Targeting Metabolic Adaptations in the Breast Cancer-Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy.

Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant as standard of care. Yet, among such patients, metastasis in liver is associated with reduced overall survival compared with other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER-targeting agents remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+ liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+ tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+ tumor metastatic sites (liver, lung, and bone), and in vivo, in liver and lung metastasis mouse models. ER+ metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to fulvestrant. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of fulvestrant treatment to reduce the metastatic burden. Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. IMPLICATIONS: These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.

Is restaging transurethral resection necessary in patients with non-muscle invasive bladder cancer and limited lamina propria invasion?

OBJECTIVES: To evaluate the influence of lamina propria invasion type at initial transurethral resection (TUR) on restaging pathology. MATERIALS AND METHODS: We reviewed prospectively maintained records of all patients with a high-grade pT1 nonmuscle invasive bladder cancer who underwent both initial and restaging TUR within 6 weeks at our center between 2001 and 2016. The pathology of second TUR specimens was analyzed with regard to the characteristics of lamina propria invasion found at initial resection. RESULTS: We included 198 patients, with a median age of 70 years (interquartile range: 63-79). Muscle was present in the initial TUR specimen in 107 patients (54%). Pathology restaging was pT0 in 73 patients (37%), pTis in 44 (22%), pTa in 27 (14%), pT1 in 50 (25%), and pT2 in 4 (2%). Eighty-seven patients (44%) had tumors with minimal lamina propria invasion at initial TUR: 53 specimens (27%) had focal invasion (few malignant cells in the lamina propria); 15 specimens (7.6%) had superficial invasion (invasion of the lamina propria to the level of the muscularis mucosae [T1a]); and 19 specimens (10%) had multifocal superficial invasion (multiple areas of T1a). Of the patients with minimal lamina propria invasion, residual disease was found in 54 patients (62%). However, none of those patients had T2 disease. CONCLUSIONS: A significant number of patients with T1 tumors have residual disease at restaging TUR as do patients with minimal lamina propria invasion. The extent of T1 invasion does not eliminate the need for repeat TUR.