Approximately 80% of breast cancers (BC) are estrogen receptor (ER)-positive and thus endocrine therapy (ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of (1) ovarian function suppression (OFS), usually obtained using gonadotropinreleasing hormone agonists (GnRHa); (2) selective estrogen receptor modulators or down-regulators (SERMs or SERDs); and (3) aromatase inhibitors (AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs (i.e. , tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ , especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs (i.e. , fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs (i.e. , anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors (palbociclib) and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.
BackgroundLung cancer is one of the most incident neoplastic diseases, and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma.MethodsData from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1047 cases; ALK alterations were determined with fluorescence in situ hybridization in 899 cases, and cMET amplifications in 788 cases.ResultsKRAS mutations were the most common genetic alterations involving 22.1% of the cases and being mutually exclusive with the EGFR mutations, which were found in 12.6% of them. BRAF mutations, ALK rearrangements, and cMET amplifications were detected in 3.2, 5.3, and 2.1% of the cases, respectively. Concomitant mutations were detected only in a few cases.ConclusionsAlmost all the genetic alterations studied showed a similar incidence in comparison with other Caucasian populations. Concomitant mutations were rare, and they probably have a scarce impact on the clinical management of Sardinians with lung adenocarcinoma. The low incidence of concomitant cMET amplifications at diagnosis suggests that these alterations are acquired in subsequent phases of the disease, often during treatment with TKIs.
In the sentinel node era, axillary dissection (ALND) for breast cancer (BC) is required much less frequently than in the past. However, complications, such as prolonged drainage output and seroma formation, are still observed. Harmonic dissection devices (HDDs) are widely used in laparoscopic and minimally invasive surgery to reduce collateral damage during tissue dissection, but its usefulness in breast surgery is unclear. The aim of this study was to evaluate the efficacy of HDDs compared to that of conventional dissection in performing ALND. One hundred thirty-nine women (median age 61 years, range 34-71 years) with confirmed pT1-2 primary infiltrating ductal BC undergoing curative surgery were enrolled in the study. The population was prospectively randomized between two age- and stage-matched arms: group A (cases)-68 (48.9 %) patients (HDD technique), versus group B (controls)-71 (51.1 %) patients (conventional technique). In group B, skin flaps were obtained using a scalpel, scissors, and electrocautery which was never used for ALND. In group A, for each operation time, the HDDs were used exclusively. The mean operative time, intraoperative blood loss, and drainage output were (A vs. B) 95 ± 22 versus 109 ± 25 min, 56 ± 12 versus 86 ± 15 mL, and 412 ± 83 versus 456 ± 69 mL, respectively (p < 0.01). Twenty-nine (20.9 %) patients developed an axillary seroma: 9 (13.2 %) and 20 (28.2 %) for groups A and B, respectively (p = 0.030). Our study confirms that in patients with BC requiring ALND the use of HDDs is more time efficient than conventional surgery, and reduces intraoperative bleeding, the amount of drainage, and the risk of seroma formation. These results may lead to several short- and long-term advantages. Thus, a careful evaluation of the cost-benefits of nontraditional tools, such as HDDs, should be performed in all patients undergoing modified radical or partial mastectomy and ALND for BC.
PurposeThe objectives of this study were to evaluate the effectiveness of nab-paclitaxel plus gemcitabine (NAB-P/GEM) regimen in an unselected population of patients with advanced inoperable or metastatic pancreatic cancer (PC), and to identify the prognostic factors influencing overall survival (OS).Experimental designPatients with age < 85 years, ECOG-performance status (PS) < 3, and adequate renal, hepatic and hematologic function were eligible. NAB-P (125 mg/m2) and GEM (1000 mg/m2) day 1,8,15 every 4 weeks were employed for 3–6 cycles or until highest response.ResultsOverall, 147 cycles (median 4, range 1–11 cycles) were administered on thirty-seven consecutive patients (median 66 years old, range 40–82) treated. The median overall progression-free survival and OS were 6.2 and 9.2 months, respectively. The G 3–4 dose-limiting toxicity were neutropenia (20.7%), severe anemia (17.2%), and cardiovascular toxicity (10.3%). PS, number of cycles, baseline CA 19–9 and LDH serum levels, were found to be significantly related to OS. The multivariate analysis showed that both number of cycles (HR = 9.14, 95% CI 1.84–45.50, p = 0.001) and PS (HR = 13.18, 95% CI 2.73–63.71, p = 0.001) were independently associated with OS.ConclusionNAB-P/GEM regimen should be used in all patients with advanced or metastatic PC, with the exception of those with serious contraindications to chemotherapy, such as severe renal or hepatic impairment or major cardiovascular diseases.
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