Tamoxifen's protection against breast cancer recurrence is not reduced by concurrent use of the SSRI citalopram.

Tamoxifen remains an important adjuvant therapy to reduce the rate of breast cancer recurrence among patients with oestrogen-receptor-positive tumours. Cytochrome P-450 2D6 metabolizes tamoxifen to metabolites that more readily bind the oestrogen receptor. This enzyme also metabolizes selective serotonin reuptake inhibitors (SSRI), so these widely used drugs - when taken concurrently - may reduce tamoxifen's prevention of breast cancer recurrence. We studied citalopram use in 184 cases of breast cancer recurrence and 184 matched controls without recurrence after equivalent follow-up. Cases and controls were nested in a population of female residents of Northern Denmark with stages I-III oestrogen-receptor-positive breast cancer 1985-2001 and who took tamoxifen for 1, 2, or most often for 5 years. We ascertained prescription histories by linking participants' central personal registry numbers to prescription databases from the National Health Service. Seventeen cases (9%) and 21 controls (11%) received at least one prescription for the SSRI citalopram while taking tamoxifen (adjusted conditional odds ratio=0.85, 95% confidence interval=0.42, 1.7). We also observed no reduction of tamoxifen effectiveness among regular citalopram users (>or=30% overlap with tamoxifen use). These results suggest that concurrent use of citalopram does not reduce tamoxifen's prevention of breast cancer recurrence.

Prevalence and predictors of distress in women taking part in surgical continuity of care for breast cancer: A cohort study.

PURPOSE: Women with breast cancer often experience distress. This cohort study investigated the prevalence of distress, predictors of distress, and changes in distress during surgical continuity of care for breast cancer (from diagnosis to commencement of adjuvant treatment). METHODS: The participants were 1079 women with breast cancer who were recruited between April 2013 and May 2014 from 11 breast surgery departments in Denmark. Distress was evaluated using the Distress Thermometer (DT) and predictors of distress were assessed with a self-administered questionnaire at the time of diagnosis (T1), at discharge (T2), and by the start of adjuvant treatment or follow-up (T3). Repeated measures ANOVA, simple and multiple linear regression, and mixed effects regression models were used to identify predictors and estimate changes in distress. RESULTS: At T1, 249 (24.3%) women reported no or minimal distress, 298 (29.1%) moderate distress, and 407 (39.8%) severe distress. The mean distress was 5.5 points on the DT, which decreased by 0.70 (95% confidence interval (CI) -0.80, -0.54) points from T1 to T3. Predictors of distress were time since diagnosis, age, prior or concurrent intake of antidepressants or sedative medicine, prior emotional status, children living at home, feelings regarding femininity and attractiveness, and hospital. CONCLUSIONS: More than two-thirds of women with breast cancer experienced moderate or severe distress. Mean distress decreased slightly during surgical continuity of care. However, for some women, distress remained unchanged or even worsened. These findings highlight the need to identify the individual women with distress and offer them adequate support and care.

Development of a questionnaire encompassing indicators of distress: a tool for use with women in surgical continuity of care for breast cancer.

PURPOSE: Women with breast cancer often experience significant distress. Currently, there are no questionnaires aimed at identifying women's unique and possible changing indicators for distress in surgical continuity of care for breast cancer. We developed and tested three questionnaires specifically for this use. METHODS AND SAMPLE: We first searched PubMed, CINAHL and PsycINFO to retrieve information on previously described indicators. Next, we conducted a focus group interview with 6 specialised nurses, who have extensive experience about consequences of breast cancer for women in surgical continuity of care. The questionnaire was tested on 18 women scheduled for breast cancer surgery. Subsequently, the women were debriefed to gain knowledge about comprehensibility, readability and relevance of items, and the time needed to complete the questionnaire. After adjustment, the questionnaires were field-tested concomitantly with a clinical study, which both consisted of a survey and an interview study. KEY RESULTS: Three multi-item questionnaires were developed specific to different time points in surgical continuity of care. The questionnaires share a core of statements divided into seven sub-scales: emotional and physical situation, social condition, sexuality, body image, religion and organisational factors. Besides the core of statements, each questionnaire has different statements depending on the time point of surgical continuity of care when it was to be responded to. CONCLUSION: The questionnaires contain comprehensive items that can identify indicators for distress in individual women taking part in surgical continuity of care. The items were understandable and the time used for filling in the questionnaires was reasonable.

