Causal association between complement system FHR-5, CTRP9, and breast carcinoma in situ: a Mendelian randomization study.

OBJECTIVE: Breast carcinoma in situ accounts for a significant number of newly diagnosed breast cancer cases. However, the cause of this type of cancer is unclear, which has led to debates regarding treatment strategies. A Mendelian randomization (MR) study was conducted to explore whether complement system or complement C1q/tumor necrosis factor-related proteins (CTRPs) are causally associated with breast carcinoma in situ. MATERIALS AND METHODS: This two-sample multivariable MR study used genome-wide association study (GWAS) data for all complement system factors and CTRPs. Summary-level statistics were obtained from the breast carcinoma in situ GWAS database. The study employed the MR-Egger method, inverse variance weighted (IVW) method, and weighted median method. Additionally, sensitivity analyses, including the MR-Egger intercept, funnel plot, and leave-one-out analysis, were conducted to address uncertainties and enhance the reliability of the findings. RESULTS: The study indicated that certain immunomodulatory molecules might increase the risk of breast carcinoma in situ, with consistent results. Specifically, CTRP9 showed a 57.0% increased risk [IVW: odds ratio (OR) 0.570 (0.350, 0.928), p < 0.05], and complement factor H (FH)-related protein 5 (FHR-5) was linked to a 67.2% higher risk [IVW: OR 0.672 (0.477, 0.947), p < 0.05]. However, no associations were found with other molecules, suggesting the relationship between immunomodulatory molecules and cancer may be context-specific. CONCLUSIONS: This MR study marks the initial identification of a direct link between FHR-5 and CTRP9 and the susceptibility to breast carcinoma in situ. Delving into the roles of immunomodulatory molecules and immune responses within the tumor microenvironment holds considerable importance for the management of breast carcinoma in situ.

Upgrade Rates of Variant Lobular Carcinoma In Situ Compared to Classic Lobular Carcinoma In Situ Diagnosed in Core Needle Biopsies: A 10-Year Single Institution Retrospective Study.

The primary aim of this study was to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS, ie, combined florid [F-LCIS] and pleomorphic [P-LCIS]) compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal was to determine the rate of progression/development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, our institutional pathology database was searched for patients with "pure" LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation was performed, and follow-up patient outcome data were obtained. One hundred twenty cases of LCIS were identified on CNB (C-LCIS = 97, F-LCIS = 18, and P-LCIS = 5). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14% (14/97), 44% (8/18), and 40% (2/5), respectively. Of the total cases, 79 (66%) were deemed rad-path concordant. Of these, the upgrade rate after excision for C-LCIS, F-LCIS, and P-LCIS was 7.5% (5 of 66), 40% (4 of 10), and 0% (0 of 3), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P = .004), even for the cases deemed rad-path concordant (P value: .036). Most upgraded cases (23 of 24) showed pT1a disease or lower. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in 8/120 (7%) cases. Six patients had died: 2 of (contralateral) breast cancer and 4 of other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should always be excised. The upgrade rate for C-LCIS (even when rad-path concordant) is higher than reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is small (7% with ∼7-year follow-up), but active surveillance is required to diagnose early-stage disease.

Tumor-suppressive action of miR-30a-5p in lung adenocarcinoma correlates with ABL2 inhibition and PI3K/AKT pathway inactivation

