Breast Cancer Research and Treatment最新文献

Purpose: Trastuzumab used for the treatment of patients with HER2-positive breast cancer induces cardiotoxicity. The NRG1/HER pathway plays a central role in human cardiovascular physiology; however, the link between exercise, NRG1, and cardiotoxicity is unclear.

Methods: Patients were randomized to receive adjuvant trastuzumab in combination with a training program (TG) or trastuzumab alone (CG). The aim of this study was to assess the effect of a 12-week supervised exercise training on the circulating level of NRG1. Secondary objectives were to assess the correlation between NRG1 level and cardiotoxicity.

Results: 89 patients were randomized (TG; n = 46; CG; n = 43), 76 have a NRG1 concentration available at baseline. After the exercise program, plasma levels of NRG1 decreased significantly in the TG (mean difference -0.20 ng/ml; 95% CI, -0.32, - 0.07) whereas they remained stable in the CG (mean difference - 0.05 ng/ml; 95% CI, - 0.20, 0.10). Notably, baseline NRG1 concentrations were higher in the TG group. However, no correlation between NRG1 changes and either cardiorespiratory fitness (V̇O₂ max) and left ventricular ejection fraction (LVEF) was observed (R = 0.087, p = 0.53; R = -0.157, p = 0.26; and R = -0.131, p = 0.33, respectively).

Conclusions: A 12-week interval training program significantly decreased NRG1 concentration in HER2-positive patients with breast cancer treated with adjuvant trastuzumab therapy, despite the trained group presenting higher baseline NRG1 values compared to the control group. In addition, this change was neither associated with V̇O₂ max nor with LVEF.

Trial registration: This trial was registered with ClinicalTrials.gov under the number NCT02433067.

Background: With the rising survival rates of breast cancer, fertility preservation has become a paramount concern for young patients throughout their anticancer treatment. We conducted a systematic review to assess and synthesize evidence and recommendations on fertility preservation in breast cancer patients to provide evidence-based clinical guidance.

Methods: According to the '6S' evidence resource model, evidence retrieval is searched from the top-down and collected relevant clinical decisions, guidelines, evidence summaries, expert consensus, recommended practices, and systematic reviews. The retrieval time limit was from the database establishment to July 2025. Two reviewers independently screened and evaluated the literature, and then extracted and summarized the evidence according to the JBI grading of evidence and recommendation system.

Results: A total of 47 publications were finally included, including 14 guidelines, 9 expert consensus, 7 recommended practices, and 17 systematic reviews. Through the induction and integration of the evidence, the evidence was finally summarized from ten aspects: treatment-related factors for fertility impairment, risk assessment of fertility impairment, genetic risk assessment and intervention, fertility preservation counseling and management, target population for fertility preservation, fertility preservation protocols, surgical treatment and fertility, post-treatment pregnancy management, post-treatment breastfeeding management and contraceptive management, and totally 50 best available evidence were formed.

Conclusions: This study summarized the best available evidence for fertility preservation in breast cancer patients from ten aspects, which can provide guidance for clinical medical staff to develop individualized fertility preservation plans and assist patients in making fertility preservation decisions, ultimately supporting young breast cancer patients in achieving the dual goals of survival and future parenthood.

Purpose: The study aims to develop and validate a predictive tool for assessing the risk of in-breast tumor recurrence (IBTR) in breast cancer patients considered candidates for intraoperative radiotherapy using electrons (IOERT).

Methods: This study included 3397 breast cancer patients treated with IOERT at a single institution between 2000 and 2016. The primary endpoint was IBTR, with or without nodal or distant metastasis. Fine and Gray regression models were used to identify predictors of IBTR. A nomogram predicting the 5- and 10-year probability of IBTR was developed based on the multivariable model and was validated both internally and externally using data from the IOERT arm of the ELIOT phase III trial (585 patients).

Results: With a median follow-up of 6.1 years (interquartile range 4.3-8.0), 265 IBTRs (7.8%) were observed, resulting in an IBTR cumulative incidence of 4.4% (95% CI 3.7-5.2) at 5 years and 13.5% (95% CI 11.7-15.5) at 10 years. Multivariable analysis revealed that age under 60, certain histologic subtypes, positive axillary nodes, and intermediate/high tumor grade were key risk factors for IBTR. The overall Harrell's concordance statistic was 0.69 (95% CI 0.66-0.73) in the internal and 0.64 (95% CI 0.57-0.71) in the external validation.

Conclusion: The nomogram has demonstrated moderate discriminative ability in predicting IBTR in the internal validation set and may be a useful tool to support treatment decision-making in breast cancer patients eligible for IOERT.

