Breast Cancer Research and Treatment最新文献

Purpose: Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes.

Methods: Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment.

Results: 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment.

Conclusion: In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Purpose: After breast cancer diagnosis and treatment, the majority of women will gain weight. The aim of this study was to describe the experiences of weight management among Australian women with breast cancer.

Methods: This is a secondary analysis of data from a qualitative study evaluating the feasibility of novel interventions for weight management after breast cancer. Participants were recruited via email invitation from a breast cancer consumer organization and breast cancer centre in Australia. Eligible participants had received treatment for breast cancer, and were fluent in English. Discussions were audio-recorded, transcribed verbatim and analysed using thematic analysis with the constant comparison method.

Results: Thirty-seven women provided data in five focus groups and one semi-structured interview. Four themes were identified: Timing, milestones and turning points; Making sense of the journey; Factors leading to weight gain; and Information and health professional support. Varying trajectories of weight gain were described, the most common being gradual or fluctuating weight gain. Weight gain was attributed to a number of related factors including becoming postmenopausal, and the impact of treatment effects. Achieving a sense of autonomy and agency assisted with weight management. An overall lack of information and support relating to weight management was highlighted.

Conclusions: There is a need for a coordinated and systematic approach to weight management after breast cancer. Further research on the role of supportive care and systems-level support is warranted to mitigate the significant public health burden of excess weight after breast cancer treatment.

Background: As the US faces a diverse aging population, racial disparities in breast cancer outcomes among elderly patients remain poorly understood. We evaluate the association of race with presenting stage, treatment, and survival of invasive breast cancer among octogenarians.

Methods: Women (≥ 80 years) with invasive breast cancer were identified in 2004-2020 NCDB. To facilitate comparison, only non-Hispanic Black and non-Hispanic White patients were included; patients of Hispanic ethnicity were excluded. Demographics, tumor characteristics, and treatments were assessed by race. Overall survival was compared using the logrank test. Multivariable logistic and Cox proportional hazard regression models were developed to evaluate the independent association of race with outcomes of interest.

Results: Of 222,897 patients, 19,059 (8.6%) were Black. Most patients had stage I ER + HER2- invasive ductal carcinoma. Black patients more frequently had greater comorbidities, low income and education, and advanced stage (p < 0.001 each; ref: White). Following adjustment, Black women had increased likelihood of Stage III/IV over time, as well as increased odds of chemotherapy (AOR 1.22, 95% CI 1.15 - 1.29) and non-operative management (AOR 1.82, 95% CI 1.72 - 1.92; ref: White). Although Black patients had lower survival rates compared to White, race was not associated with 5-year mortality following adjustment for stage, receipt of surgery, and adjuvant treatments (p = 0.34).

Conclusions: Inferior survival among elderly Black patients appears be driven by advanced stage at presentation. While such disparities are narrowing in the present era, future work must consider upstream interventions to ensure equitable outcomes for all races.

Purpose: This study aimed to assess the concordance of human epidermal growth factor receptor 2 (HER2) expression scoring by immunohistochemistry (IHC) among practicing pathologists in Japan, given the challenging nature of scoring and the critical role of HER2 status in breast cancer management.

Methods: Whole slide images (WSI) from 20 invasive breast cancer cases (1 representative WSI per case) selected to represent a diverse IHC scores and staining patterns were used in an online survey involving seven reference pathologists who established consensus HER2 IHC scores (0 to 3 +) decided by majority interpretation. Participating pathologists nationwide scored the same 20 WSI cases online using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guidelines. Deidentified case metadata were registered in the uPath system.

Results: A total of 144 participating pathologists responded. The scoring results of the participating pathologists most commonly agreed with the consensus IHC score, followed by a ± 1 point deviation and no survey responses with > 1 point deviation. The mean percentage of agreement with the consensus score for all 20 cases was 63.4%. In cases where the reference pathologists' scores were discordant, the participating pathologists also showed a lower concordance rate.

Conclusion: This study highlighted the current status of HER2 expression scoring by IHC for breast cancer among pathologists in Japan. These findings underscore the challenges in HER2 IHC scoring cases and emphasize the need for improved standardization and training, especially in the evolving landscape of HER2-targeted therapies.

Objective: To quantify the pressure levels necessary for effective Manual Lymphatic Drainage (MLD) in managing Breast Cancer-Related Lymphedema (BCRL) across various stages, and to contribute to the development of standardized protocols for MLD therapy.

Methods: The study included 42 patients with BCRL (Stages I-III) and 14 certified lymphedema therapists. Forearms and upper arm circumferences were measured pre and post a 21-day MLD intervention. A tactile sensor system recorded the applied pressure during treatment. The data were preprocessed and statistically analyzed to assess pressure patterns and their stage-specific impacts on lymphedema.

Results: The mean age of the patients was 52.4 years, and that of the therapists was 39.1 years. A statistically significant reduction in arm circumference was observed post-MLD treatment (P < 0.05). The pressure applied varied across stages: I _forearm 16.5-20.1 mmHg, I _{upper arm} 16.1-20.7 mmHg; II _forearm 16.6-19.8 mmHg, II _{upper arm} 19.7-23.8 mmHg; III _forearm 29.3-34.3 mmHg, III _{upper arm} 29.7-34.3 mmHg. No statistically significant difference was found between forearm and upper arm treatment pressures within Stages I (P = 0.283) and III (P = 0.08), while Stage II exhibited a significant difference (P < 0.001). Across the same treatment area, pressures for Stages I and II in the forearm were significantly lower than those in Stage III (P < 0.001). The treatment pressure differences between forearm stages I and II were not statistically significant (P > 0.05). Differences in upper arm treatment pressures across Stages I, II, and III were also statistically significant (P < 0.001).

