Breast Cancer最新文献

The immune background of breast cancer is highly heterogeneous and the immune system of the human body plays a dual role by both promoting and suppressing its progression. Innate immune cells are the first line of defense in the immune system and impart protection by identifying and interacting with foreign pathogens and cancer cells. Different innate immune cells like natural killer cells, macrophages, dendritic cells, and myeloid suppressor cells take part in hosting the cancer cells. Autophagy is another key component inside the tumor microenvironment and is linked to the disintegration and recycling of cellular components. Within the tumor microenvironment autophagy is involved with Pattern Recognition Receptors and inflammation. Various clinical studies have shown prominent results where innate immune cells and autophagy in combination are used for pathogen as well as cancer cell clearance. However, it is necessary to comprehend the complex tumor microenvironment so that different therapeutic approaches can be developed to enhance the suppressive actions of the cells toward breast cancer cells. In this review article, the complex interaction between immune cells and breast cancer cells and their role in developing effective immunotherapies to improve patient outcomes are discussed in detail.

Background: Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients.

Methods: Between July 2016 and January 2022, a total of 268 patients were eligible for analysis. The endpoints included in-field and out-field cervical failures, local-regional recurrence-free survival (LRRFS), SCV recurrence-free survival (SRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS).

Results: During a median follow-up of 37 months (range 3-89 months), 17 patients (6.3%) developed local-regional recurrence as the first recurrence event, with 13 having concomitant distant-metastasis (DM); 56 patients (20.9%) had DM alone. The 3-year rates of LRRFS, SRF, DMFS, RFS, and OS were 92.3%, 94.5%, 74.5%, 73.0%, and 90.0%, respectively. 89.2% of patients received RT with the cranial border at the top of hyoid bone, and 95.1% of patients received a boost not exceeding the level of cricoid cartilage. A total of 11 patients (4.1%) developed ipsilateral SCV failure, and 3 patients (1.1%) experienced cervical failure, including 2 in-field failures and 1 out-field failure. Neoadjuvant systemic therapy (NST) was administered to 234 patients (87.3%). In the multivariate analysis, non-ypN0, triple-negative subtype and cT4 at diagnosis were predictors of worse SRFS and RFS in NST subgroup.

Conclusion: Our findings suggest that radical RT with cranial border of irradiation field at the hyoid bone level lead to excellent local-regional control, and out-field cervical failure was rare. The irradiation field might not extend to mastoid process.

Background: Cryoablation is currently being investigated as a minimally invasive alternative to breast-conserving surgery. This meta-analysis investigates the local recurrence and residual tumor rates after cryoablation for small early-stage breast cancers.

Methods: A systematic search was conducted on Embase, PubMed, Google Scholar, and the International Clinical Trials Registry Platform from inception to 16 June 2024. Studies of patients with breast cancers ≤ 20 mm treated with cryoablation only or cryoablation followed by surgery were included. Pooled local recurrence rates (cryoablation only) and pooled residual tumors rates (cryoablation followed by surgery) were estimated with mixed-effects models. Between-study heterogeneity was assessed using I² statistics. Where I² exceeded 50%, outlier and influence analysis, followed by sensitivity analysis excluding outliers, were conducted.

Results: Twelve studies met inclusion criteria, of which 7 studies (530 female patients, 531 breast tumors) reported on patients treated with cryoablation only and 5 studies (220 female patients, 222 breast tumors) reported on patients treated with cryoablation followed by surgery. For studies on cryoablation only, pooled local recurrence rate was 1.1% (95% CI 0.42-3.03%) with low between-study heterogeneity (I² value = 0%; 95% CI 0.0-70.8%; p = 0.95). For studies on cryoablation followed by surgery, pooled residual tumor rate was 12.0% (95% CI 3.85-31.64%); however, substantial between-study heterogeneity (I² value = 76.1%; 95% CI 41.7-90.2%; p < 0.01) was present. Influence analysis revealed 1 outlier study. When this study was excluded, pooled residual tumor rate was 8.2% (95% CI 3.84-16.68%) with improvement in heterogeneity (I² value = 0%; 95% CI 0.0-84.7%; p = 0.64).

Conclusion: Pooled local recurrence and residual tumor rates after cryoablation are comparable to local recurrence rates after breast-conserving therapy and re-excision rates following breast-conserving surgery, respectively. These results are encouraging but should be interpreted with caution due to lack of comparative studies.

Background: In CAPItello-291, capivasertib-fulvestrant significantly improved progression-free survival (PFS) versus placebo-fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib-fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan.

Methods: Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint.

Results: Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib-fulvestrant and 41 to placebo-fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib-fulvestrant arm (hazard ratio 0.73; 95% CI 0.40-1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors, PFS favored the capivasertib-fulvestrant arm (hazard ratio 0.65; 95% CI 0.29-1.39), consistent with the global population. The adverse event profile of capivasertib-fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified.

Conclusion: Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.

Background: Pain and dysfunction of the shoulder and arm are prevalent among patients with breast cancer. This review aimed to evaluate current evidence regarding the effects of mirror therapy on pain, function, and quality of life in patients with breast cancer.

