Estrogenicity of essential oils is not required to relieve symptoms of urogenital atrophy in breast cancer survivors.

BACKGROUND: Urogenital atrophy (UA) is a common treatment-limiting side effect of endocrine therapies. Topical estrogen is effective but systemic absorption may counter aromatase inhibitor efficacy. Numerous complementary approaches are marketed for use in UA without rigorous testing of their estrogenicity. We tested multiple essential oils in cancer cell growth and estrogen reporter assays in vitro and assessed clinical outcomes with the essential oil pessaries (EOPs) in breast cancer survivors with UA. METHODS: Effects on cell growth were tested in hormone-dependent (MCF-7) and -independent (MDA-MB-231) cell lines using the sulforhodamine-B assay. An estrogen response element (ERE) luciferase reporter assay was used to assess estrogenicity directly. Antifungal activity against two common pathogenic yeasts was assessed using standard microdilution methods. EOPs were offered to breast cancer survivors with symptomatic UA and the service evaluated using serial questionnaires. RESULTS: Two essential oils, Cymbopogon martinii and Pelargonium graveolens, demonstrated marked estrogenicity, stimulating ER+ cell growth and ERE-luciferase reporter activity to levels seen with premenopausal estradiol concentrations. Additional oils were screened for estrogenicity and Lavandula angustifolia and Chamaemelum nobile identified as non/minimally estrogenic. The antifungal activity of this combination of oils was confirmed. A second cohort of breast cancer survivors with UA received the second generation EOP with comparable improvement in symptom scores suggesting that estrogenicity may not be required for optimal therapy of UA. CONCLUSION: Certain essential oils demonstrate profound estrogenicity and caution should be exercised before their use in breast cancer survivors. Our minimally estrogenic pessary will be formally tested in clinical trials.

Hormone-receptor positive breast cancer: highlights from the 39TH San Antonio Breast Cancer Symposium.

The San Antonio Breast Cancer Symposium is considered one of the most influential international meetings focusing on breast cancer management, covering several areas of study from basic research to clinical practice topics. a number of oral presentations addressing hormone receptor-positive breast cancer brought new data about critical subjects like the optimal duration of adjuvant endocrine therapy, new prognostic markers and their potential role in guiding adjuvant treatment choices, new insights into genomic alterations acquired during the metastatic process, and pharmacologic strategies to overcome resistance to endocrine therapy. This article aims at summarizing some of the presentations that, in our opinion, are expected to have an impact on clinical practice and research programs in this patient population.

New and developing chemical pharmacotherapy for treating hormone receptor-positive/HER2-negative breast cancer.

INTRODUCTION: Endocrine therapy is the mainstay of treatment for a substantial proportion of hormone receptor positive (HR+) breast cancer (BC). Indeed, patients with metastatic disease not immediately life threatening may experience long disease control across several lines of endocrine therapy. The major limitation of this therapeutic approach is primary or acquired resistance. A better understanding of endocrine resistance has resulted in newer targeted agents to be added to endocrine therapy. Areas covered: This review highlights new findings in the treatment of HR+/HER2- BC, with a particular focus on new drugs from phase 3 development onwards. Expert opinion: Combining endocrine therapy with agents targeting putative mechanisms of endocrine resistance is a newer treatment paradigm in HR+ BC. Adding a biologically targeted agent to endocrine therapy results in improved response rate, and clinical benefit rate, and prolonged progression-free survival. A clear advantage in overall survival has not yet been reported. Combination therapy allows to delay chemotherapy but increases toxicities and costs, which are critical factors in decision making in the clinical practice. Moreover, identification and validation of biomarkers of response are needed. Ongoing and future trials should elucidate the role of these compounds in the treatment of HR+/HER2- BC.

Investigational ErbB-2 tyrosine kinase inhibitors for the treatment of breast cancer.

