Breast Cancer : Basic and Clinical Research最新文献

Background: Inflammatory breast cancer (IBC) is a rare form of breast cancer with a poor prognosis. IBC is characterized by florid lymphovascular tumor emboli in the skin and the parenchyma of the breast. We hypothesized that the formation of these emboli/clusters plays a pivotal role in IBC metastasis and its rapid progression, and that their structure and function may be a key to identifying molecular biological differences between IBC and non IBC.

Methods: Mechanical methods were used to mimic the lymph fluid viscosity by adding 2.25% of PEG8000 to the media. Clusters were obtained for IBC tumor cell lines (SUM149 and IBC-3), non IBC tumor cell lines (MDA-MB-231, MDA-MB-468, and MCF7), and a non-tumorigenic human mammary epithelial cell line (MCF10A). Clusters were analyzed by light microscopy, and then prepared for and observed by transmission electron microscopy (TEM).

Results: Significant differences were seen between IBC and non IBC clusters. The TEM analysis revealed that IBC cells harbored numerous microvilli and microvesicles, both on the free outer surface and inside the cluster. Microvilli from IBC cell clusters were noted at higher density and were longer than those of non IBC cell clusters.

Conclusions: IBC tumor cell clusters exhibited distinct ultrastructural features characterized by the presence of long, crowded microvilli and numerous microvesicles. These microvilli may play an important role in the biology and aggressiveness of IBC.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and high-grade disease of neoplastic lymphoid cells within the vascular lumina of small- to medium-sized vessels. The disease carries a grim prognosis despite robust treatment protocols. We discuss the case of a 58-year-old female who presented with mammographic screening abnormality which led to more investigations and ultimately to this diagnosis. The patient had no prior history of a lymphoma or in situ and invasive carcinoma of the breast. To our knowledge, IVLBCL of the breast is a very rare and an unusual location for this type of a lymphoma and so far, only five reported cases. Through our case report, we not only discuss the case but also review literature on this rare entity.

Breast cancer is the most prevalent malignant neoplasm in females. Genetic variations in the xenobiotic metabolising cytochrome enzymes; Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in the individual susceptibility to breast cancer and its prognosis. The goal of this study is to estimate the incidence of single nucleotide polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI, and rs4646903/MSP1) and in CYP1B1 (rs1056836, Leu432Val) genes in patients with breast cancer. This case-control study included 180 female patients with breast cancer and 180 healthy control subjects from Kirkuk/Iraq. Genomic DNA was extracted from venous blood samples and tested for SNPs by the direct DNA sequencing technique. A statistical analysis was done to identify if there is any association between SNPs and the increasing odd of breast cancer and its stage, grade and molecular subtype at diagnosis. The common (reference) genotype of CYP1A1 gene rs1048943 is AA. The AG and GG variant genotypes were significantly more common in the breast cancer patients and conferred an increased odd of breast cancer and its later stages (stages III and IV) and poor differentiation (P < .01) but not with the molecular subtypes. The common genotype of CYP1A1 rs4646903 is TT. The variant genotypes TC and CC are not associated either with increased risk of breast cancer (P > .05) or with its stage, grade or molecular subtypes (P > .05). The GG genotype of CYP1B1 rs1056836 was the common genotype. The CG and CC variant genotypes were not associated with the increased risks of breast cancer (P > .05) or its stage, grade or molecular subtypes (P > .05). In conclusion, variants genotypes of CYP1A1 rs1048943 might play a role in breast cancer pathogenesis and prognosis and can have a place in cancer screening and tailored medicine in the future in the Iraqi population. Future larger scale studies including other genes might help to better understand the role of the SNP in breast risk and its prognosis.

Background: The reported association between metabolic syndrome (MetS) and breast cancer may have a significant impact on the incidence and mortality related to breast cancer. We undertook this study to find if the disease is different in patients with MetS.

