Journal of Breast Cancer最新文献

Purpose: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation.

Methods: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes.

Results: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort.

Conclusion: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Purpose: Adherence and persistence to adjuvant hormone therapy (AHT) are seldom maintained among early-stage hormone receptor-positive breast cancer (BC) survivors, despite the significant clinical benefits of long-term AHT. As the factors influencing adherence to AHT remain unclear, this study aimed to comprehensively identify such factors and classify them into specific dimensions.

Methods: PubMed, Cochrane Library, Embase, PsycINFO, and CINAHL were searched for qualified articles. The search mainly focused on three components: early-stage (0-III) BC, oral AHT administration, and adherence to AHT, with keywords derived from MeSH and entry terms. The factors identified were then classified into six categories based on a modified WHO multidimensional model.

Results: Overall, 146 studies were included; the median sample size was 651 (range, 31-40,009), and the mean age of the population was 61.5 years (standard deviation, 8.3 years). Patient- and therapy-related factors were the most frequently investigated factors. Necessity/concern beliefs and self-efficacy among patient-related factors were consistently related to better adherence than depression. Although drug side effects and medication use cannot be modified easily, a refined prescription strategy for the initiation and switching of AHT is likely to increase adherence levels.

Conclusion: An effective psychological program that encourages positive views and beliefs about medication and management strategies for each therapy may be necessary to improve adherence to AHT. Social support and a sense of belonging can be enhanced through community participation and social media for better adherence to AHT. Patient-centered communication and appropriate recommendations by physicians may be attributable to better adherence outcomes. Findings from systematically organized factors that influence adherence to AHT may contribute to the establishment of intervention strategies to benefit patients with early-stage BC to achieve optimal health.

Purpose: Association between variants rs1047972 and rs8173 of the AURKA gene in healthy women and breast cancer (BC) in a Mexican population.

Methods: Genomic DNA samples from 409 healthy women and 572 patients with BC were analyzed for variants rs1047972 and rs8173 of the AURKA gene by polymerase chain reaction-restriction fragment length polymorphism.

Results: TT genotype (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.22-5.11; p = 0.0015) and the T allele (OR, 1.16; 95% CI, 1.23-2.12; p = 0.0007) of the rs1047972 variant were associated as risk susceptibility for BC relative to the control group. Contrarily, the GG genotype (OR, 0.64; 95% CI, 0.43-0.94; p = 0.029) was associated as a protective factor of susceptibility of BC of the variant rs8173 of the AURKA gene. Differences were observed in the patients with BC who were carriers of the CT genotype of the rs1047972 variant with overweight, obesity, estrogen receptor-positive plus obesity, Ki-67 (≥ 20%) plus history familial positive of cancer; and for variant rs8173 the BC patients who were CG carriers and presented chemotherapy gastric toxicity, hormonal receptor positive plus chemotherapy gastric toxicity, and menopause status plus chemotherapy gastric toxicity (p < 0.05). Two common haplotypes were identified in the study groups: CG and TC genotypes, were associated as a protective and risk factor, respectively (p < 0.05).

Conclusion: Variants rs1047972 and rs8173 of the AURKA gene and the TC haplotype were associated as risk susceptibility factors for BC in this population.

Purpose: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables.

Methods: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital.

Results: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833-0.972). External validation confirmed an AUC of 0.833 (95% CI, 0.800-0.865).

Conclusion: Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

Purpose: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC.

Methods: The expression levels of the β₂-adrenergic receptor (β₂-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β₂-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β₂-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis.

Results: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β₂-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β₂-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth.

Conclusion: These results suggest that NE/β₂-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

Purpose: We aimed to analyze contemporary practice patterns in breast cancer radiotherapy (RT) and assess longitudinal changes over five years in Korea.

Methods: In 2022, a nationwide survey was conducted among board-certified radiation oncologists. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost.

Results: Seventy radiation oncologists from 61 (out of 101; 60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), a significant increase from 36% in 2017. HypoFx RT is commonly administered at 40-42.5 Gy in 15-16 fractions. APBI was used by 12 respondents (17%), an increase from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, indications for internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased from 47% in 2017 to 31%. For DCIS, the use of HypoFx RT increased from 25% in 2017 to 75%, and the rate of RT omissions after breast-conserving surgery (BCS) decreased from 48% in 2017 to 38%. The use of HypoFx RT for PMRT increased from 8% in 2017 to 36%.

Conclusion: The adoption of HypoFx RT after BCS for invasive breast cancer and DCIS has increased significantly, whereas the use of HypoFx PMRT has increased moderately since 2017. However, further studies are required to determine the optimal use of RNI.

