Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

Pain Improvement After Healing Touch and Massage in Breast Cancer: an Observational Retrospective Study

Background: Healing Touch (HT) and Oncology Massage (OM) are nonpharmacologic pain interventions, yet a comparative effectiveness study has not been conducted for pain in breast cancer. Purpose: This breast cancer subgroup analysis compared the effectiveness of HT vs. OM on pain. Setting: The research occurred at an outpatient setting at an academic hybrid, multi-site, community-based cancer institute and Department of Supportive Oncology across four regional locations. Participants: Breast cancer outpatients along the cancer continuum who experienced routine clinical, nonexperimentally manipulated HT or OM. Research Design: The study was an observational, retrospective, comparative effectiveness post hoc subanalysis of a larger dataset. Patients reporting pain < 2 were excluded. Pre- and posttherapy pain scores and differences were calculated. Logistic regression modeled posttherapy pain by modality, adjusting for pretherapy pain. The proportions experiencing ? 2-point (clinically significant) pain reduction were compared with chi-square tests. Intervention: The study focused on the first session of either HT or OM. Main Outcome Measures: Pre- and posttherapy pain (range: 0 = no pain to 10 = worst possible pain). Results: A total of 407 patients reported pre- and posttherapy pain scores, comprised of 233 (57.3%) who received HT and 174 (42.8%) who received OM. Pretherapy mean pain was higher in HT (M=5.1, ± 2.3) than OM (M=4.3, ± 2.1) (p < .001); posttherapy mean pain remained higher in HT (M=2.7, ± 2.2) than OM (M=1.9, ± 1.7) (p < .001). Mean difference in pain reduction was 2.4 for both HT and OM. Both HT (p < .001) and OM (p < .001) were associated

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?

Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers’ interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.

Co-Expression of Androgen Receptor and Cathepsin D Defines a Triple-Negative Breast Cancer Subgroup with Poorer Overall Survival

Background: In the triple-negative breast cancer (TNBC) group, the luminal androgen receptor subtype is characterized by expression of androgen receptor (AR) and lack of estrogen receptor and cytokeratin 5/6 expression. Cathepsin D (Cath-D) is overproduced and hypersecreted by breast cancer (BC) cells and is a poor prognostic marker. We recently showed that in TNBC, Cath-D is a potential target for antibody-based therapy. This study evaluated the frequency of AR/Cath-D co-expression and its prognostic value in a large series of patients with non-metastatic TNBC. Methods: AR and Cath-D expression was evaluated by immunohistochemistry in 147 non-metastatic TNBC. The threshold for AR positivity (AR+) was set at ≥1% of stained cells, and the threshold for Cath-D positivity (Cath-D+) was moderate/strong staining intensity. Lymphocyte density, macrophage infiltration, PD-L1 and programmed cell death (PD-1) expression were assessed. Results: Scarff-Bloom-Richardson grade 1–2 and lymph node invasion were more frequent, while macrophage infiltration was less frequent in AR+/Cath-D+ tumors (62.7%). In multivariate analyses, higher tumor size, no adjuvant chemotherapy and AR/Cath-D co-expression were independent prognostic factors of worse overall survival. Conclusions: AR/Cath-D co-expression independently predicted overall survival. Patients with TNBC in which AR and Cath-D are co-expressed could be eligible for combinatory therapy with androgen antagonists and anti-Cath-D human antibodies.