The experience of distress in relation to surgical treatment and care for breast cancer: An interview study.

PURPOSE: A diagnosis of breast cancer is a key turning point in a woman's life that may lead to her experiencing severe and persistent distress and potentially presaging a psychiatric disorder, such as major depression. In Denmark an increased standardization of care and a short hospital stay policy minimize the time of medical and nursing surveillance. Consequently, there is the potential risk that distress goes unnoticed, and therefore, untreated. Therefore, the purpose of this study was to explore the experience of distress in Danish women taking part in surgical continuity of care for breast cancer. METHODS AND SAMPLE: A phenomenological-hermeneutic approach inspired by the French philosopher Paul Ricoeur was conducted to explore the experience of distress in relation to surgical treatment and care for breast cancer. Semi-structured interviews were conducted with 12 women who recently had surgery for breast cancer at six departments of breast surgery in Denmark from May 2013 to November 2013. KEY RESULTS: The understanding of the experience of distress in the period of surgical continuity of care for breast cancer is augmented and improved through a discussion related to four identified themes: A time of anxiety, loss of identities, being treated as a person and being part of a system, drawing on theory and other research findings. CONCLUSION: Distress experienced by women in the period following diagnosis arises from multiple sources. Support and care must be based on the woman's individual experience of distress.

Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient without any detectable BRCA2 germline mutation.

Two synchronous bilateral breast carcinomas and their matched lymph node metastases from a 70-year-old man were cytogenetically analyzed. All four tumors were near-diploid, and except for the primary tumor from the right breast, had a 45,X,-Y clone in common. The loss of the Y chromosome was, however, common to all four tumors, whereas metaphase cells from peripheral blood lymphocytes showed a normal 46, XY chromosome complement. The primary tumor from the right breast was monoclonal, with loss of the Y chromosome and gain of 1q, whereas its metastasis had two related clones: the 45,X,-Y clone, and the other a more complex version of the clone in the primary tumor, with inv(3), -14, and del(16)(q13) as additional changes. The primary tumor from the left breast was polyclonal with three unrelated clones: 45,X,-Y/45,XY,-18/47,XY,+20, two of which were present in its metastasis. DNA flow cytometric studies showed diploidy for both primary tumors. No mutation in the BRCA2 gene was found on analysis of DNA from peripheral blood lymphocytes. The present findings show that del(16)(q13) is a recurrent finding among male breast carcinomas and that some of the primary cytogenetic abnormalities, as well as the pattern of chromosomal changes during the progression of sporadic breast carcinoma in the male, are similar to those in the female. In addition, the loss of the Y chromosome in the tumors but not in peripheral blood lymphocytes, suggests a possible role for this abnormality in the pathogenesis of male breast carcinoma.

Breast cancer incidence in ex-smokers in relation to body mass index, weight gain and blood lipid levels.

According to several studies breast cancer is more common among former smokers. This study explores whether this association has any relationship with anthropometric measurements or blood lipid levels. The 2082 ex-smokers (mean age 49.9 years) in the Malmö Preventive Cohort were followed for an average of 13.3 years using official cancer registries. This yielded 93 incident breast cancer cases. Oestrogen receptor (ER) status was assessed by an immunological method. Incidence of breast cancer covaried with height, body mass index, weight gain and cholesterol levels. None of these associations reached statistical significance. Incidence of breast cancer increased over quartiles of serum triglycerides, Ptrend: 0.02, relative risk (RR) for triglycerides as a continuous variable: 1.46 (1.21-1.77). Nineteen tumours were ER negative; this subgroup was similarly related to high triglycerides, 1.76 (1.40-2.21). All results were similar when BMI and cholesterol levels were entered into the model. It is concluded that breast cancer incidence covaries with triglyceride levels in ex-smokers.

