Utility Scores for Risk-Reducing Mastectomy and Risk-Reducing Salpingo-Oophorectomy: Mapping to EQ-5D.

BACKGROUND: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are the most effective breast and ovarian cancer preventive interventions. EQ-5D is the recommended tool to assess the quality of life and determine health-related utility scores (HRUSs), yet there are no published EQ-5D HRUSs after these procedures. These are essential for clinicians counselling patients and for health-economic evaluations. METHODS: We used aggregate data from our published systematic review and converted SF-36/SF-12 summary scores to EQ-5D HRUSs using a published mapping algorithm. Study control arm or age-matched country-specific reference values provided comparison. Random-effects meta-analysis provided adjusted disutilities and utility scores. Subgroup analyses included long-term vs. short-term follow-up. RESULTS: Four studies (209 patients) reported RRM outcomes using SF-36, and five studies (742 patients) reported RRSO outcomes using SF-12/SF-36. RRM is associated with a long-term (>2 years) disutility of -0.08 (95% CI -0.11, -0.04) (I2 31.4%) and a utility of 0.92 (95% CI 0.88, 0.95) (I2 31.4%). RRSO is associated with a long-term (>1 year) disutility of -0.03 (95% CI -0.05, 0.00) (I2 17.2%) and a utility of 0.97 (95% CI 0.94, 0.99) (I2 34.0%). CONCLUSIONS: We present the first HRUSs sourced from patients following RRM and RRSO. There is a need for high-quality prospective studies to characterise quality of life at different timepoints.

Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy.

INTRODUCTION: The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. METHODS: Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. RESULTS: The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21-2.38). CONCLUSION: Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

[News in breast oncology genetics for female and male population]. / Les actualités en génétique oncologique mammaire pour la population féminine et masculine.

OBJECTIVES: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers. The Sénologie commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant. In the case of proven genetic risk, surveillance, risk-reduction strategies, and the specificities of surgical and medical management (with PARP inhibitors in particular) were updated. METHODS: This summary was based on national and international guidelines on the monitoring and therapeutic management of genetic risk, and a recent review of the literature covering the last five years. RESULTS: Despite successive technical developments, the probability of identifying a causal variant in a situation suggestive of a predisposition to breast and ovarian cancer remains around 10% in France. The risk of breast cancer in women with a causal variant of the BRCA1, BRCA2, PALB2, TP53, CDH1 and PTEN genes is estimated at between 35% and 85% at age 70. The presence of a causal variant in one of these genes is the subject of different recommendations for men and women, concerning both surveillance, the age of onset and imaging modalities of which vary according to the genes involved, and risk-reduction surgery, which is possible for women as soon as their risk level exceeds 30% and remains exceptionally indicated for men. In the case of breast cancer, PARP inhibitors are a promising new class of treatment for BRCA germline mutations. CONCLUSION: A discipline resolutely focused on understanding molecular mechanisms, screening and preventive medicine/surgery, oncology genetics is currently also involved in new medical/surgical approaches, the long-term benefits/risks of which will need to be monitored.

The impact of prophylactic mastectomy on sexual well-being: a systematic review.

INTRODUCTION: Considering the increasing women's awareness of health promotion and disease prevention programs, mutation carriers are inevitably asked to face important decisions concerning the possibility of undergoing prophylactic mastectomy. Risk-reducing mastectomy (RRM) has become increasingly more common, although it has a significant impact on women's quality of life and sexual well-being. OBJECTIVES: The systematic review aims to evaluate the impact of RRM on the sexuality of women with breast cancer. METHODS: According to Cochrane Collaboration guidelines and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, the study quantified the effects of frontline work on the mental health of healthcare workers. This review followed the PRISMA guidelines. Three databases were systematically searched from inception to December 2022. The expression ("sexuality" OR "sexual" OR "sex") AND ("prophylactic mastectomy" OR "risk-reducing mastectomy") was searched in PubMed, Ovid Medline, and Embase. Twenty-two articles published in English until 2022 were selected. RESULTS: Two studies investigated sexual experience after risk-reducing surgeries as a single outcome, while other studies analyzed the relationship between sexuality and psychosocial outcomes, risk perception, and satisfaction. In all of the included studies, significant findings in sexual dysfunction were found. The most reported problems were related to sexual satisfaction and attractiveness, body image, and loss of femininity. Last, women reported changes in the relationship with their partners. CONCLUSION: RRM has a major impact on body image that affects sexual functioning and quality of life. These implications must be considered during treatment selection.

Surgical Decision Making in Genetically High-Risk Women: Quantifying Postoperative Complications and Long-Term Risks of Supplemental Surgery After Risk-Reducing Mastectomy.

BACKGROUND: Risk-reducing mastectomy (RRM) helps prevent breast cancer in high-risk women but also carries a risk of unanticipated supplemental surgeries. We sought to determine the likelihood of supplemental surgeries following RRM. METHODS: We performed a retrospective cohort study of female patients with a confirmed germline pathogenic variant (GPV) in a breast cancer susceptibility gene (BRCA1/2, PALB2 and others) who underwent bilateral or contralateral RRM at our institution between 2006 and 2022. Supplemental surgeries were defined as any operation requiring general or local anesthesia performed outside of the initially planned procedure(s). The Kaplan-Meier method was used to estimate the 5-years cumulative incidence of supplemental surgery. RESULTS: Of 560 GPV carriers, RRMs were performed in 258 (46.1%) women. The median age of the cohort was 44 years (interquartile range 37-52 years), with 33 (12.8%) patients undergoing RRM without reconstruction and 225 (87.2%) undergoing RRM with reconstruction. Following surgery, 34 patients (13.2%) developed early (< 30 days) postoperative complications, including infection, hematoma, seroma, loss of the nipple areola complex, flap necrosis, implant exposure and/or prosthesis removal. At a median follow-up of 3.8 years, 94 (36.4%) GPV carriers underwent at least one reoperation. Participants who experienced an early postoperative complication had the highest rate of reoperation (85.3% vs. 29.0%; p < 0.001) and a significantly higher likelihood of multiple additional surgical interventions (41.2% vs. 10.7%; p < 0.001). The 5-years rate of supplemental surgery was 39.2% [95% confidence interval (CI) 32.7-46.5] in the overall cohort and 31.5% (95% CI 24.9-39.3) in patients without an early postoperative complication. CONCLUSIONS: Unanticipated supplemental surgeries occur in 40% of GPV carriers following RRM and in nearly one-third of patients without early postoperative complications.

Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience.

BACKGROUND: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. CASE PRESENTATION: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. CONCLUSIONS: We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

Spectrum of histopathologic findings in risk-reducing bilateral prophylactic mastectomy in patients with and without BRCA mutations.

Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.

Impact of surgical variables on residual glandular tissue in risk-reducing mastectomies: Results of a retrospective monocentric study from a center of the German consortium for hereditary breast and ovarian cancer.

PURPOSE: Residual glandular tissue (RGT) after risk reducing mastectomy (RRME) is associated with a risk of developing breast cancer for women with a familial predisposition. We aim to examine various surgery-related variables to make risk more easily assessable and to aid in decision-making. MATERIALS AND METHODS: Pre- and postoperative breast MRI scans from 2006 to 2021 of patients with proven pathogenic mutation were included. The postoperative remaining skin flap was recorded using distance measurements at 8 equally distributed clockwise points and retromamillary. Each breast was volumetrized, as well as existing RGT. Patient-related covariates were further recorded and their influence on RGT was investigated uni- and multivariately. RESULTS: 81 patients (49 with BRCA1, 24 with BRCA2, 9 with other mutations), who were on average 39 years old, had 117 breasts analyzed. The mean follow-up was 71 months. In multivariate analysis, the independent variable skin flap thickness had a positive effect (p ≤ 0.01), while surgeon experience negatively affected RGT (p ≤ 0.05). The incision type was found to impact RGT as well, with nipple-sparing mastectomy (NSM) with inframammary fold incision leading to more RGT (p ≤ 0.01 - p ≤ 0.05), and skin-sparing mastectomy (SSM) with an inverted T incision leading to less (p ≤ 0.01). CONCLUSION: Different surgical variables have an impact on postoperative RGT, which is an important tool to quantify the risk of developing breast cancer after RRME. In order to effectively consider these variables in future preoperative/intraoperative management, they must be carefully taken into account.

Implant-Based Breast Reconstruction after Risk-Reducing Mastectomy in BRCA Mutation Carriers: A Single-Center Retrospective Study.

