Breast Cancer Research and Treatment最新文献

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.

Background: Understanding locoregional recurrence (LRR) risk is important in breast cancer, as it relates directly to breast cancer-associated mortality. Individualised LRR risk estimation should inform treatment and surveillance strategies. Increased mammographic breast density has been identified as a risk factor for the development of breast cancer. However, the precise relationship between mammographic density and breast cancer LRR remains unclear.

Aims: To perform a systematic review and relative risk meta-analysis to explore the assocation between breast mammographic density and breast cancer LRR.

Methods: A systematic review was performed as per PRISMA guidelines. Mammographic breast density (MBD) was classified as BI-RADs A-B (breast density < 50%, predominately fatty or scattered areas of fibroglandular density) or BI-RADs C-D breast density > 50%, heterogeneously dense or extremely dense). A meta-anlysis was performed using Meta-Disc and Statsdirect 2.8.0.

Results: Seven studies published between 2004 and 2023 met the inclusion criteria, comprising 3008 patients with reported mammographic breast density (MBD) (age range: 20-94 years). Overall, 59.1% (1779/3008) were classified as low MBD (BI-RADS A-B) and 40.9% (1229/3008) were classified as high MBD (BI-RADS C-D). Of these patients, 68.9% (2073/3008) were treated for invasive breast carcinoma and 31.1% had ductal carcinoma in-situ (DCIS). Breast-conserving surgery (BCS) was performed in 71.1% (2139/3008) of patients, mastectomy was performed in 28.2% (850/3008),. The median follow-up was 94.1 months, and the overall LRR rate was 12.8% (386/3008). Five of the seven studies reported a correlation between BI-RADs C-D and the development of LRR. LRR rates were lower in patients with low mammographic breast density (9.9% for BI-RADS A-B (177/1779)) compared to those with higher mammogaphic breast density (17.0% for BI-RADs C-D. (209/1229)) [P < 0.001, Chi Square]. BI-RADS C-D density on mammography was associated with an increased risk of locoregional recurrence (pooled relative risk 1.41; 95% confidence interval 1.17 to 1.70).

Conclusion: Increased mammographic breast density may be associated with an increased risk of LRR. Multidisciplinary team discussions should consider MBD as a potential prognostic factor in when considering surveillance and locoregional control after breast cancer treatment.

Background: Previous studies often combined double hormone receptor-positive (dHR +) and single HR-positive (sHR +) tumors, thus not accounting for the distinct characteristics of sHR + , particularly in the neoadjuvant setting. Moreover, adding immunotherapy to cytotoxic chemotherapy has shown encouraging efficacy in certain HR-positive early breast cancers. This study sought to assess pathological complete response (pCR) and survival outcomes in sHR + /HER2- breast cancer after neoadjuvant chemotherapy, while also investigating its specific biological traits and immune profile.

Methods: Clinical data were sourced from the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS, n = 1049), and the Surveillance, Epidemiology, and End Results (SEER, n = 21,092) database to examine neoadjuvant chemosensitivity and survival outcomes. Additionally, clinicopathological and subtype data from CHCAMS, SEER, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1052), and Fudan University Shanghai Cancer Center (FUSCC, n = 570) were analyzed to identify biological features that correlate with pCR rates and prognosis in sHR + /HER2- breast cancer. Further genomic and transcriptomic data from METABRIC, The Cancer Genome Atlas (TCGA, n = 741), and MSK-IMPCAT (n = 1535) were reviewed to uncover their potential links with endocrine and immunotherapy responses.

Results: In comparison to dHR + (ER + and PR +)/HER2- breast cancer, sHR + (ER + /PR- or ER-/PR +)/HER2- breast cancer displayed a higher pCR rate (20.2% vs. 3.2%, P < 0.001), but considerably worse survival (hazard ratio, 2.97; 95% confidence interval, 1.62-5.43, P < 0.001) within the CHCAMS neoadjuvant cohort. Clinically, sHR + /HER2- tumors were associated with higher histological grades and proliferation rates compared to dHR + /HER2- tumors, along with a greater rate of HR-low positivity (50.9% vs. 3.0%, P < 0.001) in primary tumors and a tendency to transition to triple-negative tumors in residual disease (42.7% vs. 1.8%, P < 0.001). Furthermore, sHR + /HER2- breast cancers demonstrated lower endocrine sensitivity scores, with about 20% classified as PAM50-defined basal-like subtype. Immunologically, sHR + /HER2- tumors had elevated tumor mutation burden (TMB), higher expression of immune checkpoint genes (e.g., PD-1, PD-L1, CTLA4), and greater infiltration by tumor-infiltrating lymphocytes (TILs), particularly CD8 + T cells, than dHR + /HER2- tumors.

Conclusion: Compared to dHR + /HER2- breast cancer, sHR + /HER2- cases showed a relative sensitivity to neoadjuvant chemotherapy but poorer prognosis. The immune-activated phenotype of sHR + /HER2- breast cancer indicates that it may benefit from immunotherapy approaches, but these findings warrant validation in prospective studies.

