Journal of Breast Cancer最新文献

Purpose: Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4⁺) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4⁺ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology.

Methods: We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design.

Results: The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale.

Conclusion: In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings.

Trial registration: ClinicalTrials.gov Identifier: NCT04541290.

Despite the advances in research and treatment of human breast cancer, its incidence rate continues to increase by 0.5% per year, and the discovery of novel therapeutic strategies for specific subtypes of human breast cancer remains challenging. Traditional laboratory mouse models have contributed tremendously to human breast cancer research. However, mice do not develop tumors spontaneously; consequently, genetically engineered mouse models or patient-derived xenograft models are often relied upon for more sophisticated human breast cancer studies. Since human breast cancer develops spontaneously, there is a need for alternative, yet complementary, models that can better recapitulate the features of human breast cancer to better understand the molecular and clinical complexities of the disease in developing new therapeutic strategies. Canine mammary tumors are one such alternative model that share features with human breast cancer, including prevalence rate, subtype classification, treatment, and mutational profiles, all of which are described in this review.

We present our initial experience of ultrasound (US)-guided localization of clipped metastatic axillary lymph nodes (LNs) following neoadjuvant chemotherapy (NAC). We evaluated US visibility and the successful excision rate of clipped LN after NAC in 29 consecutive patients with breast cancer. US-guided localization of clipped nodes was performed in 22 patients on the day of surgery, while seven patients underwent surgery without localization. The clips were identified in all patients with residual metastatic LNs and 6 of 12 (50%) patients without residual metastatic LNs on US. Six patients without visible clips underwent US-guided localization at the presumed previous clip insertion site. The successful excision rate of 22 LNs with localization was 100% (even though 3 of them were non-sentinel LNs) and 57% (4/7) without localization. Regardless of the presence of visible residual metastatic LNs on US after NAC, successful excision of the clipped LN with US-guided localization is feasible.

The apocrine morphology of the breast is observed in a broad pathological spectrum, ranging from benign cysts to invasive carcinomas. However, the number of clinical research investigating malignant apocrine lesions is limited. This study retrospectively reviewed the data of patients with malignant apocrine lesions admitted in a tertiary center between January 2004 and December 2021, based on the radiology-pathology correlation and the recent advances in their status to enhance the therapeutic implications of androgen receptor (AR). Among the 37 patients with lesions, 27 (73.0%) had triple-negative subtypes with predominant AR expression. The radiological features of malignant apocrine lesions did not differ from those of typical invasive ductal carcinoma or ductal carcinoma in situ. This study demonstrated that knowledge on the imaging features of malignant apocrine lesions and their histological basis could enhance the adoption of new targeted therapies in patients with this particular type of breast cancer.

Purpose: Limited treatment options and lack of treatment sensitivity biomarkers make the clinical management of triple-negative breast cancer (TNBC) challenging. Ceramide synthase 6 (CERS6) generates ceramides, which are key intermediates in sphingolipid biosynthesis and play important roles in cancer progression and resistance.

Methods: CERS6 was analyzed to determine its potential as a treatment sensitivity biomarker. CERS6 levels were determined in patients with breast cancer, and the roles and downstream signaling of CERS6 were analyzed using cellular and biochemical assays.

Results: Analysis of CERS6 expression in 195 patients with TNBC and their clinical response to chemotherapy revealed that individuals with CERS6 overexpression experienced significantly inferior responses to chemotherapy than those without CERS6 overexpression. Functional analysis demonstrated that although CERS6 overexpression did not affect TNBC cell growth and migration, it conferred chemoresistance. CERS6 inhibition significantly reduced growth, migration, and survival by suppressing the RhoA- and EGFR-mediated signaling pathways. Compared to control cells, CERS6-depleted cells were consistently less viable at different concentrations of chemotherapeutic agents.

Conclusion: Our study is the first to demonstrate that CERS6 may serve as a treatment sensitivity biomarker in patients with TNBC in response to chemotherapy. In addition, our findings suggested that CERS6 may be a therapeutic target for TNBC treatment.

Purpose: The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2-) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date.

Methods: Biopsy specimens from HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months.

Results: Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50-10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34-14.28]). Distant metastasis-free survival was significantly different between the high- and low-response groups (p = 0.004).

Conclusion: We demonstrated that the BCT score predicts NACT responsiveness in HR+/HER2- BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.

Purpose: Breast cancer is the primary cause of cancer-related death in women. Women diagnosed with estrogen receptor (ER)-positive breast cancer have prolonged treatment durations. Owing to the paucity of research and lack of consensus regarding conception planning and pregnancy for patients with ER-positive breast cancer, we aimed to assess pregnancy and survival outcomes in women with ER-positive breast cancer during and after treatment.

Methods: We conducted a systematic review of the available studies on pregnancy after ER-positive breast cancer. The assessed outcomes included overall survival (OS), disease-free survival (DFS), hormonal therapy duration, and pregnancy outcomes.

Results: Ultimately, 2,669 patients from five studies were included in this study. When all breast cancer receptor subtypes were included in the analysis, pregnancy after breast cancer was associated with a time-dependent protective effect on both DFS and OS. This protective effect was not evident when examining ER-positive patients with subsequent pregnancies, and no significant differences in DFS were observed. ER-positive patients who became pregnant received significantly lower rates of hormonal therapy. Hormonal treatment at the time of pregnancy was correlated with increased rates of termination owing to concerns about teratogenic effects.

Conclusions: Pregnancy after breast cancer did not significantly affect DFS in ER-positive patients over a follow-up period of 5-10 years from diagnosis, although did significantly affect hormonal treatment duration in the reviewed studies. Further analysis and in-depth studies are required to assess the effects of altered hormonal treatment times, as well as patient management related to pregnancy planning after breast cancer.