Breast Cancer : Basic and Clinical Research最新文献

Endocrine therapy with or without CDK4/6 inhibitors is the most commonly used frontline treatment option for metastatic hormone receptor-positive breast cancer. Approximately, 25% to 30% of women may have resistance to endocrine therapy, especially in the setting of certain genomic mutations in the tumor. This prompts the need to identify those patients who may benefit from frontline chemotherapy over endocrine therapy. Here, we present a case of a patient who presented with a de novo metastatic hormone receptor-positive breast cancer with visceral involvement (including bone marrow) as well as multiple somatic genomic alterations. The patient was treated with upfront chemotherapy, resulting in clinical and radiographic response, but rapidly progressed when she was transitioned to hormonal therapy. This report focuses on the role of upfront chemotherapy in the setting of visceral crisis including bone marrow involvement, the role of genomic alterations in contributing to endocrine resistance, and the need for biomarker-driven treatment options for hormone receptor-positive breast cancer.

Neoadjuvant chemotherapy (NAC) had been developed as a systematic approach before definitive surgery for the treatment of locally advanced or inoperable breast cancer such as inflammatory breast cancer in the past. In addition to its impact on surgery, the neoadjuvant setting has a benefit of providing the opportunity to monitor the individual drug response. Currently, the subject of NAC has expanded to include patients with early-stage, operable breast cancer because it is revealed that the achievement of a pathologic complete response (pCR) is associated with excellent long-term outcomes, especially in patients with aggressive phenotype breast cancer. In addition, this approach provides the unique opportunity to escalate adjuvant therapy in those with residual disease after NAC. Neoadjuvant chemotherapy in breast cancer is a rapidly evolving topic with tremendous interest in ongoing clinical trials. Here, we review the improvements and further challenges in the NAC setting in translational breast cancer research.

Background: Oncotype Dx is used to predict the long-term recurrence risk in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer (BC). This study aimed at establishing a correlation between clinicopathological parameters and recurrence score (RS), subsequently improving predictability and ultimately justifying the use of the multigene assay.

Materials and methods: A retrospective analysis of the pathology and clinical data of 114 female patients with BC who had Oncotype Dx testing between 2012 and 2019. The pathological parameters included are tumor cell type, tumor grade, pathological stage, and mitotic index (MI). The expression of ER, progesterone receptor (PR), HER2, and Ki67 was assessed by immunohistochemistry. A univariate and multivariate linear regression analysis was performed to assess the correlation between these parameters and the RS.

Results: In univariate analysis, age (˂40 years), higher tumor grade, and low PR expression were significantly associated with higher RS (P = .02; ˂.001; and ˂.001, respectively). Both MI and Ki67 were also strongly correlated with an increase in the RS with a P value of .01 (Spearman correlation 0.34 and 0.33). In multivariate linear regression analysis, age, MI, and Ki67 lost their significance, but both higher grade and PR remained significantly associated with a higher RS along with the tumor stage (P ˂ .001; ˂.001; and .04, respectively).

Conclusions: Tumor grade and PR immunohistochemical expression are the main predictors of RS in our study population. Other clinicopathological features were not significant predictors of change in RS in multivariate analysis.

Purpose: The study of breast cancer nearly always involves patients close to menopause or older. Therefore, young patients are mostly underrepresented. Our aim in this study was to demonstrate biological differences in breast cancer of young people using as a model available cell lines derived from people with breast cancer younger than 35 years.

Methods: Global miRNA expression was analyzed in breast cancer cells from young (HCC1500, HCC1937) and old patients (MCF-7, MDA-MB-231, HCC1806, and MDA-MB-468). In addition, it was compared with same type of results from patients.

Results: We observed a differential profile for 155 miRNAs between young and older cell lines. We identified a set of 24 miRNA associated with aggressiveness that were regulating pluripotency of stem cell-related pathways. Combining the miRNA expression data from cell lines and breast cancer patients, 132 miRNAs were differently expressed between young and old samples, most of them previously found in cell lines. MiR-23a-downregulation was also associated with poor survival in young patients.

Conclusions: Our results suggest that HCC1500 and HCC1937 cell lines could be suitable cellular models for breast cancer affecting young women. The miR-23a-downregulation could have a potential role as a poor prognosis biomarker in this age group.

Background: Viral cause of sporadic breast cancer (SBC) has been suggested based on the experimental murine model of mammary tumor caused by mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and human papillomavirus (HPV). While some studies have demonstrated the presence of viral sequences of MMTV, HPV, and EBV in breast cancer cells, others failed. These contradictions may be attributed to the geographical distribution of breast cancer incidence and/or technical variations. In the current study, we aimed to investigate the correlation of MMTV, HPV, and EBV infections with the development of breast cancer in Jordanian patients.

Methods: One hundred SBC tissue samples were subjected to laser capture microdissection for the selection of tumor cells populations. Fluorescence polymerase chain reaction (PCR) was used to detect the presence of the MMTV env-like sequences. Real-time PCR was used for HPV and EBV detection, and EBV was further confirmed by chromogen in situ hybridization (CISH).

