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Concept A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. This open-label phase IIIII trial randomised HER2-negative MBC patients 11 to either 6 cycles of three-weekly cabazitaxel (25 mgm 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87 80%CI 0.70-1.08, P 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00 95%CI 0.69-1.45, P 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09 95%CI 0.68-1.75, P 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (0.05 95%CI 0.004-0.09, P 0.03) and visual analogue scale score (7.7 95%CI 3.1-12.3, P 0.001) were higher in cabazitaxel vs paclitaxel. Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Contribution of endocrine therapy in oestrogen receptor-positive pT1a-b breast cancer Results of a retrospective study.

Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. Our retrospective observational study included 5545 patients with pT1a-b ER-positive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. Most patients (80.3% 4453) received ET and-when compared to those without ET-experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR 1.275, p 0.047, 95% CI1.003-1.620) but not OS or RFS in all patients, while in 2363 patients with pT1a-b ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR 1.502, p 0.049, 95% CI1.001-2.252), but not OS (HR 1.361, p 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours.

A yes-associated protein 1-Notch1 positive feedback loop promotes breast cancer lung metastasis by attenuating the Bone morphogenetic protein 4-SMAD family member 15 signaling.

The Notch1(Notch1 receptor 1) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the β-TrCP-mediated degradation, thereby, forming a YAP1- JAG1Notch1 positive feedback loop in the breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD15 signaling. In vivo, the YAP1- JAG1Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD15 signaling.

Resveratrol in breast cancer treatment from cellular effects to molecular mechanisms of action.

Breast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, andor doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RESs promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES.

Organoids from patient biopsy samples can predict the response of BC patients to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy has been widely used in locally advanced and inflammatory breast cancer. Generally, complete pathological response after neoadjuvant chemotherapy treatment predicts survival. Studies have shown that patient-derived organoids can be used in cancer research and drug development. Therefore, we aimed to generate a living organoid biobank from biopsy samples to predict the response of patients to neoadjuvant chemotherapy. We generated a living organoid biobank from locally advanced breast cancer patients receiving neoadjuvant chemotherapy. When the patient received neoadjuvant chemotherapy, the organoids were treated with similar drugs, thereby simulating the situation of the patient receiving treatment. We successfully constructed organoids from breast cancer biopsies, demonstrating that organoids can be generated from a small sample of tissue. The phenotype of breast cancer organoid often agreed with the original breast cancer according to the blinded histopathological analysis of HE stain tissue and organoid sections. In addition, our data confirm that the patients response to chemotherapy closely matches the organoids response to drugs. Our data indicate that patient-derived organoids can be used to predict the clinical response of breast cancer patients to neoadjuvant chemotherapy

Breast Density and Breast Cancer Screening with Digital Breast Tomosynthesis A TOSYMA Trial Subanalysis.

Background Digital breast tomosynthesis (DBT) plus synthesized mammography (SM) reduces the diagnostic pitfalls of tissue superimposition, which is a limitation of digital mammography (DM). Purpose To compare the invasive breast cancer detection rate (iCDR) of DBT plus SM versus DM screening for different breast density categories. Materials and Methods An exploratory subanalysis of the TOmosynthesis plus SYnthesized MAmmography (TOSYMA) study, a randomized, controlled, multicenter, parallel-group trial recruited within the German mammography screening program from July 2018 to December 2020. Women aged 50-69 years were randomly assigned (11) to DBT plus SM or DM screening examination. Breast density categories A-D were visually assessed according to the Breast Imaging Reporting and Data System Atlas. Exploratory analyses were performed of the iCDR in both study arms and stratified by breast density, and odds ratios and 95% CIs were determined. Results A total of 49 762 women allocated to DBT plus SM and 49 796 allocated to DM (median age, 57 years IQR, 53-62 years) were included. In the DM arm, the iCDR was 3.6 per 1000 screening examinations in category A (almost entirely fatty) (16 of 4475 screenings), 4.3 in category B (102 of 23 534 screenings), 6.1 in category C (116 of 19 051 screenings), and 2.3 in category D (extremely dense breasts) (six of 2629 screenings). The iCDR in the DBT plus SM arm was 2.7 per 1000 screening examinations in category A (12 of 4439 screenings), 6.9 in category B (154 of 22 328 screenings), 8.3 in category C (156 of 18 772 screenings), and 8.1 in category D (32 of 3940 screenings). The odds ratio for DM versus DBT plus SM in category D was 3.8 (95% CI 1.5, 11.1). The invasive cancers detected with DBT plus SM were most often grade 2 tumors in category C, it was 58% (91 of 156 invasive cancers), and in category D, it was 47% (15 of 32 invasive cancers). Conclusion The TOmosynthesis plus SYnthesized MAmmography trial revealed higher invasive cancer detection rates with digital breast tomosynthesis plus synthesized mammography than digital mammography in dense breasts, relatively and absolutely most marked among women with extremely dense breasts. ClinicalTrials.gov registration no. NCT03377036 © RSNA, 2022

Clinical Implications and Management of Non-BIA-ALCL Breast Implant Capsular Pathology.

