Attitudes of Canadian Oncology Practitioners Toward Psychosocial Interventions in Clinical and Research Settings in Women With Breast Cancer

The aim of this study was to survey Canadian oncology practitioners' attitudes toward psychosocial concerns and issues in women with breast cancer. Surveys were mailed to 351 medical, radiation and surgical oncologists and 375 oncology nurses. Standard questionnaires assessed attitudes towards psychosocial issues in women with primary and metastatic breast cancer and evaluated the practitioners' willingness to refer women to psychosocial intervention trials in the presence and absence of competing drug trials. Responses were obtained from 74% of those surveyed. Respondents reported being aware of the common occurrence of psychosocial problems in women with metastatic breast cancer, however, physicians were less likely than nurses to offer these women psychosocial support on a prophylactic basis (p < 0.0001) and they expressed greater concern than nurses about scientific validity of (p = 0.0003), and potential psychological damage from (p = 0.005), psychosocial support groups. Nurses were more likely than physicians to favour a study investigating group psychosocial support over competing drug studies (p ≤ 0.003) in the metastatic setting. Physicians were less likely than nurses to deal with weight problems prophylactically in women with primary breast cancer (p = 0.0009) and they expressed greater concern over scientific validity of psychosocial interventions addressing weight than nurses (p = 0.0008); nurses were more concerned about excessive expectations of patients regarding potential benefits of such interventions (p < 0.0001). Regardless, nurses were more likely than physicians to favour a psychosocial intervention study focused on weight management over drug studies in pre- (p = 0.0006) and postmenopausal women (p = 0.05) with primary breast cancer. Canadian oncology practitioners are aware of the common occurrence of psychosocial distress in women with breast cancer. Physicians and nurses assigned differing priorities to psychosocial interventions in both clinical and research situations. © 1997 John Wiley & Sons, Ltd.     

Modifiable risk factors for advanced vs. early breast cancer in the French E3N cohort

Advanced breast cancer (BC) is associated with heavier treatments and poorer prognosis than early BC. Despite mammographic screening, advanced BC incidence remains stable. Little is known about risk factors differentially associated with advanced BC. We analyzed factors predicting for postmenopausal advanced vs. early BC in the E3N cohort. E3N has been prospectively following 98,995 French women aged 50–65 years at baseline since 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for advanced and early invasive BC were estimated with multivariate Cox competing risk hazard models. With a median follow-up of 15.7 years, 4,941 postmenopausal BC were diagnosed, including 1,878 (38%) advanced BC. Compared to early BC, advanced BC was differentially associated with excess weight (HR 1.39 [95% CI = 1.26–1.53] vs. 1.08 [95% CI = 1.00–1.17], p_homogeneity < 0.0001) and living in a rural area (HR 1.14 [95% CI = 1.00–1.31] vs. 0.93 [95% CI = 0.82–1.04], p_homogeneity 0.02). Excess weight was the only differential risk factor for advanced BC for hormone-dependent BC and for women compliant with screening recommendations. Previous mammography was associated with reduced advanced BC risk (HR 0.86 [95% CI = 0.73–1.00]) and increased early BC risk (HR 1.36 [95% CI = 1.18–1.56], p_homogeneity < 0.0001), but only for hormone-dependent BC. Excess weight appears to be mostly associated with advanced BC, especially hormone-dependent BC. These results add to the evidence for maintaining weight within the recommended limits.     

Physical activity and mammographic breast density in a Mediterranean population: The EPIC Florence longitudinal study

A protective effect of physical activity (PA) on breast cancer (BC) risk has been suggested. Few studies have examined the influence of PA on mammographic breast density (MBD), a strong risk factor for BC. In a prospective study in Florence, Italy, we identified 2,000 healthy women with a mammogram taken 5 years after enrolment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfe's classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrolment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high‐MBD (P2 + DY Wolfe's patterns) were compared with women with low‐MBD (N1 + P1) by multivariate logistic models. Overall, high‐MBD was inversely associated with increasing levels of leisure time PA (p for trend = 0.04) and among peri‐/postmenopausal women, also with increasing levels of recreational activities (p for trend = 0.02). An interaction between PA and HRT emerged, with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers (p for interaction = 0.02). A modifying effect by body mass index (BMI) was evident among 1,025 peri‐/postmenopausal women who did not use HRT at the time of mammogram, with a stronger inverse association between recreational PA and MBD in the highest BMI tertile (OR = 0.34; 95% CI 0.20–0.57; p for interaction = 0.03). This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD, particularly in overweight/obese peri‐/postmenopausal women. © 2008 Wiley‐Liss, Inc.     

Hormone replacement therapy after treatment of breast cancer: effects on postmenopausal symptoms, bone mineral density and recurrence rates

PURPOSE: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35--50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients. PATIENTS AND METHODS: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates. RESULTS: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women < or =50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (< or =50 years: without HRT -1.99 vs. with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29). CONCLUSION: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials.     

Breast cancer survivors' beliefs about the causes of breast cancer

Objective: To explore the beliefs held by breast cancer (BC) survivors about the factors that contribute to the development of their BC. Methods: The BUPA Health Foundation Health and Well‐being after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive BC. Participants completed an enrollment questionnaire (EQ), first follow‐up questionnaire (FQ1) and a second follow‐up questionnaire (FQ2), 12 months and 24 months post‐EQ, respectively. In the FQ2, women were asked whether they believed anything contributed to the development of their BC and whether they had made lifestyle changes since the FQ1. Well‐being was assessed at the FQ2 using the Psychological General Well‐being Index (PGWB). Results: In total, 1496/1684 women completed the FQ2 and 43.5% reported belief in a factor that may have contributed to their developing BC. These women were more likely to be younger (p<0.0001) and educated beyond high school (p<0.0001). Stress (58.1%) was the most common reason given, followed by previous use of hormone therapy (17.0%) and a family history of any cancer (9.8%). Women who believed stress contributed to their BC had lower PGWB scores than other study participants (70.9 ± 16.1, n = 361 versus 77.3 ± 14.9, n = 1071, mean difference = 6.4, 95% CI: 4.6–8.2 p<0.0001) and were more likely to have made lifestyle changes since their BC diagnosis. Conclusions: Many women with BC believe that stress has contributed to their condition. Women who held this belief were more likely to adopt strategies to reduce stress than those who did not. Copyright © 2011 John Wiley & Sons, Ltd.     

DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood

Breast cancer (BC) is the leading cause of cancer‐related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the BC‐associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome‐wide methylation screening and identified a BC‐associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 × 10^?9 adjusted for cell‐type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p < 0.0001; second validation round with 189 BC case and 189 controls: p < 0.0001). In addition to cg27091787, the decreased methylation of a 650‐bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p‐value of 0.006. To note, the BC‐associated decreased HYAL2 methylation was replicated in the T‐cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early‐stage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) = 0.89], and was robust for the detection of BC in younger women as well (age < 50, AUC = 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood‐based marker for the detection of early BC.     

Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data

There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease-free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real-world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient-level data from reported DFS data and (iii) estimating treatment effect in the patient-level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient-level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.     

Changes on Bone Mineral Density after Adjuvant Treatment in Women with Non-metastatic Breast Cancer

Summary Purpose. Adjuvant therapies have prolonged survival of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). We have analyzed the effects of chemotherapy, hormone therapy with tamoxifen or both, on BMD of women with NMBC. Patients and methods. We prospectively included 168 women with NMBC (stage I–III) referred to the Medical Oncology Service of University Hospital of Canary Islands between 1997 and 2001 (55 ± 12 years; 37% premenopausal; 43 ± 13 months of follow-up). We measured lumbar and hip BMD (g/cm²) at diagnosis, after chemotherapy and after 12 months of tamoxifen. If a low BMD was detected, women were treated with bisphosphonates. Results. BMD after chemotherapy (n = 83) significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p = 0.0001), trochanter (0.701 ± 0; 0.690 ± 0, p = 0.001), intertrochanter (1.095 ± 0; 1.078 ± 0, p = 0.0001) and total hip (0.924 ± 0; 0.915 ± 0, p = 0.046) areas. Although 60% of the premenopausal women suffered amenorrhea after chemotherapy, there were not significant differences in BMD between them and women who retained menses. BMD of women who received 12 months of tamoxifen after chemotherapy increased – total hip (0.907 ± 0; 0.922 ± 0, p = 0.005) and intertrochanter (1.071 ± 0; 1.091 ± 0, p = 0.003) – or remained stable – lumbar, femoral neck, trochanter, and Ward's triangle (n = 39). When tamoxifen was the only adjuvant treatment, BMD after 12 months (n = 22) increased in trochanter area (0.644 ± 0; 0.663 ± 0, p = 0.011), and remained stable in all other sites. 50 (30%) patients were treated with bisphosphonates because of osteopenia. Conclusion. Women with NMBC are affected by early bone loss after adjuvant chemotherapy. This bone loss is attenuated by one year of tamoxifen treatment. This article presented in part at the 2000 (December) 23rd Annual San Antonio Breast Cancer Symposium, and at the 2004 (September-October) 27th World Congress of Internal Medicine at Granada, Spain.     

Duration of Hormone Replacement Therapy, Breast Tumour Size and Grade in a Screening Programme

One of the primary adverse effects of long-term use of hormone replacement therapy (HRT) is a modest increase in the risk of breast cancer. Breast tumours that develop in women using HRT have been shown to have prognostically favourable histological features but it is unclear if this is the case for both short- and long-term use. Methods. We evaluated the association between HRT use with tumour size and histologic grade in a cohort of women aged over 55 years (n = 2200) diagnosed with invasive breast cancer at subsequent screen in BreastScreen Victoria (BSV), Australia between 1993 and 2000. BSV biennially screens women aged over 40 years with the target age group 50–69 years. Multiple linear regression was used to examine predictors of log-transformed tumour size and multinomial logistic regression was used to evaluate associations of HRT with tumour grade. Results. Short-term users of HRT (5 years), were approximately 50% less likely to develop poorly-differentiated breast tumours OR 0.48 95%CI (0.28–0.82) or node-positive tumours OR 0.57 95%CI (0.35–0.94) than non-users. Long-term users of HRT (5 years) were also less likely to develop poorly-differentiated tumours OR 0.36 95%CI (0.24–0.56) but were not more likely to be node-positive than women not on HRT. Duration of HRT use was not significantly associated with tumour size. Conclusion. HRT use, regardless of duration, was associated with breast tumours that were better differentiated and not significantly larger than women not on HRT, although only short-term use was associated with fewer node-positive tumours.     

Examining the links between perceived impact of breast cancer and psychosocial adjustment: the buffering role of posttraumatic growth

Objectives: Finding positive changes in the aftermath of breast cancer (BC) may protect women against impaired adjustment. This study examines posttraumatic growth (PTG) in a sample of women receiving treatment for BC and explores the buffering role of PTG on the links between perceived impact of BC and emotional distress and quality of life (QoL). Methods: Seventy‐eight women receiving chemotherapy (n = 57) or radiotherapy (n = 21) completed the Portuguese versions of the Posttraumatic Growth Inventory, the Hospital Anxiety and Depression Scale, the World Health Organization for QoL‐Bref and Consequences sub‐scale of the Brief Illness Perception Questionnaire (assessing perceived impact of BC). Results: PTG was frequently reported and co‐existed with distress and dysfunction. A more negative perception of the impact of BC was significantly associated with higher emotional distress and impaired Physical and Psychological QoL, but was unrelated to PTG. Hierarchical regression analyses showed that PTG moderated these relationships, acting as a stress‐buffering mechanism. Among women who perceived BC as having a more negative impact on their lives, higher levels of PTG buffered this negative perceived impact on Psychological and Social QoL (p<0.01) and also on Depression (p<0.06). This effect was not found for Physical QoL and Anxiety. Conclusions: Results provide support for the stress‐buffering role of PTG. Finding positive changes in cancer experience seems to protect women from the effects of a negative perception of the impact of BC on adjustment. Psychosocial intervention programs should facilitate PTG in order to promote women's adjustment. Copyright © 2011 John Wiley & Sons, Ltd.     

Lung cancer mortality reduction by LDCT screening—Results from the randomized German LUSI trial

In 2011, the U.S. National Lung Cancer Screening Trial (NLST) reported a 20% reduction of lung cancer mortality after regular screening by low-dose computed tomography (LDCT), as compared to X-ray screening. The introduction of lung cancer screening programs in Europe awaits confirmation of these first findings from European trials that started in parallel with the NLST. The German Lung cancer Screening Intervention (LUSI) is a randomized trial among 4,052 long-term smokers, 50–69 years of age, recruited from the general population, comparing five annual rounds of LDCT screening (screening arm; n = 2,029 participants) with a control arm (n = 2,023) followed by annual postal questionnaire inquiries. Data on lung cancer incidence and mortality and vital status were collected from hospitals or office-based physicians, cancer registries, population registers and health offices. Over an average observation time of 8.8 years after randomization, the hazard ratio for lung cancer mortality was 0.74 (95% CI: 0.46–1.19; p = 0.21) among men and women combined. Modeling by sex, however showed a statistically significant reduction in lung cancer mortality among women (HR = 0.31 [95% CI: 0.10–0.96], p = 0.04), but not among men (HR = 0.94 [95% CI: 0.54–1.61], p = 0.81) screened by LDCT (p_{heterogeneity} = 0.09). Findings from LUSI are in line with those from other trials, including NLST, that suggest a stronger reduction of lung cancer mortality after LDCT screening among women as compared to men. This heterogeneity could be the result of different relative counts of lung tumor subtypes occurring in men and women.     

Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56⁺ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56⁺ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.     

Change in mammographic density across birth cohorts of Dutch breast cancer screening participants

High mammographic density is a well-known risk factor for breast cancer. This study aimed to search for a possible birth cohort effect on mammographic density, which might contribute to explain the increasing breast cancer incidence. We separately analyzed left and right breast density of Dutch women from a 13-year period (2003–2016) in the breast cancer screening programme. First, we analyzed age-specific changes in average percent dense volume (PDV) across birth cohorts. A linear regression analysis (PDV vs. year of birth) indicated a small but statistically significant increase in women of: 1) age 50 and born from 1952 to 1966 (left, slope = 0.04, p = 0.003; right, slope = 0.09, p < 0.0001); 2) age 55 and born from 1948 to 1961 (right, slope = 0.04, p = 0.01); and 3) age 70 and born from 1933 to 1946 (right, slope = 0.05, p = 0.002). A decrease of total breast volume seemed to explain the increase in PDV. Second, we compared proportion of women with dense breast in women born in 1946–1953 and 1959–1966, and observed a statistical significant increase of proportion of highly dense breast in later born women, in the 51 to 55 age-groups for the left breast (around a 20% increase in each age-group), and in the 50 to 56 age-groups for the right breast (increase ranging from 27% to 48%). The study indicated a slight increase in mammography density across birth cohorts, most pronounced for women in their early 50s, and more marked for the right than for the left breast.     

