Faculty Bibliography

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

BACKGROUND: Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes. METHODS: Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials. RESULTS: Ten patients that were confirmed to have BRCA mutations-all with high-grade and stages IIC to IV disease-survived a median of 10 years (range: 4-18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively. CONCLUSIONS: This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.