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[Abstract] Introduction. Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A. Methods. 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed. Results. Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59–35.3). Conclusions. Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity. Instituto de Salud Carlos III; RD06/0014/002 Instituto de Salud Carlos III; RD12/0042/0067

© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Simple breast conservation surgery (sBCS) has technically advanced onto oncoplastic breast procedures (OBP) to avoid mastectomy and improve breast cancer patients' psychosocial well-being and cosmetic outcome. Although OBP are time-consuming and expensive, we are witnessing an increase in their use, even for cases that could be managed with sBCS. The choice between keeping it simple or opting for more complex oncoplastic procedures is difficult. This review proposes a pragmatic approach in assisting this decision. Medical literature suggests that OBP and sBCS might be similar regarding local recurrence and overall survival, and patients seem to have higher satisfaction levels with the aesthetic outcome of OBP when compared to sBCS. However, the lack of comprehensive high-quality research assessing their safety, efficacy, and patient-reported outcomes hinders these supposed conclusions. Postoperative complications after OBP may delay the initiation of adjuvant RT. In addition, precise displacement of the breast volume is not effectively recorded despite surgical clips placement, making accurate dose delivery tricky for radiation oncologists, and WBRT preferable to APBI in complex OBP cases. With a critical eye on financial toxicity, patient satisfaction, and oncological outcomes, OBP must be carefully integrated into clinical practice. The thoughtful provision of informed consent is essential for decision-making between sBCS and OBP. As we look into the future, machine learning and artificial intelligence can potentially help patients and doctors avoid postoperative regrets by setting realistic aesthetic expectations., Eduard-Alexandru Bonci’s work has been supported by a UICC Technical Fellowship [grant number UICC-TF/2022-1429].

Background/aim: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment. Patients and methods: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment. Results: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment. Conclusion: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.Keywords: Breast cancer; chemotherapy-induced nausea and vomiting; single nucleotide polymorphism.

PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974 ). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor–positive, 25.2% (n = 131) human epidermal growth factor receptor 2–positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19–specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Purpose: To determine the clinical efficacy of epirubicin plus docetaxel or paclitaxel in the management of breast cancer. Methods: This study was a randomized controlled trial that recruited 78 patients with breast cancer treated in The First People’s Hospital of Anqing between December 2018 and March 2021. The participants were randomized to receive either epirubicin plus docetaxel (control group) or epirubicin plus paclitaxel (study group), with 39 cases in each group. Clinical outcomes, adverse events, quality of life, and prognosis of the two groups were compared. Results: Epirubicin plus paclitaxel produced greater efficacy than epirubicin plus docetaxel (p < 0.05). The combination also exhibited a higher safety profile versus epirubicin with docetaxel, as evidenced by lower incidences of nausea and vomiting, intestinal discomfort, muscle pain, and dyspnea reactions (p < 0.05). Epirubicin with paclitaxel resulted in greater improvement in quality of life in patients than epirubicin plus docetaxel (p < 0.05) as well as provided more benefits in terms of survival and recurrence control than epirubicin plus docetaxel (p < 0.05). Conclusion: Epirubicin/paclitaxel combination alleviates clinical symptoms, reduces adverse events, enhances patient prognosis, lowers the risk of postoperative recurrence, and provides superior quality of life when compared to epirubicin/docetaxel combination in breast cancer patients. Nonetheless, large-scale and better-randomized clinical trials are required to validate the findings of this study.

The association between combined healthy lifestyle and postmenopausal breast cancer risk has been studied in various cohort studies, but only few evaluated the association with estrogen/progesterone (ER/PR) receptor subtypes of breast cancer, with inconsistent results. The relationship of a healthy lifestyle score (HLS) with risk of postmenopausal breast cancer (subtypes) was investigated in the Netherlands Cohort Study. In 1986, 62,573 women aged 55–69 years provided information on dietary and lifestyle habits. The HLS was derived from information on smoking, body mass index, physical activity, Mediterranean diet adherence, and alcohol intake. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 2321 incident breast cancer cases, and 1665 subcohort members with complete data on lifestyles and confounders. The HLS showed a statistically significant inverse relationship with postmenopausal breast cancer risk, in a linear fashion. A one-point increment of the HLS was accompanied by a Hazard Ratio (HR) reduction of 20% for overall breast cancer. The associations between HLS and risk of ER/PR breast cancer subtypes were also significantly inverse, except for ER- breast cancer where the inverse association did not reach statistical significance. Per HLS-increment of one point, the HR reduction ranged from 14% for ER-breast cancer to 29% for ER + PR- breast cancer. These findings suggest that adhering to a combination of healthy modifiable lifestyle factors may substantially reduce the risk of overall postmenopausal breast cancer and its hormone receptor subtypes.

Purpose: To investigate the role and mechanisms of action of long non-coding RNA (lncRNA) (LINC00461) in breast cancer. Methods: Human breast cancer cell lines and normal mammary epithelial cell lines as well as their corresponding negative controls (NC) were cultured and co-transfected with Lipofectamine 3000. Expressions of LINC00461 and miR-607 were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), while the SLC1A3 level was evaluated by western blot. The role of LINC00461 in cell proliferation, apoptosis, cycle arrest, glycolysis, and chemoresistance was determined by MTT, colony formation, flow cytometry, and ELISA assays. Results: The LINC00461 level was overexpressed in breast cancer cell lines (p ˂ 0.05). Knockdown of LINC00461 in MCF-7 cells inhibited cell viability (p ˂ 0.01) and the degree of colony formation (p ˂ 0.001), induced cell apoptosis (p ˂ 0.001) and cycle arrest (p ˂ 0.01), and suppressed glucose consumption (p ˂ 0.001), lactate production (p ˂ 0.001), LDHA activity (p ˂ 0.05) and cisplatin sensitivity (p ˂ 0.05). Overexpression of LINC00461 in MDA-MB-468 cells resulted in reverse outcomes. LINC00461 positively regulated the expression of SLC1A3 via miR-607 in breast cancer cells. It was mechanistically established that LINC00461 is bound to miR-607 and miR-607 bound to SLC1A3, and this was confirmed by luciferase assay. Conclusion: LINC00461 induces cell proliferation, cycle arrest, glycolysis, and chemoresistance by modulating miR-607/SLC1A3 axis in breast cancer. The results lay the theoretical basis for monitoring and therapy of breast cancer.

