Assessing variability in breast cancer management across the world. Results of a questionnaire survey amongst global international experts in breast cancer management

Background: breast cancer is the most common cancer in women worldwide with an estimated 2.3 million breast cancer cases diagnosed annually. The outcome of breast cancer management varies widely across the globe which could be due to a multitude of factors. Hence, a blanket approach in standardisation of care across the world is neither practical nor feasible. Aim: to assess the extent and type of variability in breast cancer management across the globe and to do a gap analysis of patient care pathway. Method: an online questionnaire survey and virtual consensus meeting was carried out amongst 31 experts from 25 countries in the field of breast cancer surgical management. The questionnaire was designed to understand the variability in diagnosis and treatment of breast cancer, and potential factors contributing to this heterogeneity. Result: the questionnaire survey shows a wide variation in breast surgical training, diagnosis and treatment pathways for breast cancer patients. There are several factors such as socioeconomic status, patient culture and preferences, lack of national screening programmes and training, and paucity of resources, which are barriers to the consistent delivery of high-quality care in different parts of the world. Conclusion: on-line survey platforms distributed to global experts in breast cancer care can assess gaps in the diagnosis and treatment of breast cancer patients. This survey confirms the need for an in-depth gap analysis of patient care pathways and treatments to enable the development of personalised plans and policies to standardise high quality care

p53 expression in breast cancer predicts tumors with low probability of non-sentinel nodes infiltration.

AIM: Several predictive tools of non-sentinel lymph nodes neoplastic involvement when a positive sentinel lymph node is found have been described. However, molecular factors have been rarely evaluated to build these tools. The aim of this study was to establish which factors predicted non-sentinel lymph nodes infiltration in our setting, including some molecular factors. MATERIAL AND METHODS: We carried out a retrospective review of 161 patients with breast cancer and a positive sentinel lymph node who had undergone axillary lymph node dissection, none of whom had received neoadjuvant treatment. Features evaluated as predictive factors for non-sentinel node positivity were: menopausal status, tumor size, histological subtype, histological grade, lymphovascular invasion, extracapsular invasion, Ki67 index, hormonal receptors, CerbB2 and p53 expression, size of sentinel lymph node metastases and number of sentinel lymph nodes affected. RESULTS: Tumor size (P = 0.001), size of sentinel lymph node metastases (P = 0.001), lobular invasive carcinoma (P = 0.05) and lymphovascular invasion (P = 0.006) were significantly associated with non-sentinel lymph node positivity. Tumor p53 positive expression was strongly associated with non-sentinel lymph node negativity (P = 0.000). In multivariate analysis, all these factors but tumor size maintained their significance. The discrimination power of the model calculated by the area under the receiver-operator curve was 0.811 (95% confidence interval, 0.741-0.880). CONCLUSION: p53 expression in breast cancer was highly predictive of non-sentinel lymph node negativity in our study. New studies should evaluate if it would be useful to add p53 expression to other existing predictive tools.This research was funded by theinternal resources of the departments involved (Breast Functional Unit, Obstetrics and Gynecology Department, Nuclear Medicine Department and Pathology Departmen

Impact of detection mode in a large cohort of women taking part in a breast screening program

Objective: the aim of this study was to evaluate the existing survival rate and clinical-pathological differences among patients with breast cancer detected by mammographic screening. Materials and methods: this multicenter cohort study examined 1,248 patients who took part in a national screening program for the early detection of breast cancer over an eight-year period. Results: of the two patient subgroups (interval and screening), we found significant differences in the distribution of prognostic factors, with interval cases presenting at a lower mean age (p = 0.002), with higher percentages of human epidermal growth factor receptor 2 (HER-2) or triple negative and lower percentages of luminal A or luminal B carcinomas (p = 0.001), advanced stages (p<0.001), lower hormone receptor expression (p<0.001), poorer differentiation (p<0.001) and lower survival (p<0.001). Among the screening group, patients with tumors detected during the first screening round had a significantly lower mean age (p<0.001), a lower frequency of comorbidities (p = 0.038) and a lower tendency (p<0.1) to be diagnosed as triple negative breast carcinomas than incident cases. Conclusion: our results highlight that breast tumors detected during the first screening round are frequently characterized by a more benign phenotype than the rest of the screening subgroups, which could be of help when stratifying the risk of death and selecting the best treatment option for each patient

Human papillomavirus and breast cancer: no evidence of association in a Spanish set of cases.

BACKGROUND/AIM: Great controversy exists about the association between Human Papillomavirus (HPV) and breast tumors. The aim of this study was to explore the presence of HPV DNA in a large set of breast cancer cases. MATERIALS AND METHODS:/nTechniques used followed the standards for an international retrospective survey of HPV-DNA genotyping, coordinated by our own group and the DDL Laboratories in Rijswijk, the Netherlands. Paraffin-embedded samples were used. SPF-10 broad-spectrum primers were applied, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse-line probe assay./nRESULTS: A total of 78 samples were included in the study, 2 of benign conditions and 76 carcinomas, including different histological subtypes. HPV was not present in any of the specimens studied irrespective of histology, hormonal status and stage of disease. CONCLUSION: Our data do not support the involvement of HPV in breast carcinogenesis as no evidence of its presence was found.This research was funded by the internal resources of the departments involved (Breast Functional Unit, Obstetrics and Gynaecology Department and Pathology Department from Hospital del Mar; and IDIBELL from Catalan Institute of Oncology) ;sample processing at IDIBELL institute was partially funded by resources from a grant from Lilly foundation( Premio de Investigación Biomédica Preclínica /n2012 F. Xavier Bosch

