Late Breast Research Articles

Postmastectomy Late Breast Reconstruction with Transverse Rectus Abdominis Flap after Primary Closure with Latissimus Dorsi

AbstractLocally advanced breast cancer (LABC) is common in countries where organized screening is not effective. Although neoadjuvant therapy increases resectability, many patients undergo mastectomy and, in some cases, flaps are necessary for primary closure of the chest wall. Despite a worse prognosis, some of these women will achieve long-term survival and may require breast reconstruction. The literature on the subject is scarce. We present the cases of two patients with LABC undergoing neoadjuvant chemotherapy, mastectomy with extensive soft-tissue resections in the anterior chest wall, and closure with extended V-Y latissimus dorsi (LD) myocutaneous flaps. After 2 years of follow-up, they were without recurrence. They were submitted to a delayed breast reconstruction using a bipedicled transverse rectus abdominis myocutaneous (TRAM) flap. To our knowledge, this is the first publication reporting secondary reconstruction with TRAM flap after primary closure of the chest wall with LD for LABC.

Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival

BackgroundThe 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor–positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown.MethodsA patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio (LR) tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry.ResultsRSClin provided significantly more prognostic information than either the clinicopathologic factors (ΔLR chi-square, 86.2; P<0.001) or RS alone (ΔLR chi-square, 131.0; P<0.001). The model was prognostic in an independent cohort for distant recurrence by 10 years after diagnosis (standardized hazard ratio, 1.56; 95% confidence interval, 1.25 to 1.94), was associated with late distant recurrence risk between 5 and 10 years after diagnosis (standardized hazard ratio, 1.78; 95% confidence interval, 1.25 to 2.55), and approximated the observed 10-year distant recurrence risk (Lin concordance, 0.87) and 5- to 10-year distant recurrence risk (Lin concordance, 0.92).ConclusionsThe 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk. (Funded by the National Cancer Institute, National Institutes of Health [U10CA180820, U10CA180794, UG1CA189859, U10CA180868, and U10CA180822] and others.)

BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Multimodality Imaging of Postmastectomy Breast Reconstruction Techniques, Complications, and Tumor Recurrence.

For women undergoing mastectomy, breast reconstruction can be performed by using implants or autologous tissue flaps. Mastectomy options include skin- and nipple-sparing techniques. Implant-based reconstruction can be performed with saline or silicone implants. Various autologous pedicled or free tissue flap reconstruction methods based on different tissue donor sites are available. The aesthetic outcomes of implant- and flap-based reconstructions can be improved with oncoplastic surgery, including autologous fat graft placement and nipple-areolar complex reconstruction. The authors provide an update on recent advances in implant reconstruction techniques and contemporary expanded options for autologous tissue flap reconstruction as it relates to imaging modalities. As breast cancer screening is not routinely performed in this clinical setting, tumor recurrence after mastectomy and reconstruction is often detected by palpation at physical examination. Most local recurrences occur within the skin and subcutaneous tissue. Diagnostic breast imaging continues to have a critical role in confirmation of disease recurrence. Knowledge of the spectrum of benign and abnormal imaging appearances in the reconstructed breast is important for postoperative evaluation of patients, including recognition of early and late postsurgical complications and breast cancer recurrence. The authors provide an overview of multimodality imaging of the postmastectomy reconstructed breast, as well as an update on screening guidelines and recommendations for this unique patient population. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Dielectrophoretic Characterization and Computational Analysis of Peripheral Blood Mononuclear Cells from MMTV-PyMT Mammary Carcinoma Models for Late Carcinoma Detection

Breast cancer is the leading cancer in women, with 284,200 new cases and an estimated 43,600 deaths in 2021. Early detection and proper treatment can enhance outcomes. This study probes the dielectric properties of peripheral blood mononuclear cells (PBMCs) from MMTV-PyMT mice at 14+ weeks (stage IV) using a microfluidic platform for early breast cancer detection. The central hypothesis is that changes in subcellular components like the cytoskeleton, membrane, cytoplasm, and extracellular matrix at carcinoma onset regulate dielectric properties (conductivity, permittivity), affecting bioelectric signals that aid cancer detection. This is based on preliminary data showing unique PBMC dielectric properties from WT and PyMT tumor-bearing mice, identifying bioelectric signals regulating human adenocarcinoma cells. We hypothesize isolated PBMCs are altered in cancer compared to healthy bodies, evident in the MMTV-PyMT mouse model for analyzing human breast cancer mechanisms. Although specific PBMC change mechanisms are not investigated, we hypothesize these alterations can be detected using dielectrophoresis, a dielectric characterization technique utilizing non-uniform electric fields to manipulate and separate normal and cancer cells based on differing electrophysiological plasma membrane properties. Our results present dielectric properties of murine PyMT and WT PBMCs exhibiting unique cellular behavior, with numerical simulations validating these results. These unique characteristics can discriminate between cancer and non-cancer cells. This novel, label-free, rapid (~2 min), low-cost cell sorting technology detects and separates early and late breast cancer stages, leading to preclinical development and future clinical trials. The long-term goal is a non-invasive tool to determine breast cancer at earliest stages without false positives/negatives of standard mammography screening

Dosimetric feasibility study (“proof of concept”) of refractory ventricular tachycardia radioablation using proton minibeams

PurposePreclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. Material and methodsAn arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. ResultsThe average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. ConclusionThis proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

Systematic Analysis of Factors Associated with Late Breast Cancer Screening in Women in Sub-Saharan Africa from 2014 to 2020

Systematic Analysis of Factors Associated with Late Breast Cancer Screening in Women in Sub-Saharan Africa from 2014 to 2020

Persistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer

PurposeExtending adjuvant endocrine therapy (ET) beyond the standard 5 years offers added protection against late breast cancer recurrences in women with early-stage hormone receptor-positive (HR +) breast cancer. Little is known about treatment persistence to extended ET (EET) and the role that genomic assays may play. In this study, we evaluated persistence to EET in women who had Breast Cancer Index (BCI) testing.MethodsWomen with stage I-III HR + breast cancer who had BCI testing after at least 3.5 years of adjuvant ET and ≥ 7 years of follow-up after diagnosis were included (n = 240). Data on medication persistence was based on prescriptions in the electronic health record.ResultsBCI predicted 146 (61%) patients to have low – BCI (H/I)-low – and 94 (39%) patients to have high likelihood of benefit from EET (BCI (H/I)-high). Continuation of ET after BCI occurred in 76 (81%) (H/I)-high and 39 (27%) (H/I)-low patients. Non-persistence rates were 19% in the (H/I)-high and 38% in the (H/I)-low group. The most common reason for non-persistence was intolerable side effects. Patients on EET underwent more DXA bone density scans than those who stopped ET at 5 years (mean 2.09 versus 1.27; p < 0.001). At a median follow-up of 10 years from diagnosis, there were 6 metastatic recurrences.ConclusionsIn patients who continued ET after BCI testing, the rates of persistence to EET were high, particularly in patients with predicted high likelihood of benefit from EET. Use of EET is associated with increased use of DXA scans.

Rate of Conversion of Conservative Breast Surgery to Mastectomy in Patients with Early Breast Cancer Versus Late Breast Cancer after Down Staging

Rate of Conversion of Conservative Breast Surgery to Mastectomy in Patients with Early Breast Cancer Versus Late Breast Cancer after Down Staging

Abstract P2-22-01: Nuclear long non-coding RNA LINC00355 expression and treatment using antisense oligonucleotides in Estrogen Receptor positive late-stage relapse breast cancer

