Surgical Outcome Measures in a Cohort of Patients at High Risk of Breast Cancer Treated by Bilateral Risk-Reducing Mastectomy and Breast Reconstruction.

BACKGROUND: Women with breast cancer-related genetic pathogenic variants (e.g., BRCA1 , BRCA2 ) or with a strong family history carry lifetime risks of developing breast cancer of up to 80 to 90 percent. A significant proportion of these women proceed to bilateral risk-reducing mastectomy. The authors aimed to document the surgical morbidity of risk-reducing mastectomy and establish whether a diagnosis of breast cancer at the time of surgery impacted outcomes. METHODS: Clinical details of 445 women identified as having a greater than 25 percent lifetime risk of developing breast cancer who underwent risk-reducing mastectomy and breast reconstruction were interrogated for surgical outcomes such as planned, unplanned, and emergency procedures; complication rates; length of stay; and longevity of breast reconstruction. These outcome measures were recorded in women diagnosed with breast cancer perioperatively (cancer group) and those without malignancy (benign group). RESULTS: Median follow-up was similar in both groups (benign group, 70 months; cancer group, 73 months). Patients were older in the cancer group than in the benign group (43 years versus 39 years; p < 0.001). Women in the cancer group required more planned procedures to complete reconstruction than those in the benign group (four versus two; p = 0.002). Emergency procedures, unplanned surgical interventions (e.g., capsulectomy), and postreconstruction complication rates were similar between groups. One in five women overall required revision surgery. Patients with autologous reconstructions had a revision rate of 1.24 per 1000 person-years compared with 2.52 per 1000 person-years in the implant reconstruction group. CONCLUSIONS: Women contemplating risk-reducing mastectomy can be reassured that this is a safe and effective procedure but will likely take multiple interventions. This knowledge should be integral to obtaining informed consent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Uptake of bilateral-risk-reducing-mastectomy: Prospective analysis of 7195 women at high-risk of breast cancer.

BACKGROUND: Bilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups. METHODS: BRRM uptake was assessed from entry to the Manchester Family History Clinic or from date of personal BRCA1/2 test. Follow up was censored at BRRM, breast cancer diagnosis, death or January 01, 2020. Cumulative incidence and cause specific and competing risk regression analyses were used to assess the significance of factors associated with BRRM. RESULTS: Of 7195 women at ≥25% lifetime breast cancer risk followed for up to 32 years, 451 (6.2%) underwent pre-symptomatic BRRM. Of those eligible in different risk groups the 20-year uptake of BRRM was 47.7%-(95%CI = 42.4-53.2%) in 479 BRCA1/2 carriers; 9.0% (95%CI = 7.26-11.24%) in 1261 women at ≥40% lifetime risk (non-BRCA), 4.8%-(95%CI = 3.98-5.73%) in 3561 women at 30-39% risk and 2.9%-(95%CI = 2.09-4.09%) in 1783 women at 25-29% lifetime risk. In cause-specific Cox regression analysis death of a sister with breast cancer<50 (OR = 2.4; 95%CI = 1.7-3.4), mother<60 (OR = 1.9; 95%CI = 1.5-2.3), having children (OR = 1.4; 95%CI = 1.1-1.8), breast biopsy (OR = 1.4; 95%CI = 1.0-1.8) were all independently associated with BRRM uptake, while being older at assessment was less likely to be associated with BRRM (>50; OR = 0.26,95%CI = 0.17-0.41). Uptake continued to rise to 20 years from initial risk assessment. CONCLUSION: We have identified several additional factors that correlate with BRRM uptake and demonstrate continued increases over time. These factors will help to tailor counselling and support for women.

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer.

Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1/2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987-2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie's announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11-54) days after the index cancer surgery. Rates of CRRM doubled following AJ's news, from 23.9% pre-AJ to 50.0% post AJ (p < 0.001). Rates of CRRM were found to decrease with increasing age at breast cancer (p < 0.001) and tumour TNM stage (p = 0.040), and to increase with the estimated lifetime risk of breast cancer (p < 0.001) and tumour grade (p = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p < 0.001). The AJ effect appears to have been associated with higher rates of CRRM amongst breast cancer patients with increased cancer risk. CRRM rates were highest amongst younger women and those with the highest lifetime risk profile. Clinicians need to be aware of how media news can impact on the delivery of cancer related services. Communicating objective assessment of risk is important when counselling women on the merits of risk-reducing surgery.

Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987-2020).

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987-2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (≥30% lifetime risk), 37.7% at moderate risk (17-29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14-27% entered various lifestyle studies. From 1992-2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention; 10.8% women took up the offer of such treatment between 2013-2020. Since 1994, 7164 eligible women at ≥25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results.

Post-traumatic growth in adults following a burn.

It is well established that a burn can result in negative psychological consequences. Throughout the literature there is also reference to individuals reporting positive changes post-burn. The concept of 'post-traumatic growth' (PTG) refers to such individuals, whose recovery exceeds pre-trauma levels of well-being. To date there has only been one quantitative analysis directly examining PTG post-burn. The present study builds on this, examining the prevalence of PTG and related constructs, including: social support, coping styles, dispositional optimism, functioning, post-traumatic stress symptoms, severity and time since burn. Seventy-four participants recruited through a regional burns unit completed a battery of self-report questionnaires. Burn survivors were found to experience PTG, although to a lesser degree than previous research suggests (GM=1.26, range=0-4.67). Severity of burn, post-burn functioning and trauma symptoms significantly correlated with PTG. Regression analysis proposed a model explaining 51.7% of the variance, with active coping, perceived social support and avoidance coping as significant predictors of PTG. Results support the theory that distress and trauma symptoms act as a catalyst for PTG. Coping styles and social support appear to facilitate this process. Clinical implications are discussed.

Do illness perceptions and mood predict healing time for burn wounds? a prospective, preliminary study.

UNLABELLED: Some burn wounds take longer to heal than others, but this cannot be fully explained by physical factors such as burn size and depth. Research interest has therefore focussed on the potential contribution of psychological factors, such as perception of the burn and distress, to the wound healing process. OBJECTIVES: Using the framework of Leventhal's Common-Sense Model, we investigated whether patients' perceptions of their burn wounds and distress contributed to healing time, and whether this was via the mediating role of adherence to treatment recommendations. METHOD: Seventy-two adult burn-injured outpatients completed questionnaire measures of burn perceptions (Brief Illness Perception Questionnaire), distress (Hospital Anxiety and Depression Scale), trauma symptoms (Impact of Event Scale-Revised) and appearance concerns (Derriford Appearance Scale-24). Burn characteristics, healing time and adherence data were taken from clinic notes. RESULTS: Distress, trauma symptoms and appearance concerns were positively correlated with negative burn perceptions. In regression analysis, burn perceptions added significantly to the prediction of burn healing time after age, medical factors and burn characteristics had been controlled for. Adherence measures were not significantly correlated with burns perceptions. CONCLUSIONS: Our findings suggest that patients' perceptions of their burns contribute to healing time. Further research on the mechanisms of this association is warranted.

A pilot randomized trial of metacognitive therapy vs applied relaxation in the treatment of adults with generalized anxiety disorder.

Metacognitive Therapy (MCT) and Applied Relaxation (AR) were compared in a pilot treatment trial of generalized anxiety disorder (GAD). Twenty outpatients meeting criteria for DSM-IV-TR GAD were assessed before treatment, after treatment and at 6 m and 12 m follow-up. The patients were randomized and treated individually for 8-12 weekly sessions. There was no drop-out from MCT and 10% at 6 m follow-up from AR. At post-treatment and at both follow-up points MCT was superior to AR. Standardized recovery rates for MCT at post-treatment were 80% on measures of worry and trait-anxiety compared with 10% following AR. At 6 m follow-up recovery rates for MCT were 70% on both measures compared with 10% and 20% for AR. At 12 m follow-up recovery rates for MCT were 80% (worry) and 60% (trait-anxiety) compared with 10% and 20% following AR. The recovery rates for MCT are similar to those obtained in an earlier uncontrolled trial (Wells & King, 2006). The effect sizes and standardized recovery rates for MCT suggest that it is a highly effective treatment.