Impact of adjuvant chemotherapy on the survival of patients with breast cancer diagnosed by screening

The aim of this study is to determine the survival of patients with breast cancer treated with adjuvant chemotherapy (ACh) after the diagnosis by screening, taking comorbidity into account. This multicenter cohort study examined a population of patients taking part in four national screening programs for the early detection of breast cancer (localized or locally advanced), during the period 2000-2008. Of the 1248 cancers detected, 266 were prevalent (21.3%), 633 were incident (50.7%), and 349 were interval (27.9%). No significant differences were detected between the three groups in terms of the distribution of comorbidity according to the CCI. After a median follow-up of 102 months, 22.1% of the patients with interval cancer had died. The corresponding figures for the incident and prevalent cancers were 10.4% and 7.9%, respectively (P < .001). The adjusted Cox regression analysis by the stage, CCI and group revealed no differences in the risk of recurrence between the different groups according to the ACh performed. However, there were significant differences in the overall survival; for the interval cancer group without ACh, the risk of death was higher (Hazard ratio: 2.5 [1.0-6.2]) than for the other two groups. However, for the prevalent and incident groups that did not receive ACh, there was no greater risk of death. This study shows that adjuvant chemotherapy seems to benefit patients with interval breast cancer, who have a poorer prognosis than those with prevalent or incident cancer. However, the role of ACh is unclear with respect to prevalent and incident cancers when comorbidity is taken into account

Developing and validating an individualized breast cancer risk prediction model for women attending breast cancer screening

Background: Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening. Methods: Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve. Results: During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected. Conclusions: We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs

Risk of breast cancer two years after a benign biopsy depends on the mammographic feature prompting recall

Objective: We aimed to explore whether the type of mammographic feature prompting a false-positive recall (FPR) during mammography screening influences the risk and timing of breast cancer diagnosis, particularly if assessed with invasive procedures. Study design: We included information on women screened and recalled for further assessment in Spain between 1994 and 2015, with follow-up until 2017, categorizing FPRs by the assessment (noninvasive or invasive) and mammographic feature prompting the recall. Main outcome measures: Breast cancer rates in the first two years after FPR (first period) and after two years (second period). Results: The study included 99,825 women with FPRs. In both periods, the breast cancer rate was higher in the invasive assessment group than in the noninvasive group (first period 12 ‰ vs 1.9 ‰, p < 0.001; second period 4.4‰ vs 3.1‰, p < 0.001). During the first period, the invasive assessment group showed diverse breast cancer rates for each type of mammographic feature, with a higher rate for asymmetric density (31.9‰). When the second period was compared with the first, the breast cancer rate decreased in the invasive assessment group (from 12‰ to 4.4‰, p < 0.001) and increased in the noninvasive assessment group (from 1.9‰ to 3.1‰, p < 0.001). Conclusion: In the context of mammography screening, the risk of breast cancer diagnosis during the first two years after FPR was particularly high for women undergoing invasive assessment; importantly, the risk was modified by type of mammographic feature prompting the recall. This information could help to individualize follow-up after exclusion of malignancy

Intraoperative irradiation in breast cancer: preliminary results in 80 patients as partial breast irradiation or anticipated boost prior to hypo-fractionated whole breast irradiation

Data de publicació electrònica: 18-11-2021Purpose: To present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes. Materials and methods: Eighty patients treated with an Intrabeam® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits. Results: Thirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group. Conclusion: IORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI

Accuracy of sentinel node mapping in patients with biopsy-proven metastatic axillary lymph nodes and upfront surgery: preliminary results of the Multimodal Targeted Axillary Surgery (MUTAS) trial

Background: Some studies suggested that the patients included in the Z0011 trial may represent patients with ultrasound-negative axillary nodes and axillary invasion diagnosed by sentinel node (SN) biopsy. Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend SN mapping if 1 or 2 suspicious lymph nodes are identified on axillary ultrasound (AU). The aim of this preliminary phase of the Multimodal Targeted Axillary Surgery (MUTAS) trial was to establish the accuracy of SN mapping in patients with axillary involvement undergoing upfront surgery. Methods: Between September 2019 and March 2022, we recruited patients with biopsy-proven metastatic axillary nodes and upfront surgery from a single center. We performed SN mapping in these patients before the surgical intervention, which included axillary lymph node dissection. The biopsy-proven metastatic node, SNs and the remaining axillary nodes were excised separately. SN status was considered representative of the status of the remaining axillary nodes. We calculated the sensitivity, specificity, negative predictive value and positive predictive value of the SN, overall and in patients with palpable nodes, in those with non-palpable nodes and an AU leading to diagnosis of axillary involvement, in those with 1 or 2 suspicious nodes on AU, and in patients with a single suspicious node on AU. We evaluated clinical, imaging and pathology features as predictors of the status of the remaining axillary nodes, false-negatives, and false-positives. Results: We included 25 patients in this phase. The false-negative rate of SN mapping was 28% overall, 21.42% for patients with palpable nodes, 36.36% for patients with non-palpable nodes and an AU diagnosis of axillary involvement, 28.75% for those with 1 or 2 suspicious nodes on AU, and 15.38% in patients with a single suspicious node on AU. The negative predictive value was highest in patients with a single suspicious node on AU (75%). The only significant predictive factor was that FN showed a higher Ki67 index score. Conclusions: In this study, SN mapping was not reliable in patients with biopsy-proven metastatic axillary nodes and upfront surgery for any of the subgroups studied. Further research should elucidate the best staging pathways in these patients to avoid premature de-escalation

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern