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Introduction: The use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence. Methods: We conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST. Results: We identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016). Conclusion: The recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

SynopsisThis is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint.ObjectiveTo determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision.MethodA systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence.ResultsFive comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29).ConclusionThis meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.

Abstract Background A proportion of women undergoing mastectomy for breast cancer choose to undergo breast reconstruction. Evidence suggests that women’s preparedness for this surgery is low and that this may contribute to feelings of unmatched expectations and anxiety. There is substantial interest in decision-aids to remedy this. This study explores the incorporation of digitally rendered three-dimensional images into pre-operative counselling sessions as a means of enhancing patient preparedness. Methods A database of three-dimensional images was produced showing both optimal and sub-optimal aesthetic outcome, matched to participant on the basis of type of surgical reconstruction, body habitus, and skin tone. Women undergoing mastectomy for breast cancer followed by immediate reconstruction were targeted for inclusion. Participants interacted with image software during pre-operative counselling sessions by viewing, rotating, and zooming in/out to gain a more in-depth appreciation of post-operative aesthetic outcome. Semi-structured face-to-face interviews followed thereafter. Interviews were audio-recorded, transcribed, coded, and themes identified. Results Eight semi-structured interviews took place. The major emergent theme was ‘increased preparedness’ with subthemes including ‘expectation management’, ‘software interaction’, and ‘enhanced realism’. There were no prohibitively negative emotions after interacting with images. Women reported gaining ‘more of a perspective’ and feeling ‘more informed’ after viewing images. They also valued the enhanced interactivity and better appreciation of reconstructed breast symmetry that viewing three-dimensional images offered when compared to viewing two-dimensional photographs. Finally, women also commented that three-dimensional images were more realistic. Conclusions Results suggest that incorporation of three-dimensional images into pre-operative counselling sessions prior to breast reconstruction, is a fairly simple yet effective method of enhancing patient preparedness prior to surgery. Women particularly valued the ability to use the software to generate a more realistic idea of what to expect after their operation. Future work should focus on better understanding any quantifiable benefit from incorporating three-dimensional images routinely into pre-operative decision-making.

Abstract Background Many antipsychotics elevate prolactin, a hormone implicated in breast cancer aetiology however no studies have investigated antipsychotic use in patients with breast cancer. This study investigated if antipsychotic use is associated with an increased risk of cancer-specific mortality among breast cancer patients. Methods A cohort of 23,695 women newly diagnosed with a primary breast cancer between 1st January 1998 and 31st December 2012 was identified from the UK Clinical Practice Research Datalink linked to English cancer-registries and followed for until 30th September 2015. Time-dependent Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific mortality comparing use of antipsychotics with non-use, overall, and by prolactin elevating activitiy. Analyses were repeated restricting to patients with a history of severe mental illness to control for potential confounding by indication. Results In total 848 patients were prescribed an antipsychotic and of which 162 died due to their breast cancer. Compared with non-use, antipsychotic use was associated with an increased risk of breast-cancer specific mortality (HR 2.25, 95%CI 1.90–2.67), but this did not follow a dose response relation. Restricting the cohort to patients with severe mental illness attenuated the association between antipsychotic use and breast cancer-specific mortality (HR 1.11, 95%CI 0.58–2.14). Conclusions In this population-based cohort of breast cancer patients, while the use of antipsychotics was associated with increased breast cancer-specific mortality, there was a lack of a dose response, and importantly null associations were observed in patients with severe mental illness, suggesting the observed association is likely a result of confounding by indication. This study provides an exemplar of confounding by indication, highlighting the importance of consideration of this important bias in studies of drug effects in cancer patients.