Introduction ABL2 contributes to the oncogenic potential of cancers, pointing to its inhibition as a possible strategy against malignant diseases. Bioinformatics prediction of upstream effector miR-30a-5p for ABL2 allowed us to hypothesize and then validate mechanistic actions of miR-30a-5p in lung adenocarcinoma (LUAD). Materials and methods The ABL2 expression in LUAD was analyzed in the TCGA data, clinical samples, and cell lines. The shRNA-mediated silencing of ABL2 was introduced to illustrate its effect on malignant phenotypes of LUAD cells. The binding affinity between ABL2 and miR-30a-5p was verified by luciferase activity and RNA pull-down assay. Ectopic expression, knockdown methods, and PI3K inhibitor LY294002 were used to investigate their effects on in vitro biological characteristics and in vivo tumor growth of LUAD cells. Using nude mouse lung adenocarcinoma in situ and brain metastasis models to validate the inhibitory effect of miR-30a-5p on LUAD by regulating the ABL2/PI3K/AKT signaling axis. Results High expression of ABL2 and poor expression of miR-30a-5p were noticed in LUAD tissues and cell lines. Importantly, miR-30a-5p was demonstrated to target and downregulate ABL2, subsequently inactivating the PI3K/AKT pathway. miR-30a-5p inhibited the malignant phenotypes of LUAD cells by inhibiting ABL2 expression and inactivating the PI3K/AKT pathway. For in vivo experiments, miR-30a-5p was substantiated to thwart tumor tumorigenesis by regulating the ABL2/PI3K/AKT axis. In addition, miR-30a-5p suppresses the occurrence and development of in situ lung cancer and brain metastasis via the ABL2/PI3K/AKT signaling pathway. Conclusion This study underscores the inhibitory role of miR-30a-5p in LUAD through the ABL2/PI3K/AKT axis, which may be a viable target for LUAD treatment (AU)

Effects of a 12-week exercise-based intervention on weight management in overweight or obese breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.

European quality indicators developed by the European Commission Initiative on Breast Cancer: a first nationwide assessment for the Dutch setting.

PURPOSE: This observational study aims to assess the feasibility of calculating indicators developed by the European Commission Initiative on Breast Cancer (ECIBC) for the Dutch breast cancer population. METHODS: Patients diagnosed with invasive or in situ breast cancer between 2012 and 2018 were selected from the Netherlands Cancer Registry (NCR). Outcomes of the quality indicators (QI) were presented as mean scores and were compared to a stated norm. Variation between hospitals was assessed by standard deviations and funnel plots and trends over time were evaluated. The quality indicator calculator (QIC) was validated by comparing these outcomes with the outcomes of constructed algorithms in Stata. RESULTS: In total, 133,527 patients were included. Data for 24 out of 26 QIs were available in the NCR. For 67% and 67% of the QIs, a mean score above the norm and low or medium hospital variation was observed, respectively. The proportion of patients undergoing a breast reconstruction or neoadjuvant systemic therapy increased over time. The proportion treated within 4 weeks from diagnosis, having >10 lymph nodes removed or estrogen negative breast cancer who underwent adjuvant chemotherapy decreased. The outcomes of the constructed algorithms in this study and the QIC showed 100% similarity. CONCLUSION: Data from the NCR could be used for the calculation of more than 92% of the ECIBC indicators. The quality of breast cancer care in the Netherlands is high, as more than half of the QIs already score above the norm and medium hospital variation was observed. The QIC can be easy and reliably applied.

Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Avaliação de upstage das lesões de potencial maligno incerto da mama (B3) após excisão cirúrgica no Serviço de Mastologia do Instituto Nacional de Câncer / Evaluation of the upstage of breast lesions of uncertain malignant potential (B3) after surgical excision in the Mastology Service of the Instituto Nacional de Câncer

Introdução: As lesões com potencial de malignidade incerto, com risco de progressão e que podem coexistir com malignidade incerta são caracterizadas como lesões B3 da mama. O objetivo principal do trabalho consistiu em detectar as taxas de upstage para carcinoma in situ ou invasor após excisão cirúrgica, com base nos diagnósticos histológicos iniciais feitos por biópsia com agulha grossa de: hiperplasia ductal atípica, atipia epitelial plana/alterações de células colunares com atipia, papiloma/lesão papilífera com e sem atipia. Metodologia: análise retrospectiva com base nos pacientes matriculados na unidade INCA (HCIII), entre janeiro de 2018 e dezembro de 2022, que fizeram biópsia por agulha grossa com diagnóstico de lesão B3 e posteriormente submetidos à cirurgia. Resultados: O trabalho avaliou 247 pacientes e 258 lesões no total. Houve predomínio da faixa etária maior ou igual a 50 anos, idade média correspondendo a 56 anos, com preponderância de pacientes no período pós-menopausa e apenas 1 indivíduo do sexo masculino. Em relação à totalidade das lesões estudadas, a maioria foi decorrente dos papilomas sem atipia (32,94%), seguido pela hiperplasia ductal atípica (29%), atipia epitelial plana (20,15%) e papiloma com atipia (17,8%). O upstage total encontrado foi de 22,9%, cuja estratificação por lesão foi: papiloma com atipia (36,9%), hiperplasia ductal atípica (33,3%), atipia epitelial plana (13,46%) e papiloma sem atipia (11,7%). A maior quantidade de lesões neoplásicas foi decorrente de lesões in situ (19,8%), enquanto que as lesões invasoras corresponderam, portanto, à minoria (3,1%). Conclusão: Embora o estudo não compreenda todos os espectros de lesões B3, limitando-se à análise de apenas quatro entidades, comparativamente à literatura atual, os resultados vão ao encontro da maioria dos trabalhos publicados previamente

