Breast cancer-related lymphedema (BCRL) is a devastating potential complication of axillary lymphadenectomy and radiotherapy. Several effective surgical treatment measures now exist, including lymphaticovenicular anastomosis (LVA), vascularized lymph node transplant (VLNT), and vascularized lymph vessel transplant (VLVT) for fluid-predominant disease, and liposuction and radical excision for solid-predominant disease. Super-microsurgical LVA is of particular interest, owing to its minimally invasive nature and highly favorable outcomes in the hands of experienced supermicrosurgeons. As LVA techniques are refined and improved, interest is rising in utilizing it to prevent the manifestation of disease in the first place. Lymphatic microsurgical preventive healing approach (LYMPHA), also known as immediate lymphatic reconstruction (ILR), is the most widely used approach. It involves performing axillary LVA immediately following axillary lymphadenectomy. While preliminary results are favorable, the high-pressure proximal axillary venous branches used in ILR and the site’s vulnerability to damage from radiotherapy endanger the long-term patency of these anastomoses. Moreover, a theoretical oncologic concern exists regarding creating a direct conduit for the remaining malignant cells in the axilla into the circulation. Finally, coordinating ILR with axillary lymphadenectomy creates significant logistical challenges. Delayed, distally-based LVA (DD-LVA) has emerged as an alternative method that avoids these issues. This article presents an overview of the development of preemptive lymphatic reconstruction, and the senior author’s approach to the novel technique of DD-LVA.

Background: Almost all deaths from breast cancer are due to metastasis. People living with metastatic breast cancer (MBC) and their loved ones have been concerned about the lack of research progress. The purposes of this paper were to analyze breast cancer research spending in Canada, and to evaluate whether MBC research was aligned with patient priorities. The results from the MBC Priority Setting Partnership (MBC PSP) were used as an approximation of patient priorities. Methods: The data source was the Canadian Cancer Research Survey. MBC projects were identified and mapped to the patient priorities.Results: This analysis found that 18% of breast cancer research investment was directed to MBC, with a large proportion of this research investment focused on the biology of metastasis. Four of the top 10 MBC PSP priorities had not been addressed: optimal sequence of therapy, role of continuous versus intermittent treatment, benefits of early palliative care, and best methods for patient education. Conclusion: These figures provide a baseline from which any increases in MBC research and improved alignment to patient priorities can be measured. A cooperative effort by funders, researchers, patients, caregivers, and health care providers is needed to address research gaps.

Background: Tabebuia avellanedae (TA) is a tree that is indigenous to the Amazon rainforest. The experiments in the present study were designed to examine the inhibitory effects of TA, and to identify mechanistic targets for its efficacy in the estrogen-α receptor (ER-α), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) negative MDA-MB-231 model for triple negative breast cancer (TNBC). Methods: Non-fractionated aqueous extract from the inner bark of TA was used in the experiments. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression, and expressions of relevant regulatory proteins represented quantitative end points. Results: Long-term treatment for 21 days with the maximum cytostatic concentration of 2.5% TA resulted in a 90% inhibition (P=0.014) in AI colony number. Short-term treatment for 2 days with 1.0% TA (IC50) resulted in about a 1.3 fold increase (P=0.014) in G1: S+G2/M ratio, about a 1.48 fold increase (P=0.010) in the sub G0 (apoptotic) cells and about a 3.2 fold increase (P=0.014) in the pro-apoptotic caspase 3/7 activity. Mechanistically, the short-term treatment with 2.5% TA decreased Cyclin D1 expression by about 83.3%, and pRB expression by about 73.3%. Conclusion: TNBC represents an aggressive cancer notable for its resistance to conventional and targeted therapy. Non-toxic natural substances may represent testable alternatives. This study identifies potential mechanistic leads for TA as a novel naturally occurring testable alternative for secondary prevention/therapy of TNBC, and validates a novel mechanistic approach to evaluate efficacious non-toxic phytochemicals and herbs as testable alternatives against therapy resistant breast cancer.

