Encapsulated papillary carcinoma of the breast: A single institution experience.

Encapsulated papillary carcinoma (EPC) is a relatively rare form of breast cancer. To date, no evidence-based guidelines for the treatment of EPC have been established. Between January 2015 and December 2021, patients with histologically confirmed EPC of the breast were recorded in a database by The Third Hospital of Nanchang City (Nanchang, China). A total of 46 patients with EPC were retrieved from the database. Age at diagnosis ranged from 41-88 years (median age, 62 years). A total of 21 of these patients had pure EPC, 6 patients had EPC associated with ductal carcinoma in situ and 19 patients had EPC associated with invasive carcinoma. The majority of EPC cases were low nuclear grade, hormone receptor-positive and human epidermal growth factor receptor-2-negative. Additionally, myoepithelial cells were always absent in the papillae of the EPC. All patients underwent lumpectomy or mastectomy with sentinel lymph node biopsy, and almost all of the patients received adjuvant hormonal therapy. Adjuvant chemotherapy was only suggested to 4 patients who were diagnosed with axillary lymph node involvement. Subsequently, the clinicopathological features of non-invasive EPC were compared with invasive EPC. The results indicated that larger tumor sizes and axillary lymph node metastases were more common in invasive tumors. During the follow-up, only 2 patients with invasive EPC experienced recurrence or metastasis. In conclusion, a substantial proportion of invasive EPC cases display aggressive characteristics and metastatic potential, despite it being considered a subtype of carcinoma in situ with excellent prognosis, and local surgical resection is the initial method of treatment. Therefore, adjuvant endocrine therapy, radiotherapy and chemotherapy should be considered in select patients, especially in those diagnosed with invasive EPC tumors.

Comparison of a histone deacetylase inhibitor plus exemestane with exemestane alone in hormone receptor-positive advanced breast cancer that progressed on prior endocrine therapy: A meta-analysis.

Currently, endocrine therapy is the standard treatment for hormone receptor-positive advanced breast cancer (ABC). Despite the high sensitivity of anti-estrogen therapy, many breast cancer patients still experience disease progression, relapse, and reduced overall survival (OS) because of endocrine resistance. Several underlying mechanisms of this phenomenon include a change in hormone receptor expression, mutations in ESR1 and modification of important signaling pathways, but thus far none of these can be defined as the complete explanation. Additionally, it has been shown that in some breast cancers, expression of the estrogen receptor (ER) can be repressed by epigenetic modifications such as DNA methylation and histone deacetylation, and this could be a mechanism for endocrine resistance. Interestingly, although the efficacy of the combination of histone deacetylase (HADC) inhibitors and exemestane in hormone receptor-positive ABC that progressed on prior endocrine therapy has been investigated in several studies, whether pharmacologic blocking of HDAC activity acts as a therapeutic strategy remains highly controversial. Herein, we conducted a meta-analysis to evaluate the efficacy and safety of an HDAC inhibitor plus exemestane vs. exemestane alone in this setting. Our meta-analysis demonstrated that the combination group exhibited significantly prolonged progression-free survival (PFS) [hazard ratio (HR)=0.776, 95% confidence interval (CI)=0.675-0.892, P=0.000] and an improved objective response rate (ORR) (RR=1.612, 95% CI=1.085-2.396, P=0.018) compared to those treated with exemestane alone. Additionally, in terms of OS, the combination group failed to achieve a significant clinical OS benefit (HR=0.811, 95% CI=0.596-1.104, P=0.183). Although grade 3/4 toxicities were more common in the combination group, those toxicities were mostly asymptomatic and manageable. In conclusion, the addition of an HDAC inhibitor to exemestane significantly improves PFS over exemestane alone in hormone receptor-positive ABC patients who progressed on previous endocrine therapy. Identification of novel biomarkers to select patients who will benefit from this combination strategy is a high priority.

CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing.

Despite the great progress in breast cancer research and treatment, measures for efficient targeting of triple­negative breast cancer (TNBC) are still lacking. The well­established dependency of cancer cells on their microenvironment suggests that targeting the tumor niche might form a novel therapeutic approach. We identified the tumor­associated macrophage (TAM) infiltration in breast cancer tissues by immunohistochemistry, and analyzed overall survival (OS). U937 co­cultures with MDA­MB­231, MDA­MB­468 and MCF­7, respectively, to simulate in vivo cellular interactions were assessed. In hormone­independent breast cancer cell conditioned media (CM), U937 differentiates into M2 macrophage as identified by morphological changes and expression of specific surface antigens CD163 and CD204. Moreover, MDA­MB­231 recruits U937, and colony­stimulating factor 1 (CSF1) level in MDA­MB­231 and MDA­MB­468 CM is much higher than that of MCF­7. Overexpression of CSF1 in MCF­7 fails to rebuild its aggressiveness both in vitro and in vivo since CSF1 was not found extracellularly, while genetic inhibition of CSF1 in MDA­MB­231 abrogates TAM infiltration and consequently reduces tumorigenesis in non­obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Using various strategies we demonstrate that CSF1­induced TAMs specifically support breast cancer progression. Importantly, our results may reveal the efficacy of using targeted therapy against tumor niche and indicate that CSF1 inhibition may limit some breast cancer progression.