Introduction: Lesions with uncertain malignant potential, at risk of progression, and that may coexist with uncertain malignancy are characterized as B3 lesions of the breast. The main objective of the work was to detect the upstage rates for in situ or invasive carcinoma after surgical excision, based on the initial histological diagnoses made by biopsy of atypical ductal hyperplasia, flat epithelial atypia/columnar cell changes with atypia, papilloma/ Papillary lesion with and without atypia. Methodology: a retrospective analysis based on patients enrolled in the INCA unit (HCIII) between January 2018 and December 2022 who underwent a biopsy with a diagnosis of B3 lesion and subsequently received surgery. Results: The study evaluated 247 patients and 258 injuries in total. The age group was predominantly greater than or equal to 50 years, with the average age corresponding to 56 years, with a preponderance of patients in the postmenopausal period and only one male individual. Concerning all the lesions studied, the majority were due to papillomas without atypia (32.94%), followed by atypical ductal hyperplasia (29%), flat epithelial atypia (20.15%), and papilloma with atypia (17.8%). The total upstage found was 22.9%, stratified by lesion as follows: papilloma with atypia (36.9%), atypical ductal hyperplasia (33.3%), flat epithelial atypia (13.46%) and papilloma without atypia (11.7%). The largest number of neoplastic lesions resulted from in situ lesions (19.8%), while invasive lesions corresponded to the minority (3.1%). Conclusion: The study does not cover all spectrums of B3 injuries and is limited to analyzing only four entities. Compared to the current literature, the results align with most previously published studies

Comparing Breast Cancer and Cardiovascular Disease Risk and Use of Chemoprevention and Statins among Women with High-risk Breast Lesions.

Breast cancer chemoprevention with selective estrogen receptor modulators (SERM) or aromatase inhibitors (AI) remains underutilized among high-risk women. A potential barrier to chemoprevention is competing comorbidities such as atherosclerotic cardiovascular disease (ASCVD), due to concern for additional medication side effects. We conducted a retrospective cohort study among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), an important target population for chemoprevention. We compared risks for breast cancer and ASCVD, as well as use of SERMs/AIs versus statins among high-risk women (defined as a 5-year invasive breast cancer risk ≥1.67% and 10-year ASCVD risk ≥7.5%, respectively). We used clinical data extracted from the electronic health record to calculate breast cancer risk according to the Breast Cancer Surveillance Consortium model and ASCVD risk according to the 2013 American College of Cardiology/American Heart Association risk calculator. Among 298 evaluable women, mean age was 58.2 years (SD, 8.34), with 33% non-Hispanic White, 41% Hispanic, 9% non-Hispanic Black, 6% Asian, and 11% other/unknown race/ethnicity. About 98% of women met high-risk criteria for breast cancer, whereas 30% were high-risk for ASCVD. Mean 10-year risk of breast cancer was higher than mean 10-year risk of ASCVD (9.14% vs. 6.69%; P < 0.001). Among women who met high-risk criteria for both diseases, use of statins was higher compared with SERMs/AIs (58% vs. 21%; P < 0.001). Among women with AH or LCIS, statin use was higher compared with breast cancer chemoprevention among eligible women, despite having a higher mean risk of breast cancer than ASCVD. PREVENTION RELEVANCE: Among women with high-risk breast lesions, mean absolute risk of breast cancer was higher compared with cardiovascular disease; however, statin use was significantly higher than chemoprevention. To address underutilization of breast cancer chemoprevention, these drugs should be placed in the context of medications used to prevent other chronic diseases.

