A seroma is the most frequent complication of breast cancer surgery, the etiology of which remains obscure. We reviewed our data to determine the factors related to the incidence of seroma formation in our patients. A retrospective analysis of the records of 359 consecutive patients (334 Hispanic; 93%) who underwent primary surgical therapy from January 1, 1996 to December 31, 2000, with either modified radical mastectomy (MRM) or wide local excision (WLE) and axillary lymph node dissection (ALND) was performed. In all cases, removal of the breast was performed using electrocoagulation, and sharp dissection was used in the axilla. One-eighth inch closed suction round drains were used. Early arm motion was encouraged. The seroma rate was compared to the age of the patient, the presence and number of positive axillary lymph nodes, the total number of axillary lymph nodes removed, tumor size, weight of the patient, the use of neoadjuvant chemotherapy, and the type of surgery performed. The overall seroma rate was 15.8%. Seromas occurred in 19.9% of patients undergoing MRM and in 9.2% of patients undergoing breast-conserving surgery (p=0.01). The seroma rate was not influenced by any other tested variables. All seromas were easily managed with aspiration and pressure; this technical maneuver allowed seroma resolution in all patients except one following one to six aspirations. A seroma did not delay initiation of chemotherapy. No patient developed a capsule requiring excision. In our experience, a seroma is a "necessary evil;" it will occur unpredictably in a predictable number of patients.

Cancer stem cells (CSC) are the main driving force behind cancer initiation and progression. The molecular mechanisms that regulate CSC properties are poorly understood. MicroRNAs (miRNAs) play a significant role in normal and cancer tissues. Here, we show that miRNA-125a indirectly regulates TAZ, an effector molecule in the Hippo pathway, through the leukemia inhibitory factor receptor (LIFR). The miR-125a→LIFR axis affected the homeostasis of nonmalignant and malignant breast epithelial stem cells through the Hippo signaling pathway. Inhibition of miR-125a in breast cancer cells led to a significant reduction in the CSC pool. In contrast, enhanced expression of miR-125a in nonmalignant breast epithelial cells resulted in significant expansion of the stem cell pool. Gain of function and loss of function of LIFR directly correlated with the inhibition and overexpression of miR-125a, respectively. Modulation of miR-125a led to a change in the activity of TAZ and its subcellular localization. We further demonstrated that miR-125a influenced stem cells by regulating Hippo signaling through LIFR in human primary breast cancer cells confirming the data obtained from established cell lines. We suggest that miR-125a could be a potential target against CSCs that maybe used along with the existing conventional therapies.

Growth hormone receptor (GHR) plays a vital role in breast cancer chemoresistance and metastasis but the mechanism is not fully understood. We determined if GHR could be a potential therapeutic target for estrogen receptor negative (ER−ve) breast cancer, which are highly chemoresistant and metastatic. GHR was stably knocked down in ER-ve breast cancer cells and its effect on cell proliferation, metastatic behavior, and chemosensitivity to docetaxel (DT) was assessed. Microarray analysis was performed to identify potential GHR downstream targets involved in chemoresistance. GHR and ATP-binding cassette sub-family G member 2 (ABCG2) overexpression and knockdown studies were performed to investigate the mechanism of GHR-induced chemoresistance. Patient-derived xenografts was used to study the effect of GHR and ABCG2. Immunohistochemical data was used to determine the correlation between GHR, pAKT, pmTOR, and ABCG2 expressions. GHR silencing drastically reduced the chemoresistant and metastatic behavior of ER-ve breast cancer cells and also inhibited AKT/mTOR pathway. In contrast, activation, or overexpression of GHR increased chemoresistance and metastasis by increasing the expression and promoter activity, of ABCG2. Inhibition of JAK2/STAT5 signaling repressed GHR-induced ABCG2 promoter activity and expression. Further, ABCG2 knockdown significantly increased the chemosensitivity. Finally, patient-derived xenograft studies revealed the role of GHR in chemoresistance. Overall, these findings demonstrate that targeting GHR could be a novel therapeutic approach to overcome chemoresistance and associated metastasis in aggressive ER-ve breast cancers.