Olivia Pagani | University of Geneva, Switzerland (original) (raw)

Papers by Olivia Pagani

Journal of Personalized Medicine

Low uptake of genetic services among members of families with hereditary breast and ovarian cance... more Low uptake of genetic services among members of families with hereditary breast and ovarian cancer (HBOC) suggests limitations of proband-mediated communication of genetic risk. This study explored how genetic information proceeds from healthcare providers to probands and from probands to relatives, from the probands’ perspectives. Using a grounded-theory approach, we analyzed narrative data collected with individual interviews and focus groups from a sample of 48 women identified as carriers of HBOC-associated pathogenic variants from three linguistic regions of Switzerland. The findings describe the “communication chain”, confirming the difficulties of proband-mediated communication. Provider–proband communication is impacted by a three-level complexity in the way information about family communication is approached by providers, received by probands, and followed-up by the healthcare system. Probands’ decisions regarding disclosure of genetic risk are governed by dynamic and ofte...

Cancer Research

Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increa... more Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects...

Cancers, 2021

Simple Summary This cross-study comparison uses data collected over 10 years from families living... more Simple Summary This cross-study comparison uses data collected over 10 years from families living in the US and in Switzerland in order to compare genetic literacy between individuals who had genetic counselling for hereditary breast/ovarian cancer (HBOC) and one or more of their relatives who did not, and examines factors influencing genetic literacy both at the individual and at the family level. The study identifies genetic risk factors and signs of HBOC that remain unclear, even to individuals who had genetic consultation, and highlights the gaps in the dissemination of genetic information. Sensitivity analysis examines the dissemination of genetic information from the individual who had counselling to relatives within the same family that did not. Abstract Examining genetic literacy in families concerned with hereditary breast and ovarian cancer (HBOC) helps understand how genetic information is passed on from individuals who had genetic counseling to their at-risk relatives. T...

Table S1. List of ethics committees (DOCX 102 kb)

Journal of Clinical Oncology, 2018

Background: Although randomized controlled clinical trials are optimal to evaluate the effect of ... more Background: Although randomized controlled clinical trials are optimal to evaluate the effect of an experimental therapy, single-arm trials are required whenever randomization is unethical or not feasible, such as de-escalation studies. We propose using prospectively identified historical controls to place results of single-arm, de-escalation trials into context. Methods: POSITIVE is a prospective, single-arm study in young women with hormone-receptor-positive early breast cancer to determine if temporarily interrupting adjuvant endocrine therapy in order to become pregnant increases the risk of a breast cancer event. After 272 women enrolled in POSITIVE, we identified a cohort of 1499 SOFT/TEXT patients potentially eligible to enroll in POSITIVE who did not interrupt endocrine therapy. Method I used the SOFT/TEXT cohort to calculate annualized hazard rates by a piecewise exponential model. Method II used the SOFT/TEXT cohort to group-match SOFT/TEXT patients to POSITIVE patients; sample sets of SOFT/TEXT patients were randomly drawn 5000 times to obtain sets having patient, disease, and treatment characteristics more balanced with POSITIVE participants. Results: Compared with SOFT/TEXT, POSITIVE participants were younger, less likely to be overweight/ obese, had fewer positive nodes, and fewer received aromatase inhibitor or chemotherapy. The estimated 3-year breast cancer free interval event rates were 9.5% (95% CI: 7.9%,11.1%) for Method I and 9.4% (95% CI: 7.8%,10.9%) for Method II, compared with 5.8% initially assumed when POSITIVE was designed.

Annals of Oncology, 2000

Background; The combination of anthracyclines and taxanes is currently considered the first choic... more Background; The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m 2 and docetaxel (D) 75 mg/m 2 as first-line chemotherapy in ABC. Patients and methods; A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m 2. A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography. Results: Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m 2 (range 270-1020 mg/irr). One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m 2 , with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4-39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval. Conclusions: The combination of E and D in a multiinstitutional setting is an active and safe regimen in poorprognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the disease.

British journal of cancer, Jan 8, 2012

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after ... more In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function w...

The Breast, 2010

Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine... more Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) versus tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores =0.28, p=0.04, 95% CI:0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.

JNCI: Journal of the National Cancer Institute, 2012

Background Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-respon... more Background Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated the clinical relevance of CYP2D6 polymorphisms. Methods We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the randomized, phase III double-blind Breast International Group (BIG) 1-98 trial between March 1998 and May 2003 and received tamoxifen and/or letrozole treatment. Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods. Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor, intermediate, and extensive metabolizers (PM, IM, and EM, respectively; n = 4393 patients). Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval (referred to as recurrence) and treatmentinduced hot flushes according to randomized endocrine treatment and previous chemotherapy were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy (P = .35). PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype (PM or IM vs EM, HR of recurrence = 0.86, 95% CI = 0.60 to 1.24). CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes (P = .020). Both PM and IM phenotypes had an increased risk of tamoxifeninduced hot flushes compared with EM phenotype (PM vs EM, HR of hot flushes = 1.24, 95% CI = 0.96 to 1.59; IM vs EM, HR of hot flushes = 1.23, 95% CI = 1.05 to 1.43). Conclusions CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes, contrary to the hypothesis. The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen.

Cancer Treatment Reviews, 2014

Treatment of metastatic breast cancer has substantially changed in the last decades. Availability... more Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine±targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends.