Net survival of women diagnosed with breast tumours: a population-based study in Switzerland.

AIMS OF THE STUDY: Although the incidence of breast carcinoma in situ has been increasing, the prognosis of breast carcinoma in situ patients has not been extensively investigated. Thus, we aimed to compare the characteristics of invasive breast tumours based on whether or not they were preceded by a breast carcinoma in situ and to estimate the 5-year net survival of patients diagnosed with different breast tumours. METHODS: Data from women diagnosed with breast tumours between 2003 and 2016 were used in our analyses. Net survival analyses were performed using inverse probability of censoring weights (nonparametric Pohar Perme estimator). Under certain assumptions, differences in survival between the cancer population and the general population can be considered to be attributable to the cancer diagnosis (NS). RESULTS: Descriptive observation of tumour characteristics indicated that invasive breast tumours following a breast carcinoma in situ were more frequently detected at an earlier stage and had less missing information in tumour-specific variables, compared to invasive breast tumours not preceded by a breast carcinoma in situ. Breast carcinoma in situ patients had a 5-year net survival of 1.02 (95% CI: 1.01-1.03), whereas patients diagnosed with invasive breast cancer without a recorded breast carcinoma in situ had a 5-year net survival of 0.89 (95% CI: 0.88-0.90). Patients diagnosed first with breast carcinoma in situ and then with invasive breast cancer had a 5-year net survival of 0.92 (95% CI: 0.85-1.01). CONCLUSION: Invasive breast tumours that were preceded by a breast carcinoma in situ were detected more frequently at an earlier stage, compared to those that were not. The estimated 5-year net survival of patients with breast tumours was good.

Management of screening-detected lobular neoplasia in the era of digital breast tomosynthesis: A preliminary study.

PURPOSE: The purpose of this study is to determine upgrade rates of lobular neoplasia detected by screening digital breast tomosynthesis (DBT) and to determine imaging and clinicopathological features that may influence risk of upgrade. METHODS: Medical records were reviewed of consecutive women who presented with screening DBT-detected atypical lobular hyperplasia (ALH) and/or lobular carcinoma in situ (LCIS) from January 1, 2013, to June 30, 2020. Included patients underwent needle biopsy and had surgery or at least two-year imaging follow-up. Imaging and clinicopathological features were compared between upgraded and nonupgraded cases of lobular neoplasia using the Pearson's chi-squared test and the Wilcoxon signed-rank test. RESULTS: During the study period, 107 women (mean age 55 years, range 40-88 years) with 110 cases of ALH and/or LCIS underwent surgery (80.9%, n = 89) or at least two-year imaging follow-up (19.1%, n = 21). The overall upgrade rate to cancer was 5.5% (6/110), and the upgrade rate to invasive cancer was 3.6% (4/110). The upgrade rate of ALH to cancer was 4.1% (3/74), whereas the upgrade rate of LCIS to cancer was 9.4% (3/32) (p = .28). The upgrade rate of cases presenting as calcifications was 4.2% (3/71), whereas the upgrade rates of cases presenting as noncalcified findings was 7.7% (3/39) (p = .44). CONCLUSIONS: The upgrade rate of screening DBT-detected lobular neoplasia is less than 6%. Surveillance rather than surgery can be considered for lobular neoplasia, particularly in patients with ALH and in those with screening-detected calcifications leading to the diagnosis.

Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma.