Purpose: Black women with hormone receptor-positive (HR +) breast cancer are twice as likely as White women to have weakly HR + tumors (1-10% positive cells). Patients with weakly HR + tumors are less frequently prescribed ET and have 60% higher mortality than strongly HR + tumors (> 10% positive cells). We evaluated factors associated with ET prescription and self-reported use among Black women with HR + breast cancer.

Methods: Among 922 Detroit ROCS participants, we evaluated associations between demographics, socioeconomic status, and health, tumor, oncologist, and hospital characteristics and ET prescription intent and self-reported ET use. Logistic mixed-effects regression was used to account for oncologist and hospital group effects.

Results: Oncologists intended to prescribe ET to 83.4% of participants (n = 769), of which 54.4% (n = 502) reported use. In multivariable models, participants with weakly HR + tumors were 90% less likely to be prescribed ET (OR = 0.10, p < 0.0001). Other significant characteristics of ET prescription included a BMI of 25-29.9 kg/m² (OR = 0.45, p = 0.0085), HR positivity > 90% vs. 11-90% (OR = 0.37, p = 0.00045), unknown HR percentage (OR = 0.12, p < 0.0001), OncotypeDx testing (OR = 2.65, p < 0.0001), and receiving radiation (OR = 2.20, p = 0.00016). Self-reported ET use was lower among those with lower health literacy (OR = 0.017, p < 0.001), weak HR positivity (OR = 0.46, p = 0.0053), unknown HR percentage (OR = 0.074, p = 0.034), and older age at diagnosis (OR = 0.88, p = 0.002). Increased ET use was associated with an income between $60,000-$79,900 vs. < $20,000 (OR = 1.54, p = 0.035), higher comorbidity count (OR = 1.09, p = 0.0054), distant stage (OR = 2.03, p = 0.029), and surgery (OR = 2.35, p = 0.001).

Conclusion: Identifying multilevel factors related to ET use may inform strategies to improve ET uptake and survival among Black women with HR + breast cancer.

Purpose: Knowledge of the uptake and breast and ovarian cancer-preventive and survival effects of bilateral risk-reducing mastectomy (BRRM) and salpingo-oophorectomy (RR-BSO) in female BRCA1/2 carriers is essential for optimized decision-making. This study aimed to examine time trends in the number of registered unaffected BRCA1/2 carriers, BRRM and RR-BSO uptake, and oncological effects of risk-reducing surgeries in a nationwide Danish cohort with matched controls.

Methods: We included 3067 female BRCA1/2 carriers registered in the Hereditary Breast and Ovarian Cancer Registry and 30,652 age-matched controls between 2000 and 2022. Data were retrieved from national health registries. Uptake and oncological effects of risk-reducing surgeries were assessed using cumulative incidences and Cox proportional hazards models with 95% confidence intervals (CI).

Results: Annual numbers of registered unaffected BRCA1/2 carriers, BRRM, and RR-BSO increased over time. BRRM and RR-BSO uptake 10 years after genetic test varied with the age at genetic test and parity. BRRM reduced the hazard rate of breast cancer by 94% [hazard ratio (HR) 0.06, CI 0.01-0.25]. The same pattern was not found for RR-BSO (HR = 1.31, CI 0.90-1.91). Compared to controls, BRCA1/2 carriers had an increased hazard rate for breast cancer before BRRM (HR 7.49, CI 5.81-9.42).

Conclusion: BRRM's large protective effect against breast cancer in BRCA1/2 carriers was confirmed, in contrast to that of RR-BSO. There were tendencies toward a reduction in overall mortality rates after BRRM, and compared with controls, we saw tendencies toward higher mortality rates before BRRM.

Purpose: To evaluate the effect of body mass index (BMI) on oncologic outcomes in patients with breast cancer stratified by menopausal status and histological subtype. Although studies have focused on the relationship between obesity and breast cancer risk, the association between BMI and breast cancer recurrence after surgery remains controversial.

Methods: This retrospective study included patients who underwent curative surgery for breast cancer between June 2003 and November 2017. Normal weight and overweight groups were defined based on the World Health Organization classification. The primary outcome was recurrence-free survival, evaluated at 1, 5, and 10 years after curative surgery. Patients were stratified by BMI category, histological subtype, and menopausal status. The main measures included tumor characteristics, recurrence events, and survival outcomes across groups.

Results: Among 4506 patients included in the analysis, 3384 (75.1%) had luminal-type breast cancer. The overweight group (n = 1259) was associated with older age (normal weight (NW): 50.2 ±10.9 vs. overweight (OW): 56.5 ± 1.9, P < 0.001) and higher T stage (≥ T2: NW: 1226 (37.7%) vs. OW: 577 (45.8%), P < 0.001). In patients with luminal-type breast cancer, 10-year recurrence-free survival was significantly worse in the overweight group (NW 89.3% vs. OW 85.7%, P = 0.018). Subgroup analysis showed that premenopausal patients with luminal-type breast cancer who were overweight had an increased risk of recurrence (P = 0.003).

Conclusions: Obesity is a significant, potentially modifiable risk factor for recurrence in premenopausal females with luminal-type breast cancer.