Effect of aerobic exercise intervention on markers of insulin resistance in breast cancer women

Insulin may affect breast cancer (BC) risk and prognosis. Exercise reduces insulin in obese BC survivors. We designed a randomised controlled trial to test the effect of an aerobic exercise intervention (AEI) on insulin parameters and body composition in non‐obese BC women without insulin resistance. Thirty‐eight BC women were randomised into an intervention group (IG = 18) or control group (CG = 20). IG participated in a structured AEI for 3 months, while CG received only the Word Cancer Research Fund/American Institute Cancer Research (WCRF/AICR) recommendation to be physically active. Fasting insulin, homeostasis model assessment of insulin resistance (HOMA‐IR) index, metabolic parameters and body composition were collected at baseline and after the AEI. IG reduced insulin and HOMA‐IR index by 15% and 14%, while CG increased these parameters (+12% and +16%). Insulin changed differently over time in the two randomised groups (p_interaction = .04). The between‐group differences in the change of insulin (IG = ?1.2 μU/ml versus CG = +0.8 μU/ml) and HOMA‐IR index (IG = ?0.26 versus CG = +0.25) were respectively significant (p = .04) and non‐significant (p = .06). IG significantly improved lower limb muscle mass in comparison with CG (p = .03). A structured AEI may improve insulin, HOMA‐IR index and body composition in non‐obese BC survivors without insulin resistance.     

Larger axillary metastases in obese women and smokers with breast cancer- an influence by host factors on early tumor behavior

To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node-positive breast cancer.Both M/P ratios and M were larger in the 72 obese women and in the 40 nonobese smokers than in the 64 nonobese nonsmokers after control for other factors. Step-wise regression analysis demonstrated independent associations between M/P ratios and obesity (p = 0.0002), larger primary tumors (p<0.0001), more positive nodes (p< 0.0001), and smoking (p = 0.0268), as well as between M and obesity (p = 0.0201), larger primary tumors (p = 0.0093), and more positive nodes (p = 0.0001). Among the 104 nonobese women, smoking was associated both with larger M (p = 0.0257) and larger M/P (p = 0.0055). Our observations suggest more rapid growth by metastases in obese women and smokers with breast cancer, as well as earlier metastasis from their primary tumors.     

On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer

Although it has been suggested that dietary energy intake restriction may be related to reduced BRCA-associated breast cancer (BC) risk, it is currently not known whether overall diet quality could predict the BC risk among women with deleterious mutations in BRCA1 and BRCA2 (BRCA) genes who already have an elevated BC risk. To assess possible relationships between diet quality, reflected by the Alternate Healthy Eating Index (AHEI), the Diet Quality Index-Revised (DQI-R), the alternate Mediterranean Diet Index (aMED), the Canadian Healthy Eating Index (CHEI), and BRCA-associated BC risk, a case-control study was carried out within a cohort of 80 French-Canadian families with 250 members involving 89 carriers of BRCA genes affected by BC, 48 non-affected carriers and 46 non-affected non-carriers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in unconditional logistic regression models. After adjustment for age, physical activity and total energy intake, we did not detect any association between the AHEI or aMED and BC. However, a strong and significant inverse relationship was apparent between the DQI-R and CHEI and BRCA-associated BC risk. ORs comparing the highest and lowest tertiles of diet quality scores were 0.35 (95%CI = 0.12–1.02; p = 0.034 for trend) for the DQI-R and 0.18 (95%CI = 0.05–0.68; p = 0.006 for trend) for the CHEI, respectively. These inverse associations were not the result of a link with any specific component of the diet quality indexes. These results suggest that dietary guidelines reflected by the DQI-R and CHEI may constitute preventive strategies for reducing BRCA-associated BC risk.     

Incidence of second primary malignancy after breast cancer and related risk factors—Is breast-conserving surgery safe? A nested case–control study