AIM: To determine if the outcomes of patients with ILC co-occurring with LCIS are similar to pure ILC and if the presence of LCIS is a prognostic factor for ILC. METHODS: In an observational, population-based investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we analysed patients with a diagnosis of stage I-III ILC. Patients were divided into two groups: those with ILC with co-occurring ipsilateral LCIS (ILC + LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral LCIS (ILC alone). We obtained data on demographics, pathologic tumour size (pT), pathologic lymph node (pN) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 status, Ki67, treatment received, distant recurrence-free and overall survival (DRFS, OS). RESULTS: We identified 4217 patients with stage I-III ILC treated at MD Anderson between 1966 and 2021. 45% of cases (n = 1881) had co-existing LCIS. Statistically and numerically, ILC alone tended to associate with pT4 and pN3 stage (P < 0.001), ER/PR negativity (P = 0.0002), HER2 positivity (P = 0.010), higher Ki67 (P = 0.005), non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) compared to the ILC + LCIS group. The median follow-up time was 6.5 years. Patients with ILC + LCIS had better median DRFS (16.8 versus 10.1 years, Hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.60, P < 0.0001) and better median OS (18.9 versus 13.7 years, HR 0.62, 95% CI 0.56-0.69; P < 0.0001). Multivariate analysis showed the absence of LCIS to be an independent poor prognostic factor along with a higher pT stage and higher pN stage for DRFS and OS. CONCLUSION: The findings of this study suggests that the absence of ipsilateral LCIS with ILC is an independent poor prognostic factor and that further studies are warranted to understand this phenomenon.

COVID-19 related change in breast cancer diagnosis, stage, treatment, and case volume: 2019-2021.

PURPOSE: Evaluate the COVID-19 pandemic impact on breast cancer detection method, stage and treatment before, during and after health care restrictions. METHODS: In a retrospective tertiary cancer care center cohort, first primary breast cancer (BC) patients, years 2019-2021, were reviewed (n = 1787). Chi-square statistical comparisons of detection method (patient (PtD)/mammography (MamD), Stage (0-IV) and treatment by pre-pandemic time 1: 2019 + Q1 2020; peak-pandemic time 2: Q2-Q4 2020; pandemic time 3: Q1-Q4 2021 (Q = quarter) periods and logistic regression for odds ratios were used. RESULTS: BC case volume decreased 22% in 2020 (N = 533) (p = .001). MamD declined from 64% pre-pandemic to 58% peak-pandemic, and increased to 71% in 2021 (p < .001). PtD increased from 30 to 36% peak-pandemic and declined to 25% in 2021 (p < .001). Diagnosis of Stage 0/I BC declined peak-pandemic when screening mammography was curtailed due to lock-down mandates but rebounded above pre-pandemic levels in 2021. In adjusted regression, peak-pandemic stage 0/I BC diagnosis decreased 24% (OR = 0.76, 95% CI: 0.60, 0.96, p = .021) and increased 34% in 2021 (OR = 1.34, 95% CI: 1.06, 1.70, p = .014). Peak-pandemic neoadjuvant therapy increased from 33 to 38% (p < .001), primarily for surgical delay cases. CONCLUSIONS: The COVID-19 pandemic restricted health-care access, reduced mammography screening and created surgical delays. During the peak-pandemic time, due to restricted or no access to mammography screening, we observed a decrease in stage 0/I BC by number and proportion. Continued low case numbers represent a need to re-establish screening behavior and staffing.

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

BACKGROUND: The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). METHODS: Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. RESULTS: A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). CONCLUSIONS: For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

Re-examining content validity of the BREAST-Q more than a decade later to determine relevance and comprehensiveness.