BackgroundBreast cancer is the most common malignancy among Iranian women. In recent years, the study of dysfunction in the expression of cell-cell junction genes and the related proteins in the malignant process has been at the center of attention. MethodsIn this study, 50 patients were selected who had both cancerous tissue and adjacent healthy tissue. The expression of the desmoglein 2 gene was evaluated. Healthy and cancerous tissue were compared using routine hematoxylin and eosin staining. The total protein was also compared between these two groups. The ultrastructural examination was performed.ResultsThe real-time polymerase chain reaction results showed a decrease in the expression of the desmoglein 2 gene in all tumor samples compared to the healthy samples (p-value ConclusionOverall, the findings showed that the association between desmoglein 2 gene expression and alterations in cellular connections leads to impaired cellular connections, which is an important risk factor for breast cancer. This result proposed the understudy gene as a new biomarker in the development of breast cancer.

Background Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. Methods We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. Results Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. Conclusions Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Background: The dysfunctions in the metabolism of iron has an important role in many pathological conditions, ranging from disease with iron deposition to cancer. Studies on malignant diseases of the breast reported irregular expression in genes associated with iron metabolism. The variations are related with findings which have prognostic significance. This study evaluated the relationship of the expression levels of transferrin receptor 1 (TFRC), iron regulatory protein 1 (IRP1), hepcidin (HAMP), ferroportin 1 (FPN1), hemojuvelin (HFE2), matriptase 2 (TMPRSS6), and miR-122 genes in the normal and malignant tissues of breast cancer patients. Methods & Results: The normal and malignant tissues from 75 women with breast malignancies were used in this study. The patients did not receive any treatment previously. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used in figuring the levels of gene expression associated with the iron metabolism. When the malignant and normal tissues gene expression levels were analyzed, expression of TFRC increased (1.586-fold); IRP1 (0.594 fold) and miR-122 (0.320 fold) expression decreased; HAMP, FPN1, HFE2 and TMPRSS6 expressions did not change. FPN1 and IRP1 had a positive association, and this association was statistically significant (r=0.266; p=0.022). IRP1 and miR-122 had a positive association, and this association had statistical significance (r=0.231; p=0.048) Conclusions: Our study portrayed the important association among genes involved in iron hemostasis and breast malignancy. The results could be used to establish new diagnostic techniques in the management of breast malignancies. The alterations in the metabolism of malignant breast cells with normal breast cells could be utilized to achieve advantages in treatment.

Breast cancer is the most common type of malignancy in women and radiotherapy (RT) is an important part of treatment. Although it reduces cancer recurrence, it has been shown to cause accerelerated athnerosclerosis. This study aimed to compare the results of myocardial perfusion scintigraphy (MPS) for ischemia investigation with coronary angiography (CAG) findings and to investigate the effect of RT on the development of coronary artery disease in breast cancer patients who underwent RT. The results of 660 patients were analyzed and compared with each other in terms of clinical, demographic, laboratory parameters and MPS results. The mean age was 57.5 years and all of them were female. When the groups were compared, the Gensini score and marking of the left anterior descending artery (LAD) area as ischemic area localization were found more, but angiographically, the rate of severe stenosis in the area indicated by MPS was found to be lower in the RT group (p < 0.001). While the sensitivity of MPS in the RT group was 67.5% and non-RT group was 88.5% (p < 0.001), the result of our study shows that the sensitivity of the MPS test is significantly lower in the patient group receiving RT.

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.

Purpose HER2 overexpression has a central role in breast cancer carcinogenesis and is associated with poor prognosis if untreated. Lately, identification of HER2-low breast cancer has been proposed to select patients for novel HER2-directed chemotherapy and includes cancers with immunohistochemistry 1 + or 2 + with negative FISH, encompassing approximately 55–60% of all breast carcinomas. In early-stage breast cancer, the prognostic significance of HER2 low-disease is less well understood, with a particular paucity of data evaluating the prevalence and implications of HER2-low status in invasive lobular carcinoma (ILC). Methods We evaluated 666 stage I-III ILC tumors from a prospectively maintained institutional database, comparing clinicopathologic features and disease-free survival (DFS) using a multivariable Cox proportional hazards model. Results HER2-low status was common in this cohort of patients with ILC, but most clinicopathologic features did not differ between HER2-low and HER2-negative cases. However, when adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse disease-free survival (DFS) than those with HER2-negative tumors (hazard ratio 2.0, 95% confidence interval 1.0–4.1, p = 0.05). Conclusion This difference in DFS supports the notion that HER2-low and HER2-negative early stage ILC may differ clinically, despite similar clinicopathologic features. Further investigation into the potential benefit of HER2 targeted therapy in HER2-low early-stage breast cancer, and specifically lobular cancer, is warranted to ensure optimal outcomes in this distinct tumor subtype.

