Faculty Bibliography

Breast cancer is a heterogeneous disease, with different subtypes having a distinct biological, molecular, and clinical course. Assessments of standard clinical and pathological features have traditionally been used to determine the use of adjuvant systemic therapy in patients with early stage breast cancer; however, the ability to identify those who will benefit from adjuvant chemotherapy remains a challenge, leading to the overtreatment of some patients. Advances in molecular medicine have substantially improved the accuracy of gene-expression profiling of breast tumours, resulting in improvements in the ability to predict a patient's risk of breast cancer recurrence and likely response to endocrine therapy and/or chemotherapy. These genomic assays, several of which are commercially available, have aided physicians in tailoring treatment decisions for patients at the individual level. Herein, we describe the available data on the clinical validity of the most widely available assays in patients with early stage breast cancer, with a focus on the development, validation, and clinical application of these assays, in addition to the anticipated outcomes of ongoing prospective trials. We also review data from comparative studies of these assays and from cost-effectiveness analyses relating to their clinical use.

The huge communities of residential microbes, including bacteria, viruses, Archaea, and Eukaryotes, that colonize humans are increasingly recognized as playing important roles in health and disease. A complex populous ecosystem, the human gastrointestinal (GI) tract harbors up to 1011 bacterial cells per gram of luminal content, whose collective genome, the gut metagenome, contains a vastly greater number of individual genes than the human genome. In health, the function of the microbiome might be considered to be in dynamic equilibrium with the host, exerting both local and distant effects. However, 'disequilibrium' may contribute to the emergence of disease, including malignancy. In this review, we discuss how the intestinal bacterial microbiome and in particular how an 'estrobolome,' the aggregate of enteric bacterial genes capable of metabolizing estrogens, might affect women's risk of developing postmenopausal estrogen receptor-positive breast cancer. Estrobolome composition is impacted by factors that modulate its functional activity. Exploring variations in the composition and activities of the estrobolome in healthy individuals and in women with estrogen-driven breast cancer may lead to development of microbiome-based biomarkers and future targeted interventions to attenuate cancer risk.

Recent attention has focused on the antitumor immune response in breast cancer, in particular, the role of tumor-infiltrating lymphocytes (TILs). In certain breast cancer subtypes, the presence of TILs has prognostic value and is associated with clinical outcome and improved survival. The potential predictive value of TILs has also been investigated in regard to cytotoxic and antihuman epidermal growth factor receptor 2 (HER-2) therapies, but could also serve as a selection marker for novel immunotherapies. In this article, we review the current literature on TILs in breast cancer and discuss how TILs are emerging as a promising biomarker in mediating antitumor immunity.

The standard platinum-based treatment of previously untreated advanced ovarian cancer continues to evolve because despite high response rates to first-line treatment, a majority of patients relapse. Several randomized multicenter phase III clinical trials demonstrated that intraperitoneal (IP) chemotherapy is superior to standard intravenous (IV) chemotherapy following primary optimal debulking surgery. However, the challenge of further improving efficacy and reducing toxicity remains. The underlying rationale for use of IP therapy is based on the pharmacologic principle that peritoneal tumors can be exposed to higher doses of drug for longer periods of time than can be accomplished with systemic delivery. IP drug delivery to tumors is hampered by poor drug penetration which is multifactorial. Research addressing mechanisms by which improved drug penetration or direct delivery to tumors can be achieved are key areas of interest. This review will discuss the potential role of consolidation with platinum based IP chemotherapy during interval debulking surgery following neoadjuvant chemotherapy for patients with advanced disease.

Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and aggressive variant of invasive ductal carcinoma. IMPC has been reported to account for 3-6% of all breast cancers, and these tumors have been associated with a strong tendency to invade lymphatics with early spread to regional lymph nodes. Patients and methods: We present a case of this rare type of breast cancer diagnosed in a male patient and summarize the current literature to date. Results: Review of the literature on invasive micropapillary breast carcinoma revealed 27 retrospective cohort studies and case series. Significant heterogeneity of inclusion criteria and follow up data prevented meta-analysis. Tumors with an IMPC component demonstrated an early and high rate of lymphatic metastasis compared to invasive ductal carcinoma, however, no significant association was found between IMPC and decreased overall survival. Conclusions: The IMPC data currently available indicates a strong trend towards a higher initial stage at diagnosis and possibly an increased risk of loco-regional recurrence, but remains underpowered to elucidate the prognostic effect of IMPC phenotype on survival. Further studies are warranted to establish the potential of this unique histologic phenotype to serve as a prognostic indicator and guide tumor-specific oncologic therapy