Results: Mouse mammary tumor virus, HPV, and EBV were detected in SBC in 11%, 21%, and 23%, respectively. Only 3 of 52 (5.7%) positive cases demonstrated multiple virus infections. However, 49 of 52 (94%) of the positive cases revealed the presence of 1 type of viral sequences. Consequently, 52% of the studied breast cancer cases were infected with at least 1 type of the aforementioned viruses.

Conclusions: The current cohort suggests that MMTV, HPV, and EBV have a potential role in the development of breast cancer and adding more reasons to proceed with the quest of a possible viral origin of breast cancer.

Invasive lobular carcinoma with extracellular mucin is an uncommon pattern of invasive breast carcinoma. The 5th Edition of the World Health Organization Classification of Breast Tumors states that it is unknown whether these tumors are a subtype of mucinous carcinoma or invasive lobular carcinoma. Invasive lobular carcinoma with extracellular mucin frequently presents as a palpable mass and may be more likely to be grade 2 to 3 and HER2-positive than classic invasive lobular carcinoma. This case of pleomorphic invasive lobular carcinoma with extracellular mucin was detected by imaging only and was HER2-amplified, suggesting that a subset of these tumors may be clinically occult with an aggressive phenotype. Invasive lobular carcinoma with extracellular mucin is infrequently encountered and awareness of this entity is helpful in avoiding misdiagnosis.

Purpose: We examined the association of adipose tissue distribution with type 2 diabetes (T2D) in breast cancer patients.

Methods: Participants (N = 238) diagnosed with breast cancer at 20-75 years old who received breast cancer treatment at a major hospital from January 1, 2012, to December 31, 2017, with at least one completed and identifiable abdominal or pelvic computed tomography (CT) scan and data regarding race and ethnicity were included. Thirty-two breast cancer patients were identified as T2D patients after their breast cancer diagnoses. The adipose tissue distribution (visceral fat area [VFA], subcutaneous fat area [SFA], and the ratio of VFA to SFA [VFA/SFA]) was quantified on CT images of the third lumbar vertebra. T2D status was retrieved from patients' electronic medical records. The association of adipose tissue distribution with T2D in women with breast cancer was examined using multivariable logistic regression.

Results: Participants with T2D had significantly smaller SFA compared to those without T2D (odds ratio [OR] = 0.88, 95% confidence interval [95% CI] = 0.81-0.96, per 10 cm² SFA). A positive association of VFA/SFA ratio with T2D was observed (OR = 19.57, 95% CI = 3.26-117.42, per unit VFA/SFA), although the estimate was imprecise.

Conclusions: The amount of subcutaneous adipose tissue was inversely associated with T2D, and the ratio of the amount of visceral adipose tissue to the amount of subcutaneous adipose tissue was positively associated with T2D in breast cancer patients.

Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, MDA-MB-231), and human normal mammary epithelial cells (MCF-10A), under different levels of glycemic stress. These were used to study both benign and malignant breast tissue behaviors. Benign cells (MCF-10A) recorded higher Young's modulus values than malignant cells (MCF-7 and MDA-231) under normoglycemic conditions, which agrees with the current literature. Moreover, exposure to high glucose (for 48 hours) decreased Young's modulus in both benign and malignant cells, to the effect that the cancer cells showed a complete loss in elasticity with high glucose. This provides a possible insight into a link between glycemic stress and cytoskeletal strength. This work suggests that reducing glycemic stress in cancer patients and those at risk can prove beneficial in restoring normal cytoskeletal structure.

Purpose: We have shown previously that a preoperative paravertebral nerve block is associated with improved postoperative recovery in microvascular breast reconstruction. The purpose of this study was to compare the outcomes of a complete enhanced recovery after surgery (ERAS) protocol with complete regional anesthesia coverage to our traditional care with paravertebral block.

Patients and methods: This was a retrospective cohort study of 83 patients who underwent autologous breast reconstruction by T.M.M. between May 2014 and February 2018 at a tertiary academic center. Patients in the ERAS group were additionally administered acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin, a transversus abdominis plane block (liposomal or plain bupivacaine), and primarily oral opioids postoperatively. The patients were mobilized earlier with more rapid diet progression. All patients received a preoperative paravertebral block.

Results: Forty-four patients in the ERAS cohort were compared with 39 retrospective controls. The 2 groups were similar with respect to demographics and comorbidities. The ERAS cohort required significantly less opioids (291 vs 707 mg oral morphine equivalent, P < .0001) with unchanged postoperative pain scores and a shorter time to oral only opioid use (16.0 vs 78.2 hours, P < .0001). Median length of stay (3.20 vs 4.62, P < .0001) and time to independent ambulation (1.86 vs 2.88, P < .0001) were also significantly decreased in the ERAS cohort. Liposomal bupivacaine use did not significantly affect the results (P ⩾ .2).

Conclusions: Implementation of a robust enhanced recovery protocol with complete regional anesthesia coverage was associated with significantly decreased opioid use despite unchanged pain scores, with improved markers of recovery including length of stay, time to oral only narcotics, and time to independent ambulation.