Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab

Breast cancer related lymphedema (BCRL) is frequent but strategies for an individualized risk assessment are lacking. We aimed to define whether tumor-specific pathological features, coupled with clinical and therapeutic data, could help identify patients at risk. Data from 368 patients with node-positive breast cancers were retrospectively collected, including 75 patients with BCRL (0.4\u207b25.6 years follow-up). BCRL was assessed during the standard follow-up oncology visits using the circumferential measurement. Clinicopathologic and therapeutic factors associated with BCRL were integrated into a Cox proportional hazards regression model. Lymphovascular invasion (LVI) was more common in BCRL patients (n = 33, 44% vs. n = 85, 29%, p = 0.01), akin extra nodal extension (ENE) of the metastasis (n = 57, 76% vs. n = 180, 61%, p = 0.02). Sentinel lymph node excision without axillary dissection and extra-axillary radiotherapy were BCRL-unrelated. A higher number of BCRL-positive patients were treated with taxane-based chemotherapy with or without trastuzumab, compared to BCRL-negative patients (p < 0.01). Treatment with trastuzumab and/or taxanes, adjusted for systemic infections, laterality, therapy, and pathological features (i.e., LVI and ENE), had a significant impact in BCRL-free survival (p < 0.01). This work offers new insights on BCRL risk stratification, where the integration of clinical, therapeutic, and tumor-specific pathological data suggests a possible role of anti-human epidermal growth factor receptor 2 (HER2) therapy in BCRL pathogenesis

Mismatch Repair Protein Loss as a Prognostic and Predictive Biomarker in Breast Cancers Regardless of Microsatellite Instability

BackgroundBreast cancers that harbor mismatch-repair (MMR) deficiency and/or microsatellite instability (MSI) might be sensitive to immune checkpoint blockade, but there are currently no specific guidelines for assessing MMR status in breast cancer. Here, we sought to define the clinical value of MMR immunohistochemistry (IHC) and MSI analysis in breast cancers.MethodsWe subjected 444 breast cancers to MMR IHC and MSI analysis. Cases were classified as MMR-proficient (pMMR), MMR-deficient (dMMR), and MMR-heterogeneous (hMMR) based on the loss of immunoreactivity; MSI was defined by instability in the five indicators recommended by the National Cancer Institute for endometrial and colorectal cancers. Correlation of MMR status with patients\u2019 survival was assessed using the Kaplan-Meier estimator. Statistical tests were two-sided.ResultsLoss of MMR proteins was homogeneous (dMMR) in 75 patients (17%) and heterogeneous (hMMR) in 55 (12%). Among luminal breast cancers, there were similar frequencies of dMMR and hMMR tumors. Overall, the rate of discrepancy between IHC and MSI analysis was high (91%). Women with Luminal B-like dMMR carcinomas (n\u2009=\u200944) showed shorter overall survival (median\u2009=\u200977\u2009months, range\u2009=\u20090\u2013115\u2009months) than those with pMMR (n\u2009=\u2009205) or hMMR (n\u2009=\u200935) tumors (median\u2009=\u200984\u2009months, range\u2009=\u20090\u2013127\u2009months) (P\u2009=\u2009.008). On the contrary, patients with estrogen receptor-negative breast cancers treated with chemotherapy lived longer in cases of dMMR (n\u2009=\u20099) than pMMR (n\u2009=\u200933) or hMMR (n\u2009=\u20097) tumors, with 87\u2009months of median survival (range\u2009=\u200973\u2013123\u2009months) for the former compared with 79\u2009months (range\u2009=\u20098\u2013113\u2009months) for the latter two categories (P\u2009<\u2009.001).ConclusionsImmunohistochemistry and MSI are not interchangeable tests in breast carcinomas. MMR protein loss is a more common event than MSI and shows intra-tumor heterogeneity. MMR IHC allows the identification of clinically relevant subclasses of breast cancer patients, provided that multiple areas of the tumor are analyzed

Metabolic Changes and Metabolic Syndrome During the Menopausal Transition

Please check the hierarchy of the section headings and confirm if correct

Medical Treatment of Myomas

Uterine fibroids or myomas are the most frequent benign neoplasm during fertile life in women. It originates from the smooth muscle cells of the uterus (myometrium) [1], and it is frequently found at a gynecological examination or at ultrasound in almost 30 % of the women above 35 years of age. Myomas are usually asymptomatic, but in 30 % of the women, they can induce a variety of symptoms such as dysmenorrhea, menorrhagia, pelvic discomfort, infertility, recurrent abortion, and when there several myomas and/or when they are quite large and heavy, they can induce diseases for the compression of the tissues and/or organs close to the uterus, such as the bladder [2]

Functional Hypothalamic Amenorrhea as Stress Induced Defensive System

Since the activity of the reproductive axis is quite complex and modulated and/or affected by several neurotransmitters, neuromodulators and hormones, it is easy to understand that minimal changes of the equilibrium of few of these substances might induce changes of the reproductive axis leading to the amenorrheic condition. Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It might be considered strange, but such negative hypothalamic response to stress is nothing else than a defensive system. In primate females and in human females in particular, an adaptive mechanism during stress is represented by the reduction of reproductive axis activity, blocking a function that is not essential to survive. Some intermediate steps, such as poly- or oligo-menorrhea can anticipate the occurrence of the amenorrheic condition, which is the last and worst stage of this clinical adaptive response to stress

Standard test methods for rating of solar reflectance of built-up surfaces and potential use of satellite remote sensors

More and more attention is being paid to the solar reflectance of built-up surfaces due to its influence on the summer heating of buildings and urban areas and the consequent effects on energy needs for air conditioning, as well as on the peak load of the electric grid. Several standard test methods are available for measuring solar reflectance in the laboratory or in the field, based on different devices and approaches. A convergence of some methods has been achieved by rating programs in the U.S. and, more recently, in Europe and other areas. However, laboratory or field measurements are impractical for characterizing a large number of urban surfaces—whether it is for identifying critical issues, developing policies, or verifying compliance with building requirements. In this regard, satellite remote sensors have recently become available, through which it is possible to estimate the reflectance of roof and pavement surfaces thanks to a spatial resolution that is suitable for identifying and characterizing individual built-up surfaces. In the present paper, the most-used standard test methods for rating of solar reflectance are reviewed. Subsequently, some publicly accessible satellite sensors are examined, through which comparable measurements could be obtained

PCOS from Lifestyle to the Use of Inositol and Insulin Sensitizers

PCOS patients are typically characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries, and these aspects are frequent in a high percentage of women during the reproductive life. PCOS frequently show overweight and/or obesity and are characterized by a higher production of androgens and reduced sensitivity to insulin. In fact it is of great importance to note that more than 40–45% of all PCOS patients show overweight up to obesity and that these patients have a modest up to an exaggerated hyperinsulinism in response to the standard oral glucose tolerance test (OGTT). What is relevant to point out is that such reduced insulin sensitivity can be observed also in 10–15% of the normal weight PCOS, thus confirming that hyperinsulinism can show up not only in relation to obesity or to excess of fat tissue but also as an intrinsic abnormal ability to control glucose metabolism. Recent data clearly demonstrated that reduced insulin sensitivity can be gained with a specific attention to lifestyle, including not only a diet but also certain degree of physical activity. However, a specific effect on hyperinsulinemia can be achieved using glucose sensitizer drugs, such as metformin, so that to reduce the negative modulation exerted by hyperinsulinemia on the reproductive axis as well as on neuroendocrine control of reproduction with relevant effects also on adrenal function and neurosteroid production. The evolution of therapeutical approach to PCOS proposed in recent years the use of inositol in two of the isomers at present available, that is myo-inositol (MYO) and D-chiro-inositol (DCI). These two compounds are tightly linked one to the other since MYO is transformed by an epimerase in DCI, having each tissue its own conversion rate, likely due to the specific needs for the two different molecules. In general both these compounds work as specific modulators of the intracellular second messenger activated by the insulin linkage with its own membrane receptor. Recent data demonstrated also that integrative administration of MYO in lean PCOS ameliorated insulin response to OGTT and that both MYO and DCI reduced insulin response to OGTT in overweight or obese PCOS. Both isomers have been demonstrated to improve also ovarian function and LH response to GnRH stimulation, typically abnormal in PCOS patients. Though impossible to state what of the two isomers play the main role, it appears clear that the metabolic impairment(s) are great part of the casual factor(s) of the abnormal reproductive function in PCOS

Pharmacological and Integrative Treatment of Stress-Induced Hypothalamic Amenorrhea

Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies