The global burden of cancer is growing and a wide disparity in the incidence, malignancy and mortality of different types of cancer between each sex has been demonstrated. The sex specificity of cancer appears to be a relevant issue in the management of the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Sex hormones are presumably the leading actors of sex differences in cancer, especially estrogens. They modulate gene expression, alter molecules and generate disparities in effectiveness and side effects of anticancer therapies. Recently immunotherapy aims to improve anticancer treatment strategies reducing off-target effects of chemotherapy and direct cancer cells killing. It is recognized as a fruitful strategy to treat and possible to cure cancer. Immunotherapeutic agents are used to activate or boost the activation of the immune system to fight cancer cells through physiological mechanisms often evaded in the offensive march of the disease. These therapeutic strategies have allowed new successes, but also have serious adverse effects including non-specific inflammation and autoimmunity. Sex and gender issues are of primary importance in this field, due to their recognized role in inflammation, immunity and cancer, and the clarification and understanding of these aspects is a necessary step to increase the responses and to diminish the adverse effects of immunotherapy. This review describes the available knowledge on the role of sex and gender in cancer immunotherapy, and will offer insights to stimulate the attention and practice of clinicians and researchers in a gender perspective of new cancer treatment strategies.

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) plays a crucial role in the control of cellular growth, proliferation, survival, metabolism, angiogenesis, transcription, and translation. In most human cancers, alterations to this pathway are common and cause activation of other downstream signaling pathways linked with oncogenesis. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both tumor immunity and angiogenesis. Inflammation is a hallmark of cancer, playing a central role in the tumor dynamics, and immune cells can exert antitumor functions or promote the growth of cancer cells. In this context, mTOR may regulate the activity of macrophages and T cells by regulating the expression of cytokines/chemokines, such as interleukin (IL)-10 and transforming growth factor (TGF-β), and/or membrane receptors, such as cytotoxic T-Lymphocyte protein 4 (CTLA-4) and Programmed Death 1 (PD-1). Furthermore, inhibitors of mammalian target of rapamycin are demonstrated to actively modulate osteoclastogenesis, exert antiapoptotic and pro-differentiative activities in osteoclasts, and reduce the number of lytic bone metastases, increasing bone mass in tumor-bearing mice. With regard to the many actions in which mTOR is involved, the aim of this review is to describe its role in the immune system and bone metabolism in an attempt to identify the best strategy for therapeutic opportunities in the metastatic phase of solid tumors.

Neuroendocrine breast cancer (NEBC) is a rare histotype of breast carcinoma that presents, in most cases, positive hormone receptors and negative HER2. Indeed, the analysis of gene expression profiles revealed that NEBC belongs mainly to the luminal subtype. Cases of HER2-positive and triple-negative NEBC are rare. The cardinal treatment of early NEBC is surgery, similar to the treatment of invasive non-special histological type carcinoma. The use of radiotherapy follows the criteria applied in infiltrating breast cancer of non-special histotype. In the post-operative phase, therefore after the surgical treatment of mammary quadrantectomy, or mastectomy associated with homolateral sentinel lymph node removal ± axillary dissection, based on the histopathological characteristics of the tumor, the use of chemotherapy (anthracycline + taxane) and/or hormone therapy, whether or not associated with anti-HER2 therapy (trastuzumab) is the rule. Literature data report the use of cisplatin and etoposide, as in small cell lung cancers. Most of the information currently available derive from single case reports or a series of clinical cases; it follows the difficulty of formulating definite recommendations on the correct management of this histological type of breast cancer. This review describes available knowledge on this rare entity to improve the diagnostic and therapeutic strategies and offer insights to stimulate exploration of the many aspects still unknown.

Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to select first-line therapy for patients with metastatic breast cancer (MBC), but considering the high number of level II alterations, according to the ESMO scale for clinical actionability of molecular targets (ESCAT), it is suggested to include patients in molecular screening programs in order to be able to offer targeted therapies for specific genomic alterations. This article aims at reviewing the most recent literature related to the most used methodologies/approaches for molecular diagnostics and variants’ classification, summarizing the internationally published molecular screening studies in support of MTB activity and, in the end, discussing MTBs’ current position and role in Italy, the number of which is increasing, also thanks to the thrust of institutions.

Breast cancer (BC) diagnosis and treatment have become a cumulative long-standing chronic disease impairment, causing stress and turning into an allostatic load (AL) framework. This study aimed to investigate the relationship between physical issues and mental health in patients with BC after medical treatment. We conducted an observational study of 61 female patients with BC, and clinical and psychological markers have been detected. We conducted descriptive statistics, ANOVA analyses, correlations, and mediation analyses to verify the effect of the comorbidity index on psychological dimensions. The findings showed high levels of distress and moderate pain, and 32.8% of the patients showed moderate physical impairment. Significant effects of “age” and “physical issues” were found. The adult group reported a higher incidence of physical issues, and the group of patients reporting moderate physical impairment seemed more depressed than patients with mild physical issues. Finally, the comorbidity condition mediated the presence of signs of depression. Patients with BC seemed to experience negative emotions related to comorbidities associated with compromised activities of daily living. Our findings highlighted allostatic overload as a predictive framework to better understand the mental health of women with BC diagnoses to tailor effective psychological treatments for enhanced recovery.