Women with BRCA gene mutations have a higher lifetime risk of developing breast cancer. Furthermore, cancer is usually diagnosed at a younger age compared to the wild-type counterpart. Strategies for risk management include intensive surveillance or risk-reducing mastectomy. The latter provides a significant reduction of the risk of developing breast cancer, simultaneously ensuring a natural breast appearance due to the preservation of the skin envelope and the nipple-areola complex. Implant-based breast reconstruction is the most common technique after risk-reducing surgery and can be achieved with either a submuscular or a prepectoral approach, in one or multiple stages. This study analyzes the outcomes of the different reconstructive techniques through a retrospective review on 46 breasts of a consecutive, single-center case series. Data analysis was carried out with EpiInfo version 7.2. Results of this study show no significant differences in postoperative complications between two-stage tissue expander/implant reconstruction and direct-to-implant (DTI) reconstruction, with DTI having superior aesthetic outcomes, especially in the prepectoral subgroup. In our experience, the DTI prepectoral approach has proven to be a safe and less time-consuming alternative to the submuscular two-stage technique, providing a pleasant reconstructed breast and overcoming the drawbacks of subpectoral implant placement.

Uptake and Effectiveness of Risk-Reducing Surgeries in Unaffected Female BRCA1 and BRCA2 Carriers: A Single Institution Experience in the Czech Republic.

Unnafected female carriers of BRCA1 and BRCA2 pathogenic/likely pathogenic variants (P/LPVs) are at higher risk of breast cancer (BC) and ovarian cancer (OC). In the retrospective single-institution study in the Czech Republic, we analyzed the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) on the incidence of BC and OC in BRCA1/2 carriers diagnosed between years (y) 2000 to 2020. The study included 496 healthy female BRCA1/2 carriers. The median follow-up was 6.0 years. RRM was performed in 156 (31.5%, mean age 39.3 y, range 22-61 y) and RRSO in 234 (47.2%, mean age 43.2 y, range 28-64 y) BRCA1/2 carriers. A statistically significant increase of RRM (from 12% to 29%) and RRSO (from 31% to 42%) was observed when comparing periods 2005-2012 and 2013-2020 (p < 0.001). BC developed in 15.9% of BRCA1/2 carriers without RRM vs. 0.6% of BRCA1/2 carriers after RRM (HR 20.18, 95% CI 2.78- 146.02; p < 0.001). OC was diagnosed in 4.3% vs. 0% of BRCA1/2 carriers without vs. after RRSO (HR not defined due to 0% occurrence in the RRSO group, p < 0.001). Study results demonstrate a significant increase in the rate of prophylactic surgeries in BRCA1/2 healthy carriers after 2013 and the effectiveness of RRM and RRSO on the incidence of BC and OC in these populations.

Factors Influencing Residual Glandular Breast Tissue after Risk-Reducing Mastectomy in Genetically Predisposed Individuals Detected by MRI Mammography.

PURPOSE: This study seeks to evaluate MR imaging morphological factors and other covariates that influence the presence of residual glandular tissue after risk-reducing mastectomy in patients with a familial predisposition. METHODS: We analyzed women of a high-risk collective with pathogenic mutation (BRCA1 (n = 49), BRCA2 (n = 24), or further mutation (n = 9)). A total of 117 breasts were analyzed, 63 left and 54 right, from a cohort of 81 patients, who were on average 40 years old. The mean follow-up was 63 months (range 12-180 months, SD = 39.67). Retrospective analysis of MR imaging data from 2006-2022 of patients of a high-risk collective (all carriers of a pathogenic mutation) with contralateral (RRCM) or bilateral risk-reducing mastectomy (RRBM) was performed. In the image data the remaining skin flap thickness by distance measurements at eight equally distributed, clockwise points and the retromamillary area, as well as by volumetry of each breast, was elected. Residual glandular tissue was also volumetrized. In addition, patient-related covariates were recorded and their influence on postoperative residual glandular tissue and skin flap thickness was analyzed by uni- and multivariate regressions. RESULTS: A significant association with postoperative residual glandular tissue was shown in multivariate analysis for the independent variables breast density, skin flap mean, and surgical method (all p-values < 0.01). A negatively significant association could be seen for the variables preoperative breast volume (p-values < 0.01) and surgeon experience (most p-values < 0.05-<0.1). CONCLUSION: Postoperative residual glandular tissue is an important tool for quantifying the risk of developing breast cancer after risk-reducing mastectomy. Different effects on residual glandular tissue were shown for the independent variables breast density, skin flap, surgical method, preoperative breast volume, and surgeon experience, so these should be considered in future surgical procedures preoperatively as well as postoperatively. Breast MRI has proven to be a suitable method to analyze the skin flap as well as the RGT.