Background: In this work a new method for the Mean Glandular Dose evaluation in digital breast tomosynthesis (DBT) is presented. Methods: Starting from the experimental-based dosimetric index, 2ABD, which represents the average absorbed breast dose, the mean glandular dose MGD2ABD was calculated using a conversion function of glandularity f(G), obtained through the use of Monte Carlo simulations.Results: f(G) was computed for a 4.5 cm thick breast: from its value MGD2ABD for different compressed breast thicknesses and glandularities was obtained. The comparison between MGD2ABD estimates and the dosimetric index provided in the current dosimetry protocols, following the Dance's approach, MGDDance, showed a good agreement (<10%) for all the analyzed breast thicknesses and glandularities. Conclusion: The strength of the proposed method can be considered an accurate mean glandular dose assessment starting from few and accessible parameters, reported in the header DICOM of each DBT exam.

Background: The aim of the present study was to investigate the added value of F-18 fludeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) compared with conventional imaging modalities for the evaluation of locoregional and distant sites of recurrence in breast cancer patients. Methods: From May 2013 to September 2016, 109 patients with suspected recurrent breast cancer who underwent conventional imaging and F-18 FDG PET/CT with an interval of 6 weeks were consecutively enrolled (mean age: 52.66 years; range: 29?79). Histopathologic results and clinical follow up based on the gold-standard imaging modality or serial imaging were considered as the reference for verification of F-18 FDG PET/CT findings. Results: Of 109 patients, 81 were found to have at least one site of recurrence (74.31%). Local recurrence was correctly identified in 32/32 patients following PET/CT, which was higher than that on conventional imaging (20/32, 62.5%). PET/CT detected 27 additional nodal metastases compared with conventional imaging (59 vs. 32, 45.76%), most frequently in the hilar/mediastinal region (n=27), followed by the supraclavicular lymph nodes (n=20, 62.5%), internal mammary lymph nodes (n=6, 18.77%), and axillary basin (n=6, 18.77%). Additional sites of distant metastasis were identified in 41 patients (37.61%) following F-18 FDG PET/CT imaging, 48.78% of which were localized in the skeletal system (n=20), 21.95% in the liver (n=9), 12.19% in the lungs (n=5), 12.19% in the brain (n=5), and 4.87% in the adrenal glands (n=2). Conclusion: F-18 FDG PET/CT serves as a useful supplement to conventional imaging techniques by identifying additional sites of disease recurrence in patients with breast cancer, which may change the preferred treatment strategy, particularly in regions that are not routinely evaluated by conventional imaging.

Background: The reactive oxygen species (ROS) generated in the biological systems play an important role in pathological conditions and specific normal cellular processes, such as signaling pathways and drug sensitivity. Methods: Intracellular ROS was determined using (2'-7'dichlorofluorescin diacetate) DCFH-DA fluorimetric probe, malondialdehyde as lipid peroxidation index detected by the Thiobarbituric acid reactive substances method. Cells' protein carbonyl contents were assessed with 2,4-Dinitrophenylhydrazine (DNPH) derivatization spectrophotometrically at 360-385 nm. Results: The oxidative stress induces ROS (p?0.05), MDA (Malondialdehyde) (p?0.05), and protein carbonylation (p?0.01) was significantly higher in HER2-positive BT-474, SK-BR-3, and MDA-MB-453 compared to the HER2-negative MDA-MB-231 and MCF-7 cell lines. Conclusion: We hypothesized that increased oxidative stress in HER2-positive cell lines is due to the oncogenic function of the HER2 and PI3K/Akt signaling activation, resulting in glycolysis induction. It is assumed that HER2-positive cell lines with high ROS levels are more vulnerable to further damage by increased ROS levels induced by pro-oxidant anticancer agents.