Risk of second primary malignancy (SPM) is increasing. We aimed to assess the incidence and related risk factors of SPM among breast cancer (BC) patients from this nested case–control study using the SEER database. BC patients with SPM were identified as the case group and SPM-free patients were defined as the control group. Propensity score matching of cases with controls by the year of the first primary BC diagnosis was conducted at the ratio of 1:5, and 97,242 BC patients were enrolled from 1998 to 2013 after the matching. The incidence of SPM in BC patients stratified by age groups and cancer sites was compared to the general population using the adjusted standardized incidence ratio (SIR) and the risk factors for SPM were examined using Cox proportional hazard regressions. Our study showed BC patients had excess risk for SPM than the general population (adjusted SIR for all cancer sites = 12.94, p < 0.001) and the incidence of SPM among them decreased with age. The risk of SPM was significantly related to the following demographical and clinical variables: age (40–59 vs. 18–39, HR = 1.33; 60–79 vs. 18–39, HR = 2.39; ≥80 vs. 18–39, HR = 2.84), race (black vs. white, HR = 1.12), histological type (lobular BC vs. ductal BC, HR = 1.15), radiotherapy (HR = 1.33), marital status (married vs. single, HR = 0.88) and estrogen receptor status (positive vs. negative, HR = 0.85). Consistent results were found in subgroup analysis stratified by contralateral-breast SPMs and nonbreast SPMs.     

Waist circumference and risk of breast cancer in Korean women: A nationwide cohort study

Although postmenopausal breast cancer (BC) risk has been linked to adiposity, associations between adiposity and premenopausal BC remain unclear. To address this question, we investigated the association of BC risk with measures of adiposity, including body mass index (BMI) and waist circumference (WC), in a large cohort of Asian women. We used a nationwide cohort of adult Korean women selected from the National Health Insurance Corporation database merged with national health examination data from 2009 to 2015. A total of 11,227,948 women were tracked to retrospectively identify incident cases of BC. Our analysis used Cox proportional hazards models to calculate hazard ratios and assess the association of BC risk with BMI and/or WC in both pre‐ and postmenopausal women. BMI and WC were robustly associated with increased risk for postmenopausal BC (p_trend<0.001 for both BMI and WC) but not with premenopausal BC. Association between WC and premenopausal BC was only statistically significant when considering BMI (p_trend=0.044). In contrast, postmenopausal BC was negatively associated with WC when considering BMI (p_trend=0.011). In premenopausal women, WC may predict increased BC risk when considering BMI. However, in postmenopausal women, WC is not superior to BMI as an indicator of BC risk.     

Breast ultrasonography (BU) in the screening protocol for women at hereditary-familial risk of breast cancer: has the time come to rethink the role of BU according to different risk categories?

This article evaluates the breast cancer (BC) screening efficacy of biannual ultrasound (US) in three different risk categories. In a single-center, prospective, nonrandomized comparison study, BRCA mutation carriers and women with high risk (HR) or intermediate risk (IR) received mammography (MMG), ultrasound, (US) and Magnetic Resonance Imaging (MRI), scheduled according to the risk categories. Single and combined sensitivity were evaluated in specific groups of risk and the US performance at six-monthly interval was notably considered. Among 2,313 asymptomatic women at different risk (136 mutation carriers, 1,749 at HR and 428 at IR) 211 developed a BC, of which 193 (91.5%) were screen detected BC (SDBC) and 18 (8.5%) were interval BC (IBC). The SDBC detection rate (DR) was 11.2 per 1.000 person-years (37.9, 8.5 and 16.1 for BRCA, HR and IR, respectively); 116 BC were detected by MMG (DR = 6.6 × 1,000 persons-years), 62 by US (DR = 3.6 × 1,000 persons-years) and 15 by MRI, that was applied only in 60 BRCA women (DR = 37 × 1,000 persons-years). At the six-monthly US, 52 BC were detected (DR = 3.0 × 1,000 persons/years), of which 8 were BRCA-related. The most sensitive technique was MRI (93.7%) followed by MMG (55%) and US (29.4%). Combined sensitivity for MMG plus US was 100% in HR and 80.4% for IR women (p < 0.01). In BRCA mutated patients, MRI alone with annual US performed after six months, could be offered. In HR patients, MMG plus biannual US provide the most sensitive diagnosis and for IR group an annual MMG could be sufficient.     

A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden)

Objectives: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula. Methods: The cohort consisted of 6586 women, aged 50–64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry. Results: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9–5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4–5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas. Conclusion: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.