Patient-reported outcomes post prophylactic risk-reducing mastectomy: improved breast and psychosocial satisfaction yet poorer physical well-being.

BACKGROUND: Few studies have investigated patient-reported outcomes (PROs) for patients with high breast cancer risk undergoing elective risk reduction mastectomy and reconstruction. These patients incur operative risk in the absence of active cancer, which renders their treatment experience unique. This study aimed to identify longer-term quality of life (QoL) issues that persist in this patient cohort. METHODS: A cross-sectional cohort study assessed PROs in 48 women with high breast cancer risk who attended the Royal Melbourne Hospital Risk Management Clinic, at least 12 months post-mastectomy and reconstruction, with surgery between 2011 and 2020, using the BREAST-Q© Likert surveys. The BREAST-Q© internationally validated QoL instrument scales survey data from 0 (worst) to 100 (best) in 14 domains addressing satisfaction and psychosocial issues. RESULTS: There was higher overall breast and psychosocial satisfaction, with scores of 11 and four, respectively, yet lower chest, abdomen and sexual well-being scores with 14, three and four, respectively, in contrast to normative BREAST-Q© data from >1000 women without prior breast cancer or breast operations. High average scores >90 were found for patient satisfaction with surgical, medical and office staff. Twenty-one patients had an average score of 63 for satisfaction with breast implants, while 27 patients post-DIEP had average scores >72 for abdominal well-being, appearance and overall outcomes. Higher mean QoL outcomes were found with DIEP flap in all domains, compared with breast implant reconstruction. CONCLUSION: QoL assessment with PROs 12 months post-risk reduction mastectomy and reconstruction demonstrated higher psychosocial well-being, yet highlights physical implications, with patients experiencing reduced chest, abdomen and sexual well-being, compared with normative BREAST-Q© control data. Higher mean QoL outcomes were found with DIEP flap compared with breast implant reconstruction. PROs studies can identify unmet needs and facilitate change in service provision.

Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: results of a prospective cohort study.

BACKGROUND: Women carrying BRCA1/2 pathogenic variants are exposed to elevated risks of developing breast cancer (BC) and are faced by a complex decision-making process on preventative measures, i.e., risk-reducing mastectomy (RRM), and intensified breast surveillance (IBS). In this prospective cohort study we investigated the effect of anxiety, personality factors and coping styles on the decision-making process on risk management options in women with pathogenic variants in BRCA1/2. METHODS: Breast cancer unaffected and affected women with a pathogenic variant in the BRCA1 or BRCA2 gene were psychologically evaluated immediately before (T0), 6 to 8 weeks (T1) and 6 to 8 months (T2) after the disclosure of their genetic test results. Uptake of RRM and IBS was assessed at T2. Psychological data were gathered using questionnaires on risk perception, personality factors, coping styles, decisional conflict, depression and anxiety, including the Hospital Anxiety and Depression Scale (HADS). We performed tests on statistical significance and fitted a logistic regression based on significance level. RESULTS: A total of 98 women were included in the analysis. Baseline anxiety levels in women opting for RRM were high but decreased over time, while they increased in women opting for intensified breast surveillance (IBS). Elevated levels of anxiety after genetic test result disclosure (T1) were associated with the decision to undergo RRM (p < 0.01; OR = 1.2, 95% CI = 1.05-1.42), while personal BC history and personality factors seemed to be less relevant. CONCLUSIONS: Considering psychosocial factors influencing the decision-making process of women with pathogenic variants in BRCA1/2 may help improving their genetic and psychological counselling. When opting for IBS they may profit from additional medical and psychological counselling. TRIAL REGISTRATION: Retrospectively registered at the German Clinical Trials Register under DRKS00027566 on January 13, 2022.

Autologous Breast Reconstruction with Free Nipple-Areola Graft after Circumareolar (Skin Reducing) Mastectomy.