Background: The spasm and/or contracture of the pectoralis major contribute to the post-breast surgery pain. The purpose of our study was to evaluate changes in the post-breast surgical pain syndrome after the infiltration of botulinum-toxin type-A (BTX-A), according to the type of surgery and the reconstitution of the botulinum-toxin. Methods: This retrospective study was conducted at the Rehabilitation Department with two cohorts: BTX-A reconstituted with saline solution (SS group) or with levobupivacaine (LV group). Data about pectoralis major contracture and pain (global, at night, at rest and during activity) before the infiltration and six weeks after that were collected from the medical records and compared between SS and LV groups, and between conservative breast surgery and mastectomy cases. Results: in the study, 48 women aged 53.3 (±11.10) years were included, with 26 (54.2%) in SS group and 22 (45.8%) in LV group. There were no differences between both groups except transitory paresis (3.8% vs 22.7%; P=0.022). In all patients, baseline circumstances vs after 6 weeks were compared, and we found significant differences in contracture (1,77 (±0.57) vs 0.97 (±0.79)), VAS global (5.45 (±1.92) vs 3.46 (±2.48)), VAS night (3.17 (±3.13) vs 1.61 (±2.29)), VAS rest (2.14 (±2.56) vs 1.21 (±1.98)) and VAS activity (4.31 (±2.55) vs 2.78 (±2.58)). We found higher improvements in the breast conservative surgery. Conclusion: A significant lower pain and contracture after BTX-A injection in the pectoralis major was observed, but its reconstitution in levobupivacaine may not be an effective method to increase the analgesic effect. There were higher improvements in the breast conservative surgery than in the mastectomy.

Background: Pathological complete response (pCR) following neoadjuvant systemic treatment(NAST) for breast cancer is associated with improved prognosis; however, a large proportion of patients have residual disease. Oestrogen Receptor (ER) and HER2 status have been shown to affect likelihood of achieving pCR, with ER positive tumors being more treatment resistant. As hormone receptor status is heterogeneous within tumors, we postulated that, following NAST, ER expression would change in patients with residual disease, as the ER negative cells within the tumor are more treatment sensitive. Methods: A retrospective case series of patients treated with NAST prior to surgery at our institution was conducted. Information collected included demographic data, tumor grade, hormone receptor and HER2 status both before and after treatment, and pCR rates.Results: Of the 44 patients included, half achieved pCR. HER2 status (P=0.01), and subtype (P=0.008) were significantly associated with pCR. HER2 positive/ER negative tumors were most likely to undergo pCR. Approximately 80% of residual disease was ER positive. Higher levels of ER expression were also associated with increasing residual cancer burden (RCB) class (P=0.037). There was no trend between change in ER or HER2 expression following NAST. Median change in ER expression was 80% to 90% (P= 0.89), HER2 intensity changed from 3.0 to 2.2 (P=0.67) following treatment. Conclusion: Consistent with the literature, we have shown associations between ER and HER2 status and PCR, and between ER expression and residual disease burden. Our study was not able to demonstrate a significant trend in hormone and HER2 expression.

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Background: Phyllodes tumors are rare fibroepithelial neoplasm of the breast, representing 0.3 to 0.5% of all female breast neoplasms. The term ‘‘phyllodes tumor” by the World Health Organization (WHO) categorizes it into benign, borderline, and malignant tumors based on histopathological characteristics. Malignant phyllodes tumor is an uncommon but aggressive breast malignancy and accounts for approximately 25% of all phyllodes tumors.Case Presentation: A 23-year-old female patient Gravida 0 Para 0, previously healthy, with no family history of breast or ovarian cancer was referred to our institution for managing a right breast mass increasing in size over a period of 1 month associated with reddish-brown discoloration of the skin. Breast ultrasound showed an isodense oval mass measuring approximately 16x14x12cm in the right lower outer quadrant of her breast. Core biopsy and FNA done revealed a low grade phyllodes tumor. MRI of breasts showed a huge mass of the right breast occupying all quadrants, measuring 15x14.5 cm in its greatest axis with involvement of the pectoralis major muscle, with no evidence of suspicious axillary lymphadenopathy. Distant metastatic work-up with CT scan of chest abdomen and pelvis and a PET scan did not show distant metastasis. Hence, the patient underwent right total mastectomy with a final pathology compatible with malignant phyllodes tumor. She is on regular follow up and 18 months post-surgery is still disease free.Conclusion: Management of malignant phyllodes tumor remains debatable, especially when it comes to the effect of adjuvant radiotherapy and chemotherapy. From a surgical perspective, whether phyllodes tumors should be considered as epithelial breast cancers or as soft tissue sarcoma is another debate. On the other hand, although challenging, accurate identification of phyllodes tumor initially may aid in decreased recurrence.