A comparison of the characteristics,treatment and outcome after 5 years,of Australian women aged 70 + with those aged < 70 years at the time of diagnosis of breast cancer

BackgroundManagement of older women with breast cancer (BC) is challenging, as age-related comorbidities may limit treatment. We present 5-year follow-up data from women aged 70 years or older (70 +), at the time of diagnosis of their BC, compared with younger women (< 70 years).MethodsData is from an Australian cohort study of women with their first episode of invasive BC (Bupa study). Participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQ) for 5 years (FQ1–5). Data collected included details of the BC and its treatment. Psychological wellbeing was measured by the Psychological General Wellbeing Index (PGWB).ResultsAt diagnosis, 274 (16%) women were aged 70 + and of them, 90% were aged 70–79 years. Compared with women aged < 70 years, the women aged 70 + were less likely to have positive nodes, they were less likely to receive radiotherapy and chemotherapy and were more likely to have pre-existing cardiovascular morbidities. By FQ5 women aged 70 + were less likely to be taking oral adjuvant endocrine therapy (OAET) and were more likely to have died from causes other than BC. At FQ5, women 70 + reported less anxiety and better self-control.ConclusionsWomen aged 70 +, compared to < 70 years, had less advanced disease, received radiation and chemotherapy less often, were more likely to have cardiovascular disease at the time of diagnosis, were less likely to be taking OAET at the 5-year assessment, and were more likely to die of causes other than breast cancer.     

Hormone replacement therapy after treatment for breast cancer: physicians' attitudes towards randomized trials

Purpose. Physician support is required for successful patient recruitment to a large randomized controlled trial (RCT) designed to determine the safety and benefits of short-term hormone replacement therapy (HRT) after breast cancer (BC). Methods. A survey was mailed to 1899 Canadian gynaecologists, family physicians, medical, radiation and surgical oncologists to assess willingness to refer patients to an RCT of HRT after BC. Results. Of 538 physicians, 420 (78%) reported that they would be willing to refer a woman after BC to an RCT of HRT versus placebo. Variables predicting willingness to refer included: support for HRT in well women (p = 0.04) and after BC (p = 0.0001); support for clinical trials (p = 0.0001); ongoing BC trials at the physicians' institution (p = 0.003); currently prescribing HRT to women after BC (p = 0.03); and beneficial results in ongoing RCTs of HRT in well women (p = 0.02). Conclusions. An RCT of short-term HRT after BC may be feasible among Canadian physicians.     

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.     

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.     

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.     

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.     

Psychological well-being outcomes in disease-free survivors of mid-low rectal cancer following curative surgery

Objective: The aim of this cross‐sectional study was to evaluate psychological well‐being outcomes in disease‐free survivors who previously underwent radical surgery for rectal adenocarcinoma. Methods: All patients with rectal adenocarcinoma who underwent primary surgery at a single institution from 1990 to 2002 were considered for inclusion in the study. We identified and sent questionnaires to 145 patients after excluding those who had died or had recurrent disease. One hundred and seventeen patients (men/women: 74/43; median age: 65 years) returned the questionnaires. Patients' well being was evaluated using the Psychological General Well‐Being Index (PGWBI) questionnaire. The mean PGWBI score was compared with normative data of the general population. The impact of patient‐, tumor‐ and treatment‐related factors on patients' long‐term psychological well‐being status was also evaluated. Results: Compared with the general population, study patients had significantly better anxiety, depressed mood, positive well being, general health, vitality scales and global index scores. On multivariate analysis, positive well being was independently affected by time from diagnosis (36 months; p=0.025) and occurrence of early major complications (p=0.024). Variables that were independently associated with worse self‐control included primary education (p=0.04) and the presence of fecal urgency (p=0.049). General health was negatively affected by time from diagnosis (36 months; p=0.047) and fecal urgency (p=0.009). Conclusions: Patients who have survived cancer are likely to re‐evaluate the importance of everyday events and this may explain why they had better PGWBI scores. This study also identified that a short time from diagnosis, early adverse events and bowel dysfunction had a negative impact on patients' well being. Copyright © 2010 John Wiley & Sons, Ltd.     

Risk of metachronous breast cancer after BRCA mutation–associated ovarian cancer

BACKGROUND:

This study sought to estimate the risk of breast cancer (BC) after a diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast cancer, early onset) genes (BRCA‐OC).

METHODS:

The Memorial Sloan‐Kettering Cancer Center and the University of Pennsylvania, clinical genetics databases were searched to identify women with BRCA‐OC who participated in genetic testing and follow‐up studies from 1995 to 2009. The primary objective was to determine the risk of developing BC after BRCA‐OC. Overall survival (OS) and BC‐free survival (BCFS) were determined by the Kaplan‐Meier method; patients were censored at the time of last follow‐up.

RESULTS:

A total of 164 patients had BRCA‐OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior to BRCA testing (median time to testing, 2.4 years [0.01‐55 years]). Median follow‐up from OC for those not developing BC was 5.8 years (0.25‐55.6 years). There were 46 deaths, but none were due to BC. The 5‐ and 10‐year OS were 85% (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous BC diagnoses. The 5‐ and 10‐year BCFS were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A subset of 64 women were tested either before or within 12 months of BRCA‐OC. In this pseudo‐incident subset, 5‐ and 10‐ year OS was 71% (95% CI = 0.53, 0.83) and 62% (95% CI = 0.44, 0.75), respectively, and 5‐ and 10‐year BCFS were 100% and 87% (95% CI = 0.56, 0.96), respectively.

CONCLUSIONS:

OS was dominated by OC deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation carriers. These results support nonsurgical management of BC risk in women with BRCA‐OC. Cancer 2013. © 2012 American Cancer Society.     

Post-treatment regret among young breast cancer survivors

Objective: The study addresses: (1) what women regret about their breast cancer treatment 5 years later, and (2) what characteristics of disease and treatment predict post‐treatment regret. Method: Interviews were conducted with breast cancer survivors in the San Francisco Bay Area. Participants were interviewed following diagnosis. Five years later, women were asked whether they had any regrets about their cancer treatment (N=449). Qualitative analysis was used to identify regret content, and logistic regression was used to determine what characteristics of treatment predicted regret. Results: Forty two point five percent women in the sample regretted some aspect of the treatment. The most common regrets were primary surgery (24.1%), chemotherapy and/or radiation (21.5%), reconstruction (17.8%), and problems with providers (13.1%). In addition, women regretted inactions (59.2%) (actions that they did not take) more than actions that they did take (30.4%). This represents a novel finding in the study of post‐treatment regret, which has largely focused on regrets over actions. Quantitative analysis revealed that women who were anxious about the future (OR=1.32; p=0.03) or had problems communicating with physicians (OR=1.26; p=0.02) during treatment were more likely to express regret 5 years later. In addition, women with new or recurrent cancers 5 years later were significantly more likely to regret some aspect of their primary treatment (OR=5.81; p<0.001). Conclusion: This research supports addressing the psychosocial aspects of cancer care and improving physician‐patient communication. Evidence is also provided for addressing the unique emotional needs of women with recurrent cancers, who may experience an undue burden of regret. Copyright © 2010 John Wiley & Sons, Ltd.     

Pain and quality of life after surgery for breast cancer

Background. In breast cancer (BC) patients, conservative surgery (CS) followed by irradiation or immediate breast reconstruction (IBR) after modified radical mastectomy (MRM) has been proposed in the attempt to avoid the negative impact of MRM on feminine body image. Regardless of the type of operation, BC patients may feel pain even without recurrent disease with poor adjustment in terms of quality of life (QL). Methods. We adopted a questionnaire comprising the short form of the McGill Pain questionnaire, and a previously validated questionnaire able to identify four subscales exploring physical well-being, physical autonomy, relational life and psychological well-being. The questionnaire was mailed in 1999 to a consecutive series of 757 (CS: 481 cases; MRM + IBR with skin expander: 93 cases; MRM: 183 cases) disease-free patients treated for BC between March 1995 and March 1998. Results. The final analysis assessed the data relating to 529 patients who underwent axillary dissection. Pain was reported by 39.7% of women with higher incidence in patients who underwent CS than in those who underwent MRM ± IBR, but this difference did not reach statistical significance (p = 0.07). The only statistically significant difference (p < 0.05) between the surgical groups was the pain appearance that occurred earlier in the CS patients and later in the MRM + IBR patients. No other differences were observed. The women with pain had significantly worse QL scores on all of the subscales than those without. Conclusion. Pain after surgery for BC distress almost one-third of patients, regardless of the type of treatment, and had a negative effect on patients QL. The different surgical procedures may marginally influence the quantitative characteristics of pain.     

Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians

Background Although the connection between diet, lifestyle and hormones suggests that nutritional and lifestyle factors may exert an influence in the etiology of breast cancer (BC), it is not clear whether these factors operate in the same way in women with BRCA1 and BRCA2 (BRCA) gene mutations who already have an elevated BC risk.Methods A case–control study was conducted within a cohort of 80 French-Canadian families with 250 members involving 89 carriers of mutated BRCA gene affected with BC and 48 non-affected carriers. A validated semi-quantitative food frequency questionnaire was used to ascertain dietary intake, and a lifestyle core questionnaire, to gather information on physical activity and other lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in unconditional logistic regression models.Results After adjustment for age, maximum lifetime body mass index (BMI) and physical activity, a positive association was found between total energy intake and BRCA-related BC risk. OR was 2.76 (95%CI: 1.10–7.02; p=0.026 for trend), when comparing the highest tertile of intake with the lowest. The intake of other nutrients and dietary components was not significantly associated with the risk of BC. Age at the time the subjects reached maximum BMI was significantly related to an elevated BC risk (OR=2.90; 95%CI: 1.01–8.36; p=0.046 for trend). In addition, a direct and significant relationship was noted between maximum weight gain since both age 18 and 30 years and BC risk. The ORs were 4.64 (95%CI: 1.52–14.12; p=0.011 for trend) for weight gain since age 18 years and 4.11 (95%CI: 1.46–11.56; p=0.013 for trend) for weight gain since age 30 years, respectively. No overall association was apparent between BRCA-related BC risk and BMI, smoking, and physical activity.Conclusion The results of this preliminary study suggest that weight control in adulthood through dietary energy intake restriction is an important factor for the prevention of BRCA-related BC risk.     

Young women with family history of breast cancer and their risk factors for benign breast disease

BACKGROUND:

Breast cancer (BC) patients wonder how their daughters might reduce their risk. The authors investigated childhood/adolescent risk factors for benign breast disease (BBD), a well‐documented risk factor for BC, among girls with a family history.

METHODS:

GUTS (the Growing Up Today Study) includes females, aged 9 to 15 years in 1996, who completed annual questionnaires during 1996 to 2001, then in 2003, 2005, and 2007. Participants provided information regarding alcohol, menarche, height, and body mass index (BMI; kg/m²). Peak height growth velocity (PHV; in./y) was estimated from longitudinal heights. On 2005‐2007 surveys, 6888 women (18‐27 years old) reported whether they were diagnosed with biopsy‐confirmed BBD (n = 67 cases); 6741 women (noncases) reported no BBD. Participants' mothers reported their own biopsy‐confirmed BBD and BC, and BC in their sisters and mothers. Stratified by family history, logistic models investigated BBD risk factors.

RESULTS:

Young women whose mothers or aunts had BC were more likely to be diagnosed with BBD (odds ratio [OR], 2.34; P = .01), as were those with maternal BBD (OR, 1.59; P = .095). Adolescents with BC family history (mother, aunt, grandmother) who consumed alcohol (7 drinks/wk) doubled their BBD risk (OR, 2.28; P = .01), similar to those with maternal BBD (OR, 1.96; P = .02). Girls whose mother or aunt had BC saw their BBD risk elevated with higher PHV (OR, 1.82 [inch/yr]; P = .05). Among girls with no family history, BBD risk appeared to be related to other factors: childhood BMI, adolescent waist circumference, and adult height.

