Breast cancer (BC) is the most common malignancy affecting women. It is a highly heterogeneous disease broadly defined by the differential expression of cell surface receptors. In the United States, triple negative breast cancer (TNBC) represents 15 to 20% of all BC. When compared with other subtypes of BC, TNBC tends to present in younger women, and has a higher mortality rate of 40% in advanced stages within the first 5 years after diagnosis. TNBC has historically had limited treatment options when compared to other types of BC. The mainstay of treatment for TNBC remains cytotoxic chemotherapy despite the emergence of new biologic and targeted agents. Defining the specific tumor molecular profile including PDL-1 and androgen receptor testing is expanding treatment options in the clinical setting. Identifying more targetable, novel biomarkers that may better define therapeutic targets or prognostic markers is currently underway. TNBC nomenclature is expected to be updated in favor of other nomenclature which would help direct therapy, and further redefine TNBC’s heterogeneity. Given the continuous advances in the field of TNBC, this review assesses the latest developments in basic characterization, subtyping, and treatment of TNBC, including novel drug developments with antibody-drug conjugates, immune checkpoint inhibitors, PARP inhibitors and androgen receptor targeted agents. Future trials are necessary in the face of these innovations to further support the use of new therapies in TNBC and the detection of the appropriate biomarkers.

Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer

SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3–4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.

Background How the immune microenvironment changes during neoadjuvant chemotherapy of primary breast cancer is not well understood. Methods We analyzed pre- and post-treatment samples from 60 patients using the NanoString PanCancer IO360™ assay to measure the expression of 750 immune-related genes corresponding to 14 immune cell types and various immune functions, and assessed TIL counts and PD-L1 protein expression by immunohistochemistry. Treatment associated changes in gene expression levels were compared using t-test with Bonferroni correction. TIL count, PD-L1 protein and immune metagenes were compared using Wilcoxon test. Baseline immune markers were correlated with pathologic complete response (pCR) using estrogen receptor and treatment arm adjusted logistic regression. Results At baseline, high TIL counts and high expression of chemoattractant cytokines (CCL21, CCL19) and cytotoxic T cell markers were associated with higher pCR rate. High expression of stromal genes (VEGFB, TGFB3, PDGFB, FGFR1, IGFR1), mast and myeloid inflammatory cell metagenes, stem cell related genes (CD90, WNT11, CTNNB1) and CX3CR1, and IL11RA were associated with residual disease (RD). After treatment, in cases with pCR, TIL counts and most immune genes decreased significantly. Among RD cases, TIL counts and PD-L1 expression did not change but cellular stress and hypoxia associated genes (DUSP1, EGR1), and IL6, CD36, CXCL2, CD69 and the IL8/VEGF metagene increased. Conclusions Activated T cells in the tumor microenvironment are associated with pCR whereas stromal functions are associated with residual disease. Most immune functions decrease during neoadjuvant chemotherapy but several immunotherapy targets (PD-L1, IL6, IL8) remain expressed in RD suggesting potential therapeutic strategies.

Breast cancer patients are increasingly seeking Complementary and Alternative Medicine (CAM) therapies with the hope of alleviating the burden of the disease and improving their quality of life (QOL). The objective of this study was to assess the prevalence, types, socio-demographic and disease-related correlates as well as characteristics of CAM use (including disclosure to treating physicians) among breast cancer patients in Beirut, Lebanon. A secondary objective was to evaluate the association between CAM use and QOL. A cross-sectional survey was conducted on breast cancer patients recruited from two major referral centers in Beirut: a philanthropic hospital and a private academic medical center. In face-to-face interviews, participants completed a questionnaire of three sections: socio-demographic and lifestyle characteristics, breast cancer condition, and CAM use. Three to four weeks following these interviews, the secondary QOL assessment was carried out via telephone using the Arabic version of the Functional Assessment of Cancer Therapy-Breast questionnaire. The main outcome in this study, CAM use, was defined as using CAM at least once after breast cancer diagnosis. A total of 180 breast cancer patients completed the survey (response rate: 94.6 %). Prevalence of CAM use was 40 %. Using multivariate logistic regression, CAM use was negatively associated with age (OR: 0.96, CI: 0.92-0.99), treatment at the philanthropic hospital (OR: 0.13, CI: 0.05-0.35) and was positively associated with an advanced stage of the disease (OR: 4.20, CI: 1.65-10.69). Among study participants recruited from both sites, the most commonly used CAM was ‘special food’ followed by ‘herbal teas’, ‘diet supplements’ and ‘Spiritual healing’. Only 4 % of CAM users cited health professionals as influencing their choice of CAM and only one in four patients disclosed CAM use to their treating physician. There was no significant association between CAM use and QOL. The findings of this study revealed a prevalent CAM use among Lebanese breast cancer patients. Furthermore, physicians’ role in orienting CAM use was found to be marginal as patients relied mainly on family and media for their choice of CAM and were less likely to disclose CAM use to their treating physicians.

Heat shock proteins (Hsps) are highly conserved proteins working as molecular chaperones for several cellular proteins essential for normal cell viability and growth, and have numerous cytoprotective roles. The expression of Hsps is induced in response to a wide variety of physiological and environmental stress insults, including anticancer chemotherapy, thus allowing the cell to survive lethal conditions. Cancer cells experience high levels of proteotoxic stress and rely upon stress-response pathways for survival and proliferation, thereby becoming dependent on proteins such as stress-inducible Hsps. Owing to the implication of Hsps in cancer, Hsp inhibition has recently emerged as an interesting potential anticancer strategy. Many natural and synthetic Hsp inhibitors molecular compounds are in development and many are being evaluated as potential cancer therapies. One of the Hsps in particular, Hsp90, has several client proteins and is emerging as a particularly exciting cancer target due to the prospect of simultaneously inhibiting chaperoning of numerous oncogenic proteins. This review describes the function of Hsps focusing on current efforts in exploiting the attributes of Hsps as potential targets for anticancer therapy.