Materials and methods: Patients with biopsy-proven breast cancer were divided into groups based on the presence or absence of MetS (according to the IDF definition of 2006) and also based on menopausal status. The presence of known risk and prognostic factors were also recorded, and the groups were compared.

Results: A total of 305 patients were recruited, of which 191 (62.6%) had MetS. Patients with MetS were older than those without (52.1 versus 48.3 years, P = .014) and had a lower incidence of nulliparity (4.1% vs 12.8%, P = .005) and dense breasts (2.9% in MetS vs 10.8% in no MetS, P = .009). On further dividing into premenopausal and postmenopausal, these differences persisted only in premenopausal patients. MetS group had a lower number of HER2-positive tumours (14.3% for MetS, 23.9% for no MetS; P = .036). After dividing into premenopausal and postmenopausal, significant differences were observed in distant metastases (5.4% in MetS vs 16.1% in no MetS, P = .045) and in grade (higher grade in MetS, P = .05) in premenopausal patients. In postmenopausal patients, difference was observed in HER2 positivity (12.3% in MetS vs 28.8% in no MetS, P = .008).

Conclusions: Breast cancer in patients with MetS may not be significantly different from breast cancer in patients without MetS.

Introduction: Breast cancer (BC) is a major public health problem among women. However, BC screening uptake is abysmally low among Nigerian women. This study evaluated the association of BC fear and perceived self-efficacy with BC screening (clinical breast exam [CBE] and mammography) among middle-aged Nigerian women.

Methods: A community-based cross-sectional study was conducted among middle-aged women in Enugu State, southeast Nigeria. The data were collected between September 2019 and February 2020. The BC screening uptake, fear, and self-efficacy were assessed using the validated Breast Cancer Screening Questionnaire (BCSQ), Champion Breast Cancer Fear Scale (CBCFS), and Champion's Mammography Self-Efficacy Scale (CMSES). Data were analyzed using frequencies and percentages, chi-square test, and univariate analysis of variance. Bivariate and multivariable logistic regression models were used to examine independent associations between selected sociodemographic factors, cancer fear, perceived self-efficacy, and BC screening.

Results: The mean age of the participants was 55.3 years (SD: 5.75). More than half of the women (51%) reported having a BC screening in the past 12 months. However, only 12.5% and 16.9% reported having a CBE or mammogram in the past 12 months. The prevalence of a high, moderate, and low level of fear was 68%, 22.3%, and 9.8%, respectively. The prevalence of a high, moderate, and low self-efficacy level was 50.6%, 37.5%, and 12.0%, respectively. The multivariable logistics regression analysis showed that women aged 50-59 years and 60-64 years were 3.5 times (adjusted odds ratio [AOR] = 3.50, 95% confidence interval [CI]: 2.07-5.89, P < .0001), and 5.92 times (AOR = 5.92 95% CI: 2.63-13.35, P < .0001), respectively, more likely to perform mammogram than those aged 40-49 years. Women with a high level of self-efficacy were 2.68 times (AOR = 2.68, 95% CI: 1.15-6.26, P < .0001) more likely to use mammographic screening than those with low self-efficacy. Although not statistically significant, women with a moderate level of BC fear were 0.56 times less likely to use mammogram than women with a low level of BC fear.

Conclusion: A low proportion of women underwent CBE or mammography. Women had a high level of BC fear and a moderate level of self-efficacy for BC screening. The findings emphasize the need for health educational and psychosocial interventions that improve self-efficacy and promote regular BC screening among middle-aged women.

Purpose: Tumor lysis syndrome (TLS) is a rare but life-threatening phenomenon that occurs mainly in patients with aggressive hematologic or highly chemotherapy sensitive solid tumors such as high-grade neuroendocrine carcinoma or testicular cancer. Tumor lysis syndrome is exceedingly rare in hormone receptor-positive, HER2-negative breast cancer. Furthermore, TLS following treatment with alpelisib, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor used to treat PIK3CA-mutated (gene encoding p110α subunit of PI3K), hormone receptor positive advanced breast cancer, has never been described in patients with nonhematologic malignancies.