Abstract Background Optimising breast cancer treatment remains a challenge. Resistance to therapy is a major problem in both ER- and ER+ breast cancer. Tumour recurrence after chemotherapy and/or targeted therapy leads to more aggressive tumours with enhanced metastatic ability. Self-renewing cancer stem cells (CSCs) have been implicated in treatment resistance, recurrence and the development of metastatic disease. Methods In this study, we utilised in vitro, in vivo and ex vivo breast cancer models using ER+ MCF-7 and ER- MDA-MB-231 cells, as well as solid and metastatic breast cancer patient samples, to interrogate the effects of FKBPL and its peptide therapeutics on metastasis, endocrine therapy resistant CSCs and DLL4 and Notch4 expression. The effects of FKBPL overexpression or peptide treatment were assessed using a t-test or one-way ANOVA with Dunnett’s multiple comparison test. Results We demonstrated that FKBPL overexpression or treatment with FKBPL-based therapeutics (AD-01, pre-clinical peptide /ALM201, clinical peptide) inhibit i) CSCs in both ER+ and ER- breast cancer, ii) cancer metastasis in a triple negative breast cancer metastasis model and iii) endocrine therapy resistant CSCs in ER+ breast cancer, via modulation of the DLL4 and Notch4 protein and/or mRNA expression. AD-01 was effective at reducing triple negative MDA-MB-231 breast cancer cell migration (n ≥ 3, p

Aromatase inhibitors are used to treat oestrogen receptor positive breast cancers but the molecular basis for the response of patients is unclear. Here, the authors use samples from an aromatase inhibitor clinical trial and show that tumours from poor responders have more mutations than good responders and also more frequently harbour p53 mutations.

Abstract Multifocal (MF)/multicentric (MC) breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ~10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort of BRCA1/2 mutation carriers with breast cancer from Northern Ireland via cross‐sectional analysis. Data from 211 women with BRCA1/2 mutations (BRCA1‐91, BRCA2‐120) and breast cancer were collected including age, tumour focality, size, type, grade and receptor profile. The prevalence of multifocality/multicentricity within this group was 25% but, within subgroups, prevalence amongst BRCA2 carriers was more than double that of BRCA1 carriers (p = 0.001). Women affected by MF/MC tumours had proportionately higher oestrogen receptor positivity (p = 0.001) and lower triple negativity (p = 0.004). These observations are likely to be driven by the higher BRCA2 mutation prevalence observed within this cohort. The odds of a BRCA2 carrier developing MF/MC cancer were almost four‐fold higher than a BRCA1 carrier (odds ratio: 3.71, CI: 1.77–7.78, p = 0.001). These findings were subsequently validated in a second, large independent cohort of patients with BRCA‐associated breast cancers from a UK‐wide multicentre study. This confirmed a significantly higher prevalence of MF/MC tumours amongst BRCA2 mutation carriers compared with BRCA1 mutation carriers. This has important implications for clinicians involved in the treatment of BRCA2‐associated breast cancer, both in the diagnostic process, in ensuring that tumour focality is adequately assessed to facilitate treatment decision‐making, and for breast surgeons, particularly if breast conserving surgery is being considered as a treatment option for these patients.

INTRODUCTION:Current evidence suggests that patients who have latissimus dorsi (LD) breast reconstruction following mastectomy for breast cancer can experience long-term shoulder dysfunction. However, as there is no standardised assessment or follow-up period within the literature, findings are conflicting. This research aimed to investigate the impact on daily living of immediate and delayed LD breast reconstruction in women following mastectomy for breast cancer. METHODS:Both qualitative and quantitative methods of enquiry were used. A focus group study explored the musculoskeletal consequences of surgery as perceived by the women (n = 15) and their healthcare professionals (n = 11). A questionnaire survey was administered (n = 159), including a range of outcome measures to quantify both the physical and psychosocial impact of LD breast reconstruction. Dyad interviews were also conducted in order to determine the impact of surgery on function and activities of daily living (ADL) from the woman's perspective and that of her significant other (n = 8). RESULTS:The qualitative studies highlighted a lack of preparedness and unrealistic expectations regarding functional recovery among women and their significant others'. Post-surgery it was apparent that women weighed up reduced shoulder function against survival, demonstrating resilience in their approach to coping with this adaptive way of living. The survey identified low to moderate effect on the outcomes assessed (n = 159), however, node removal significantly impacted certain aspects of quality of life (p