Introduction: Lymphedema remains a risk for 13–34% of breast cancer patients who require an axillary dissection (ALND) and radiation. Immediate lymphovenous anastomosis (LVA) may mitigate lymphedema by up to 30% by restoring the physiologic lymphatic drainage immediately after ALND. Currently, completion of ALND (cALND) versus radiation after neoadjuvant therapy (NAC) is being addressed by the Alliance A11202 trial, leaving a paucity of data to guide practice. Our study describes the implementation process of LVA into clinical practice after NAC for node-positive breast cancer in the current clinical context. Methods: We reviewed a prospective database of LVA in node-positive patients (cT1-4,Nany) who received NAC followed by axillary surgery ± immediate LVA from October 2021 to 2022. The evolution of the surgical approach is described. Specifically, patients who downstaged to clinically negative nodes post-NAC were offered targeted SLNB with dual-tracer and intraoperative frozen section (FS). Patients were reminded that the standard of care for any node positive is cALND. Immediate cALND with LVA was performed for grossly positive nodes or all positive SLNs; cALND was omitted for those with negative SLNs. For a microscopic disease on a frozen section, a shared decision was made pre-operatively, given each patient’s differing valuations of the benefit and risks of cALND ± LVA versus no cALND with planned regional radiation postoperatively. LVA was offered as an option as part of our institutional evaluation of the procedure. Results: A total of 15 patients were included; the mean age was 49.9 (range 32–75) with stage IIA to IIIB breast cancer. Of these, 6 (40%) were triple negative, 5 (33.3%) HER-2 positive, and 4 (26.7%) ER/PR+ HER-2 negative. There were 13 women (86.7%) who had persistent axillary adenopathy based on clinical and/or ultrasound assessment, with 8 patients proceeding directly to ALND with LVA. Among these patients, 3 (37.5%) had pathologic nodal disease, and 5 (62.5%) were node negative, confirming the limitations of pre-operative imaging. As a result, the subsequent 7 (46.7%) underwent targeted SLNB with FS, with 3 patients (42.9%) avoiding an ALND as a result of a negative FS. A total of 4 patients (57.1%) had 1 or more positive lymph nodes on FS: 3 proceeded with a cALND and LVA, and 1 patient (14.2%) opted for no cALND based on a pre-operative discussion and received adjuvant radiation and chemotherapy. Of the 11 patients who underwent ALND and LVA, 1 patient (9.1%) developed lymphedema at 6.9 months following their surgery. The accuracy, sensitivity, and specificity of pre-operative US were 46.7%, 85.7%, and 12.5% and intraoperative FS were 88.0%, 72.7%, and 100%, respectively. Conclusions: As adjuvant nodal radiation and systemic therapy continue to improve, the benefit of a cALND in patients with the limited residual disease remains unclear as we await the outcomes from clinical trials. In the era of clinical uncertainty, we propose a nuanced approach to the axilla by utilizing a shared decision model with patients, incorporating targeted SLNB with FS and completion node dissection when required and desired by the patient, coupled with LVA in a simple stepwise treatment pathway.

PURPOSE Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates ( P < .0001) and 3-year overall survival (OS) rates ( P < .0001). TNBC was associated with increased risk for visceral metastases ( P = .0005), lower risk for bone recurrence ( P = .027), and shorter postrecurrence survival ( P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival ( P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC ( P < .0001). CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.

OBJECTIVE: The role of baseline and post-treatment standardized uptake value (SUV(max)) values in predicting pathological response in patients with breast cancer after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Thirty patients with invasive ductal breast cancer were included in this retrospective study. F-18 fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) examinations were performed before and after NAC. Pretreatment SUV(max) (SUV(max) I), post-treatment SUV(max) (SUV(max) II) and ΔSUV(max) values of primary breast cancer were obtained. Breast tumor pathology preparations were examined for the evaluation of tumor response according to the Miller and Payne classification. Patients were grouped as responding to treatment (pCR) and unresponsive to treatment (nonpCR). In all analyses, p

Objective: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors. Methods: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI). Results: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021–19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders. Conclusion: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

Breast cancer remains one of the most common cancers in women worldwide, and despite significant improvements in treatment modalities, the prognosis of this cancer is still poor. Herbs and plant extracts have been associated with various health benefits, and traditional folk medicine is still receiving great interest among patients as proven by accumulated records, tolerable side effects of herbal compounds compared to their synthetic counterparts, and low cost. Curcumin is a polyphenol identified as the main active ingredient in turmeric and has been used in the treatment of various diseases and ailments. Additionally, the pharmacological activities of curcumin on many cancers have been investigated substantially due to its ability to regulate many signaling pathways involved in cancer tumorigenesis and metastasis. However, the low solubility and bioavailability of curcumin limit its benefits, urging the need for new curcumin formulations and delivery systems. Nanotechnology has been widely publicized in cancer treatment not only to overcome the limitations of poorly soluble and physiologically unstable compounds but also to improve the delivery of the drug to the diseased site and cellular uptake. In this review, we summarized the main anti-tumor effect of curcumin and its mode of action on breast cancer and focused on the anticancer efficacy of various and recent curcumin nanoformulations and delivery systems. Such nanotechnological systems could pave the way to address a new future direction in this research area, enhancing the therapeutic potential of curcumin in the treatment of breast cancer. In the next few years, there will be more focus on developing curcumin-based materials for breast cancer treatment.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (

The purpose of the study was to explore the associations of sub-ethnicity to the survivorship experience of Asian American breast cancer survivors and identify the multiple factors that influenced their survivorship experience. This was a secondary analysis of the data among 94 Asian American breast cancer survivors from a larger ongoing study. Instruments included: questions on background characteristics, the perceived isolation scale, the Personal Resource Questionnaire, the Memorial Symptom Assessment Scale-Short Form, and the Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using hierarchical logistic and multiple regression analyses. After controlling for other factors, being a Japanese American (ref. = being a Chinese American) was significantly associated with pain scores (odds ratio [OR] = −0.32, p

Tamoxifen exposure is a recognised risk for primary endometrial cancer. This case serves as a reminder to meticulously check the past medical history and inform patients of the risk-benefit of treatment as part of a shared-decision making process.

