisciplinary conference. The 267 lesions included 149 papillomas and 118 other high-risk lesions. The 149 papillomas included 119 benign papillomas, 17 atypical papillomas, 6 papillomas with adjacent atypical ductal hyperplasia (ADH), 7 papillomas with adjacent atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS). The 118 high-risk lesions included 43 ADH, 36 radial scar (RS), 23 ALH, 13 LCIS, 2 flat epithelial atypia (FEA), and 1 mucocele-like lesion (ML). The patients were recommended for surgery or follow-up using established guidelines.

Results: 90 (60.4%) patients with papillomas, who did not undergo immediate excision and were followed, had a median follow-up time of 61.6 months; 70 patients had a follow-up time > 2 years (25.1-103.4 months). Two patients (2.1%) with benign papilloma had history of breast cancer and developed carcinoma in 62.7 at the lumpectomy site and 40.8 months at the biopsy site which showed 2 mm benign papilloma; both papillomas were sufficiently sampled, and we believe the recommendation of follow-up to both patients was appropriate. 65 (55.1%) patients with other high-risk lesions, who did not undergo excision and were followed, had a median follow-up time of 64.1 months; 50 patients had a follow-up time > 2 years (24.2-101.6 months). Four (6.2%) of these 65 patients developed carcinoma during follow-up including 2 patients with ADH who were recommended for surgery but chose for follow-up; 1 patient with ALH developed invasive carcinoma in a different quadrant at 76.6 months; and 1 patient with RS developed invasive carcinoma in the same quadrant at 51.2 months. In the 112 patients who underwent immediate excision, all upgrades (n = 15) occurred in patients who were recommended for surgery. During follow-up of these 112 patients, 2 patients developed carcinoma and both had benign pathology in the excisional specimens.

Conclusions: This long-term follow-up study confirms that a multidisciplinary conference can successfully triage patients with high-risk breast lesions to surgery or follow-up with established guidelines and careful pathology, radiology, and clinical evaluations. Patients with high-risk breast lesions have increased cancer risk and should be followed.

Purpose: Limited data is available assessing sequencing of antibody drug conjugates (ADCs) in patients with hormone receptor-positive (HR +), human epidermal growth factor 2 (HER2)-negative, HER2-low, and triple-negative metastatic breast cancer (MBC), including patients with brain metastases (BrM) or leptomeningeal disease (LMD). This study assesses the efficacy and safety of sequential sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) in MBC and impact on chemotherapy (CTX).

Methods: This is a single-center, retrospective, cohort study in adult patients with HR + , HER2-negative, or low MBC who received T-DXd and/or SG.

Results: A total of 112 patients were divided into three cohorts: ADCs given sequentially (cohort A), ADC then CTX (cohort B), or CTX between ADCs (cohort C). The median progression-free survival (mPFS) in cohort A was 4.5 months for SG before T-DXd and 3.1 months for T-DXd before SG. In cohort B, mPFS was 3.1 months for CTX following T-DXd. For CTX following SG, mPFS for CTX was 2.5 months. In patients who received both ADCs, PFS was 2.1 months. In cohort C, mPFS for SG following T-DXd and CTX was 2.1 months and 3.3 months for T-DXd following SG and CTX. The mPFS for ADC1 was longer than ADC2 (5.5 months SG, 3.4 months T-DXd). Those with BrM and/or LMD demonstrated stable disease.

Conclusion: Sequential administration of ADCs results in a shorter PFS. CTX efficacy is impacted by prior ADC administration. Outcomes for patients with BrM and LMD do not differ for those without recurrence to the brain.

Background: Routine post-operative mammograms (RPMs) are performed at some institutions after breast-conserving surgery (BCS) in patients who presented with malignant calcifications in order to rule out residual malignancy. However, their clinical utility and optimal application remain uncertain.

Aim: To evaluate whether patients diagnosed with breast malignancy due to calcifications on mammography benefit from RPMs after BCS.

Methods: After institutional review board approval, we conducted a retrospective cohort study of patients presenting with malignant calcifications on initial screening mammograms who underwent RPMs at our institution between 2018 and 2022. Patients with positive surgical margins or those who underwent imaging for clinical indications were excluded. Imaging findings, pathology results, and clinical characteristics were analyzed to identify factors associated with residual malignancy.

Results: During the study period, 2054 patients underwent BCS, of whom 306 (15%) had a post-operative mammogram within three months of surgery, and 218 fitted the final inclusion category. Suspicious residual calcifications after BCS were identified in 22 of 218 patients (10%), of whom 19 underwent biopsy and 3 proceeded directly to surgery. Residual malignancy was confirmed by biopsy in 9 patients (4%), with a positive predictive value of 41%. Multivariate analysis demonstrated that younger age and the extent of calcifications on preoperative mammograms were independently associated with residual malignancy on RPM.

Conclusions: RPMs were found to be more beneficial for patients aged 50 years or younger, and for patients with extensive calcifications on preoperative mammograms. Tailoring RPM use to these subgroups may improve diagnostic efficiency and reduce unnecessary interventions.