Åsa Olsson

Relationships between Nordic Dogroses (Rosa L. sect. Caninae, Rosaceae) Assessed by RAPDs and Elliptic Fourier Analysis of Leaflet Shape

Abstract The taxonomy of the dogroses (Rosa sect. Caninae) is notoriously problematic and all the members of the section are characterized by a form of unbalanced meiosis (so-called “canina meiosis”). We used a novel combination of random amplified polymorphic DNA (RAPD) markers and elliptic Fourier analysis of leaflet shape to investigate relationships within and between the seven common dogrose taxa in the Nordic countries. A between-individual genetic distance matrix calculated on the basis of the presence/absence of RAPD bands was used in a non-metric multidimensional scaling analysis. Population data from elliptic Fourier analysis of leaflet shape were analyzed with canonical variates analysis. Elliptic Fourier analysis of leaflet shape provided a valuable complement to traditional, often subjectively-assessed, morphological characters and detected subtle patterns of within- and between-taxon differentiation that are generally consistent with the relationships recognized in the current taxonomic treatments of the section. In contrast, RAPDs emphasize the discontinuities between three groups of taxa and suggest that R. canina and the two subspecies of R. dumalis, as well as the taxon-pair R. sherardii and R. villosa subsp. mollis, are more closely related than can be concluded on the basis of morphological characters. Communicating Editor: Alan Whittemore

Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study

Long‐term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40–50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow‐up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (−0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow‐up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83–4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01−1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02−1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

Parity in relation to survival following breast cancer.

AIM The present study examines the association between parity and survival following breast cancer diagnosis. METHODS Medical records of 4453 women diagnosed with breast cancer in Malmö, Sweden, between 1961 and 1991 were analysed. All women were followed until 31 December 2003, using the Swedish Cause-of-Death Registry. Breast cancer specific mortality rate was calculated in different levels of parity. Corresponding relative risks, with 95% confidence intervals (CI), were obtained using Coxs proportional hazards analysis. All analyses were adjusted for potential prognostic factors and stratified for age, menopausal status and diagnostic period. RESULTS As compared to women with one child, nulliparity (RR 1.27: 95% CI 1.09-1.47), and high parity (four or more children) (1.49: 1.20-1.85) were positively associated with a high mortality from breast cancer. When adjusted for potential confounders, the association was only statistically significant for high parity (1.33: 1.07-1.66). In the analyses stratified on age and menopausal status, there was a similar positive association between high parity and breast cancer death in all strata, although only statistically significant among women older than 45 years of age or postmenopausal. Nulliparity was associated with breast cancer death in women that were younger than 45 years of age (1.28: 0.79-2.09) or premenopausal (1.30: 0.95-1.80), but these associations did not reach statistical significance. There was no association between nulliparity and breast cancer death in women older than 45 years of age or postmenopausal. All associations were similar in analyses stratified for diagnostic period. CONCLUSION Women with four or more children have a poor breast cancer survival as compared to women with one child.

Tumour-related factors and prognosis in breast cancer detected by screening.

Breast cancer detected by screening has an unexplained prognostic advantage beyond stage shift compared with cancers detected clinically. The aim was to investigate biological factors in invasive breast cancer, with reference to mode of detection and rate of death from breast cancer.

Breast density and mode of detection in relation to breast cancer specific survival: a cohort study.

BackgroundThe aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density.MethodsThe study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%.ResultsAfter adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change.ConclusionsHigh breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could not explain differences in survival according to detection mode.

Body mass index and breast cancer survival in relation to the introduction of mammographic screening

AIMS Mammographic screening reduces mortality in breast cancer. It is not known if this reduction is more pronounced in certain groups. Obesity has been associated with worse survival following breast cancer diagnosis. This study investigates BMI in relation to breast cancer mortality, and if this association is affected by invitation to mammographic screening. METHODS In 1976, a randomised mammographic screening trial, inviting 50% of all women aged 45-69 years (n=42 283), was set up in Malmö, Sweden. BMI in relation to breast cancer mortality was examined separately in women invited or not invited to screening in the trial. The analyses also included a historical control-group diagnosed before the screening trial. The study included 2974 women diagnosed in 1961-1991. Relative risks (RR) with a 95% confidence interval was obtained from a Cox proportional hazard analysis and in the analysis of all women, follow-up was limited to 10 years. RESULTS Obese women (BMI> or =30) not invited to mammographic screening had a higher adjusted RR of dying of breast cancer as compared to normal weight women (2.08:1.13-3.81) in the 10-year follow-up. In women invited to screening there was no association between BMI and breast cancer mortality. In the historical control group, mortality was increased in overweight women (BMI: 25-30), RR=1.27:0.99-1.62, and obese women, RR=1.32:0.94-1.84, but these associations totally disappeared in the multivariate analysis, following adjustment for tumour size and stage. CONCLUSIONS Overweight and obese women may be a group that profit from mammographic screening to more than normal weight women.

Do mammographic tumor features in breast cancer relate to breast density and invasiveness, tumor size, and axillary lymph node involvement?

Background Breast density and mammographic tumor features of breast cancer may carry prognostic information. The potential benefit of using the combined information obtained from breast density, mammographic tumor features, and pathological tumor characteristics has not been extensively studied. Purpose To investigate how mammographic tumor features relate to breast density and pathological tumor characteristics. Material and Methods This retrospective study was carried out within the Malmö Diet and Cancer Study: a population-based cohort study recruiting 17,035 women during 1991–1996. A total of 826 incident breast cancers were identified during follow-up. Mammography images were collected and analyzed according to breast density and tumor features at diagnosis. Pathological data were retrieved from medical reports. Mammographic tumor features in relation to invasiveness, tumor size, and axillary lymph node involvement were analyzed using logistic regression yielding odds ratios (OR) with 95% confidence intervals (CI) and adjusted for age at diagnosis, mode of detection, and breast density. Results Tumors presenting as an ill-defined mass or calcifications were more common in dense breasts than tumors presenting as a distinct mass or with spiculated appearance. Invasive cancer was more common in tumors with spiculated appearance than tumors presenting as a distinct mass (adjusted OR, 5.68 [1.81–17.84]). Among invasive tumors, an ill-defined mass was more often large (>20 mm) compared with a distinct mass, (adjusted OR, 3.16 [1.80–5.55]). Conclusion Tumors presenting as an ill-defined mass or calcifications were more common in dense breasts. Spiculated appearance was related to invasiveness, and ill-defined mass to larger tumor size, regardless of mode of detection and breast density. The potential role of mammographic tumor features in clinical decision-making warrants further investigation.

Overweight in relation to tumour size and axillary lymph node involvement in postmenopausal breast cancer patients—Differences between women invited to vs. not invited to mammography in a randomized screening trial

OBJECTIVES Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women. METHODS In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45-69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index >or=25) as a determinant for large tumours (>20mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement. RESULTS In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening. CONCLUSION Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early.