The breast implant capsule is a dynamic structure that forms following the implantation of a device. Although normally benign, increased awareness of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) highlights that disease may arise from the capsule. BIA-ALCL presents as a late seroma or mass but explains few of the late seromas found in breast implant patients. To date, many of these seromas lack a clear cause and are often described as idiopathic. Several benign and malignant breast implant capsular diseases can cause a late seroma or mass, including breast implant-associated squamous cell carcinoma. Similar to early reports of BIA-ALCL, these conditions are rare and largely limited to case reports or series. The purpose of this special topic is to present a narrative review highlighting capsular abnormalities that contribute to the formation of late seroma or mass in an attempt to broaden the differential diagnosis and help plastic surgeons identify the cause. Specifically, we review the presentation and management of BIA-ALCL, synovial metaplasia, capsular epithelialization, late hematoma, double capsule, breast cancer, squamous cell carcinoma, mesenchymal tumor, and B-cell lymphoma. Although rare, plastic surgeons should consider these capsular conditions as causes of late seromas and masses. Usually, these conditions may be diagnosed by following the National Comprehensive Cancer Network screening guidelines for BIA-ALCL. Thorough evaluation and workup of late seromas and masses may lead to improved characterization of these rare breast implant capsular conditions and improve our understanding of their pathophysiology and management.

Fold Flaps to the Rescue in Postmastectomy Breast Reconstruction.

Ischemic complications following postmastectomy breast reconstruction are not uncommon and can lead to reconstructive failure, especially with implant reconstruction. The authors propose a simple local flap for management of such complications. This flap is easily raised from the upper abdomen or lateral chest as a medially or laterally based fasciocutaneous flap, and the donor site is hidden in the inframammary or lateral mammary fold. The authors present a case series of these fold flaps that were used to manage complications following implant-based breast reconstruction. All patients between 2007 and 2021 who underwent a fold flap for breast reconstruction salvage were queried from a prospectively maintained database. Demographic variables, clinical factors, and surgical details were analyzed. Outcomes assessed included complications, appropriate wound healing, and reconstructive salvage. Fourteen patients underwent thoracoepigastric or thoracoabdominal fold flaps following breast reconstruction for soft-tissue coverage with an underlying prosthesis. The mean age was 54 years, mean body mass index was 30 kgm 2 , and mean follow-up duration was 18.5 months. Fold flap indications included mastectomy skin flap necrosis ( n 9), infection ( n 4), and chronic seroma ( n 1). Eleven reconstructions (79%) were salvaged and three (21%) required eventual prosthesis explantation secondary to infection or delayed wound healing. Fold flaps are a reliable option for managing ischemic complications following postmastectomy breast reconstruction. The benefits include improved soft-tissue coverage with a high salvage rate. These flaps are simple to raise, and their donor site is concealed within the folds. Furthermore, they provide a reliable early option to manage complications and potentially prevent reconstructive failure. Therapeutic, IV.

The Lumbar Artery Perforator Flap in Breast Reconstruction.

The lumbar artery perforator flap is a valuable alternative in breast reconstruction whenever the deep inferior epigastric perforator flap is not feasible because of insufficient or unavailable abdominal tissue. The advantage is the ideal shape and consistency of the flap, in addition to the option to perform a nerve anastomosis with the cluneal nerve. The anatomy is consistent, but there are some technical issues related to the short perforator and difficult surgical exposure in the lower back region. The inclusion of a vascular interposition graft improved the authors results and facilitated their technical challenges and final inset of the flap. These videos guide the surgeon through the different steps involved in a breast reconstruction with the lumbar artery perforator flap.

Sensory Restoration in Abdominally Based Free Flaps for Breast Reconstruction Using Nerve Allograft.

Neurotization in breast reconstruction can be performed with the aid of nerve grafts and conduits to decrease the tedious dissection and overcome size mismatch. However, there has yet to be a formal analysis of this approach. The goal of this study was to evaluate sensory recovery after neurotized abdominally based free flaps for breast reconstruction using the authors novel technique and analyze factors that could affect sensory recovery. A novel technique using processed nerve allograft in combination with a nerve conduit was used. Dynamic and static sensation recovery tests were performed in patients who underwent neurotized or nonneurotized abdominally based free flap reconstructions. Demographics, surgical details, and complications were analyzed. Statistical analyses were performed using chi-square and Mann-Whitney tests. Fifty patients (78 breasts) were analyzed 60 breasts with neurotized reconstruction and 18 breasts without. For patients with more than 12 months of follow-up, the neurotized cohort demonstrated improved dynamic tests compared to the nonneurotized cohort (38 ± 21.69 versus 56.17 ± 20.8, respectively P 0.014). Factors associated with decreased sensory return in patients who underwent neurotized reconstruction were diabetes, higher body mass index, skin-sparing mastectomy, higher American Society of Anesthesiologists class, history of radiation therapy, or history of hormonal therapy. This is the first study to report on outcomes of neurotized autologous breast reconstruction using a nerve graft and conduit technique. The authors approach resulted in improved sensory outcomes compared to those in patients who did not undergo sensory reconstruction. Importantly, factors that can interfere with sensory recovery were identified. Therapeutic, III.

StatPearls

Breast lumps or masses are very common, particularly among women of reproductive age. Over 25% of women are affected by breast disease in their lifetime, and the vast majority of these cases will present initially as a new breast mass in the primary care setting. Breast masses have a wide range of causes, from physiological adenosis to highly aggressive malignancy. Although the majority of breast masses present in adult women, children and men can also be affected. Indeed, male breast cancer is a well-documented condition and requires a considered index of suspicion for its timely diagnosis and intervention. Breast cancer is the most common type of cancer in women worldwide, with an incidence of approximately 12%, and therefore although the vast majority of breast lumps are benign, a thorough and structured approach is required in all cases. In general, the approach should follow the triple-assessment pathway of clinical examination, radiological imaging, and pathology analysis. Such an approach will be described in this article, with examples throughout of the common breast pathologies encountered.

PDQ Cancer Information Summaries

This PDQ cancer information summary has current information about the treatment of adult breast cancer. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (Date Last Modified) is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.

PDQ Cancer Information Summaries

This PDQ cancer information summary has current information about breast cancer screening. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (Date Last Modified) is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Screening and Prevention Editorial Board.