Abstract Late-stage relapse also known as late recurrence breast cancer is a metastatic disease that occurs more than five years after initial adjuvant endocrine therapy treatment. The 5-year relative survival rate is less than 30% and there are limited treatment options for patients with late-stage relapse because of poor performance status. We hypothesize that long non-coding RNA (lncRNA) protein interactions regulate genes to promote late-stage relapse and these interactions can be targeted using RNA therapeutics. To address this, we used RNA-sequencing to identify LINC00355 to be up-regulated in 24 late-stage relapse samples compared to a unique cohort of 72 primary breast cancer samples. Analysis of 480 primary breast cancer samples from The Cancer Genome Atlas (TCGA) also shows decrease expression of LINC00355 compared to late-stage relapse. To better assess LINC00355 cell type expression, we analyzed 26 publicly available primary breast cancer single cell sequencing data samples and detected 0.90% or less of cells expressing LINC00355, which was restricted to cancer epithelial cells. Due to cellular localization playing an important role in lncRNA function, we isolated nuclear and cytoplasmic lysates and orthogonally validated with RNAscope in situ hybridization (RNA-ISH) to show that LINC00355 is located in the nucleus of MCF7 long-term estrogen deprived (MCF7 LTED) cells. LTED cells are deprived of estrogen for longer than three years meant to recapitulate the acquired resistance to aromatase inhibitors. Next, we determined that LINC00355 binds to MENIN protein to regulate p27KIP expression to promote proliferation with UV crosslinking immunoprecipitation and chromatin immunoprecipitation qPCR of LINC00355 overexpression and mutant constructs. Furthermore, RNA-ISH assays validated high nuclear expression of LINC00355 and RNA-ISH protein co-detection assays showed co-localization of LINC00355-MENIN interaction in a panel of late-stage relapse breast cancer patient tissues compared to primary tissues. Lastly to determine clinical significance, we treated MCF7 LTED cells with two locked nucleic acid antisense oligos (ASOs) targeting LINC00355 to observe a significant decrease in proliferation, cell viability, and invasion. Overall, this is the first study to show the importance of lncRNA-protein interactions and therapeutically target lncRNAs with ASOs in late-stage relapse breast cancer. Moving forward, we intend to further understand how LINC00355 contributes to the progression of late-stage relapse with the intent of creating novel cancer diagnostics and therapies. Citation Format: DeAnna Wells, Kyla Gelev, Prasanth Thunuguntla, Reyka Jayasinghe, Li Ding, Jieya Shao, Cynthia Ma, Jessica Silva-Fisher. Nuclear long non-coding RNA LINC00355 expression and treatment using antisense oligonucleotides in Estrogen Receptor positive late-stage relapse breast cancer [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 P2-22-01.

Abstract P2-03-18: Clinical use of Breast Cancer Index for prediction of late breast cancer recurrence and prediction of benefit in extended endocrine therapy: A single institution experience