Intra-urban differences in breast cancer mortality: a study from the city of Malmö in Sweden.

STUDY OBJECTIVE: To assess whether in an urban population stage at breast cancer diagnosis is related to area of living and to what extent intra-urban differences in breast cancer mortality are related to incidence respectively stage at diagnosis. DESIGN: National registries were used to identify cases. Mortality in 17 residential areas was studied in relation to incidence and stage distribution using linear regression analysis. Areas with high and low breast cancer mortality, incidence and proportion of stage II+ tumours at diagnosis were also compared in terms of their sociodemographic profile. SETTING: City of Malmö in southern Sweden. PATIENTS: The 1675 incident breast cancer cases and 448 deaths that occurred in women above 45 years of age in Malmö 1986-96. MAIN RESULTS: Average annual age standardised breast cancer mortality ranged between residential areas, from 35/10(5) to 107/10(5), p = 0.04. Mortality of breast cancer was not correlated to incidence, r = 0.22, p = 0.39. The ratio of stage II+/0-I cancer incidence varied between areas from 0.45 to 1.99 and was significantly correlated to breast cancer mortality, r = 0.53, p = 0.03. Areas with high proportion of stage II+ cancers and high mortality/incidence ratio were characterised by a high proportion of residentials receiving income support, being foreigners and current smokers. CONCLUSIONS: Within this urban population there were marked differences in breast cancer mortality between residential areas. Stage at diagnosis, but not incidence, contributed to the pattern of mortality. Areas with high proportion of stage II+ tumours differed unfavourably in several sociodemographic aspects from the city average.

Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden.

AIM: This study investigates the potential relation between breast cancer location and axillary lymph node involvement (ALNI). METHODS: Out of all cases with unilateral first-time diagnosis of invasive breast cancer in Malmö, Sweden, between 1961 and 1991, 3472 underwent axillary dissection. The association between tumour location and ALNI was investigated using logistic regression analysis (adjusted for potential confounders) yielding odds ratios (OR), with a 95% confidence interval. All analyses were repeated in different birth-year cohorts. RESULTS: Outer tumours (upper outer or lower outer quadrants), as compared to inner (upper inner and lower inner quadrants), were associated with a statistically significant risk of ALNI, OR: 1.31 (1.11-1.55). Central tumours were also associated with ALNI, OR: 2.61 (2.08-3.27). Among women born before 1909, corresponding OR:s for outer tumours was 1.61 (1.19-2.18), and for central tumours 3.50 (2.32-5.28). CONCLUSIONS: Outer and central breast tumours are associated with a high risk of axillary lymph node involvement.

Survival in breast cancer and age at start of oral contraceptive usage.

In general, findings in studies on oral contraceptives (OCs) and breast cancer have not indicated prognosis to be worse among users of OCs. In few studies, however, has age at the start of OC usage been considered as a prognostic factor. In the present study, prognosis in breast cancer is compared with OC usage, particularly with age at the start of OC usage, among 193 consecutive patients at the Department of Oncology, University Hospital, Lund. An earlier series of 193 breast cancer patients at Malmö General Hospital is included for comparisons. In the Lund series, five-year survival was 62% among women who started to use OCs before the age of 20.78% among those who started to use OCs between the ages of 20 and 25, and 86% among non-users and those who started to use OCs after the age of 25 (p = 0.009, test for homogeneity). Although age was found to be a prognostic factor in the Lund series (RR = 0.90, p = 0.001), this was not so in the earlier (older) Malmö series. The relationship with age differed significantly between the two series (p = 0.003), suggesting the apparent effect of age at diagnosis to be a cohort effect due to the introduction of OCs during the 'sixties. The age-specific relationship between survival and OC usage would seem to indicate the presence of a biological mechanism in which OCs may participate during precancerous and early stages of breast cancer.