Approximately 15%-25% of breast lymphatic drainage passes through the internal thoracic (internal mammary) lymphatic system, draining the inner quadrants of the breast. This study aimed to use lymphosonography to identify sentinel lymph nodes (SLNs) in the axillary and internal thoracic lymphatic systems in patients with breast cancer. Seventy-nine patients received subcutaneous ultrasound contrast agent injections around the tumor. Lymphosonography was used to identify SLNs. In 14 of the 79 patients (17.7%), the tumor was located in the inner quadrant of the breast. Lymphosonography identified 217 SLNs in 79 patients, averaging 2.7 SLNs per patient. The 217 identified SLNs in the 79 patients were located in the axillary lymphatic system; none were located in the internal thoracic (internal mammary) lymphatic system, although it was expected in two to four patients (i.e., 4-11 SLNs). These results implied that SLNs associated with breast cancer are predominantly located in the axillary lymphatic system.

Fertility preservation is a major concern in young patients diagnosed with breast cancer and planning to receive multimodality treatment, including gonadotoxic chemotherapy with or without age-related decline through long-term endocrine therapy. Most breast cancer patients undergo multimodality treatments; many short-term and long-term side effects arise during these therapies. One of the most detrimental side effects is reduced fertility due to gonadotoxic treatments with resultant psychosocial stress. Cryopreservation of oocytes, embryos, and ovarian tissue are currently available fertility preservation methods for these patients. As an adjunct to these methods, in vitro maturation or gonadotropin-releasing hormone agonist could also be considered. It is also essential to communicate well with patients in the decision-making process on fertility preservation. It is essential to refer patients diagnosed with breast cancer on time to fertility specialists for individualized treatment, which may lead to desirable outcomes. To do so, a multimodal team-based approach and in-depth discussion on the treatment of breast cancer and fertility preservation is crucial. This review aims to summarize infertility risk related to currently available breast cancer treatment, options for fertility preservation and its details, barriers to oncofertility counseling, and psychosocial issues.

Neuroendocrine carcinoma of the breast is a rare malignant tumor which, with the features of Merkel cells is even rarer. Herein, we report a case of small cell carcinoma with Merkel cell features in a 52-year-old female. Microscopically, the tumor was characterized by diffuse and consistent small round cells that were de-adherent. The tumor cells had round or oval nuclei with delicate chromatin and small nucleoli, the cytoplasm was sparse and eosinophilic. Additionally, the tumor was accompanied by high-grade ductal carcinoma in situ. Immunohistochemical staining showed that infiltrating tumor cells were positive for neuroendocrine markers, and punctately positive for CK20. The patient underwent modified radical mastectomy, axillary lymph node dissection, and postoperative adjuvant chemotherapy. No recurrence or metastasis was observed during follow-up period. Primary breast small cell carcinoma with Merkel cell features is rare and easily misdiagnosed as Merkel cell carcinoma. Early diagnosis and treatment may improve patient prognosis.

Purpose: Due to improved therapy, early diagnosis, and growing incidence rates, the number of long-term breast cancer survivors is increasing. Survivors can still be affected by aftercare, resulting in reduced quality of life (QoL). Thus, in this study, we investigated possible predictors of decreased physical and social functioning in breast cancer survivors.

Methods: In a German multicenter prospective study, we enrolled 759 female patients with breast cancer before surgery (t1), and contacted them again 5 years after surgery (t4). Data on QoL were assessed at t4 using the European Organization for Research and Treatment of Cancer QoL Core Questionnaire (EORTC QLQ-C30) and its breast cancer module EORTC QLQ-BR23. Predictors of decreased physical and social functioning were analyzed using logistic regression with odds ratios as effect estimates and 95% confidence intervals. Thresholds for the clinical importance of detrimental effects on QoL were defined according to Giesinger.

Results: Questionnaires from 759 patients were retrieved at t1. Of these, 456 participated in the study at t4. Poor QoL 5 years after diagnosis was reported by 20%-50% of the participants. Age, mastectomy, chemotherapy, education, employment, cohabitation, psychiatric comorbidities at t1, anxiety, depression, and intensity of physical activity emerged as predictors of decreased physical and social functioning 5 years after diagnosis.

Conclusion: Relief of symptoms and improvement in the QoL should be priorities in aftercare. Detecting patients with a decreased QoL is a rising challenge. Healthcare providers should take special care of patients aged 50-59 years, patients with psychiatric comorbidities and depression, and patients who have undergone mastectomy.