Abstract Background: The decision to extend adjuvant endocrine therapy beyond five years is often individualized. Breast Cancer Index (BCI) (Biotheranostics, Inc.) is a validated multigene-expression tissue-based analytic tool used in early hormone-positive breast cancer to predict the response to extended endocrine therapy, based on the HOXB13/IL17BR ratio (H/I ratio), and prognosis 5-10 years after diagnosis, based on the molecular grade index (MGI) and H/I ratio. It is presumed that if BCI shows a high likelihood of benefit from endocrine therapy (BCI-high), the treating clinician would recommend extended adjuvant endocrine therapy and if the primary prediction shows a low likelihood of benefit (BCI-low), the clinician would recommend discontinuation of therapy; however, this may not always be practiced. The Clinical Treatment Score post-5 years (CTS5) is a validated clinicopathologic tool that provides a calculated risk assessment of late distant recurrence (LDR). Clinicians may use the calculated CTS5 score in deciding whether to extend adjuvant endocrine therapy and forego additional prognostic testing, such as BCI. The aim of the study is to understand how clinicians integrate BCI results into medical decision making and to determine the correlation with CTS5 scores in making the decision to offer extended endocrine therapy. Methods: This is a single institution retrospective study. All patients within Henry Ford Health Systewho had BCI testing ordered, between April 2016 and January 2022, were included. Recommendations regarding extended endocrine therapy were collected. CTS5 scores were calculated based on patient’s age, tumor size, tumor grade, and number of involved lymph nodes. If available, the 21-gene recurrence scores (Oncotype-DX) and Ki-67 scores were collected for additional comparison. Results: A total of 165 female patients were included in this study. The average age at diagnosis was 58.5 ± 10.4 years old; 116 (70%) were Caucasian, 35 (21%) were African American; 132 patients (80%) were post-menopausal. The decision regarding extending endocrine therapy was concordant with BCI predictive results in 93.3% of patients; endocrine therapy was continued in 87% of patients in the BCI-high group and discontinued in 95% of patients in the BCI-low group (p&amp;lt; 0.001). In comparing the categorical results of BCI predictive scores (low vs. high) and the CTS5 results (low vs. intermediate vs. high) univariate analysis did not detect a statistically significant relationship. In comparing BCI prognostic LDR risk percentage with the CTS5 LDR (5–10 year) risk percentage, a statistically significant, but weak, positive correlation was observed (Pearson correlation coefficient of 0.38487, p-value= &amp;lt; 0.0001). The odds of a BCI-high primary prediction were 1.031 (95% CI: 1.005, 1.057) times higher for every-one percentage increase in Ki-67 (p-value=0.0172), 1.052 (95% CI: 1.003, 1.057) times higher for every one-unit increase in Oncotype-DX score (p-value=0.0353) and 1.232 (95% CI: 124, 1.351) times higher for every-one percentage increase in BCI prognostic LDR risk assessment (p-value &amp;lt; 0.0001). No statistically significant association was found between the BCI predictive score and age, race, stage, lymph node involvement, and HER2 receptor positivity. Conclusions: This single-institution study revealed that clinicians make decisions regarding extended endocrine therapy that are usually concordant with BCI predictive results. CTS5 results weakly correlate with BCI prognostic results but may not provide conclusive information to support a clinical decision. For patients with early hormone-receptor positive breast cancer the BCI tissue-based analysis may influence a decision regarding extending endocrine therapy. Citation Format: Rebecca Chacko, Manasi M. Godbole, Kylie Springer, Haythem Ali, Vrushali Dabak. Clinical use of Breast Cancer Index for prediction of late breast cancer recurrence and prediction of benefit in extended endocrine therapy: A single institution experience [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 P2-03-18.

Clinicopathologic and sociodemographic factors associated with late relapse triple negative breast cancer in a multivariable logistic model: A multi-institution cohort study

BackgroundMost metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features. MethodsWe included patients diagnosed with stage I–III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p < 0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. ResultsA total 2210 TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5–15.9; p < 0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0–1.8; p = 0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts. ConclusionsA risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation.

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

BackgroundBreast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among women younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC).MethodsA descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Reports of core or incision biopsy, Wide Local Excision or Mastectomy with or without axillary lymph node dissection specimen and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p < 0.05.ResultsA total of 2418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (< 40 years) and 54.29 (IQR: 16.86) in the LOBC group (≥ 40 years). Invasive carcinoma—No Special Type was the commonest tumour type with grade III tumours being the commonest in both categories of patients. Perineural invasion was the only statistically significant pathologic parameter with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67 > 20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80% vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC.ConclusionEOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger study is recommended to identify the association between relevant pathological features and early onset breast cancer in Ghana. Again, further molecular and genetic studies to understand the molecular genetic drivers of the general poorer pathological features of EOBCs and its relation to patient outcome in our setting is needed.

Milky secretion after late breast reconstruction with latissimus dorsi musculocutaneous flap with implant

Milky secretion after late breast reconstruction with latissimus dorsi musculocutaneous flap with implant

Health system barriers influencing timely breast cancer diagnosis and treatment among women in low and middle-income Asian countries: evidence from a mixed-methods systematic review

