Current medical treatment of estrogen receptor-positive breast cancer

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 (i) ovarian function suppression (OFS), usually obtained using gonadotropin-releasing hormone agonists (GnRHa), (ii) selective estrogen receptor modulators or down-regulators (SERMs or SERDs), (iii) 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

Cancer survivors: surveillance or not surveillance?

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Prognostic factors of survival in patients treated with nab-paclitaxel plus gemcitabine regimen for advanced or metastatic pancreatic cancer: A single institutional experience.

The 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 DESIGN: Patients 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. RESULTS: Overall, 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. CONCLUSION: NAB-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

the metabolomic scent of cancer disease progression in soft tissue sarcoma a case report

Background: The purpose of this case report is to describe the potential that metabolomics breath analysis may have in cancer disease monitoring. The advances in mass spectrometry instrumentation allow the accurate real-time analysis of volatile metabolites exhaled in the breath. The application of such non-invasive devices may provide innovative and complementary monitoring of the physio-pathological conditions of cancer patients. Case presentation: A 59-year-old Caucasian woman with spindle cell malignant mesenchymal sarcoma of the presacral region started a first-line therapy with non-pegylated liposomal doxorubicin and ifosfamide associated with pelvic radiant treatment. After two cycles of chemotherapy plus radiotherapy, a significant pulmonary disease progression was reported. Thus, a second-line therapy with trabectedin was administered. However, after only two cycles of treatment a re-staging computed tomography scan reported further cancer disease progression of the target pulmonary lesions as well as occurrence of new satellite bilateral nodules. Real-time analysis of breath exhaled volatile organic compounds, performed by select ion flow tube mass spectrometry (SIFT-MS) during the follow-up of the patient, showed a specific metabolic pattern not observed in the breath of other soft tissue sarcoma patients who achieved clinical benefit from the treatments. Conclusions: This case report revealed the importance of the non-invasive real-time volatile organic compounds breath analysis to distinguish individual specific chemo-resistance phenotypes among soft tissue sarcoma patients. Such observation seems to suggest that breath metabolomics may be particularly useful for monitoring cancer disease progression in soft tissue sarcoma patients where only cost-effective diagnostic tools, such as positron emission tomography and computed tomography, are available

Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma

We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5mg/m(2) given intravenously over 24hours every 21days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy

Adjuvant hormonal therapy in women with early-stage breast cancer

For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer

Prognostic factors for survival in patients with breast cancer and liver metastases.

In patients with breast cancer (BC) the liver is one of the site of distant metastases, accounting for about 15% of patients. Isolated liver metastases (LMs) are uncommon, and the presence of extra-hepatic disease usually represents a contraindication to liver resection. Liver metastasis of BC origin is usually life limiting, and the patient needs treatment. Surgical resection of parts of the liver is considered the only potentially curative therapy, but unfortunately only few patients are suitable for liver resection. The 5-year survival of patients with LMs from colorectal cancer ranges from 20% to 25%, while the survival period after resection to manage LMs from BC is unclear, due to the limited number of studies, ranging between 36-42 months. The aims of this study was to identify factors predictive of survival of women with LMs from BC who underwent liver resection, and to evaluate possible relationship between survival, age, primitive tumor size, number of LM, CA 15-3, ER and PR rate. The medical charts of 11 women (median age 57 years, range 39-67 years) with LM and no evidence of extra-hepatic disease who had undergone curative surgery for BC were reviewed retrospectively. All patients received 6-12 cycles of neoadjuvant chemotherapy (anthracyclines) alone or chemotherapy plus hormone therapy (tamoxifen or aromatase inhibitors) prior to liver resection (wedge resection or segmentectomy), and those with disease progression were excluded. All LMs were metachronous, 7 patients had a single LM, 3 had two LMs, and 1 had three LMS. The baseline data were: size of the primitive BC=25.8\ub16.4 mm, number of LMs=1.4\ub10.68, ER=46.6\ub133.8%, PR=48.3\ub134.2%, CA15-3=84.7\ub133.1 U/mL. The median survival rate was 32 months (range 12-77 months). As expected, there was a significant correlation between ER and both PR (R=0.95, p< 0.001) and CA 15-3 (R=0.64, p=0.034), and between CA 15-3 and both PR (R=0.67, p=0.024) and number of LMs (R=0.69, p=0.017). At univariate analysis younger age, number of LMS, and size of the primitive tumor were associated with poorer prognosis, while at multivariate analysis only the age (R=0.81, p=0.002) of the patients was an independent factor of survival. In conclusion, the survival of patients with BC and LMs is independent of hormone-receptor status and serum CA 15-3 levels at the time of liver resection