Anne-Déborah Bouhnik

Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time

BACKGROUND In premenopausal women with hormone receptor-positive breast cancer (BC), 5 years of tamoxifen is recommended. Little is known about reasons for interruption in this population. The aim was to estimate the incidence of tamoxifen interruption and its correlates among younger women. PATIENTS AND METHODS Using a prospective cohort Elippse 40 of women with BC aged ≤ 40 diagnosed between 2005 and 2008, we studied 196 women. Tamoxifen interruption was defined as two or more consecutive months without dispensed prescription of tamoxifen, based on pharmacy refill database. Two periods were studied: between tamoxifen initiation and 16 months after BC diagnosis, and between 16 and 28 months. RESULTS Among women treated with tamoxifen, 42% interrupted within the first 2 years of treatment. During the first period, treatment interruptions were associated with a lack of understandable information about endocrine treatment and insufficient social support. During the second period, another set of factors were associated with interruption: treatment side-effects, no longer fearing cancer relapse, lack of social support, no opportunity to ask questions at the time of diagnosis, and fewer treatment modalities. CONCLUSIONS Improving information and patient-provider relationship might prevent interruption. Particular attention should be paid to women with little social support.

Early discontinuation of tamoxifen intake in younger women with breast cancer: Is it time to rethink the way it is prescribed?

BACKGROUND Tamoxifen is the main recommended adjuvant hormonal treatment for premenopausal women with hormone-responsive early breast cancer. Little data is available on compliance and persistence to tamoxifen intake in younger women. METHODS Using the French National Health Insurance System database, we constituted a cohort of 288 women who were diagnosed with breast cancer and received at least one supply of tamoxifen for breast cancer between September 2005 and July 2011. Medical records and mailed questionnaires provided complementary sources of data. Time to treatment discontinuation and associated predictors were studied using techniques for censored data. RESULTS Among women who received a prescription of tamoxifen, 6.1% (16) did not fill any prescription. After 2 years of tamoxifen intake, 29.7% (95%confidence interval (CI) 24.1-36.4) had discontinued their treatment; after 3 years this percentage increased to 39.5% (95% CI 32.9-47.0). The risk of treatment discontinuation rose sharply during the 1st year of treatment and remained approximately constant in the second year. After multivariate adjustment, tamoxifen discontinuation increased significantly with low social support (Hazard Ratio (HR) = 2.1; 95%CI 1.2-3.4), and self-reporting of non-compliance behaviour (HR = 2.2; 95% CI 1.3-3.7). CONCLUSION The consequences of high treatment discontinuation rates in younger women with long potential life expectancy may be significant. There is an urgent need to acknowledge and tackle compliance issues in the field of oncology, unless we are willing to accept inefficient prescriptions of efficacious drugs.

Time to prophylactic surgery in BRCA1/2 carriers depends on psychological and other characteristics

Purpose: To investigate the medical and psychosocial factors determining the time to prophylactic surgery of unaffected women carriers of a deleterious BRCA1/2 mutation.Methods: Prospective study on a French national cohort of unaffected BRCA1/2 carriers (N = 244); multivariate Cox proportional hazard modeling.Results: Median follow-up time was 2.33 years (range, 0.04–6.84 years). Time to surgery was shorter when the psychological impact of BRCA1/2 result disclosure was stated to be higher (P ≤ 0.01). Those who intended to opt for prophylactic surgery before being tested did so faster and more frequently after test disclosure than those who were undecided/opposed. The older the women were, the faster their uptake of risk-reducing salpingo-oophorectomy (adjusted hazard ratio >2.95; P < 0.001) was; the uptake of those with at least two children was also faster (adjusted hazard ratio = 2.51; [1.38–4.55]). Those who opted most quickly for risk-reducing mastectomy more frequently had a younger child at the time of testing (adjusted hazard ratio = 4.63 [1.56–13.74]). Time to surgery was shorter when there was a first-degree relative with ovarian/breast cancer (P ≤ 0.01).Conclusion: Time to prophylactic surgery depends on the stated psychological impact of disclosure and on womens cognitive anticipation of surgery after adjusting on sociodemographic characteristics.