BackgroundGlobally, breast cancer is the most common cancer type and the leading cause of cancer mortality among women in developing countries. A high prevalence of late breast cancer diagnosis and treatment has been reported predominantly in Low- and Middle-Income Countries (LMICs), including those in Asia. Thus, this study utilized a mixed-methods systematic review to synthesize the health system barriers influencing timely breast cancer diagnosis and treatment among women in Asian countries.MethodsWe systematically searched five electronic databases for studies published in English from 2012 to 2022 on health system barriers that influence timely breast cancer diagnosis and treatment among women in Asian countries. The review was conducted per the methodology for systematic reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, while health system barriers were extracted and classified based on the World Health Organization (WHO)‘s Health Systems Framework. The mixed-methods appraisal tool was used to assess the methodological quality of the included studies.ResultsTwenty-six studies were included in this review. Fifteen studies were quantitative, nine studies were qualitative, and two studies used a mixed-methods approach. These studies were conducted across ten countries in Asia. This review identified health systems barriers that influence timely breast cancer diagnosis and treatment. The factors were categorized under the following: (1) delivery of health services (2) health workforce (3) financing for health (4) health information system and (5) essential medicines and technology. Delivery of health care (low quality of health care) was the most occurring barrier followed by the health workforce (unavailability of physicians), whilst health information systems were identified as the least barrier.ConclusionThis study concluded that health system factors such as geographical accessibility to treatment, misdiagnosis, and long waiting times at health facilities were major barriers to early breast cancer diagnosis and treatment among Asian women in LMICs. Eliminating these barriers will require deliberate health system strengthening, such as improving training for the health workforce and establishing more healthcare facilities.

Frequency of Pathogenic Germline Mutations in Early and Late Onset Familial Breast Cancer Patients Using Multi-Gene Panel Sequencing: An Egyptian Study.

Precision oncology has been increasingly used in clinical practice and rapidly evolving in the oncology field. Thus, this study was performed to assess the frequency of germline mutations in early and late onset familial breast cancer (BC) Egyptian patients using multi-gene panel sequencing to better understand the contribution of the inherited germline mutations in BC predisposition. Moreover, to determine the actionable deleterious mutations associated with familial BC that might be used as biomarker for early cancer detection. Whole blood samples were collected from 101 Egyptian patients selected for BC family history, in addition to 50 age-matched healthy controls. A QIAseq targeted DNA panel (human BC panel) was used to assess the frequency of germline mutations. A total of 58 patients (57.4%) out of 101 were found to have 27 deleterious germline mutations in 11 cancer susceptibility genes. Of them, 32 (31.6%) patients carried more than one pathogenic mutation and each one carried at least one pathogenic mutation. The major genes harboring the pathogenic mutations were: ATM, BRCA2, BRCA1, VHL, MSH6, APC, CHEK2, MSH2, MEN1, PALB2, and MUTYH. Thirty-one patients (30.6%) had BRCA2 mutations and twenty (19.8%) had BRCA1 mutations. Our results showed that exon 10 and exon 11 harbored 3 and 5 mutations, respectively, in BRCA1 and BRCA2 genes. Our analysis also revealed that the VHL gene significantly co-occurred with each of the BRCA2 gene (p = 0.003, event ratio 11/21), the MSH2 gene (p = 0.01, 4/10), the CHEK2 gene (p = 0.02, 4/11), and the MSH6 gene (p = 0.04, 4/12). In addition, the APC gene significantly co-occurred with the MSH2 gene (p = 0.01, 3/7). Furthermore, there was a significant mutually exclusive event between the APC gene and the ATM gene (p = 0.04, 1/36). Interestingly, we identified population specific germline mutations in genes showing potentials for targeted therapy to meet the need for incorporating precision oncology into clinical practice. For example, the mutations identified in the ATM, APC, and MSH2 genes. Multi-gene panel sequencing was used to detect the deleterious mutations associated with familial BC, which in turns mitigate the essential need for implementing next generation sequencing technologies in precision oncology to identify cancer predisposing genes. Moreover, identifying DNA repair gene mutations, with focus on non-BRCA genes, might serve as candidates for targeted therapy and will be increasingly used in precision oncology.

