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Introdução: A infecção pelo vírus linfotrópico de células T humanas tipo 1 e tipo 2 (HTLV- 1/2) pode causar doenças graves como leucemias de células T do adulto e mielopatias. A transmissão vertical ocorre durante o aleitamento materno ou pelo colostro doado em bancos de leite. Até abril de 2022 não existiam programas de triagem ou vigilância sorológica da infecção pelo HTLV 1/2 em gestantes no Brasil, o que aumentava o risco de transmissão vertical. A portaria GM/MS n° 175 incluiu a obrigatoriedade da pesquisa de anticorpos IgG anti HTLV 1/2 durante o pré-natal em gestantes atendidas no nosso país, aumentando assim o roll de doenças investigadas nesse período. Objetivo: O objetivo deste estudo foi avaliar a presença de anticorpos IgG específicos anti- HTLV 1/2 em amostras de soro de gestantes atendidas em Unidades Básicas de Saúde (UBS) do município de São Bernardo do Campo, São Paulo, Brasil, no período de outubro a dezembro de 2022, por imunoensaios enzimáticos. Método: Estudo observacional no qual foram testadas 594 amostras de soro de gestantes residentes no município de São Bernardo do Campo, São Paulo, no período de outubro a dezembro de 2022, que procuraram o Laboratório de Análises Clínicas do Centro Universitário FMABC para realizar a sorologia para HTLV 1/2 utilizando imunoensaios enzimáticos (ELISA e Immunoblotting) da empresa Symbiosis®, disponíveis no laboratório. Resultados: Foram analisadas 594 amostras de soro de gestantes residentes no município de São Bernardo do Campo que procuraram o laboratório de Análises Clínicas do Centro Universitário FMABC com solicitação médica para pesquisa de anticorpos IgG anti -HTLV 1/2. A média de idade dessas gestantes foi de 27 anos. A pesquisa de anticorpos foi feita utilizando teste ELISA da empresa Symbiosis® e confirmados pelo método Western blotting. Das 594 amostras testadas,apenas 1 amostra foi reagente para anticorpos IgG no ELISA e no W.blotting, o que corresponde a 0,17% de soroprevalência. Conclusão: Esses resultados sugerem baixa prevalência de infecções por HTLV 1/2 na população, porém o rastreio destes vírus em gestantes em acompanhamento pré-natal é de suma importância, para se evitar a transmissão vertical durante o aleitamento materno ou em bancos de leite.

Abstract In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

Summary: Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9–82.2) and 57.3% (51.7–63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6–80.2) and 50.7% (45.0–56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3–84.2) and 65.3% (59.8–70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0–83.1) and 61.5% (55.9–67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age

The increased use of neoadjuvant chemotherapy (NACT) has changed the approach to breast surgery. NACT allows de-escalation of surgery by both increasing breast conservation rates (up to 40%), the initial goal of this chemotherapy, and in particular it permits reduces axillary surgery. Furthermore, in relation to the molecular characteristics of the tumor we can have a pathological complete response (pCR) ranging from 20 to 80%.In clinically node positive (cN+) patients who converted to clinically node-negative (cN0) various prospective studies have demonstrated that the false negative rate (FNR) of the sentinel node biopsy (SNB) were higher than the acceptable 10% and strategies to reduce the FNR in cN + patients are being investigated.But all the effort to reduce the FNR does not have clinical prognostic significance. This has already been demonstrated in the literature in different randomized trials with long term follow up.The 10-year follow-up of our study confirmed our preliminary data that the use of standard SNB without the use of clip is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.In fact, the axillary recurrences were less than 2%. Similar positive data with different follow up were also confirmed by other studies that used SNB alone without TAD. All these studies, with encouraging results on the follow up, confirm that SN surgery alone for selected patients who have an excellent response to NACT is rationale and not oncologically inferior to AD during a short- and long-term follow-up.

Aim: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR

Background: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a “less intensive” or personalized approach. Patients and methods: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1–3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. Results: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33–76), with mostly pre- and peri-menopausal (65%) and stage I–II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5–100%; interquartile range, IQR: 87.5–100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73–92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77–94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3–4.7) two distant events were observed, and all patients were alive at the date of last visit. Conclusions: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from “pure” DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

Background: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. Patients and methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. Results: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p

Background: Breast cancers show variations in the number and biological aggressiveness of cancer stem cells that correlate with their clinico-prognostic and molecular heterogeneity. Thus, prognostic stratification of breast cancers based on cancer stem cells might help guide patient management. Methods: We derived a 20-gene stem cell signature from the transcriptional profile of normal mammary stem cells, capable of identifying breast cancers with a homogeneous profile and poor prognosis in in silico analyses. The clinical value of this signature was assessed in a prospective-retrospective cohort of 2, 453 breast cancer patients. Models for predicting individual risk of metastasis were developed from expression data of the 20 genes in patients randomly assigned to a training set, using the ridge-penalized Cox regression, and tested in an independent validation set. Findings: Analyses revealed that the 20-gene stem cell signature provided prognostic information in Triple-Negative and Luminal breast cancer patients, independently of standard clinicopathological parameters. Through functional studies in individual tumours, we correlated the risk score assigned by the signature with the proliferative and self-renewal potential of the cancer stem cell population. By retraining the 20-gene signature in Luminal patients, we derived the risk model, StemPrintER, which predicted early and late recurrence independently of standard prognostic factors. Interpretation: Our findings indicate that the 20-gene stem cell signature, by its unique ability to interrogate the biology of cancer stem cells of the primary tumour, provides a reliable estimate of metastatic risk in Triple-Negative and Luminal breast cancer patients independently of standard clinicopathological parameters. Keywords: Breast cancer, Cancer stem cells, Prognostic signatures, Biomarkers, Metastasis

The aim of the present systematic review was to evaluate the hypothesis of an association between periodontitis and the development of cancer.Two reviewers independently screened electronic and manual sources for pertinent articles. Primary outcome measures were the occurrence of neoplasm diagnosis in exposed and non-exposed groups, reported to evaluate association between cancer and periodontitis.Of the 490 initially retrieved papers 10 were included in the qualitative synthesis and eight in the quantitative synthesis; the eight papers covered six studies. Considering hazard ratios, a statistically significant association was found for all cancers studied (1.14; CI 95%: 1.04, 1.24), digestive tract cancer (1.34; CI 95%: 1.05, 1.72), pancreatic cancer (1.74; CI 95%: 1.21, 2.52), prostate cancer (1.25; CI 95%: 1.04, 1.51), breast cancer (1.11; CI 95%: 1.00, 1.23), corpus uteri cancer (2.20; CI 95%: 1.16, 4.18), lung cancer (1.24; CI 95%: 1.06, 1.45), hematological cancer (1.30; CI 95%: 1.11, 1.53), esophagus / oropharyngeal cancer pooled together (2.25; CI 95%: 1.30, 3.90) and Non-Hodgkin lymphoma (1.30; CI 95%: 1.11, 1.52).Despite the sparse scientific evidence and considering the low statistical power of the results, this systematic review revealed a substantial lack of studies with standardized and comparable methods to speculate about the association between periodontitis and cancer; more studies are need in order to explore further the scientific evidence of such correlation.