Discussion: The study provides quantitative evidence on the pressure ranges needed for MLD across different stages of BCRL. It highlights the importance for stage-specific pressure adjustments to optimize treatment outcomes. These findings contribute to the existing body of knowledge on MLD and offer valuable data that could inform the development of rehabilitation technologies, including intelligent robots and visualization systems, as well as enhance therapist training programs.

Purpose: To generate a model for predicting nodal response to neoadjuvant systemic treatment (NAST) in biopsy-proven node-positive breast cancer patients (cN+) that incorporates tumor microenvironment (TME) characteristics and could be used for planning the axillary surgical staging procedure.

Methods: Clinical and pathologic features were retrospectively collected for 437 patients. Core biopsy (CB) samples were reviewed for stromal content and tumor-infiltrating lymphocytes (TIL). Orange Datamining Toolbox was used for model generation and assessment.

Results: 151/437 (34.6%) patients achieved nodal pCR (ypN0). The following 5 variables were included in the prediction model: ER, Her-2, grade, stroma content and TILs. After stratified tenfold cross-validation, the logistic regression algorithm achieved and area under the ROC curve (AUC) of 0.86 and F1 score of 0.72. Nomogram was used for visualization.

Conclusions: We developed a clinical tool to predict nodal pCR for cN+ patients after NAST that includes biomarkers of TME and achieves an AUC of 0.86 after tenfold cross-validation.

Purpose: Adolescent and young adult (AYA) patients with breast cancer generally have poor prognoses and a higher risk of secondary cancers compared to those at the same cancer stage. Notably, AYA patients in Asia exhibit a higher incidence rate of breast cancer, with Luminal A as the predominant molecular subtype, which contrasts with the trends observed in Western countries. This study aims to compare the efficacy of Taxane/Anthracycline combination-based regimens (TACB) versus Anthracycline-based regimens (AB) in AYA patients with stage I-II breast cancer, focusing on different molecular subtypes.

Methods: This study utilized data from the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Cancer Registry (TCR) from 2011 to 2019. The study cohort included patients aged 15 to 39 years who were diagnosed with stage I-II breast cancer and received either TACB or AB regimens. Propensity score matching and Cox proportional hazards regression models were used to calculate the hazard ratios (HR) for recurrence.

Results: The results showed that TACB regimens significantly reduced the risk of recurrence compared to AB regimens across all patients (aHR 0.73, 95% CI 0.55-0.97). Specifically, for low/middle-recurrence risk groups, the aHR was 0.68 (95% CI 0.49-0.96), and for high-recurrence risk groups, it was 0.43 (95% CI 0.21-0.87). The analysis further indicated no significant differences in recurrence risk between AYA and non-AYA patients using TACB regimens.

Conclusion: The TACB regimens showed a more favorable prognosis than AB regimens across all molecular subtypes. Furthermore, TACB regimens not only outperformed AB treatments but also closed the gap in prognostic outcomes between AYA and non-AYA patients. We believe the findings of this study are highly reliable and can provide valuable guidance for physicians in choosing the most appropriate treatment strategies for AYA patients with stage I-II breast cancer.

Purpose: Despite of very rare, breast cancer patients with double heterozygosity (DH) variants in BRCA1 and BRCA2 genes have been identified in other ethnic groups and seem to be associated with distinctive phenotypes. However, little is known about the frequency and clinical characteristics of Chinese breast cancer patients with BRCA1/2 DH variants.

Methods: Four hundred and eleven unrelated patients with BRCA1 or BRCA2 pathogenic variants (PVs) were identified in a large series of unselected breast cancer patients. Another two siblings with metachronous bilateral breast cancer were referred for genetic counseling, after which BRCA1/2 DH variants were detected.

Results: Four unrelated breast cancer patients with BRCA1/2 DH were identified in the cohort of 411 patients with BRCA1 or BRCA2 PVs, the frequency of BRCA1/2 DH was 0.97%. In total, six BRCA1/2 DH patients from five families were found in this study. In two families, the hereditary pattern of DH was speculated to have originated from both sides of the family. BRCA1/2 DH patients were more likely to have a family history of breast cancer than patients with a BRCA1 (100% vs. 29.2%, P = 0.004) or BRCA2 (100% vs. 29.6%, P = 0.004) single PV. BRCA1/2 DH patients were more likely to be triple-negative breast tumors than patients with single BRCA2 PVs (66.7% vs. 14.1%, P = 0.020), which was comparable to the findings in patients with single BRCA1 PVs (66.7% vs. 56.9%, P = 1.00).

Conclusion: Chinese patients with BRCA1/2 DH exhibit a high percentage of family history of breast cancer. The tumor pathological features of BRCA1/2 DH carriers are similar to those of BRCA1 PV carriers.

Purpose: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC.

Methods: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay.

Results: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk.

Conclusions: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Purpose: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results.

Methods: Postmenopausal women with HR+ BC who were 45-57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method.

Results: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85-2.81), DRFS (HR = 1.51; 95% CI 0.73-3.11), OS (HR = 1.64; 95% CI 0.75-3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84-4.63) when compared with patients without OFR.

Conclusion: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.