PURPOSE: The BREAST-Q is the most used patient-reported outcome measure (PROM) in breast cancer surgery. The purposes of this study were to re-examine the content validity of BREAST-Q cancer modules (mastectomy, lumpectomy and reconstruction) and to determine the need for new scales. METHODS: Interviews were conducted with women with breast cancer (Stage 0-4, any treatment), and were audio-recorded and transcribed verbatim. Deductive (based on original BREAST-Q conceptual framework) and inductive (new codes from the data) content analysis approaches were used to analyze the data. The number of codes that mapped to BREAST-Q were recorded. RESULTS: Dataset included 3948 codes from 58 participants. Most of the breast (n = 659, 96%) and all psychosocial (n = 127, 100%), sexual (n = 179, 100%) and radiation-related (n = 79, 100%) codes mapped to BREAST-Q Satisfaction with Breast, Psychosocial Wellbeing, Sexual Wellbeing and Adverse Effects of Radiation scales, respectively. For the physical wellbeing codes (n = 939) for breast/chest and arm, 34% (n = 321) mapped to the Physical Wellbeing-Chest scale. Most of the abdomen codes (n = 311) mapped to Satisfaction with Abdomen (n = 90, 76%) and Physical Wellbeing-Abdomen (n = 171, 89%) scales. Codes that did not map (n = 697, 30%) covered breast sensation and lymphedema. Concerns related to fatigue, cancer worry, and work impact were most reported and did not map to BREAST-Q. CONCLUSION: The BREAST-Q, which was developed using extensive patient input more than a decade ago, is still relevant. To ensure the BREAST-Q remains comprehensive, new scales for upper extremity lymphedema, breast sensation, fatigue, cancer worry, and work impact were developed.

The effectiveness of an ultrafast breast MRI protocol in the differentiation of benign and malignant breast lesions.

AIM: To evaluate the effectiveness of an ultrafast breast magnetic resonance imaging (MRI) protocol in differentiating benign and malignant breast lesions. MATERIALS AND METHODS: Fifty-four patients with Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions were recruited between July 2020 to May 2021. A standard breast MRI was performed with the inclusion of the ultrafast protocol between the unenhanced sequence and the first contrast-enhanced sequence. Three radiologists performed image interpretation in consensus. Ultrafast kinetic parameters analysed included the maximum slope (MS), time to enhancement (TTE), and arteriovenous index (AVI). These parameters were compared using receiver operating characteristics with p-values of <0.05 considered to indicate statistical significance. RESULTS: Eighty-three histopathological proven lesions from 54 patients (mean age 53.87 years, SD 12.34, range 26-78 years) were analysed. Forty-one per cent (n=34) were benign and 59% (n=49) were malignant. All malignant and 38.2% (n=13) benign lesions were visualised on the ultrafast protocol. Of the malignant lesions, 77.6% (n=53) were invasive ductal carcinoma (IDC) and 18.4% (n=9) were ductal carcinoma in situ (DCIS). The MS for malignant lesions (13.27%/s) were significantly larger than for benign (5.45%/s; p<0.0001). No significant differences were seen for TTE and AVI. The area under the ROC curve (AUC) for the MS, TTE, and AVI were 0.836, 0.647, and 0.684, respectively. Different types of invasive carcinoma had similar MS and TTE. The MS of high-grade DCIS was also similar to that of IDC. Lower MS values were observed for low-grade (5.3%/s) compared to high-grade DCIS (14.8%/s) but the results were not significant statistically. CONCLUSION: The ultrafast protocol showed potential to discriminate between malignant and benign breast lesions with high accuracy using MS.

Management of Lobular Neoplasia Diagnosed by Core Biopsy.

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.

Should low-risk DCIS lose the cancer label? An evidence review.