Mass lesions are one of the breast cancer tumors. Mammogram images are the first screening tool to detect tumors in the women breast, but due to radiologist fatigue, number of false positive (FP) and false negative (FN) rates are increased. The main objective of this paper is to develop an intelligent computer aided diagnosis (CAD) system that can accurately detect mass lesions in digitized mammogram images. The proposed method has three stages. The first stage is a preprocessing stage, where the mass lesion is enhanced using a customized Laplacian filter. Then, multi-statistical filters are implemented to detect a potential mass lesion in the mammogram images. In the final stage, the number detected FP regions are reduced using five texture features. The proposed algorithm is evaluated using 45 mammogram images and the algorithm achieved an accuracy rate of 97% in detecting mass lesion with 83% sensitivity rate and 98% specificity rate.

Background: Many women with early-stage breast cancer are predicted to be at sufficiently low risk for recurrence that they may forego chemotherapy. Nevertheless, some low-risk women will experience a local recurrence, and for them the risk of death increases significantly thereafter. The utility of initiating chemotherapy at the time of local recurrence has not been adequately addressed. The purpose of this study is to identify, in a hospital-based series of patients with early-stage breast cancer who were not treated with chemotherapy, those factors which predict death post local recurrence. Methods: We identified 135 women who were diagnosed with early-stage breast cancer (node-negative

B-cell leukemia/lymphoma 11A (BCL11A) is a transcription factor that regulates the expression of genes involved in cell division or apoptosis. A link between high BCL11A expression and a worse prognosis has been demonstrated in patients with various cancers. The aim of this study was to investigate the expression pattern of BCL11A in breast cancer (BC) cases and mastopathy samples and to correlate the results with the clinicopathological data. The expression of the BCL11A protein was investigated using immunohistochemistry (IHC) on 200 cases of BC and 13 mastopathy samples. The level of BCL11A mRNA was determined using real-time PCR in 22 cases of BC and 6 mastopathy samples. The expression of BCL11A was also examined at the protein and mRNA levels in BC cell lines. A higher expression level of BCL11A in BC cases was shown compared to mastopathy samples. The expression level of BCL11A in BC cases and in the studied cell lines decreased with the increasing grade of histological malignancy (G). It was also negatively correlated with the primary tumor size. A significantly lower expression of BCL11A was found in BC that did not express estrogen or progesterone receptors and in triple-negative cases. The results of our research suggest that BCL11A may be relevant in the development of BC.

Purpose Statins are the most widely prescribed cholesterol lowering medications and have been associated with both improved and unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of statins and breast cancer outcomes (death and recurrence) in a large, representative sample of New Zealand (NZ) women with breast cancer. Methods Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic statin use. Results Of the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63–0.86). The association was attenuated when considering a subgroup of ‘new’ statin users (HR: 0.91; 0.69–1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77; 0.63–0.94), postmenopausal women (HR: 0.74; 0.63–0.88), and in women with advanced stage disease (HR: 0.65; 0.49–0.84). Conclusion In this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2− γδ T cells, with equivalent representation of Vδ1+ and Vδ1− cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2− T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2− γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2− γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2− T-cell receptors. Human tumor-derived Vδ2− γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2− T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2− γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.

Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms.

BackgroundBreast surgeons must maintain contemporary knowledge regarding appropriate referral for neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. To date, the greatest benefit is seen in stage II-III HER2-enriched and triple negative breast cancers (TNBC). This study is the first audit of use of NACT in Australia and New Zealand to stratify data by BC biological subtype. MethodsProspective data from 116,745 patients between 2010 and 2019 was provided by the Breast Surgeons of Australia and New Zealand (BreastSurgANZ) Quality Audit (BQA) of Breast Cancer Care. Annual rates of NACT use were determined and change across time analysed with fractional regression. Data from 2018 to 2019 were combined and stratified by biological subtype (LumA, LumB HER2-neg, LumB HER2-pos, HER2 enriched, TNBC, Other basal-like), and age (= 75 years) and compared using negative binomial regression. ResultsThe use of NACT increased annually (OR 1.26, P < 0.001), and the use of additional adjuvant chemotherapy (ACT) decreased (OR 0.78, P < 0.001). A significantly greater use of NACT was noted in patients with TNBC and HER2+ BC, and in all patients aged

Aldehyde dehydrogenase (ALDH) enzymes are involved in the growth and development of several tissues, including cancer cells. It has been reported that targeting the ALDH family, including the ALDH1A subfamily, enhances cancer treatment outcomes. Therefore, we aimed to investigate the cytotoxicity of ALDH1A3-affinic compounds that have been recently discovered by our group, on breast (MCF7 and MDA-MB-231) and prostate (PC-3) cancer cell lines. These compounds were investigated on the selected cell lines as single treatments and in combination with doxorubicin (DOX). Results showed that the combination treatment experiments of the selective ALDH1A3 inhibitors (compounds 15 and 16) at variable concentrations with DOX resulted in significant increases in the cytotoxic effect on the MCF7 cell line for compound 15, and to a lesser extent for compound 16 on the PC-3 cell line, compared to DOX alone. The activity of compounds 15 and 16 as single treatments on all cell lines was found to be non-cytotoxic. Therefore, our findings showed that the investigated compounds have a promising potential to target cancer cells, possibly via an ALDH-related pathway, and sensitize them to DOX treatment.

PURPOSE Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/ P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.