Purpose: Breast cancer (BC) is a leading public-health issue affecting women on a global scale. Thanks to the widespread implementation of screening programs and the improvement in therapies, women with BC live longer but they also are more likely to experience an increased risk of other diseases. Reasons for this increased risk include genetics, shared risk factors, and adverse effects from BC treatment. Therefore, this research aimed to analyse the risk of myocardial infarction (MI) and stroke in women with BC, considering the potential side effects of treatments.

Methods: For the analysis, we used data coming from the Piedmont Longitudinal Study (PLS), an administrative cohort based on the record-linkage among census data and several health-administrative databases involving more than 4 million inhabitants. The study population comprised women aged 30-75 years from the PLS study, excluding those with myocardial infarction or stroke at baseline. To analyse the investigated associations, competing risk analyses were performed, through the Cause-Specific Proportional Hazards model.

Results: Among 1,342,333 women ranging from 30 to 75 years old, 19,203 had a BC diagnosis, of whom 206 (1.1%) experienced a subsequent MI and 203 (1.1%) a stroke. Women with BC showed an increased risk for MI (HR: 1.20; 95% CI 1.05-1.38) and for stroke (HR: 1.58; 95% CI 1.38-1.82). Chemotherapy was observed to be the major risk factor for MI in BC women, while no different risk by therapy was found for stroke.

Conclusion: The results supported the hypothesis about the toxic effect of BC therapies, suggesting that clinicians should routinely and actively screen for treatment-related toxicities in women with BC and that researchers should prioritize personalized treatments to minimize potentially devastating side effects.

Purpose: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) before the age of 40 years face increased breast cancer (BC) risk. Dutch guidelines recommend annual magnetic resonance imaging (MRI) and mammography at ages 30-60 years starting eight years after RT. Dual-modality screening is burdensome and may increase false positive rates. We therefore compared the diagnostic value of each individual modality with MRI and mammography combined.

Methods: Results of dual-modality BC screenings performed in 2005-2021 at two Dutch survivorship clinics were used to estimate sensitivity and specificity for each modality and MRI and mammography combined.

Results: We retrospectively reviewed 550 screening rounds in 134 HL survivors (median follow-up: 3 years) during which 19 early-stage tumors occurred. Sensitivity was 79% (95% Confidence Interval (CI): 54-94) for MRI alone, 63% (95% CI: 38-84) for mammography alone and 95% (95% CI: 74-100) for both modalities combined. Specificity was 89% (95% CI: 86-91) for MRI alone, 97% (95% CI: 95-98) for mammography alone and 86% (95% CI: 83-89) when combining modalities. Additional ultrasound was performed in 15.3% of screening rounds (in 74.4% due to MRI findings) and puncture/biopsy in 8.0%.

Conclusions: In conclusion, to obtain a sufficiently high screening sensitivity in female HL survivors treated with chest RT, we recommend screening with both MRI and mammography. However, MRI is associated with a high false positive rate. Our findings inform survivors and clinicians about effectiveness of BC screening and its burden.

Purpose: Determine the association between the Breast Cancer Surveillance Consortium v2 model (BCSC) risk score and advanced and non-advanced invasive breast cancer (IBC).

Methods: We estimated BCSC 5-year invasive breast cancer risk for 11,915 participants in a prospective screening cohort with median follow-up of 6.9 years prior to breast cancer diagnosis. Individuals in the top 25% by age of BCSC risk standard were considered high-risk, those in the bottom 75% low-risk. We obtained cancer outcomes, including American Joint Committee on Cancer (AJCC) prognostic pathologic stage, from the San Francisco Mammography Registry and an institutional cancer registry. We examined the associations of BCSC risk scores with advanced (≥ AJCC prognostic stage II) and non-advanced (AJCC prognostic stage I) IBC using Fisher's exact test and logistic regression.

Results: Of 11,915 participants, 4,005 (34%) were high-risk. There were 254 incident IBC cases, of which 40 (16%) were advanced and 214 (84%) were non-advanced. The median 5-year BCSC risk score for women with and without IBC was 1.83% and 1.45%, respectively (p < 0.001). High BCSC risk among women diagnosed with breast cancer was associated with non-advanced cancer (OR = 2.25, 95% CI = 1.71-2.95, p < 0.0001), but not with advanced cancer (OR = 1.20, 95% CI = 0.63-2.29, p = 0.57) compared to women not diagnosed with breast cancer.

Conclusion: High BCSC risk scores were associated with high rates of non-advanced IBC. As non-advanced cancers are more likely to be hormone receptor-positive, BCSC may optimally identify candidates for endocrine risk reduction.

