Differences in Management of Older Women Influence Breast Cancer Survival: Results from a Population-Based Database in Sweden

BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50–84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70–84 y of age compared to women aged 50–69 y, and the difference was most pronounced in stage IIB–III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone

Breast Cancer in Young Women: Poor Survival Despite Intensive Treatment

The general aim of the thesis was to gain increased insight into the long-term prognosis for young women with breast cancer. In a population-based cohort of 22,017 women with breast cancer, we studied prognosis by age. Women aged <35 (n=471), 35–39 (n=858) and 40–49 (n=4789) were compared with women aged 50–69. The cumulative 5-year relative survival ratio (RSR) and the relative excess risk (RER) of mortality were calculated. Women <35 years of age had a worse survival than middle-aged women, partly explained by a later stage at diagnosis. After correction for stage, tumor characteristics and treatment, young age remained an independent risk factor for death. The excess risk of death in young women was only present in stage I-II disease and was most pronounced in women with small tumors. For in-depth studies on a large subpopulation from the original cohort (all 471 women aged <35 and a random sample of 700 women aged 35–69), we collected detailed data from the medical records, re-evaluated slides and produced TMAs from tumor tissue. Breast cancer- specific survival (BCSS), distant disease-free survival (DDFS) and locoregional recurrence- free survival (LRFS) by age were analysed. In a multivariate analysis, age <35 and age 35– 39 years conferred a risk in LRFS but not in DDFS and BCSS. The age-related differences in prognosis were most pronounced in early stage luminal Her2-negative tumors, where low age was an independent prognostic factor also for DDFS (HR 1.87 (1.03–3.44)). To study the importance of proliferation markers for the long-term prognosis in young women, protein expression of Ki-67, cyclin A2, B1, D1 and E1 was analysed in 504 women aged <40 and in 383 women aged ≥40. The higher expression of proliferation markers in young women did not have a strong impact on the prognosis. Proliferation markers are less important in young women, and Ki-67 was prognostic only in young women with Luminal PR+ tumors. Age <40 years was an independent risk factor of DDFS exclusively in this subgroup (adjusted HR 2.35 (1.22-4.50)). The only cyclin adding prognostic value beyond subtype in young women was cyclin E1. In a cohort of 469 women aged <40 and 360 women aged ≥40 we examined whether Her2 status assessed by silver enhanced in situ hybridization (SISH) for all cases, would reveal a proportion of women undiagnosed by routine Her2 testing and whether this would affect their prognosis. With SISH testing for all women, the Her2-positive rate increased from 20.0% to 24.4% (p<0.001), and similarly for women aged <40 and ≥40 years. Young women had Her2+ breast cancer twice as often as middle-aged women. Her2 amplification was present in 4.6% of cases scored 0 with IHC, while the corresponding proportions for scores 1+, 2+ and 3+ were 36.0%, 83.7% and 96.8%, respectively. All Her2 amplified cases, both true positive and false negative, had a significantly worse BCSS than the true negative cases

Breast Cancer, Sickness Absence, Income and Marital Status. A Study on Life Situation 1 Year Prior Diagnosis Compared to 3 and 5 Years after Diagnosis

Background: Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income. Materials: We conducted a matched cohort study including 4,761 women 40–59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993–2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95 % confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis. Findings: Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95 % CI 1.40–1.58) or disability pension (RR = 1.47, 95 % CI 1.37–1.58) than had women without breast cancer. W

Optimization of compliance in epidemiologic research and disease prevention : With special emphasis on PAP-smear screening

The aim of this thesis was to investigate factors affecting attendance in screening for cervical cancer, and to evaluate various measures aimed at increasing compliance to self-administered postal questionnaires and screening for cervical cancer. A population-based randomized controlled trial including 2000 men and women aged 20-79 years and living in Sweden was conducted to investigate compliance to postal questionnaires. In a randomized 2 3 factorial design three factors were tested: 1) preliminary notification or not, 2), questionnaire length, and 3) mention of a possible telephone contact or not. Preliminary notification increased the response rate by 7%, a short questionnaire with 5%, whereas mention of a possible telephone contact did not influence attendance. Combinations of preliminary notification and short questionnaires increased the response rate by 16%, whereas young age, male gender and urban residence lowered the response rate. The relation between non-attendance to screening for cervical cancer (Pap smear screening) and sociodemographic factors, gynecological examinations, risk behavior, general health behavior, knowledge, attitudes and beliefs was investigated in a population-based case-control study with 430 non-attenders and 514 attenders at Pap smear screening in Uppsala county. Non-attendance was more likely among women who had not used oral contraceptives, who had not taken their own initiative to a Pap smear, who had visited different gynecologists, and who had visited a physician very often or not at all. Regular condom use, living in rural/semirural areas, and not knowing the recommended screening interval were all associated with non-attendance, whereas socioeconomic status was not, when tested in a multivariate model. Multivariate analysis also showed that non-attendance was more likely among women who did not perceive cervical cancer to be as severe as other malignancies, who did not perceive the benefits of a Pap smear, who had time-consuming and economical barriers, and who did not feel anxious about the test results or cervical cancer. The results were strengthened with increasing time since the last smear or if self-reported attendance status was used instead of true attendance. Non-attenders also kept holding on harder to their preferences than did attenders, stating that they would not participate if their preferences were not met and were less likely to intend to participate in future screening. Among the non-attenders, 57% underestimated the time lapse since the last smear. Modifications of the invitation and call-recall system for Pap smear screening was investigated in a randomized controlled trial including all 12,240 women invited to organized screening during 17 weeks in 2001 in Uppsala County. Three successive interventions were tested: 1) modified invitation vs. the standard invitation letter, 2) reminder letter vs. no reminder letter, and 3) phone reminder vs. no phone reminder. Whereas the modified invitation did not increase attendance, a reminder letter increased the proportion attending by 9%, and a phone reminder by 31%. Combinations of modified invitation, written reminder and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled. Keywords: Compliance; epidemiological studies, self-administrated postal questionnaires, response rate; Pap smear screening, cervical cancer; non-attendance, socioeconomic factors, gynecological history, attitudes, beliefs, knowledge; manipulations, information, reminders; randomized controlled trial; case-control study

Swedish Law on Personal Data in Biobank Research: Permissible But Complex

This chapter describes the regulatory and organisational infrastructure of biobank research in Sweden, and how the introduction of the GDPR affects the possibilities to use biobank material in future research. The Swedish legislator has chosen a rather minimalistic approach in relation to the research exception in Article 89 GDPR and has only enacted limited general exceptions to the data protection rules. This may be partly explained by the comprehensive right to public access to official documents which gives researchers vast access to information held in registries, albeit conditioned on abiding by secrecy and confidentiality rules. The Swedish legislation implementing the GDPR includes a general exception from the data protection rules in relation to the right to access to official documents, which researchers also benefit from. However, confidentiality rules for different categories of information differ between sectors, which hinders an effective use of the registries in research. The regulatory regime for using biobank and registry data in Sweden thus involves both data protection and secrecy rules, which makes the legal landscape permissible but complex. The operationalisation of the research exception in Article 89 GDPR is analysed against this background. Special attention is given to the possibility to link personal information derived from biobanks with personal information from other data sources, including large national population based statistical registries as well as information from national clinical registers

Breast cancer survival by age and stage at diagnosis.

<p>Cumulative 5-year RSR and the estimated RER and 95% CI by stage at diagnosis of women aged 20–69 years, diagnosed with primary breast cancer of all stages between 1992 and 2005 (22 017 women).</p

Treatments given to women with stage I breast cancer by age and tumour size.

<p>Proportions of women aged 20–69 years, diagnosed with primary breast cancer stage I between 1992 and 2005 (9656 women), receiving specific treatments, by tumour size and age at diagnosis.</p