Breast Cancer Research and Treatment, 2008

Purpose-To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET)... more Purpose-To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. Patients and methods-In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ERnegative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively-defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Results-Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (p=0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (p = 0.07), or for the cohort with one positive node (p = 0.03). Conclusions-Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Annals of Oncology, 2006

Henoch-Schö nlein purpura (HSP) during treatment with anastrozole introduction The aromatase enzy... more Henoch-Schö nlein purpura (HSP) during treatment with anastrozole introduction The aromatase enzyme is responsible for oestrogen biosynthesis from androgens in postmenopausal women. Aromatase inhibitors (AIs) reduce oestrogen levels by decreasing aromatase activity and induce objective remissions in a significant proportion of postmenopausal women with advanced hormone-dependent breast cancer (BC) [1]. The third-generation AIs are currently considered the most effective first-line endocrine treatment of advanced endocrineresponsive BC since superior antitumour activity has been repeatedly demonstrated versus tamoxifen in large phase III

Annals of Oncology, 2008

BACKGROUND: The role of chemotherapy in addition to combined endocrine therapy for premenopausal ... more BACKGROUND: The role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly. METHODS: From 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees. RESULTS: Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not. CONCLUSIONS: The perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this population.

Annals of Oncology, 1999

Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the se... more Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile. Patients and methods: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with ^2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m 2 and D 75 mg/m 2 to E 120 mg/m 2 and D 85 mg/m 2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography. Results: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) <0.1 x 10 9 /l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m 2 and D 75 mg/m 2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m 2 and D 75 mg/m 2. The MTD with G-CSF support was established at E 120 mg/m 2 and D 85 mg/m 2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 x 10 9 /l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotoxicity. Antitumour activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30+), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months. Conclusions: The combination of E and D proved to be an effective and safe regimen in poor-prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimens.

Cancers, 2022

Background: An increase in breast cancer (BC) incidence in young women (YW) as well as disparitie... more Background: An increase in breast cancer (BC) incidence in young women (YW) as well as disparities in BC outcomes have been reported in Switzerland. We sought to evaluate treatment and outcome differences among YW with BC (YWBC). Methods: YW diagnosed with stage I-III BC between 2000–2014 were identified through nine cancer registries. Concordance with international guidelines was assessed for 12 items covering clinical/surgical management, combined in a quality-of-care score. We compared score and survival outcome between the two linguistic-geographic regions of Switzerland (Swiss-Latin and Swiss-German) and evaluated the impact of quality-of-care on survival. Results: A total of 2477 women were included. The median age was 37.3 years (IQR 34.0–39.4 years), with 50.3% having stage II BC and 70.3% having estrogen receptor positive tumors. The mean quality-of-care score was higher in the Latin region compared to the German region (86.0% vs. 83.2%, p < 0.0005). Similarly, 5- and 10...

Young women with early breast cancer represent a specific patient population with unique disease ... more Young women with early breast cancer represent a specific patient population with unique disease characteristics and psychosocial needs. A dedicated multidisciplinary approach is required to ensure the best treatment options and survival opportunities. The chapter will address in detail the epidemiology and biology, diagnostic challenges, genetic counselling and testing, loco-regional and medical treatments and survivorship issues. Specific research questions will also be critically discussed.

Clinical Breast Cancer, 2021

In the last decade, endocrine therapy strategies in perimenopausal women with hormone-responsive ... more In the last decade, endocrine therapy strategies in perimenopausal women with hormone-responsive early breast cancer (BC) have changed and now ovarian function suppression (OFS) is recommended for the majority of patients. Side effects of OFS mimic menopausal symptoms, including hot flushes, sweats, weight gain, and sexual dysfunction, which may negatively impact quality of life (QoL). Aims of the Take Care Project are the education of physicians and patients to have all the information (medical and nonmedical) they need to manage menopausal symptoms by distributing educational materials useful to face menopause. Four different areas have been identified by surveys conducted among physicians and young patients: for each area, interventions and tools have been elaborated by a doctor and nonphysician professionals of these identified areas, to offer the widest information available. Clinical and practical suggestions have been provided. Based on the evidence given, we strongly suggest setting up a multidisciplinary team for the treatment planning of young patients with BC, which could help patients to face and manage their new menopause condition. The reduction of side effects and the improvement in QoL should be the best ally to treat young patients with BC.

Journal of Evidence-Based Medicine, 2018

Objective: The purpose of this study was to assess knowledge, attitudes and practice of medical d... more Objective: The purpose of this study was to assess knowledge, attitudes and practice of medical doctors in some selected public hospitals towards Clinical Pharmacy Services in Ethiopia. Methodology: Cross sectional study design was employed to assess knowledge, attitude and practices of medical doctors towards clinical pharmacy services. The study population was selected using simple random sampling technique. Self-administered questionnaires were used to extract relevant information from the study subjects. The data was entered, cleaned and analyzed by using SPSS version-20. Results: The mean age of the study participants was 28.2 ± 5.2 years with a range between 20-53 years and 87.1% were males. 89.6% of the respondents are general practitioner and 8(8.6%) with different specialization with year of experience 2.94 + 3(0.5-22 year). Majority of respondents are knowledgeable regarding to clinical pharmacists as a member of medical teams and their services in reducing medication related errors and health related costs. More than 74% of the respondents were highly satisfied by the role of clinical pharmacists in counseling of patients regarding to safe and appropriate use of medications, prevention, detection and management adverse drug reactions. The present study depicted that lack of support from administration (70%); shortage of staff (63.4%) and lack of adequate support by the health care team (62.4%) were the major limitations to practice clinical pharmacy service in the hospitals. Conclusions: Physicians undoubtedly considered that pharmacists are drug information experts. Nevertheless, their anticipation of pharmacists as providers of quality clinically-focused pharmacy services was little. Physicians were willing to collaborate with clinical pharmacists in monitoring drug therapy and improving patient care by identifying medication errors.

Senologie - Zeitschrift für Mammadiagnostik und -therapie, 2008