Purpose: The standard first-line treatment for patients with hormone receptor-positive (HR +) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer is cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET). Optimal therapy after CDK4/6 inhibitors remains to be determined. We aimed to define the appropriate second-line treatment after CDK4/6 inhibitors in a real-life population.

Methods: Patients who had received CDK4/6 inhibitors with aromatase inhibitors (AIs) for HR + /HER2- metastatic breast cancer were included from March 2017 to May 2021 at five French cancer centers.The primary objective was to describe second-line treatment after primary treatment with CDK4/6 inhibitors plus AIs.

Results: We included 381 patients who received CDK4/6 inhibitors combined with AIs as first-line therapy. Patients with progressive disease (N = 165) benefited from a second-line of treatment: 69 (41.8%) were treated with chemotherapy, while 90 (54.6%) received endocrine therapy (ET alone: 59, 35.8%; ET plus targeted therapy: 31, 18.8%).Patients on chemotherapy were younger compared to those receiving ET (p = 0.011). Patients experiencing earlier progression were more likely to benefit from chemotherapy than ET (p = 0.001). Patients with visceral disease at diagnosis were more often treated with chemotherapy. Second-line median PFS was 6.4 months (95% CI [5.0-12.9]) for chemotherapy and 8.4 months (95% CI [5.4-11.7]) for ET ± targeted therapy, with no significant difference (HR 1.08, 95% CI [0.73-1.59], p = 0.70).

Conclusion: This French real-world study demonstrates limited progression-free survival benefits across all second-line strategies after CDK4/6 inhibitor progression, highlighting an urgent clinical need for more effective post-progression therapies.

Purpose: Inflammatory breast cancer (IBC) has been hypothesized to represent a distinct molecular subtype. However, few IBC-specific gene expression patterns have been identified, and previous genomic studies of IBC have been small with limited information on social determinants.

Methods: We identified 153 IBC cases in the Carolina Breast Cancer Study (total N = 4,739). RNA expression was measured on the NanoString platform (N = 74 IBC, 2,696 non-IBC) and used to determine molecular subtypes, including PAM50, immune, homologous recombination deficiency (HRD), and P53 status. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of associations between IBC and patient demographic, molecular, and social characteristics using logistic regression, and compared differences in gene expression using ANOVA.

Results: Women with IBC were associated with Black and under 50 compared to non-IBC. IBC was associated with rural address (OR = 1.53) and poverty (OR = 1.61). Molecularly, IBC was associated with HER2-enriched (OR = 6.14), Luminal B (OR = 2.90), P53 Mutant-like (OR = 1.79), and high HRD (OR = 1.90). Neither adiposity nor immune subtype was significantly associated with IBC. Only six of 219 genes measured were significantly differentially expressed between IBC and non-IBC, including HER2-related (ERBB2, FGFR4, GRB7) and P53-related genes (BTG2, LOC400043, MAP2K4).

Conclusion: Although not associated with immune subtypes, IBC showed differences in HER2 and P53 pathways. The association of IBC with rurality and poverty underscores the importance of health care access for timely diagnosis and treatment of IBC.

Purpose: To evaluate whether reduced doses (RD) of trastuzumab deruxtecan (T-DXd) or sacituzumab govitecan (SG) provide similar outcomes to the approved standard doses (SD) in metastatic breast cancer (mBC).

Methods: This retrospective cohort included mBC patients receiving at least one cycle of SG (April 2021-May 2024) or T-DXd (February 2020-December 2024). Primary outcomes were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and Log-Rank tests estimated and compared PFS and OS from treatment initiation. Subgroup analyses were performed by HER2 and hormone receptor status.

Results: 48 patients received SG (24 RD vs. 24 SD) and 66 received T-DXd (29 RD vs. 37 SD). Median PFS for SG was 3 months in both SD (95% CI, 2-10) and RD (95% CI, 2-8; p = 0.8). Median OS for SG was 10 months (95% CI, 7-13) for SD and 11 months (95% CI, 5-30; p = 0.4) for RD. For T-DXd, median PFS was 10.4 months for SD (95% CI, 7.0-14.5) and 11.2 months for RD (95% CI, 5.4-31.1; p = 0.8), while median OS was 18.3 months (95% CI, 13.9-NA) for SD and 28.1 months (95% CI, 18.2-NA; p = 0.9) for RD. Overall response rates were similar between patients receiving RD and SD SG or T-DXd.

Conclusions: This real-world data suggest RD of SG or T-DXd achieve outcomes comparable to SD, supporting prospective evaluation of lower-dose regimens.