BRCA1/2 carriers: their childbearing plans and theoretical intentions about having preimplantation genetic diagnosis and prenatal diagnosis

Purpose:To assess the impact of BRCA1/2 test results on carriers’ reproductive decision-making and the factors determining their theoretical intentions about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND).Methods:Unaffected BRCA1/2 mutation carriers of childbearing age (N = 605; 449 women; 151 men) were included at least 1 year after the disclosure of their test results in a cross-sectional survey nested in a national cohort. Multivariate adjustment was performed on the data obtained in self-administered questionnaires.Results:Response rate was 81.0%. Overall, 32.5% and 50% said that they would undergo PGD/PND, respectively, at a theoretical next pregnancy, whereas only 12.1% found termination of pregnancy (TOP) acceptable. Theoretical intentions toward PGD did not depend on gender/age, but were higher among those with no future childbearing plans (adjusted odds ratio (AOR) 95% confidence interval (CI): 3.5 (1.9–6.4)) and those having fewer relatives with cancer (AOR 1.5 95% CI (1.0–2.3)). Greater TOP acceptability was observed among males and those with lower educational levels; 85.4% of respondents agreed that information about PGD/PND should be systematically delivered with the test results.Conclusions:The closer to reproductive decision-making BRCA1/2 carriers are, i.e., when they are more likely to be making future reproductive plans, the less frequently they intend to have PGD. Carriers’ theoretical intentions toward PND are discussed further.Genet Med 2012:14(5):527–534

International variation in physicians’ attitudes towards prophylactic mastectomy – Comparison between France, Germany, the Netherlands and the United Kingdom

PURPOSE Prophylactic mastectomy (PM) has proven to be the most effective method to reduce the risk of breast cancer in high-risk women. The present study aimed to present and compare the attitudes towards PM among physicians in France, Germany, the Netherlands and the United Kingdom (UK). PATIENTS AND METHODS An international sample of 1196 general practitioners (GPs) and 927 breast surgeons (BS) were surveyed using a mailed questionnaire. RESULTS Only 30% of the French and 27% of the German GPs were of opinion that PM should be an option for an unaffected female BRCA1/2 mutation carrier, as compared to 85% and 92% of the GPs in the Netherlands and UK, respectively. Similarly, 78% of the French and 66% of the German BS reported a positive attitude towards PM, as compared to 100% and 97% of the BS in the Netherlands and UK, respectively. In the whole sample of GPs, a positive attitude towards PM was associated with country of residence, being female, and having more knowledge of breast/ovarian cancer genetics, while among BS there was a positive association with country of residence and having more knowledge of breast/ovarian cancer genetics as well, and, in addition, with a higher number of newly diagnosed breast cancer patients last year. CONCLUSION These results demonstrated the international variations in the attitude towards PM among physicians. This might reflect that different policies are adopted to prevent breast cancer in women at-risk.

Physicians’ and patients’ adherence to antiretroviral prophylaxis after sexual exposure to HIV: results from South-Eastern France

Abstract French national guidelines for the management of HIV non-occupational post-exposure (nPEP) were issued in 1998 and updated in 2003. NPEP is available and free of charge in all emergency or AIDS care units of French hospitals. A regional survey was carried out to study physicians’ adherence to national guidelines, and determinants of adherence to nPEP follow-up in individuals sexually exposed to HIV. The survey was based on retrospective data collection of all consultations for nPEP made in the three AIDS information centers in South-Eastern France (January 2001–December 2002). Information included personal data, type of exposure, and treatment at the first visit after exposure and during follow-up. Exposures were classified into high risk (treatment highly recommended), moderate risk (treatment possibly recommended) and negligible risk (treatment never recommended) categories, according to the level of HIV risk of sexual transmission as indicated by the French national nPEP guidelines. Among the 910 sexual exposures, 56%, 37%, and 4% were classified as cases with high, moderate, and no risk respectively. NPEP was prescribed to 85% of cases. HIV risk of sexual exposure was significantly associated with nPEP receipt though more than half of the cases with negligible risk received nPEP. Independent characteristics associated with non-adherence to nPEP follow-up were younger age, being referred to hospital by a physician, sexual exposure with a casual partner or sexual assault, and “moderate risk” exposure. Better information should be provided to physicians prescribing nPEP to limit over-prescription while new strategies should be implemented to improve follow-up of individuals receiving nPEP, especially those who are younger or survivors of sexual assault.

The labour market, psychosocial outcomes and health conditions in cancer survivors: protocol for a nationwide longitudinal survey 2 and 5 years after cancer diagnosis (the VICAN survey)

Introduction Today, a growing need exists for greater research into cancer survivorship, focusing on different spheres of the day-to-day life of diagnosed patients. This article describes the design and implementation of VICAN (VIe après le CANcer), a national survey on French cancer survivors. Method and analysis The target population included patients aged 18–82, diagnosed with cancer between January and June 2010, and registered in one of the three main French Health Insurance Schemes. It was restricted to 12 tumour sites. Sampling was stratified using a non-proportional allocation, based on age at diagnosis (18–52 and 53–82) and tumour site. Data were collected from telephone interviews with patients 2 and 5 years after diagnosis, a medical survey completed by the physician who initiated cancer treatment, and information from the national medicoadministrative database on reimbursement data and hospital discharge records. First data collection, 2 years after diagnosis, occurred between March and December 2012. Second data collection, 5 years after diagnosis, will be conducted in 2015. Analyses will be conducted on various outcomes: quality of life, health status and psychosocial conditions, with a particular focus on the impact of cancer diagnosis on the labour market. The variety of measurements included in the survey will enable us to control a wide range of factors. Ethics and dissemination The methodology of the VICAN survey was approved by three national ethics commissions. Results of the study will be disseminated through national and international research conferences, and in articles published in international peer-reviewed journals.

Complementary or Alternative Medicine as Possible Determinant of Decreased Persistence to Aromatase Inhibitor Therapy among Older Women with Non-Metastatic Breast Cancer

Purpose Aromatase inhibitor therapy (AI) significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. Methods We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. Results Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2–12.1) at 1 year, to 15.6% (95%CI: 12.2–19.8) at 2 years, 20.8% (95%CI: 16.7–25.6) at 3 years, and 24.7% (95%CI: 19.5–31.0) at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM) (HR = 3.2; 95%CI: 1.5–6.9) or suffering from comorbidities (HR = 2.2; 95%CI: 1.0–4.8) were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2–0.91) were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. Conclusion AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Self-Reported Cognitive Impairment After Breast Cancer Treatment in Young Women from the ELIPPSE40 Cohort: The Long-Term Impact of Chemotherapy

Abstract:  Cognitive impairment (CI) is common after cancer treatments, but little is known about the long‐term evolution of CI, especially in premenopausal women. Since September 2005, all consecutive women included in the French National Health Insurance Fund registry with a diagnosis of primary breast cancer, aged 18–40 years and living in South Eastern France, were asked to participate in a cohort study, including telephone interviews, medical data, and prescription refills of psychotropic drugs and adjuvant endocrine therapy. At each interview, CI is defined as self‐report of frequent memory loss and attention deficits. As of February 2010, 222 women with available medical data had taken part in the 10‐, 16‐, and 28‐month telephone interviews, with CI being reported by 37.4%, 36.5%, and 42.3% of participants, respectively. Tranquilizers’ dispensation was associated with CI self‐report at all three interviews; chemotherapy was reported only at the 28‐month interview. At 28 months, besides chemotherapy and tranquilizer’s dispensation, having a low educational level and not being a native French woman were also independently associated with CI. Reports of CI were common in young women and primarily related to psycho‐social vulnerabilities and cancer treatment. As they affect quality of life, long‐term CI complaints deserve greater consideration.

Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

Breast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population‐based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the womens age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy‐proven primary nonmetastatic breast cancer, aged 65–80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio‐demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75–80 years received chemotherapy more than four times less often than women aged 65–74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco‐Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population.