Endocrine therapy forms the backbone treatment for patients with estrogen receptor (ER) positive tumors in both the adjuvant and metastatic setting. Aromatase inhibitors (AI) are the most common endocrine treatment option. Mutation of ESR1, the gene encoding ERα, is a common mechanism of resistance to AIs which leads to ligand independent activity of ERα. Camizestrant (AZD9833) is a next generation SERD and pure ER antagonist that is in Phase 3 trials (SERENA-4: NCT04711252; SERENA-6: NCT04964934). Here we report the preclinical and clinical activity of camizestrant in patients with ESR1 wild-type (ESR1wt) and mutant (ESR1m) tumors. The binding affinities of camizestrant, fulvestrant, and estradiol to wt ERα and ERα variants with mutations in the ligand binding domain were assessed. All three compounds exhibited reduced binding to mutant forms of ERα compared with wt ERα; the Y537S mutation had the greatest impact on binding. This was reflected in requirement for greater concentrations of camizestrant and fulvestrant to degrade and antagonize mutated ERα and to impact cellular proliferation in MCF-7 cells that expressed Y537S ESR1m compared to ESR1wt MCF-7 cells. Furthermore, while a 3 mg/kg dose of camizestrant achieved a maximal anti-tumor effect in a ESR1wt patient derived xenograft model, a 10 mg/kg was required for maximal effect in a D538G ESR1m model. Considering this difference between ESR1m and ESR1wt, pharmacokinetic/pharmacodynamic modelling of preclinical data predicted that a camizestrant dose of 75 mg would be maximally efficacious in patients with ESR1m tumors. Indeed, analysis of ESR1m circulating tumor DNA levels in patients from the SERENA-1 (NCT03616587) Phase 1 trial showed a clear effect of 14 days treatment with 75 mg camizestrant resulting in a >2-fold reduction in ESR1m variant allele frequency in 12/13 (92%) cases with complete clearance of ESR1m ctDNA in 7/13 (54%) cases. Interestingly, the clinical activity of camizestrant was higher in heavily pretreated patients with metastatic breast cancer with ESR1m tumors compared to those with no detectable mutation (ESR1m not detected). At a camizestrant dose of 75 mg, median progression-free survival was 8.3 months (maturity 12/15) in patients with ESR1m tumors compared to 5.6 months (8/9) in those with ESR1m not detected (data cut-off 6 October 2021). Camizestrant-induced ERα degradation was seen in both groups (mean reduction in H-score 42% in ESR1m tumors (n= 12 evaluable pairs) and 46% in tumors with ESR1m not detected (n=7)). Whole transcriptome analysis revealed a trend towards higher ERα activity at baseline in ESR1m tumors compared to ESR1m not detected; ERα activity reduced on treatment in both groups. Consistent with the clinical activity data, camizestrant induced more profound reductions in cell proliferation in ESR1m tumors compared to ESR1m not detected tumors (as seen by greater reductions in Ki67-positive tumor cells). These data demonstrate the activity of camizestrant in patients with ESR1m tumors. Clinical activity along with degradation and antagonism of the ERα is also seen in patients with tumors in which ESR1 mutations are not detected. In this heavily pre-treated Phase 1 patient population from SERENA-1, ESR1m may be a predictive biomarker to enrich for patients with maintained endocrine sensitivity. The SERENA-6 trial is investigating the efficacy and safety of camizestrant plus a CDK4/6 inhibitor in patients with metastatic breast cancer and detectable ESR1m. We acknowledge Helen Heffron, PhD, from InterComm International who provided medical writing support funded by AstraZeneca. Citation Format: Christopher Morrow, Larissa Carnevalli, Richard D. Baird, Tim Brier, Carmela Ciardullo, Natalie Cureton, Mandy Lawson, Robert McEwen, Myria Nikolaou, Anne Armstrong, Begoña Bermejo, Emiliano Calvo, Eva Ciruelos, Javier Garcia-Corbacho, Erika Hamilton, Jason Incorvati, Peter Kabos, Mafalda Oliveira, Manish R Patel, Manuel Ruiz-Borregó, Nicholas Turner, Chris Twelves, Christos Vaklavas, Danielle Carroll, Steven Ching, Nevena Cvetesic, Michelle DuPont, Lisa Gibbons, Alastair Mathewson, Rhiannon Maudsley, Pablo Morentin Gutierrez, Avinash Reddy, Jaime Rodriguez-Canales, Susana Ros, Dhivya Sudhan, Andy Sykes, David Whitson, Teresa Klinowska, Justin Lindemann. The next generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) is active against wild type and mutant estrogen receptor α [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-13.

PurposeThe aim of this study was to develop a prioritization strategy for scheduling immediate screening mammographic interpretation and possible diagnostic evaluation.MethodsA population-based cohort with screening mammograms performed from 2012 to 2020 at 126 radiology facilities from 7Breast Cancer Surveillance Consortium registries was identified. Classification trees identified combinations of clinical history (age, BI-RADS® density, time since prior mammogram, history of false-positive recall or biopsy result), screening modality (digital mammography, digital breast tomosynthesis), and facility characteristics (profit status, location, screening volume, practice type, academic affiliation) that grouped screening mammograms by recall rate, with ≥12/100 considered high and ≥16/100 very high. An efficiency ratio was estimated as the percentage of recalls divided by the percentage of mammograms.ResultsThe study cohort included 2,674,051 screening mammograms in 925,777 women, with 235,569 recalls. The most important predictor of recall was time since prior mammogram, followed by age, history of false-positive recall, breast density, history of benign biopsy, and screening modality. Recall rates were very high for baseline mammograms (21.3/100; 95% confidence interval, 19.7-23.0) and high for women with ≥5 years since prior mammogram (15.1/100; 95% confidence interval, 14.3-16.1). The 9.2% of mammograms in subgroups with very high and high recall rates accounted for 19.2% of recalls, an efficiency ratio of 2.1 compared with a random approach. Adding women