BACKGROUND: Population mammographic screening for breast cancer has led to large increases in the diagnosis and treatment of ductal carcinoma in situ (DCIS). Active surveillance has been proposed as a management strategy for low-risk DCIS to mitigate against potential overdiagnosis and overtreatment. However, clinicians and patients remain reluctant to choose active surveillance, even within a trial setting. Re-calibration of the diagnostic threshold for low-risk DCIS and/or use of a label that does not include the word 'cancer' might encourage the uptake of active surveillance and other conservative treatment options. We aimed to identify and collate relevant epidemiological evidence to inform further discussion on these ideas. METHODS: We searched PubMed and EMBASE databases for low-risk DCIS studies in four categories: (1) natural history; (2) subclinical cancer found at autopsy; (3) diagnostic reproducibility (two or more pathologist interpretations at a single time point); and (4) diagnostic drift (two or more pathologist interpretations at different time points). Where we identified a pre-existing systematic review, the search was restricted to studies published after the inclusion period of the review. Two authors screened records, extracted data, and performed risk of bias assessment. We undertook a narrative synthesis of the included evidence within each category. RESULTS: Natural History (n = 11): one systematic review and nine primary studies were included, but only five provided evidence on the prognosis of women with low-risk DCIS. These studies reported that women with low-risk DCIS had comparable outcomes whether or not they had surgery. The risk of invasive breast cancer in patients with low-risk DCIS ranged from 6.5% (7.5 years) to 10.8% (10 years). The risk of dying from breast cancer in patients with low-risk DCIS ranged from 1.2 to 2.2% (10 years). Subclinical cancer at autopsy (n = 1): one systematic review of 13 studies estimated the mean prevalence of subclinical in situ breast cancer to be 8.9%. Diagnostic reproducibility (n = 13): two systematic reviews and 11 primary studies found at most moderate agreement in differentiating low-grade DCIS from other diagnoses. Diagnostic drift: no studies found. CONCLUSION: Epidemiological evidence supports consideration of relabelling and/or recalibrating diagnostic thresholds for low-risk DCIS. Such diagnostic changes would need agreement on the definition of low-risk DCIS and improved diagnostic reproducibility.

A review of quantitative diffusion-weighted MR imaging for breast cancer: Towards noninvasive biomarker.

Quantitative diffusion-weighted imaging (DWI) is an important adjunct to conventional breast MRI and shows promise as a noninvasive biomarker of breast cancer in multiple clinical scenarios, from the discrimination of benign and malignant lesions, prediction, and evaluation of treatment response to a prognostic assessment of breast cancer. Various quantitative parameters are derived from different DWI models based on special prior knowledge and assumptions, have different meanings, and are easy to confuse. In this review, we describe the quantitative parameters derived from conventional and advanced DWI models commonly used in breast cancer and summarize the promising clinical applications of these quantitative parameters. Although promising, it is still challenging for these quantitative parameters to become clinically useful noninvasive biomarkers in breast cancer, as multiple factors may result in variations in quantitative parameter measurements. Finally, we briefly describe some considerations regarding the factors that cause variations.

Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?

BACKGROUND: The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour. METHODS: This descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017-2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed. RESULTS: ER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population. CONCLUSION: These morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.

Increasing socioeconomically disadvantaged patients' engagement in breast cancer surgery decision-making through a shared decision-making intervention (A231701CD): protocol for a cluster randomised clinical trial.

INTRODUCTION: Socioeconomic disparities for breast cancer surgical care exist. Although the aetiology of the observed socioeconomic disparities is likely multifactorial, patient engagement during the surgical consult is critical. Shared decision-making may reduce health disparities by addressing barriers to patient engagement in decision-making that disproportionately impact socioeconomically disadvantaged patients. In this trial, we test the impact of a decision aid on increasing socioeconomically disadvantaged patients' engagement in breast cancer surgery decision-making. METHODS AND ANALYSIS: This multisite randomised trial is conducted through 10 surgical clinics within the National Cancer Institute Community Oncology Research Program (NCORP). We plan a stepped-wedge design with clinics randomised to the time of transition from usual care to the decision aid arm. Study participants are female patients, aged ≥18 years, with newly diagnosed stage 0-III breast cancer who are planning breast surgery. Data collection includes a baseline surgeon survey, baseline patient survey, audio-recording of the surgeon-patient consultation, a follow-up patient survey and medical record data review. Interviews and focus groups are conducted with a subset of patients, surgeons and clinic stakeholders. The effectiveness of the decision aid at increasing patient engagement (primary outcome) is evaluated using generalised linear mixed-effects models. The extent to which the effect of the decision aid intervention on patient engagement is mediated through the mitigation of barriers is tested in joint linear structural equation models. Qualitative interviews explore how barriers impact engagement, especially for socioeconomically disadvantaged women. ETHICS AND DISSEMINATION: This protocol has been approved by the National Cancer Institute Central Institutional Review Board, and Certificate of Confidentiality has been obtained. We plan to disseminate the findings through journal publications and national meetings, including the NCORP network. Our findings will advance the science of medical decision-making with the potential to reduce socioeconomic health disparities. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03766009).