Androgen receptor expression and outcome of neoadjuvant chemotherapy in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancers (TNBC) include a heterogeneous group of diseases, characterized by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC that shows an overexpression of the androgen receptor (AR) defines the phenotype known as "luminal androgen receptor" (LAR), while the absence of the AR defines a "quadruple negative breast cancer" (QNBC). Several reports have associated AR positivity with a lower response to neoadjuvant chemotherapy (NAC), while divergent data have been reported about the impact of AR positivity on survival. The aim of this study was to retrospectively review our series of patients with TNBC tested for AR and submitted to NAC and compare pathologic complete response (pCR) rates in patients with a LAR phenotype or with QNBC. PATIENTS AND METHODS: The clinical records of all patients with TNBC tested for AR that underwent NAC at our Institution from January 1, 2015 to June 30, 2019 were reviewed. Histopathological features as well as ER, PgR, Ki67, HER2 values, clinical and pathological stage, and results of BRCA gene expression profiling were registered for all patients. RESULTS: Of the 145 TNBC patients treated by NAC, 20 (13.8%) had a LAR phenotype, while 125 (86.2%) had a QNBC. Overall, a pCR was achieved in 52 patients (35.8%). Patients with LAR phenotype had a lower rate of pCR as compared to patients with QNBC phenotype (25% vs. 37.6%). High Ki67 values (>50%) were observed less frequently in patients with a LAR phenotype (50% vs. 76.8% in QNBC). CONCLUSIONS: Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.

New trends in breast cancer surgery: a therapeutic approach increasingly efficacy and respectful of the patient.

The surgical management of breast cancer has undergone continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long, but constant, despite the controversies that appeared every time a new procedure came to light. Today, the aesthetic satisfaction of breast cancer patients coupled with the oncological safety is the goal of the modern breast surgeon. Breast-conserving surgery with adjuvant radiotherapy is considered the gold standard approach for patients with early stage breast cancer and the recent introduction of "oncoplastic techniques" has furtherly increased the use of breast-conserving procedures. Mastectomy remains a valid surgical alternative in selected cases and is usually associated with immediate reconstructive procedures. New surgical procedures called "conservative mastectomies" are emerging as techniques that combine oncological safety and cosmesis by entirely removing the breast parenchyma sparing the breast skin and nipple-areola complex. Staging of the axilla has also gradually evolved toward less aggressive approaches with the adoption of sentinel node biopsy and new therapeutic strategies are emerging in patients with a pathological positivity in sentinel lymph node biopsy. The present work will highlight the new surgical treatment options increasingly efficacy and respectful of breast cancer patients.

Stearoyl-CoA desaturase 1 and paracrine diffusible signals have a major role in the promotion of breast cancer cell migration induced by cancer-associated fibroblasts.

BACKGROUND: Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration. METHODS: Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-ß or basic fibroblast growth factor. RESULTS: A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors. CONCLUSION: These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.

Update on oncoplastic breast surgery.

Oncoplastic surgery of the breast (OPS) has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic surgical procedures associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. Thanks to oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adequate tumor clearance. As OPS continues to gain acceptance and diffusion, an optimal and systematic approach to these techniques is becoming increasingly necessary. This article has the aim to review the essential principles and techniques associated with oncoplastic surgery, based on the data acquired through an extensive search of the PUBMED and MEDLINE database for articles published using the key words "breast cancer oncoplastic surgery". This review analyzes possible the advantages", classifications, indications, and the criteria for a proper selection of oncoplastic techniques to facilitate one's ability to master these procedures and make OPS a safe and an effective procedure.

The role of oxidized regenerate cellulose to prevent cosmetic defects in oncoplastic breast surgery.