Methods: In the following case, we present a patient with hormone receptor-positive, HER2-negative, PIK3CA-mutated metastatic breast cancer who developed TLS 12 days after starting fulvestrant and alpelisib.

Results: Patient was promptly treated with improvement in her renal function to baseline without requiring renal replacement therapy. Alpelisib was resumed at a reduced dose with no further complications.

Conclusion: Through this case, we discuss the potential complications of TLS and the importance of prompt recognition and treatment.

Background: Spindle cell carcinoma (SpCC) of the breast is a rare histological type, a subtype of metaplastic carcinoma characterized by atypical spindle cell and epithelial carcinoma. The proportions of the spindle cell and epithelial components vary among tumours. Due to its rarity, biological characteristics of this disease have been poorly studied.

Methods: In total, 10 patients with SpCC were surgically treated at our institution from January 2007 to December 2018. We retrospectively investigated these SpCC cases, focusing on the differences between spindle cell and epithelial components. Microsatellite status was also examined.

Results: Nine cases were triple-negative breast cancer (TNBC). The rates of high tumour grade were 70% in spindle cell components and 56% in epithelial components (P = .65), while the mean Ki67 labelling index were 63% and 58%, respectively (P = .71). Mean programmed death ligand 1 (PD-L1) expression in these components was 11% and 1%, respectively (P = .20). All 10 tumours were microsatellite stable. Patient outcomes of triple-negative SpCC did not differ from those of propensity-matched patients with conventional TNBC.

Conclusions: Spindle cell components showed higher values in factors examined, although there was no statistically significant difference. Our data reveal that these 2 components of SpCC may be of different biological nature.

The taro plant, Colocasia esculenta, contains bioactive proteins with potential as cancer therapeutics. Several groups have reported anti-cancer activity in vitro and in vivo of taro-derived extracts (TEs). We reported that TE inhibits metastasis in a syngeneic murine model of Triple-Negative Breast Cancer (TNBC).

Purpose: We sought to confirm our earlier studies in additional models and to identify novel mechanisms by which efficacy is achieved.

Methods: We employed a panel of murine and human breast and ovarian cancer cell lines to determine the effect of TE on tumor cell viability, migration, and the ability to support cancer stem cells. Two syngeneic models of TNBC were employed to confirm our earlier report that TE potently inhibits metastasis. Cancer stem cell assays were employed to determine the ability of TE to inhibit tumorsphere-forming ability and to inhibit aldehyde dehydrogenase activity. To determine if host immunity contributes to the mechanism of metastasis inhibition, efficacy was assessed in immune-compromised mice.

Results: We demonstrate that viability of some, but not all cell lines is inhibited by TE. Likewise, tumor cell migration is inhibited by TE. Using 2 immune competent, syngeneic models of TNBC, we confirm our earlier findings that tumor metastasis is potently inhibited by TE. We also demonstrate, for the first time, that TE directly inhibits breast cancer stem cells. Administration of TE to mice elicits expansion of several spleen cell populations but it was not known if host immune cells contribute to the mechanism by which TE inhibits tumor cell dissemination. In novel findings, we now show that the ability of TE to inhibit metastasis relies on immune T-cell-dependent, but not B cell or Natural Killer (NK)-cell-dependent mechanisms. Thus, both tumor cell-autonomous and host immune factors contribute to the mechanisms underlying TE efficacy. Our long-term goal is to evaluate TE efficacy in clinical trials. Most of our past studies as well as many of the results reported in this report were carried out using an isolation protocol described earlier (TE). In preparation for a near future clinical trial, we have now developed a strategy to isolate an enriched taro fraction, TE-method 2, (TE-M2) as well as a more purified subfraction (TE-M2F1) which can be scaled up under Good Manufacturing Practice (GMP) conditions for evaluation in human subjects. We demonstrate that TE-M2 and TE-M2F1 retain the anti-metastatic properties of TE.

