Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Precision Medicine is becoming the new paradigm in healthcare as it enables better resources allocation, treatment optimization with a potential side-effects reduction and consequent impact on quality of life and survival. This revolution is being catalyzed by liquid biopsy technologies, which provide prognostic and predictive information for advanced cancer patients, without the analytical and procedural drawbacks of tissue-biopsy. In particular, circulating tumor DNA (ctDNA) is gaining momentum as a clinically feasible option capable to capture both spatial and temporal tumor heterogeneity.

Carbon nanotube capsules enhance the in vivo efficacy of cisplatin.

Unlabelled: Over the past few years, numerous nanotechnology-based drug delivery systems have been developed in an effort to maximize therapeutic effectiveness of conventional drug delivery, while limiting undesirable side effects. Among these, carbon nanotubes (CNTs) are of special interest as potential drug delivery agents due to their numerous unique and advantageous physical and chemical properties. Here, we show in vivo favorable biodistribution and enhanced therapeutic efficacy of cisplatin (CDDP) encapsulated within ultra-short single-walled carbon nanotube capsules (CDDP@US-tubes) using three different human breast cancer xenograft models.

Long-term survival and BRCA status in male breast cancer: a retrospective single-center analysis.

Background: Male breast cancer (MBC) is rare. Given the paucity of randomized trials, treatment is generally extrapolated from female breast cancer guidelines.

Methods: This is a retrospective analysis of all male patients presenting with MBC at the Department of Oncology at University Federico II of Naples between January 1989 and January 2014.

Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up.

Studies on well characterized, large populations of estrogen receptor (ER)/progesterone receptor (PgR)/HER2-negative [triple-negative (TN)] breast cancer (BC) patients with long-term follow-up are lacking. In this study, we analyze clinical outcomes of TN BC and implications of epidermal growth factor receptor (EGFR) expression. Clinical and biologic features, time to first recurrence (TTFR), and overall survival (OS) were compared in 253 TN versus 1,036 ER positive, PgR positive, HER2-negative [estrogen-driven (ED)] BC.

Die and let live: harnessing BikDD to combat breast cancer stem cells.

One of the possible mechanisms contributing to the intrinsic resistance of cancer stem cells (CSCs) to conventional therapies is the inefficiency of activating the apoptotic machinery. In a recent study by Lang and colleagues, the engineered constitutively active pro-apoptotic protein BikDD, which works by inhibiting multiple Bcl-2 family members, was tested in various preclinical breast cancer models. Delivered to cells via an innovative cancer cell-specific gene-therapy approach, BikDD showed potent activity against CSCs and synergized with lapatinib and paclitaxel treatment.

Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy.

Background: Tumorigenic breast cancer cells that express high levels of CD44 and low or undetectable levels of CD24 (CD44(>)/CD24(>/low)) may be resistant to chemotherapy and therefore responsible for cancer relapse. These tumorigenic cancer cells can be isolated from breast cancer biopsies and propagated as mammospheres in vitro. In this study, we aimed to test directly in human breast cancers the effect of conventional chemotherapy or lapatinib (an epidermal growth factor receptor [EGFR]/HER2 pathway inhibitor) on this tumorigenic CD44(>) and CD24(>/low) cell population.

Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer.

Prevention trials using incidence or mortality as endpoints require a large number of participants and long follow-up. Trials using biomarkers as endpoints would potentially require fewer participants, less time, and significantly less resources to test promising new agents for breast cancer prevention. To test this idea, a randomized trial of tamoxifen for 1 year versus observation for 1 year was conducted to determine whether tamoxifen can cause regression of hyperplastic breast tissue, whether it changes the biomarker phenotype of premalignant disease or normal breast epithelium, and if biomarkers can be used as early surrogate indicators of response to tamoxifen.

Neoadjuvant trastuzumab induces apoptosis in primary breast cancers.

Purpose: Greater understanding of the cellular response in trastuzumab-treated patients will provide insight into the clinical management of patients.

Patients And Methods: We performed a neoadjuvant trial in 35 patients with locally advanced HER-2/neu overexpressing breast cancers who received weekly trastuzumab given as a single agent for the first 3 weeks, followed by a combination of trastuzumab and docetaxel for 12 weeks before surgery. Sequential core biopsies were taken at baseline and within weeks 1 and 3 after the first dose of trastuzumab.

Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.

Introduction: Invasive lobular carcinoma (ILC) comprises approximately 10% of breast cancers and appears to have a distinct biology. Because it is less common than infiltrating ductal carcinoma (IDC), few data have been reported that address the biologic features of ILC in the context of their clinical outcome. In the present study we undertook an extensive comparison of ILC and IDC using a large database to provide a more complete and reliable assessment of their biologic phenotypes and clinical behaviors.

Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases.

Purpose: To determine whether progesterone receptor (PgR) status provides additional value to estrogen receptor (ER) status and improves prediction of benefit from endocrine treatment among patients with primary breast cancer.

Patients And Methods: Clinical outcomes of patients in two large databases were analyzed as a function of steroid receptor status. The first database (PP), contained 3,739 patients who did not receive any systemic adjuvant therapy and 1,688 patients who received adjuvant endocrine therapy but no chemotherapy.

Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer.

Background: More efficacious and safer hormonal agents are needed for breast cancer treatment and prevention. Idoxifene is a novel selective estrogen receptor modulator (SERM) that, in preclinical models, has greater antiestrogenic but lower estrogenic activity than tamoxifen.

Patients And Methods: Three hundred and twenty-one postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer were randomized to receive either tamoxifen or idoxifene as initial endocrine therapy for advanced disease.

Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor.

Background: Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma.

Reversible and irreversible cardiac dysfunction associated with trastuzumab in breast cancer.

One of the newest agents used in the treatment of breast cancer is trastuzumab (Herceptin), a new recombinant DNA-derived humanized monoclonal antibody against the proto-oncogene, HER-2/neu gene product. However, despite its proven clinical efficacy, serious adverse effects leading to trastuzumab-induced cardiomyopathy have been described in up to 27% of patients receiving combination therapy with anthracyclines. There has been little published on the clinical syndrome of trastuzumab-induced cardiomyopathy.

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.

Purpose: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment.

Patients And Methods: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP).

Adenoid cystic carcinoma of the breast: molecular markers, treatment, and clinical outcome.

Background: The objective of this study was to comprehensively characterize the clinical and biologic features of adenoid cystic carcinoma (ACC) and to assess the implications for management in a large cohort of patients.

Methods: From a database of 50,000 patients, 28 were identified with ACC for which clinical follow-up and biologic information was available. The biologic features examined included estrogen receptor and progesterone receptor status, DNA ploidy, and S-phase fraction.

Estrogen receptor and breast cancer.

Breast cancer, the most common malignancy in women, was already known to be associated with the steroid hormone estrogen more than a century ago. The discovery of the estrogen receptor (ER) provided us not only with a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with antiestrogens. In this paper we will sketch the important role of ER in the development, progression, and treatment of the disease, which is complicated by the receptor's interaction with co-regulatory proteins, its cross-talk with other signal transduction pathways, and its involvement in the development of antiestrogen resistance.