Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.

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Gene expression profiling predicts clinical outcome of breast cancer

Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a...

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A Gene-Expression Signature as a Predictor of Survival in Breast Cancer

background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)

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Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer

Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Nocturia: An Uncommon Presentation of Lower-Limb Lymphedema

Lymphedema is always initially treated by combined decongestive physiotherapy (CDP). Those cases, refractory to CDP, may be managed by surgical therapy. One of the most used microsurgical procedures is represented by the technique of lymphatic‐venous anastomosis (LVA). But very few papers report long term results of LVA. The aim of this study is to assess the long‐term patency of multiple lymphatic‐venous anastomosis (MLVA) for the treatment of secondary lymphedemas.

Long‐term patency of multiple lymphatic‐venous anastomoses in cancer‐related lymphedema: A single center observational study

According to the recent St Gallen Consensus Conference helded in 1998, almost every breast cancer patient, both node positive and node negative, should be treated with some form of adjuvant therapy'>, Such recommendations, listed in the Table, are mainly based on the Early Breast Cancer Trialists' Group results'v\" demonstrating a survival benefit for almost patients treated with adjuvant chemotherapy, or tamoxifen, and in particular with the administration of chemotherapy and tamoxifen. In fact, following adjuvant chemoand/or hormonal therapy, the proportional reduction in risk of recurrence and death are similar in high and low risk patients. Adjuvant polychemotherapy is able to produce an absolute improvement of approximately 7% in node negative patients and 11 % in node positive patients in 10-year survival for women aged under 50 years, and approximately 2% in node negative and 3% in node positive patients for those aged 50-69 years\". The metanalysis of randomized trials using tamoxifen has also shown a proportional reduction in risk of recurrence and death similar for node negative and node positive patients. According to the different risks, the absolute reduction in recurrence and mortality were greater in node positive women. In the studies of 5 years of adjuvant tamoxifen, the absolute improvements in lO-year survival were 10.9% for node positive and 5.6% for node negative women, irrespective of age and menopausal status!\", However, adjuvant therapy is worthwhile only if improvement in outcome is greater than costs and toxicity, because the number of patients who benefit compared to the total number of patients treated depends on the risk profile: the low the risk, the lower the proportion of patients who benefit. Nevertheless, even a modest gain in survival is generally accepted to apply adjuvant therapy, as indicated in a recent survey of American breast cancer patients in which the median acceptable extension of life expectancy as a benefit from adjuvant chemotherapy was only 3-6 months\". In the early ninety, the main question was whether a patients was at risk enough to justify toxicity from chemotherapy, so that adjuvant chemotherapy was restricted only to patients with positive nodes while node negative breast cancer patients were considered at a very good prognosis. Available data at that time were contradictory or missing, not providing much informations on the magnitude of the benefit in this group of patients, because none of the trials at that time have yet shown a survival benefit or, when observed, it was misleading due to small number of patients or short follow up time!\". Nowadays, the question is shifted to whether the risk of an individual patient is low enough to justify avoiding from adjuvant treatment, knowing that adjuvant therapy has the potential to improve outcome in almost all breast cancer patients. As a consequence, in node negative patients, instead of asking \"why use chemotherapy?\" we now have to ask \"why not?\". When not to use adjuvant chemotherapy is now a matter for individual patients and physicians to evaluate survival odds versus toxicity, using what clues they have about the risk of recurrence, such as tumor size, grade, and hormonal receptor status.

Adjuvant therapy for patients with node negative breast cancer.

A Case of Plasmacytoid Variant of Bladder Cancer With a Single Penile Metastasis and a Complete Response to Carboplatin-Based Chemotherapy and Review of the Literature.

Estrogen (ER) and progesterone (PgR) receptors were evaluated in the tumor tissue (T) and in the mammary gland far from malignancy (D) in 36 breast cancers. Results were correlated with the pathological grading of the tumor and the axillary nodal status. It is suggested that a lower cancer malignancy with negative nodes and lower values of pathological grading (G1-G2) may be associated with a high level of ER in the mammary parenchyma far from the tumor (D).

Francesco Boccardo

Papers

Nocturia: An Uncommon Presentation of Lower-Limb Lymphedema

Long‐term patency of multiple lymphatic‐venous anastomoses in cancer‐related lymphedema: A single center observational study

Adjuvant therapy for patients with node negative breast cancer.

A Case of Plasmacytoid Variant of Bladder Cancer With a Single Penile Metastasis and a Complete Response to Carboplatin-Based Chemotherapy and Review of the Literature.

Hormone receptors in breast cancer: a conservative determination of receptors' presence in tumor tissue and ipsilateral normal mammary gland.