PIP: In general, findings in studies on oral contraceptives (OCs) and breast cancer have not indicated prognosis to be worse among OC users. In a few studies, however, age at the initiation of OC usage does seem to be a factor to consider. In this study, prognosis in breast cancer cases is compared to OC usage, particularly with age at the onset of OC usage, among 193 consecutive patients at the Department of Oncology, University Hospital, Lund. An earlier series of 193 breast cancer patients at Malmo General Hospital is included for comparison. In the Lund series, 5-year survival rate was 62% among women who began OC use before the age of 20, 78% among those who began between ages 20-25, and 86% among those who were nonusers or who started to use OCs after age 25 (p=0.009, test for homogeneity). Although age was found to be a prognostic factor in the Lund series (RR=0.90, p=0.001), this was not so in the earlier (older) Malmo series. The relationship between ages differed significantly between the 2 series (p=0.003), suggesting the apparent effect of age at diagnosis to be a cohort effect due to the introduction of OCs during the 1960s. The age-specific relationship between survival and OC usage would seem to indicate the presence of a biological mechanism in which OCs may play a role in the precancerous and early stages of breast cancer.

Primary hyperparathyroidism: intraoperative PTH-measurements.

BACKGROUND: With the development of rapid assays and intraoperative measurement of intact parathyroid hormone (PTH), new strategies in the handling of patients with primary hyperparathyroidism (pHPT) have evolved. AIM: The aim of our study was to illustrate the performance of the intraoperative PTH measurement as a predictor of successful cure. MATERIAL AND METHODS: From September 1999 to April 2002 143 patients with pHPT underwent a parathyroid operation (bilateral neck exploration with identification of all parathyroid glands) with intraoperative measurements of plasma PTH (immediately prior to surgery (T0) and 5 minutes after gland excision (T5)). A positive test result was defined as plasma PTH values at T5 below 20% of T0 or a value in the normal range below 7.6 pmol/l. Hence T5 values above 20% of T0 and above 7.6 pmol/l were considered test negative. RESULTS: 122 patients (85%) were test positive and cured, 11 patients (8%) were test negative but cured, and 10 patients (7%) were test negative and not cured by the primary operation. Consequently, the sensitivity of the test was 0.92 and the specificity 1.00. CONCLUSIONS: The rapid PTH test used is a reliable predictor of a successful outcome in pHPT patients undergoing parathyroid surgery.

Predictors of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study.

AIM: To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation. METHODS: We conducted a population-based study in Denmark. Patients were categorized according to age group, surgery type, and glucocorticoid use before surgery: never, current (0-90 days), and former (>90 days). We calculated the risk of re-operation due to post-surgical bleeding within 14 days after surgery, risk differences, and risk ratios of re-operation associated with age group, surgery type, and glucocorticoid use. RESULTS: 19,919 women were studied; 508 were re-operated. 3573 of the 19,919 women ever used glucocorticoids. Older age and mastectomy increased the risk of post-surgical bleeding compared with breast conserving surgery and younger age among both ever and never users of glucocorticoids. The crude risk of re-operation was 2.5% among never users of glucocorticoids, 2.6% among ever users and 4.0% among current users. Women aged ≥80 who were ever users of glucocorticoids and who had a mastectomy had 8.1% risk of re-operation due to post-surgical bleeding, whereas women <80 years old who never used glucocorticoids and who had breast conserving surgery had a 1.7% risk of re-operation. CONCLUSIONS: Older age, mastectomy, and - in some women - glucocorticoid use add an extra risk of re-operation due to bleeding. Clinicians and their patients can use this information to evaluate the patient-specific risk of this complication.

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.

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 Cox's 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.