CONCLUSIONS:

Adolescents with family history may reduce their risk by avoiding alcohol. Separate risk factors were observed among girls with family history versus girls with no family history, possibly reflecting different causes of BC. Cancer 2011;. © 2011 American Cancer Society.     

Unbalanced estrogen metabolism in thyroid cancer

Well‐differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age‐matched controls. Thirty‐eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen‐DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen‐DNA adducts might play a role in the initiation of thyroid cancer.     

Second operation is not related to psychological outcome in breast cancer patients

To examine the effect of multiple surgical treatments on psychological outcomes in women with early stage breast cancer (BC) in a prospective follow‐up study. Questionnaires for depressive symptoms (CES‐D), fatigue (FAS), anxiety (STAI‐State), physical health (WHOQOL‐100), psychological health (WHOQOL‐100) and overall quality of life and general health (WHOQOL‐100) were completed before diagnosis (Time‐1) and 1 (Time‐2), 3 (Time‐3), 6 (Time‐4) and 12 (Time‐5) months after the last surgical treatment. From the 217 participating women with early stage BC, 78 (35.9%) needed an additional surgical treatment. Using general linear model (repeated measures), psychosocial outcomes over time were investigated for the breast conserving therapy and mastectomy group, accounting for type of surgery, disease stage and hormonal therapy. Psychological outcomes did not significantly change over time, with the exception of anxiety [Wilks' Lambda = 0.72, F (4,86) = 8.55, p < 0.0001, partial eta squared = 0.29]. On average, women with 1 and women with 2 surgical treatments did not differ on any outcome measure. No interaction effects were found, indicating that changes in outcomes over time were the same for both groups. Women who had a repeat surgical treatment did not score differently on psychological outcome measures compared with women who were treated “efficiently.”     

Contralateral risk-reducing mastectomy in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

The purpose of this study is to determine the prevalence and predictors of contralateral risk-reducing mastectomy (CRRM) in Australasian women at high familial risk of a second primary breast cancer (BC). Participants were women with unilateral BC and a strong family history of the disease, including BRCA1/2 mutation carriers. Data were collected through interview, self-administered questionnaire and review of pathology and surgical reports. Associations between CRRM and potential predictors were assessed using multivariate logistic regression. Of 1,018 women (median follow-up 11.1 years), 154 (15%) underwent CRRM, 43% of these within 12 months of initial BC surgery. More likely to undergo CRRM were women who were younger at BC diagnosis (odds ratio [OR] = 0.94 per year of age, P < 0.001), were diagnosed more recently (OR = 1.16 per calendar year, P < 0.001), underwent mastectomy as initial definitive BC treatment (OR = 5.2, P < 0.001) and underwent risk-reducing salpingo-oophorectomy (OR = 3.4, P < 0.001). BRCA1/2 mutation status, axillary nodal status and receipt of chemotherapy were not independently associated with CRRM uptake. A contralateral BC event (invasive or in situ) occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. The contralateral event rate was 15.1 per 1,000 women-years for non-CRRM women and 0.7 per 1,000 women-years for CRRM women; P < 0.0001. Younger women with more recently diagnosed BC treated with mastectomy are more likely to elect CRRM. Neither BRCA1/2 mutation status, nor the competing risk of BC recurrence and death, appears to influence decision making.     

Worse quality of life in young and recently diagnosed breast cancer survivors compared with female survivors of other cancers: A cross‐sectional study

