In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons’ and radiologists’ attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the choice of lipid species for the interpretation of lipidomic profiles.

Background: The authors investigated aesthetic outcome and patient satisfaction in women who have undergone deep inferior epigastric artery perforator (DIEP) flap reconstruction in the setting of postmastectomy radiotherapy. Patients who underwent DIEP flap reconstruction without postmastectomy radiotherapy were the control group. Methods: Participants who had undergone DIEP flap reconstruction between September 1, 2009, and September 1, 2014, were recruited, answered the BREAST-Q, and underwent three-dimensional surface-imaging. A panel assessed the aesthetic outcome by reviewing these images. Results: One hundred sixty-seven women participated. Eighty women (48 percent) underwent immediate DIEP flap reconstruction and no postmastectomy radiotherapy; 28 (17 percent) underwent immediate DIEP flap reconstruction with postmastectomy radiotherapy; 38 (23 percent) underwent simple mastectomy, postmastectomy radiotherapy, and DIEP flap reconstruction; and 21 (13 percent) underwent mastectomy with temporizing implant, postmastectomy radiotherapy, and DIEP flap reconstruction. Median satisfaction scores were significantly different among the groups (p < 0.05). Post hoc comparison demonstrated that women who had an immediate DIEP flap reconstruction were significantly less satisfied if they had postmastectomy radiotherapy. In women requiring radiotherapy, those undergoing delayed reconstruction after a simple mastectomy were most satisfied, but there was no significant difference between the immediate DIEP flap and temporizing implant groups. Median panel scores differed among groups, being significantly higher if the immediate reconstruction was not subjected to radiotherapy. There was no significant difference in panel assessment among the three groups of women who had received radiotherapy. Conclusions: Patients who avoid having their immediate DIEP flap reconstruction irradiated are more satisfied and have better aesthetic outcome than those who undergo postmastectomy radiotherapy. In women requiring radiotherapy and who wish to have an immediate or “delayed-immediate” reconstruction, there were no significant differences in panel or patient satisfaction. Therefore, immediate DIEP flap reconstruction or mastectomy with temporizing implant then DIEP flap surgery are acceptable treatment pathways in the context of post-mastectomy radiotherapy.

Breast cancer (BC) metastasis accounts for the majority of deaths from BC. The rate of metastasis to uncommon sites is on the rise due to the more effective therapy prolonging survival and to the early detection on imaging. The evaluation of patient-reported symptoms is essential in detecting a recurrence as early as possible, which may impact survival. Hence, the knowledge of even the rare sites of BC metastasis is of paramount importance for the clinical interpretation of new symptoms in BC survivors. The term “unusual metastasis” defines a systemic failure with a frequency of ≤1% at each site and according to this unusual metastasis involve the central nervous system, secretory/endocrine organs and glands, internal organs and structures, and gynecological organs. The literature search was performed using the electronic database PubMed up to December 2018, with the following key words: {[rare(Title/Abstract)] OR [unusual(Title/Abstract)] OR [unconventional(Title/Abstract)]} AND {[metastases(Title/Abstract)] OR [metastasis(Title/Abstract)]} AND {[breast(Title/Abstract)]} AND {[cancer(Title/Abstract)] OR [tumor(Title/Abstract)] OR [tumour(Title/Abstract)] OR [neoplasm(Title/Abstract)]}. The search was limited to papers in English language. Of the 3,086 papers found, 757 were excluded as reporting animal models, 378 were not in English language, 1 was a duplicate of the same research, 1,414 did not report on BC metastases, 108 were previous review reviews on BC or tumour to tumour metastases; 428 papers were included in this review. Despite the improvements in BC management, most deaths from cancer result from metastases that are resistant to conventional therapies. In general, it is uncommon to find isolated rare metastases, the vast majority of these develops together with metastases in other sites, thus highlighting a worsening systemic disease. However, the early detection of even rare metastases represents the only chance to control the disease and prolong survival while waiting for the development of more effective systemic therapies.