Investigation of the effect of early and late breast milk enrichment on growth parameters in preterm infants: A randomized clinical trial

Background and aims: This study aimed to investigate and compare the effect of early and late breast milk fortification on growth parameters in preterm infants. Methods: In this clinical trial, 90 preterm infants (28-32 weeks) admitted to the neonatal intensive care unit (NICU) of Hajar Hospital in Shahrekord, Iran were randomly divided into three groups. The fortification was performed when the milk intake reached 30 (group A), 70 (group B), and 100 cc/kg (group C). The height, weight, and head circumference of newborns were measured at the beginning of birth and 4 weeks after the birth. The incidence of sepsis and necrotizing enterocolitis, and milk tolerance were investigated as well. All analyses were conducted with Stata software, and P values&lt;0.05 were considered statistically significant. Results: The value changes in the height, weight, and head circumference in all three groups at 4 weeks were significant (P&lt;0.001). The mean weight changes in the A, B, and C groups were 727.33±163.85, 947.33±155.38, and 808.66±168.82, indicating a statistically significant difference (P&lt;0.001). Further, the mean change of weight after 4 weeks showed statistically significant differences (P&lt;0.001) among the A, B, and C groups. The weight gain in the B group was significantly higher than that of the A and C groups (P&lt;0.05); however, no significant difference was observed in the mean weight gain between the A and C groups (P=0.264). Conclusion: The breast milk fortification when the milk intake reached 70 cc/kg had better efficiency on neonatal weight gain compared with the early and delayed fortification.

Clinico-pathologic factors associated with the occurrence of early and late metastatic spread in a cohort of breast cancer patients.

Distant metastatic spread in breast cancer patients is a complex phenomenon involving several prognostic factors. We focused our analysis on early metastatic breast cancer (EMBC) (occurring during the first 36 months) versus late metastatic breast cancer (LMBC) (occurring beyond 3 years) in order to ascertain their possible differential predictive factors. diagnostic, surgical, and follow-up data were assessed for consecutive patients with breast cancer undergoing surgery between 1997 and 2019. We analysed the predictive factors for distant metastasis using both univariate and multivariate analysis. The median follow-up for this cohort of 2708 patients was 89 months. The median metastasis-free interval (FMI) for metastasis patients was 38 months (17 months for EMBC group and 76 months for LMBC group). Distant metastases developed in 12.9% (350/2708); 48% (168/350) of them as EMBC and 52% (182/350) as LMBC. Loco-regional recurrence and nodal extracapsular extension were the only common predictors for both. EMBC and LMBC appeared as two separate conditions, with a different outcome. In the EMBC group, tumour proliferation related factors were significant (histological grade, tumour size, body mass index), whereas for LMBC, other slow-acting factors seemed to be involved (screening program, tumour burden, bilateral tumour).

MRI for Evaluation of Complications of Breast Augmentation.

Breast augmentation is one of the most common aesthetic procedures performed in the United States. Several techniques of breast augmentation have been developed, including the implantation of breast prostheses and the injection of autologous fat and other materials. The most common method of breast augmentation is to implant a prosthesis. There are different types of breast implants that vary in shape, composition, and the number of lumina. The rupture of breast implants is the leading cause of implant removal. The rupture rate increases substantially with the increasing age of the implant. Most implant ruptures are asymptomatic. Implant complications can be grouped into two categories: local complications in the breast and adjacent soft tissue, and systemic complications associated with rheumatologic or neurologic symptoms. The onset of local complications may be early (infection and periprosthetic collections including seromas, hematomas, or abscesses) or late (capsular contraction, implant rupture, gel bleed, or breast implant-associated anaplastic large cell lymphoma). Although mammography is the imaging modality for breast cancer screening, noncontrast breast MRI is the imaging modality of choice for evaluation of the integrity of breast implants and the complications of breast augmentation, for equivocal findings at conventional imaging, and as a supplement to mammography in patients with free injectable materials. The fifth edition of the Breast Imaging Reporting and Data System (BI-RADS) provides a systematic outline for MRI evaluation of patients with breast implants. Silicone- and water-selective sequences provide useful supplemental information to confirm intracapsular and extracapsular rupture. Breast MRI for evaluation of implant integrity does not require intravenous contrast material. The use of MRI contrast material in patients with breast augmentation is indicated when infection or malignancy is suspected. Radiologists should have a thorough understanding of the different techniques for breast augmentation, normal imaging features, and complications specific to breast augmentation. An invited commentary by Ojeda-Fournier is available online. ©RSNA, 2022.