INTRODUCTION: ErbB2 overexpression and/or gene amplification is present in 20% of all breast cancers and characterizes an aggressive form of this disease. Despite the availability of several active drugs that have yielded substantial survival improvements, most patients with ErbB2-positive metastatic disease will develop tumor progression, either because of primary or acquired resistance. Therefore, research has focused on drugs that can more efficiently interfere with ErbB2 and with other members of the epidermal growth factor receptor family. AREAS COVERED: This review focuses on those investigational drugs that inhibit ErbB2 tyrosine kinase activity (TKIs) for treating breast cancer. EXPERT OPINION: ErbB-targeting TKIs show encouraging activity in patients with ErbB-positive tumors that are resistant to conventional ErbB-therapies (mostly trastuzumab), confirming pre-clinical observations. Efficient interference with the ErbB-network signaling implies also a potential use in ErbB2-normal tumors, where the phenotype is sustained by ErbB-aberrant signaling. Finally, early data suggests that ErbB-targeting TKIs could be active in treating patients with activating ErbB2 mutations. Ongoing and future research efforts should elucidate what is, according to the peculiarities of these compounds, their positioning in the treatment of women with breast cancer.

Breast cancer in BRCA mutation carriers: medical treatment.

About 10% of breast cancers are associated with the inheritance of autosomal dominant breast cancer susceptibility alleles BRCA1 and BRCA2. Until recently, the medical management of BRCA mutation-associated breast cancer has not differed from that of the sporadic breast cancer counterpart. However, there is mounting evidence that this molecular alteration confers sensitivity or resistance to systemic therapies that can be exploited in terms of medical management. For example, studies support the use of platinum salts chemotherapy in BRCA mutated cancers. Moreover, a number of targeted therapies are showing activity in BRCA mutation carriers. Above all, BRCA defective tumor cells are particularly sensitive to Poly(ADP-ribose) polymerase (PARP) inhibitors. This review will summarize the state of the art of the medical treatment of breast cancer in BRCA mutation carriers, with a particular focus on chemotherapies and targeted therapies.

Clinical utility of exemestane in the treatment of breast cancer.

Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its clinical use, and its side effects. Exemestane is a steroidal third-generation AI now used in all treatment settings for breast cancer. In the metastatic disease, it has been extensively investigated as the first-, second-, and further-line treatment and it is now registered for the treatment of postmenopausal women with advanced estrogen-receptor-positive breast cancer whose disease has progressed following antiestrogen therapy. A potential lack of cross-resistance with nonsteroidal AIs has been described, giving additional therapeutic opportunities in sequences of endocrine agents. Exemestane is also approved for the adjuvant treatment of postmenopausal early breast cancer, either as upfront monotherapy for 5 years, as a switch following 2-3 years of tamoxifen, or as extended therapy beyond 5 years of adjuvant treatment. New promising data also showed a beneficial effect in young premenopausal early breast cancer patients, when administered together with ovarian suppression. Interesting results have also emerged when exemestane has been investigated as neodjuvant treatment as well as preventive agent in healthy women at high risk for breast cancer. Exemestane is generally well tolerated, with a side effect profile similar to that of other AIs, including menopausal symptoms, arthralgia, and bone loss. In conclusion, exemestane can be considered an effective and well-tolerated endocrine treatment option for all stages of breast cancer.

Linifanib: current status and future potential in cancer therapy.

Angiogenesis is one of the major mechanisms controlling tumor proliferation and metastatic spreading. Targeting of pro-angiogenic factors and their downstream effectors represents an appealing therapeutic option in the treatment of different cancer types. Linifanib (ABT-869) is a novel tyrosine-kinase inhibitor (TKI) inhibitor and its anti-angiogenic activity has been explored in numerous clinical trials. Here, we review preclinical development of linifanib focusing on its pharmacodynamic and pharmacokinetic characteristics and briefly summarize its evaluation in clinical trials. Linifanib selectively targets VEGFR and PDGFR and has low off-target inhibitory activity. Preclinical and early-phase trials have been showing promising efficacy results However, although signals of anti-tumor activity have been proven in some malignancies, linifanib late-phase development has been facing some challenges due to limited efficacy and increased toxicities. New strategies aimed at finding biomarkers of response and minimizing toxicities are needed to allow the further development of a promising compound.

Breast cancer: current and future endocrine therapies.

Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.

18F-FDG PET/CT impact on testicular tumours clinical management.

