Institute of Oncology of Southern Switzerland IOSI

Viganello, Switzerland

Institute of Oncology of Southern Switzerland IOSI

Viganello, Switzerland

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Leyland-Jones B.,Avera Cancer Institute | Gray K.P.,Dana-Farber Cancer Institute | Abramovitz M.,VM Institute of Research | Bouzyk M.,AKESOgen Inc. | And 25 more authors.
Breast Cancer Research and Treatment | Year: 2015

Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T>C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95 % CI = 0.67–1.0), and ESR1 rs2077647 (T>C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95 % CI = 0.53–0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T>C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95 % CI = 0.58–0.98, Pinteraction = 0.08), whereas patients with rs4986938 (G>A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95 % CI = 1.01–1.84, Pinteraction = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity. © 2015, Springer Science+Business Media New York.

Regan M.M.,Dana-Farber Cancer Institute | Regan M.M.,Harvard University | Pagani O.,International Breast Cancer Study Group | Pagani O.,Institute of Oncology of Southern Switzerland IOSI | And 20 more authors.
Breast | Year: 2013

Objectives: In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? Methods: TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. Results: TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane+OFS versus tamoxifen+OFS, a combined analysis of TEXT and SOFT became the primary analysis (. n=4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen+OFS versus tamoxifen alone (. n=2045). The first reports are anticipated in mid- and late-2014. Conclusions: We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer.Trial RegistrationTEXT: NCT00066703SOFT: NCT00066690. © 2013 Elsevier Ltd.

PubMed | Breast Unit of Southern Switzerland, Translational Research Coordination and Central Pathology Office, Italian National Cancer Institute, Dana-Farber Cancer Institute and 5 more.
Type: Journal Article | Journal: Breast cancer research : BCR | Year: 2016

Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT).Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade 2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models.There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74%) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23% of women, was associated with a reduced incidence of grade 2 hot flashes/sweating (univariate odds ratio (OR)=0.78; 95% CI 0.63-0.97; P=0.03), more strongly in patients assigned exemestane+OFS (TT vs CT/CC: OR=0.65, 95% CI=0.48-0.89) than assigned tamoxifen+OFS (OR=0.94, 95% CI=0.69-1.27, interaction P=0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found.The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane+OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow NCT00066703, registered August 6, 2003.

Di Lascio S.,Institute of Oncology of Southern Switzerland IOSI | Di Lascio S.,Breast Unit of Southern Switzerland CSSI | Pagani O.,Institute of Oncology of Southern Switzerland IOSI | Pagani O.,Breast Unit of Southern Switzerland CSSI
Breast Care | Year: 2014

A distinctive subset of metastatic breast cancer is represented by the so called 'oligometastatic' disease, characterized by single/few detectable metastatic lesions. A more aggressive multidisciplinary approach can be considered in this patient population: available data report favorable results of 'radical' local therapy for limited metastatic disease at least in a subset of selected patients. Selection bias and the retrospective nature of data do not allow for generalization of the results: the use of such approaches must be individualized and managed within a multidisciplinary team of dedicated specialists. Improvement in surgical and radiation techniques, development of new tools to deliver local chemotherapy, and new procedures (i.e. cryosurgery, laser and microwave ablation) mandate careful evaluation of such single and combined modalities in controlled clinical trials. A more accurate identification of patients with limited metastases and better definition of treatment endpoints will also allow correct patient selection for locally aggressive therapies. This paper focusses on local treatment of the primary tumor and of the most frequent distant disease sites in the presence of oligometastatic disease. © 2014 S. Karger GmbH, Freiburg.

Christinat A.,Institute of Oncology of Southern Switzerland IOSI | Lascio S.D.,Institute of Oncology of Southern Switzerland IOSI | Pagani O.,Institute of Oncology of Southern Switzerland IOSI
Journal of Thoracic Disease | Year: 2013

Breast cancer in young women (<40 years) is a rare and complex clinical and psychosocial condition, which deserves multidisciplinary and personalized approaches. In young women with hormone-receptor positive disease, 5 years of adjuvant tamoxifen, with or without ovarian suppression/ablation, is considered the standard endocrine therapy. The definitive role of adjuvant aromatase inhibitors has still to be elucidated: the upcoming results of the Tamoxifen and EXemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) trials will help understanding if we can widen our current endocrine therapeutic options. The optimal duration of adjuvant endocrine therapy in young women also remains an unresolved issue. The recently reported results of the ATLAS and aTToM trials represent the first evidence of a beneficial effect of extended endocrine therapy in premenopausal women and provide an important opportunity in high-risk young patients. In the metastatic setting, endocrine therapy should be the preferred choice for endocrine responsive disease, unless there is evidence of endocrine resistance or need for rapid disease and/or symptom control. Tamoxifen in combination with ovarian suppression/ablation remains the 1st-line endocrine therapy of choice. Aromatase inhibitors in combination with ovarian suppression/ablation can be considered after progression on tamoxifen and ovarian suppression/ablation. Fulvestrant has not yet been studied in pre-menopausal women. Specific age-related treatment side effects (i.e., menopausal symptoms, change in body image and weight gain, cognitive function impairment, fertility damage/preservation, long-term organ dysfunction, sexuality) and the social impact of diagnosis and treatment (i.e., job discrimination, family management) should be carefully addressed when planning long-lasting endocrine therapies in young women with hormone-receptor positive early and advanced breast cancer © Pioneer Bioscience Publishing Company.

Christinat A.,Institute of Oncology of Southern Switzerland IOSI | Pagani O.,Institute of Oncology of Southern Switzerland IOSI
Breast | Year: 2013

In unselected populations, less than 10% of breast cancers are associated with germline mutations in predisposing genes. Breast cancer type 1 and 2 (BRCA1 and BRCA2) susceptibility genes are the most common involved genes and confer a 10-30 times higher risk of developing the disease compared to the general population. A personal or family history suggestive of inherited breast cancer syndrome may be further evaluated to assess the risk of genetic predisposition and the presence of a genetic mutation. Breast cancer genetic counseling should include a careful risk assessment with associated psychosocial evaluation and support, possible molecular testing, personalized discussion of results. Knowledge of BRCA status can influence individualized cancer risk-reduction strategies. i.e. active surveillance, prophylactic surgery and/or pharmacoprevention. © 2013 Elsevier Ltd.

Rossi L.,Institute of Oncology of Southern Switzerland IOSI | Pagani O.,Institute of Oncology of Southern Switzerland IOSI
Breast Care | Year: 2015

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation. © 2015 S. Karger GmbH, Freiburg.

PubMed | Institute of Oncology of Southern Switzerland IOSI
Type: | Journal: Breast (Edinburgh, Scotland) | Year: 2016

The outcome of advanced breast cancer has significantly improved over recent decades. As a consequence, the complex needs of patients living with the disease and their care-givers should be addressed not only in terms of supportive and palliative care but also of survivorship requirements. The multidisciplinary approach to advanced breast cancer should encompass - early in the history of the disease - not only physical but also functional, social, psychological and spiritual domains. It is important to clearly define the disease context with patients and families (chronic preferred to incurable), addressing the concept of uncertainty, and tailoring the treatment strategy according to both disease status and individual priorities. Specific psychosocial needs of young and elderly women and male patients - i.e. social security, job flexibility, rehabilitation (including sexuality), home and child care - should be recognized and supported. This review will address the key questions associated with survivorship in this disease context, recognizing the dearth of specific data and the urgent need for targeted clinical research and tailored interventions.

PubMed | Institute of Oncology of Southern Switzerland IOSI
Type: Case Reports | Journal: Breast disease | Year: 2015

Bisphosphonates are widely used both in the multidisciplinary management of bone metastases, especially osteolytic lesions from solid tumors or multiple myeloma, and of osteoporosis.Aseptic osteonecrosis, especially of the jaw, is among the well-known, although uncommon, side effects of bisphosphonates. Osteonecrosis of other bones has been very rarely reported with the use of bisphosphonates.We describe a rare case of osteonecrosis of the distal femur associated with the use of bisphosphonates in a 74 years old female patient with metastatic breast cancer.

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