Axillary lymph node metastases are a key prognostic factor in breast cancer treatment. Our aim was to evaluate how tumor size, tumor location, and imaging results correlate to axillary lymph node diseases for patients with stage I-III HER2/neu+ breast cancer. This is a single-institution retrospective chart review of female breast cancer patients diagnosed with primary invasive Her2/neu+ breast cancer who were treated with upfront surgical resection from 2000–2021. Of 75 cases, 44/75 (58.7%) had nodal metastasis, and there was a significant association of larger tumor size to nodal metastases (p ≤ 0.001). Patients with negative nodes had a smaller mean tumor size (n = 30; 15.10 mm) than patients with positive nodes (n = 45; 23.9 mm) (p = 0.002). Preoperative imaging detected suspicious nodes in 36 patients, and ultrasound detected the most positive nodes (14/18; p = 0.027). Our data confirms that tumor size at diagnosis is correlated with a higher likelihood of axillary involvement in patients with Her2/neu+ breast cancer; notably, a large proportion of Her2/neu+ breast cancers have metastatic involvement of axillary lymph nodes even with small primary lesions.

(1) Background: Precision oncology is opening new treatment opportunities for patients suffering from solid tumors. In the last two decades, the advent of CDK4/6 inhibitors, immunotherapy, and antibody–drug conjugates (ADC) improved survival outcomes for advanced or metastatic breast cancers (BC). Nevertheless, some patients progress to approved therapies and still maintain good clinical conditions. (2) Methods: With the aim to estimate the accrual rate to experimental precision oncology treatments, we collected molecular and clinical characteristics of BC patients evaluated at Phase 1 Unit of Fondazione Policlinico Gemelli. Clinical data were retrieved from hospital records. Molecular analysis was performed using Next-Generation Sequencing (NGS) FoundationOne CDx on tissue or blood. (3) Results: Among the 38 BC patients referred to our unit, 35 completed the genomic analysis. All patients were female with advanced (mean number of metastatic sites: 3, range 1–6) BC. Median age at our evaluation was 52 (IQR, 48–59). ECOG PS was good in 97% of the study population, although heavily pre-treated (median number of systemic treatments: 5, IQR 3–7). Half of referred patients were HR+/HER2− BC, with 39% triple negative breast cancer (TNBC). NGS testing was performed on relapsed disease among most (71%) participants, in particular lymph nodes and soft tissue. Liquid biopsy was requested in 23% of cases. The median time from sample collection to NGS testing was 1 month and from diagnosis 54 months. The median value of mutations, VUS, and TMB were 6, 11, and 5, respectively. TP53, PIK3CA, BRCA2, ESR1, and RAD21 were the genes with the highest number of molecular alterations. In 5 patients (14%), the molecular analysis was helpful to assign targeted therapy in the context of clinical trials with a median progression-free survival of 5 months. (4) Conclusions: HR+/HER2− and TNBC were the most frequent subtypes referred for NGS testing. Tissue biopsy of relapsed disease was feasible in 71% of cases. The molecular analysis offered a new treatment opportunity in 14% of patients. The real benefit of these treatments remains to be evaluated in larger cohorts.

Aim and objectives: To assess the adherence of a nursing care model in a multidisciplinary breast cancer unit in a tertiary hospital to the recommended competencies and quality indicators.Background: Aligning the competencies of the breast care nurse with international recommendations for this role helps better fulfil patient needs, increases satisfaction and ensures continuity of care.Design: Cohort study.Methods: Breast care nursing was assessed in all patients treated at the Functional Breast Unit from 1 July 2016 to 30 June 2017. Patients were followed for 1 year. Sociodemographic, clinical and pathological data, treatments performed and nursing interventions were collected. The strobe checklist has been used to report this study. Results: We analysed nursing interventions carried out in 382 patients attended over 1 year in a multidisciplinary breast cancer unit. All patients with early disease had contact with the nurse at different times during their primary treatment. Only 58% of patients with advanced disease had contact with the nurse during their first year of illness. Moreover, first contact with the nurse was delayed by more than a week from diagnosis, the interval recommended by international guidelines.Conclusion: The nursing care model meets the core competencies defined for the breast care nurse in patients with early breast cancer, but the first visit should be organised earlier, and follow-up should extend beyond the completion of primary treatment.Relevance to clinical practice: This study evaluated the breast care nurse model in one breast cancer unit according to international guidelines. Nursing care adhered to most guideline requirements in patients with early breast cancer, but not in those with advanced disease. New models of care need to be developed for women with advanced breast cancer in order to achieve true patient-centred care.

Background Breast cancer care has been affected by the COVID-19 pandemic. This systematic review aims to describe the observed pandemic-related changes in clinical and health services outcomes for breast screening and diagnosis. Methods Seven databases (January 2020–March 2021) were searched to identify studies of breast cancer screening or diagnosis that reported observed outcomes before and related to the pandemic. Findings were presented using a descriptive and narrative approach. Results Seventy-four studies were included in this systematic review; all compared periods before and after (or fluctuations during) the pandemic. None were assessed as being at low risk of bias. A reduction in screening volumes during the pandemic was found with over half of studies reporting reductions of ≥49%. A majority (66%) of studies reported reductions of ≥25% in the number of breast cancer diagnoses, and there was a higher proportion of symptomatic than screen-detected cancers. The distribution of cancer stage at diagnosis during the pandemic showed lower proportions of early-stage (stage 0–1/I-II, or Tis and T1) and higher proportions of relatively more advanced cases than that in the pre-pandemic period, however population rates were generally not reported. Conclusions Evidence of substantial reductions in screening volume and number of diagnosed breast cancers, and higher proportions of advanced stage cancer at diagnosis were found during the pandemic. However, these findings reflect short term outcomes, and higher-quality research examining the long-term impact of the pandemic is needed

Cancer is a major health problem worldwide and the second leading cause of death following cardiovascular diseases. Breast cancer is the leading cause of mortality and morbidity among women and one of the most common malignant neoplasms prompt to metastatic disease. In the present review, the mechanisms of the major cell adhesion molecules involved in tumor invasion are discussed, focusing on the case of breast cancer. A non-systematic updated revision of the literature was performed in order to assemble information regarding the expression of the adhesion cell molecules associated with metastasis. This work was supported by a scholarship with the reference SFRH/BD/146489/2019. info:eu-repo/semantics/publishedVersion

Genetics and predictive tests are changing breast cancer prevention, both in terms of subjective experience and risk reducing practices. The aim of the article is to address two main research questions: What does the genetic information mean for subjects? How does prevention and risk-reducing practice change in relation to genetic information? Through qualitative research on breast cancer experience conducted in Italy at the National Cancer Institute of Rome, it was possible to answer these questions by including women who received a genetic response for the BRCA mutation. What emerges is that the genetic information shapes risk-reducing prac-tice, fostering genetic responsibilities within the family. This seems to encourage woman to perceive radical risk-reducing strategies such, as a mastectomy or oophorectomy, as the main - and often mandatory - solution to face breast cancer risk thereby underestimating the health risks and psychological burden involved in preventive surgery.

Objective: Breast cancer (BC) remains to be one of the most diagnosed cancer types among women around the world. Drug repurposing is suggested to be a convenient alternative for drug development in cancer treatment. Ivermectin, the antiparasitic agent produced by the bacterium Streptomyces avermitilis, is currently being examined thoroughly in oncology and has begun to be seen as a potential drug candidate for BC therapy. However, studies are limited, and the exact anti-tumorigenic mechanism is not yet clarified in breast cancer. Methods: For elucidating the molecular mechanisms of Ivermectin’s potential anticancer effects, we have examined its in vitro effects on BC cells in terms of cell viability, intracellular ROS levels, glutathione levels, mitochondrial membrane potential, apoptosis, and DNA damage. Results: Ivermectin induces apoptosis via oxidative stress and DNA damage in BC cells. Conclusion: The in vitro mechanistic studies of promising anticancer agents for repurposing are essential guides for drug developers. For this purpose, ivermectin should be further studied as a drug candidate for its potential in the treatment of breast cancer.

Background A subset of patients with estrogen receptor (ER)-positive, HER2-negative, and node-negative breast cancer experience recurrences. Predicting patients who will have recurrences within 5 years of surgery is essential so that patients can be selected to receive adjuvant chemotherapy. The 95-gene classifier (95-GC) has been validated as a method to differentiate patients into high and low-risk groups for early recurrence. Methods In this study, we performed 95-GC analysis on 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients who underwent surgery for ER-positive, HER2-negative, and node-negative breast cancer and did not receive adjuvant chemotherapy. We associated the obtained high- and low-risk groups with clinicopathological characteristics and recurrence-free survival (RFS).Results We classified 12 out of 56 patients into the high-risk recurrence group. We found significantly higher KI67 scores in patients in the high-risk group. Other clinicopathological characteristics were not associated with the 95-GC risk groups. Patients in the 95-GC low-risk group had a significantly better prognosis than those in the high-risk group (p = 0.0387). The 5-year RFS rate was 97.6% in the low-risk group and 74.1% in the high-risk group, while the 10-year RFS rates were 90.1% and 74.1%, respectively.Conclusions Our study shows that the 95-GC score can accurately predict RFS within 5 years of surgery for ER-positive, HER2-negative, and node-negative breast cancer using FFPE tissue samples. These prediction models could help assign patients to the most effective treatment regimen.

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.

(1) Background: Strong evidence supports the persuasive positive effects of exercise for cancer patients and survivors. Different approaches of exercise programs have been established; however, the special interests of young adults (YAs) with cancer have rarely been considered in exercise interventions. Therefore, the study YOUng EXercisers (YOUEX) aimed to investigate exercise preferences in YAs. (2) Methods: YOUEX was a three-arm, patient preference-based non-randomized, longitudinal, pre–post exercise intervention, offering three different exercise modules to YAs during or after acute therapy (Module 1: online supervised group-based (M1); Module 2: online unsupervised (M2); Module 3: in-person supervised (M3)). The intervention period was 12 weeks with another 12-week follow-up period, the modules could be changed or amended after 6 and 12 weeks. (3) Results: 92 YAs were allocated to the study. At baseline, 50 YAs (54%) chose M2, 32 YAs (35%) M1 and 10 YAs (11%) M3. The analysis revealed high acceptability and feasibility of the online exercise programs (M1, M2). There was a high impact of the COVID-19 pandemic on the execution of M3. YAs showed diverse preferences in module selection due to differences in, e.g., cancer therapy status or favored level of supervision. (4) Conclusions: YAs need personalized exercise programs that consider their individual interests and needs. Online exercise programs can be a promising addition to existing exercise opportunities. They are an effective way to increase physical activity levels in YAs. German Foundation of Young Adults with Cancer

In response to breast cancer diagnostic regional wait times exceeding both national and provincial standards and to symptomatic patient referrals for diagnostic mammography taking longer than abnormal screening mammography referrals, the Rae Fawcett Breast Health Clinic (RFBHC) was opened in 2017 in a mid-sized Canadian hospital serving both urban and rural-remote communities. We investigated whether the RFBHC improved wait times to breast cancer diagnosis, improved compliance with national and provincial breast cancer standards, and decreased the wait time disparity associated with referral source. Statistical analyses of wait time differences were conducted between patients who were diagnosed with breast cancer prior to and after the RFBHC establishment. Study group compliance with national and provincial standards and wait time differences by referral source were also analysed. A survey was administered to assess overall patient experience with the RFBHC and clinic wait times. RFBHC patients had a shorter mean wait to breast cancer diagnosis (24.4 vs. 45.7 days, p ≤ 0.001) and a shorter mean wait to initial breast cancer treatment (49.1 vs. 78.9 days, p ≤ 0.001) than pre-RFBHC patients. After the RFBHC establishment, patients who attended the RFBHC had a shorter mean wait time to breast cancer diagnosis (24.4 vs. 36.9 days, p = 0.005) and to initial treatment (49.1 vs. 73.1 days, p ≤ 0.001) than patients who did not attend the clinic. Compliance with national and provincial breast cancer standards improved after the RFBHC establishment and the wait time disparity between screening mammography referrals and symptomatic patient referrals decreased. Survey results indicate that the RFBHC is meeting patient expectations. We concluded that the establishment of a breast health clinic in a Canadian center serving urban and rural-remote communities improved breast diagnostic services.

Refereed/Peer-reviewed Background: There is a recognized need for evidence to inform breast cancer screening guidelines and services for transgender people, who face barriers to accessing appropriate and inclusive health care. Aims: This review summarized evidence for breast cancer risk and screening guidelines in transgender individuals, including the potential impact of gender-affirming hormone therapy (GAHT); factors that may influence screening decision-making and behaviors; and considerations for providing culturally safe, high-quality screening services. Methods: A protocol was developed based on the Joanna Briggs Institute scoping review methodology. Searches were performed in Medline, Emcare, Embase, Scopus, and the Cochrane Library for articles reporting information on the provision of culturally safe, high-quality breast cancer screening services for transgender people. Results: We identified 57 sources for inclusion: 13 cross-sectional studies, 6 case reports, 2 case series, 28 review or opinion articles, 6 systematic reviews, 1 qualitative study, and 1 book chapter. Evidence on rates of breast cancer screening among transgender people and the association between GAHT and breast cancer risk was inconclusive. Factors negatively associated with cancer screening behaviors included socioeconomic barriers, stigma, and lack of health provider awareness of transgender health issues. Breast cancer screening recommendations varied and were generally based on expert opinion due to the lack of clear evidence. Considerations for providing culturally safe care to transgender people were identified and mapped to the areas of workplace policies and procedures, patient information, clinic environment, professional conduct, communication, and knowledge and competency. Discussion: Screening recommendations for transgender individuals are complicated by the lack of robust epidemiological data and clear understanding of the role GAHT may play in breast cancer pathogenesis. Guidelines have been developed based on expert opinion and are subsequently not uniform or evidence based. Further work is required to clarify and consolidate recommendations.

Purpose To obtain reference norms of EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L, based on a population of Spanish non-metastatic breast cancer patients at diagnosis and 2 years after, according to relevant demographic and clinical characteristics. Methods Multicentric prospective cohort study including consecutive women aged ≥ 18 years with a diagnosis of incident non-metastatic breast cancer from April 2013 to May 2015. Health-related quality of life (HRQoL) questionnaires were administered between diagnosis and beginning the therapy, and 2 years after. HRQoL differences according to age, comorbidity and stage were tested with ANOVA or Chi Square test and multivariate linear regression models. Results 1276 patients were included, with a mean age of 58 years. Multivariate models of EORTC QLQ-C30 summary score and EQ-5D-5L index at diagnosis and at 2-year follow-up show the independent association of comorbidity and tumor stage with HRQoL. The standardized multivariate regression coefficient of EORTC QLQ-C30 summary score was lower (poorer HRQoL) for women with stage II and III than for those with stage 0 at diagnosis (− 0.11 and − 0.07, p p p p Conclusion These HRQoL reference norms can be useful to interpret the scores of women with non-metastatic breast cancer, comparing them with country-specific reference values for this population.

Purpose The number of M1-like and M2-like tumour-associated macrophages (TAMs) and their ratio can play a role in breast cancer development and progression. Early clinical trials using macrophage targeting compounds are currently ongoing. However, the most optimal detection method of M1-like and M2-like macrophage subsets and their clinical relevance in breast cancer is still unclear. We aimed to optimize the assessment of TAM subsets in different breast cancer subtypes, and therefore related TAM subset numbers and ratio to clinicopathological characteristics and clinical outcome. Methods Tissue microarrays of 347 consecutive primary Luminal-A, Luminal-B, HER2-positive and triple-negative tumours of patients with early-stage breast cancer were serially sectioned and immunohistochemically stained for the pan-macrophage marker CD68 and the M2-like macrophage markers CD163, CSF-1R and CD206. TAM numbers were quantified using a digital image analysis algorithm. M1-like macrophage numbers were calculated by subtracting M2-like TAM numbers from the total TAM number. Results M2-like markers CD163 and CSF-1R showed a moderate positive association with each other and with CD68 (r ≥ 0.47), but only weakly with CD206 (r ≤ 0.06). CD68 + , CD163 + and CSF-1R + macrophages correlated with tumour grade in Luminal-B tumours (P Conclusion In conclusion, macrophages and their subsets can be detected by means of a panel of TAM markers and are related to unfavourable clinicopathological characteristics in Luminal-B breast cancer. However, their impact on outcome remains unclear. Preferably, this should be determined in prospective series.

Introduction-Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance.Methods and Results-In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PALDcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5 lM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis.Conclusion-Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.