PURPOSE: Testicular tumour is the most common malignancy in young men. The diagnostic work-up is mainly based on morphological imaging. The aim of our study was to evaluate the clinical impact of (18)F-FDG PET/CT in patients with testicular tumour. METHODS: We retrospectively evaluated all patients studied by (18)F-FDG PET/CT at our centre. Inclusion criteria were: pathological confirmation of testicular tumour, contrast-enhanced CT scan performed within a month of the PET/CT scan, and clinical/imaging follow-up performed at the Oncology Unit of our hospital. Overall, 56 patients were enrolled and 121 PET/CT scans were evaluated. (18)F-FDG PET/CT was performed following standard procedures and the results were compared with clinical, imaging and follow-up data. Clinicians were contacted to inquire whether the PET/CT scan influenced the patient's management. Answers were scored as follows: start/continue chemotherapy or radiotherapy, indication for surgery of secondary lesions, and clinical surveillance. RESULTS: On a scan basis, 51 seminoma and 70 nonseminoma (NS) cases were reviewed. Of the 121 cases. 32 were found to be true-positive, 74 true-negative, 8 false-positive and 6 false-negative by PET/CT. PET/CT showed good sensitivity and specificity for seminoma lesion detection (92% and 84%, respectively), but its sensitivity was lower for NS forms (sensitivity and specificity 77% and 95%, respectively). The PET/CT scan influenced the clinical management of 47 of 51 seminomas (in 6 chemotherapy was started/continued, in 3 radiotherapy was started/continued, in 2 surgery of secondary lesions was performed, and in 36 clinical surveillance was considered appropriate), and 59 of 70 NS (in 18 therapy/surgery was started/continued, and in 41 clinical surveillance was considered appropriate). CONCLUSION: Our preliminary data demonstrate the potential usefulness of PET/CT for the assessment of patients with testicular tumour. It provides valuable information for the clinical management, particularly for clinical surveillance, post-therapy assessment and when relapse is suspected.

A bizarre abdominal cystic lesion.

In spite of careful intraoperative precautions and gauze counts, mistakes can still occur during surgery. In the case reported, a retained gauze leaved during a surgical approach for removing a solid-cystic papillary tumor localized in the pancreatic tail, caused both persistent abdominal discomfort and the presence of an abdominal cystic lesion at imaging techniques. When a previous operative history is present, a foreign body should be taken into account in the differential diagnosis of a patient with an intra-abdominal cystic mass. Finally, radio-opaque marker should be routinely used by surgeons in order to reach a correct diagnosis in operated patients having retained gauze.

Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision.

Nipple discharge (ND) is a common symptom seen in breast cancer clinics. The primary aim of this study was to identify preoperative risk factors for breast cancer in patients with pathologic ND. The secondary aim was to assess the clinical and pathological effectiveness of physical examination, galactography, cytological examination of the discharge, selective duct excision and ductoscopy. All patients operated on between 1975 and 2008 who presented with ND as their only symptom was analyzed. Discharge's characteristics, cytological data and galactography reports were recorded. The relationship between each individual finding and the risk of breast cancer was calculated. For each diagnostic tool, the sensitivity, specificity and complication rates were calculated and compared. Nine-hundred-fifteen patients underwent selective duct excision. Two-hundred-nineteen patients (23.9%) were found to be affected by carcinoma. In 100/330 (30.3%) patients with bloody discharge and in 42/239 (17.6%) patients with serous secretion cancer was detected (P = 0.004, P = 0.013, respectively). Patients with sero-sanguinous or coloured discharge had the same risk of cancer as the population analyzed (23.9%, P = NS). Galactographic finding of irregular stenosis seemed to be associated with a higher risk of cancer (P = 0.0001). Cytological findings C5 and C4 were associated with cancer (P = 0.001). Selective duct excision showed highest sensitivity and specificity. In conclusion, the well established role of bloody secretion is confirmed. The supposed benign aetiology of serous, coloured or sero-sanguinous discharge is questionable. The high specificity of the cytological exam justifies routine examination of the ND. Selective duct excision can be considered as the diagnostic gold-standard.