BACKGROUND: Breast conserving surgery (BCS) combined with postoperative radiotherapy has become the gold standard of locoregional treatment for the majority of patients with early-stage breast cancer, offering equivalent survival and improved body image and lifestyle scores as compared to mastectomy. In an attempt to optimize the oncologic safety and cosmetic results of BCS, oncoplastic procedures (OPP) have been introduced in recent years combining the best principles of surgical oncology with those of plastic surgery. However, even with the use of OPP, cosmetic outcomes may result unsatisfying when a large volume of parenchyma has to be removed, particularly in small-medium size breasts. AIM: The aim of this article is to report our preliminary results with the use of oxidized regenerate cellulose (ORC) (Tabotamp fibrillar, Johnson & Johnson; Ethicon, USA) as an agent to prevent cosmetic defects in patients undergoing OPP for breast cancer and to analyze the technical refinements that can enhance its efficacy in optimizing cosmetic defects. METHODS: Different OPP are selected based on the location and size of the tumor as well as volume and shape of the breast. After excision of the tumor, glandular flaps are created by dissection of the residual parenchyma from the pectoralis and serratus muscles and from the skin. After careful haemostasis, five layers of ORC are positioned on the pectoralis major in the residual cavity and covered by advancement of the glandular flaps. Two additional layers of ORC are positioned above the flaps and covered by cutaneous-subcutaenous flaps. RESULTS: The use of ORC after OPP has shown promising preliminary results, indicating a good tolerability and positive effects on cosmesis. CONCLUSIONS: This simple and reliable surgical technique may allow not only to reduce the rate of post-operative bleeding and infection at the surgical site but also to improve cosmetic results.

Conservative treatment of the central breast cancer with nipple-areolar resection: an alternative oncoplastic technique.

Conservative surgery with radiation therapy is the standard treatment for early-stage breast cancer. Nevertheless, the patients with subareolar breast cancer have been often excluded from breast-conserving surgery and treated with mastectomy because of the unacceptable cosmetic effect associated with the resection of the nipple-areola complex (NAC), as well as oncologic concerns about multicentricity or multifocality associated with these tumours. We show a conservative "oncoplastic technique" in which the resection of the central portion of the breast, including the NAC, can allow a wide excision of the tumour with uninvolved margins of resection and good cosmetic results.

Conservative and radical oncoplastic approches in the surgical treatment of breast cancer.

In the attempt to optimise the balance between the risk of local recurrence and the cosmetic outcomes in breast surgery, new surgical procedures, so-called oncoplastic techniques, have been introduced in recent years. The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage of the oncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: excision of the tumour by reduction mammoplasty, tumour excision followed by remodelling mammoplasty, mastectomy with immediate reconstruction of the breast and partial mastectomy with reconstruction. Careful patient selection and preoperative planning are key components for the success of any oncoplastic operation for breast cancer. Accurate preoperative evaluation of the clinical and biological features of the tumour as well as of the morphological aspects of the breast allow the surgeon to make a decision if a conservative or radical approach is preferable and select the most effective oncoplastic surgical technique. In this review we summarise the indications, advantages and limitations of several oncoplastic procedures.

Update in the treatment of locally advanced breast cancer: a multidisciplinary approach.

Locally advanced breast cancer represents a wide variety of neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. According to the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. The clinical treatment of locally advanced breast cancer is complex and should be tailored to the individual patient. In this paper we discuss the options of management of locally advanced breast cancer, focusing on a multidisciplinary approach through a combined-modality care involving surgery, radiotherapy and systemic therapy.

Management of locally advanced breast cancer. Mini-review.

The term locally advanced breast cancer (LABC) encompasses a heterogeneous group of breast neoplasms; in the last revision of the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. LABC constitutes up to 20% of breast cancer in medically underserved populations in the United States and up to 75% of breast cancers in developing countries. The prognosis depends on tumor size, extent of lymph node involvement, and the presence or absence of an inflammatory component. The clinical management of LABC is complex and should be tailored to the individual patient. However, a multidisciplinary approach is always recommended combining surgery, radiotherapy and systemic therapy (chemotherapy and/or hormone therapy). In this paper, we discuss the possible options in the management of operable (stage IIIA) and inoperable (stage IIIB-IIIC) LABC.