Literature focusing on health‐related quality of life (HRQoL) by cancer site among women only is scarce. This study examines HRQoL of breast cancer (BC) survivors compared with female survivors of other cancers, and to understand which subgroups of BC survivors were particularly at risk of reduced HRQoL. We placed emphasis on young (<50 years) and recently diagnosed (≤5 years) survivors, where the deficits in HRQoL were most pronounced. The cross‐sectional study consisted of 2,224 BC survivors, 8,504 non‐cancer controls and 2,205 other cancer survivors in the Karma study. We examined HRQoL differences using linear regression analyses in the whole cohort and in a subset of young and recently diagnosed BC survivors (n = 242) and female survivors of other cancers (n = 140) with comparable ages at diagnosis (43.6 vs 43.6, p = 0.917) and time since diagnosis (2.3 vs 2.8 years, p < 0.001). HRQoL was assessed using the EORTC QLQ‐C30 questionnaire. While only cognitive functioning was significantly compromised in BC survivors compared with survivors of other cancers when women of all ages were included, young BC survivors reported significantly lower HRQoL on multiple functional scales (global quality of life, emotional, role, social and cognitive functioning) and experienced more fatigue and insomnia. BC survivors with any prior medical history of mental disorders reported poorer HRQoL than those without such a history. We also observed a close–knit relationship between tumor and treatment characteristics. BC survivors perform poorly in HRQoL in comparison with female survivors of other cancers. Our results emphasize the importance of age‐ and gender‐appropriate comparison groups.     

The relationship between knowledge of family history and cancer characteristics at diagnosis in women newly-diagnosed with invasive breast cancer

Aim To document the prevalence of family history of breast cancer (BC) amongst women newly-diagnosed with invasive BC and to explore the relationship between family history and cancer size and stage. Methods A cross-sectional analysis was conducted on baseline questionnaire data from a cohort study of 1,684 women diagnosed with invasive BC within the previous 12 months and recruited between 2004 and 2006 in Victoria, Australia. Results Women with affected first degree relative(s) were more likely to have a smaller BC (odds ratio for ≤10 mm 1.74, 95% CI: 1.32–2.29) and stage I BC (odds ratio 1.31, 95% CI: 1.01–1.70) at diagnosis than women with no affected relatives. There was no significant difference in BC size and stage between women with only affected second degree relatives and women with no affected relatives. Conclusions Women with a first degree relative with BC had smaller, earlier stage cancers at diagnosis, possibly reflecting more diligent use of breast screening amongst women who considered themselves at increased risk of developing the disease.     

Dual tumor‐suppressors miR‐139‐5p and miR‐139‐3p targeting matrix metalloprotease 11 in bladder cancer

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep‐sequencing revealed that two miRNA, microRNA‐139‐5p/microRNA‐139‐3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome‐wide gene expression analysis, in silico analysis and dual‐luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan–Meier method. Gain‐of‐function studies showed that miR‐139‐5p and miR‐139‐3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR‐139‐5p and miR‐139‐3p. Kaplan–Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR‐139‐5p or miR‐139‐3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.     

Cancer patients' reluctance to disclose their emotional distress to their physicians: a study of Japanese patients with lung cancer

Purpose: To explore cancer patients' concerns about emotional disclosure (ED) to their physicians, and to investigate the factors associated with them. Subjects and Methods: Randomly selected ambulatory patients with lung cancer participated in this study. An 18‐item questionnaire to assess patients' beliefs regarding ED to their physicians was developed for this study. Factor analysis was used to extract the underlying factors of this scale. Patients were asked to answer this questionnaire along with other self‐administered questionnaires. Results: Complete data were available from 104 patients. Four factors were extracted by factor analysis: ‘Hesitation to disturb the physicians by ED’, ‘No perceived need for ED’, ‘Negative attitude towards ED’, and ‘Fear of a negative impact of ED’. All factors reached standards of internal consistency. The prevalence of the above concerns, in that order, among the patients was 68, 67, 46, and 20%. Patients with high distress levels were significantly more likely to endorse ‘Negative impact’ (p=0.02). Older patients were more likely to report ‘Negative attitude’ (p=0.06), whereas male patients were more likely than females to report ‘Hesitation’ (p=0.05). Conclusion: Knowledge of such patient‐related barriers should better prepare physicians to build good communication channels with their cancer patients. Copyright © 2007 John Wiley & Sons, Ltd.     

Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14–1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11–1.65), 1.26 (95% CI: 1.00–1.60), and 1.40 (95% CI: 1.01–1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04–2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78–2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13–1.53) (p_interaction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.