Conclusions: These studies provide further support for the continued examination of biologically active components of Colocasia esculenta as potential new therapeutic entities and identify a method to isolate sufficient quantities under GMP conditions to conduct early phase clinical studies.

Background: Breast cancer is the most common cancer in women, and the second overall, following lung cancer. Breast cancer can occur at any age, with an increased incidence in women 40 years and above. Worldwide the incidence is around 1 million cases per year, 60% of the cases reported from low- and middle-income countries. The current study was conducted to determine knowledge, attitude, and practices related to breast cancer, the associated risk factors, and screening methods in women presenting to a health care facility from resource-poor settings in Pakistan.

Methods: A cross-sectional study design was used, and participants were recruited phase-wise from three major outpatient departments (OPDs) (Gynecology and Obstetrics OPD, Medical OPD, and Surgical OPD). Data were collected through the validated "Breast Cancer Awareness Measure" developed by Cancer Research UK, King's College London, and University College London in 2009. Data were analyzed through Statistical Package for Social Sciences software (SPSS) version 23.0. Students's T-Test, ANOVA, and linear regression analysis were conducted.

Results: A total of 430 women were invited for participation in the study from the 3 main OPDs, and 400 took part in the study (response rate = 93.02%). The mean age of the women was 33.62 years ± 12.3 years, and the mean years of formal education were 5.05 ± 6.3 years. Less than a quarter of the participants were aware of the breast cancer warning signs, and 23.3% recognized the pain in the armpit or one of the breasts as a sign of breast cancer. The proportion of women aware of age-related and lifetime risk of getting breast cancer was 15.0%. Furthermore, only 2.5% performed breast self-examination at least once a month. Women identified many barriers like embarrassment, transport, and confidentiality issues in seeking medical help.

Conclusion: Overall, women had poor knowledge of breast cancer, related warning signs, breast self-examination, risk factors, and screening methods.

Background: Sentinel lymph node biopsy (SLNB) provides staging information and guides adjuvant therapy in early breast cancer (EBC). Routine SLNB in oncogeriatricians with low-risk EBC remains controversial.

Aims: To evaluate axillary management in elderly patients diagnosed with oestrogen receptor positive (ER+), clinically lymph node negative (cLN-) EBC, and to assess whether SLNB affects further axillary management or adjuvant chemotherapy (ACTX) decision making.

Methods: Female patients aged > 65 years, diagnosed with ER+, human epidermal growth factor receptor-2 negative (HER2-), and cLN- breast cancer (BC), who underwent surgery and SLNB were included. Clinicopathological predictors of ACTX and completion axillary lymph node dissection (CALND) were determined. Kaplan-Meier analyses assessed survival outcomes.

Results: A total of 253 patients were included (median age: 72 years, range: 66-90), all underwent SLNB; 50 (19.8%) had lymphatic metastasis on SLNB (SLNB+). Of these, 19 proceeded to CALND (38.0%), 10 (52.6%) of whom had further axillary disease (ALND+). 20 of the 50 SLNB+ patients received ACTX (40.0%) as did 31 of the 203 SLNB- patients (15.2%) (P < .001). Oncotype DX (ODX) testing was utilized in 82 cases (32.8%). Younger age (P < .001), SLNB+ (P < .001) and ODX score (P = .003) were all associated with ACTX prescription. ODX > 25 (OR: 4.37, 95% CI: 1.38-13.80, P = .012) independently predicted receiving ACTX. Receiving ACTX and proceeding to CALND did not improve disease-free (P = .485 and P = .345) or overall survival (P = .981 and P = .646).

Conclusions: Routine SNLB may not be necessary in elderly patients diagnosed with ER+, cLN- EBC. Future oncogeriatric practice is likely to see genomic testing guiding ACTX prescription in this group.