Methods: Five bibliographic databases in English and Chinese, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from inception to May 15, 2024. Randomized controlled trials comparing the effects of mirror therapy to conventional treatment were eligible for inclusion. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Meta-analyses were performed to determine the effects of mirror therapy.

Results: Four randomized controlled trials were included, with a total of 311 patients with breast cancer. All included studies were scored six to seven on the PEDro scale, indicating good quality. No adverse events related to mirror therapy were reported. Compared to conventional treatment, mirror therapy demonstrated significantly reduced pain (SMD: - 1.17, 95% CI: - 1.64 to - 0.70, p < 0.001), improved upper extremity function (SMD: 1.03, 95% CI: 0.05-2.02, p = 0.04), and enhanced quality of life (SMD: 0.43, 95% CI: 0.07-0.79, p = 0.02).

Conclusions: Mirror therapy is feasible and effective for upper extremity pain and dysfunction following breast cancer surgery. Clinicians may consider mirror therapy as an adjunctive intervention for breast cancer postoperative rehabilitation to advance the quality of care.

Background: In Japan, biennial mammography screening has been recommended for the early detection of breast cancer (BC) in women aged 40 years or above since 2004 by the Ministry of Health, Labor and Welfare. The purpose of this study is to estimate the economic impact of BC screening on work productivity, using a new measure called the productivity-adjusted life-year (PALY).

Methods: We used a dynamic life table modeling approach to estimate the work productivity of female patients aged 40-64 years diagnosed with BC in 2019 over the year of diagnosis and the subsequent 5 years. Changes in life-years, PALYs, and gross domestic product (GDP) were assessed by changing the screening detection rate from the current (34.2%) to an ideal (100%) percentage. Each input for modeling was obtained from the most recent public database available.

Results: BC patients were estimated to lose 1903 in life-years, 3596 in PALYs, and US$281 million in GDP at the current screening detection rate compared with the ideal detection rate. On the other hand, the following gains are expected when the current screening detection rate was increased to 40-80%; life-years gain; 168-1325, PALYs gain; 317-2503, GDP gain: US$25-196 million.

Conclusion: This study has used modeling to show that detecting BC without screening is associated with a lower work productivity and an economic and life-years loss. Encouraging BC screening may be beneficial to maintaining work productivity after diagnosis.

Background: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer.

Methods: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models.

Results: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases.

Conclusion: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

The therapy for breast cancer (BC), to date, still needs improvement. Apart from traditional therapy methods, biological therapy being explored opens up a novel avenue for BC patients. Integrin β1 (ITGβ1), one of the largest subgroups in integrin family, is a key player in cancer evolution and therapy. Recent researches progress in the relationship of ITGβ1 level and BC, finding that ITGβ1 expression evidently concerns BC progression. In this chapter, we outline diverse ITGβ1-based mechanisms regarding to the promoted effect of ITGβ1 on BC cell structure rearrangement and malignant phenotype behaviors, the unfavorable patient prognosis conferred by ITGβ1, BC therapy tolerance induced by ITGβ1, and lastly novel inhibitors targeting ITGβ1 for BC therapy. As an effective biomarker, ITGβ1 undoubtedly emerges one of targeted-therapy opportunities of BC patients in future. It is a necessity focusing on scientific and large-scale clinical trials on the validation of targeted-ITGβ1 drugs for BC patients.

Background: Identifying whether there is residual carcinoma in remaining suspicious calcifications after neoadjuvant chemotherapy (NAC) in breast cancer patients can provide crucial information for surgeons in determining the most appropriate surgical approach. Therefore, we investigated factors predicting calcifications without residual carcinoma (ypCalc_0) or with residual carcinoma (ypCalc_ca) and aimed to develop a prediction model for patients exhibiting residual suspicious calcifications on mammography but complete response on MRI after NAC.

Methods: This retrospective study included breast cancer patients undergoing NAC, showing residual suspicious mammographic calcifications but complete response on MRI between January 2019 and December 2020 (development set) and between January 2021 and December 2022 (validation set). Multivariable logistic regression analysis identified significant factors associated with ypCalc_0. The prediction model, developed using a decision tree and factors from logistic regression analysis, was validated in the validation set.

Results: The development set included 134 women (mean age, 50.6 years; 91 with ypCalc_0 and 43 with ypCalc_ca) and validation set included 146 women (mean age, 51.0 years; 108 with ypCalc_0 and 38 with ypCalc_ca). Molecular subtype (P = .0002) and high Ki-67 (P = .02) emerged as significant independent factors associated with ypCalc_0 in the development set. The prediction model, incorporating hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ with high Ki-67 as ypCalc_0 predictors, and HR+/HER2- cancers or HR+/HER2+ or triple-negative (TN) cancers with low Ki-67, as ypCalc_ca predictors, achieved an area under receiver operating characteristic curve of 0.844 (95% CI 0.774-0.914) in the validation set.

Conclusion: Minimized surgery may be considered for managing residual calcifications in HR-/HER2+ with high Ki-67 cancers, while complete excision is recommended for HR+/HER2- breast cancers or for HR+/HER2+or TN breast cancers with low Ki-67.