Introduction of skin-sparing mastectomy (SSM) led to a paradigm shift in breast reconstruction. Primary reconstructions have become the therapy of choice. At the same time, immediate autologous reconstructions are oncologically safe and aesthetically pleasing. Our preferred SSM incision is the circumareolar with removal of nipple and areola (NAC). Adjustment of the skin envelope is well accomplished in mild-to-moderate ptotic breasts. We describe our technique consisting of circumareolar incision in SSM, keeping the NAC as a free graft, and immediate autologous reconstruction and immediate free NAC grafting on the flap. Aesthetic indications are slight asymmetries, ptotic breasts, large breasts where the reconstructed breast will be smaller than the original breast and where a Wise pattern is not indicated. Oncologic indications are risk-reducing mastectomies and tumors close to the NAC where resection would compromise the vitality of the NAC. We evaluated the healing of the NAC and the NAC position with regard to the breast shape. From 2019-2022, 296 autologous flaps were used for breast reconstruction. In 36 flaps, this technique was applied. Eighteen flaps were bilateral (nine patients). In total, we performed 15 inner thigh flaps and 21 DIEP flaps. No flap or NAC loss occurred. There was no wound healing complication at the breast, and no adjuvant chemotherapy or radiation therapy needed to be postponed. The advantages of this technique are (1) scar reduction with only one periareolar scar on the breast, which is also well concealed; (2) oncological safety in relation to the nipple and optimal visibility of the mastectomy cavity, which allows a meticulous mastectomy, especially important in risk-reducing mastectomies; (3) generally, fewer wound healing problems, especially fewer than with Wise pattern incision; (4) primary adjustment of the skin envelope and positioning of the NAC are easier to perform than in a secondary procedure; and (5) that the NAC is spared, and no secondary reconstruction is necessary. Disadvantages are that (1) the NAC must heal as a free graft and (2) that the sensitivity of the NAC is lower than in pedicled NAC transposition.

Perfil psicológico prequirúrgico de las mujeres con riesgo aumentado de cáncer de mama / Preoperative psychological profile of women with increased risk of breast cancer

Objetivo: analizar los niveles de sintomatología ansiosa y depresiva, imagen corporal y calidad de vida en un grupo de mujeres con vulnerabilidad genética de cáncer de mama que se iban a someter a una mastectomía reductora de riesgo. Método: 184 mujeres participaron en este estudio, todas ellas tenían riesgo aumentado de cáncer de mama, bien por ser portadoras de una mutación BRCA1/2 o por agregación familiar. Los instrumentos utilizados fueron: Escala de Ansiedad y Depresión Hospitalaria, Escala de Imagen Corporal, European Organisation for Research and Treatment of Cancer calidad de vida oncológica C30y BR23. Resultados: Los resultados de este estudio mostraron que las participantes presentaban niveles clínicos en sintomatología ansiosa y subclínicos en sintomatología depresiva. Sin embargo, se encontraban en niveles normativos en imagen corporal y calidad de vida. Las participantes con antecedentes oncológicos manifestaban, mayor insatisfacción con la imagen corporal, niveles inferiores en las escalas de funcionamiento físico, cognitivo y global de la calidad de vida, así como mayor fatiga, dolor general, en el brazo y en la mama en comparación con las mujeres sin diagnósticos previos. Conclusiones: Las mujeres sin mutación poseían mayor sintomatología en la mama y en el brazo que las mujeres con mutación, las cuales presentaban más dificultades económicas que las mujeres no portadoras. Evidenciando la necesidad de realizar una intervención psicológica antes de la cirugía especialmente en este colectivo (AU)

Aim: analyze depressive and anxiety symptomatology, body image and quality of life in a group of women with genetic vulnerability to breast cancer who were going to undergo a risk-reducing mastectomy. Method:184 women participated in this study, all of whom had an increased risk of breast cancer, either because they were BRCA1/2 mutation carriers or because they had several affected relatives. The psychological instruments used were: Hospital Anxiety and Depression Scale, Body Image Scale, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and BR23. Results: The results of this study showed that the participants presented clinical anxiety symptomatology and subclinical depressive symptomatology. However, all the sample were at normative levels in body image and quality of life. Participants with previous diagnosis of cancer showed, higher dissatisfaction with their body image, lower levels on the scales of physical, and cognitive and global functioning on quality of life, as well as higher fatigue, more general pain also in the breast and in the arm compared to women without diagnosis. Conclusions: BRCA1/2 non-mutation carriers showed more symptomatology in the breast and in the arm fatigue than BRCA1/2 mutation carriers. BRCA1/2 mutation carriers had more economic difficulties than non-carriers. It is highly recommended a psychological intervention before a risk-reducing surgery. (AU)

Satisfaction and Quality of Life of Healthy and Unilateral Diseased BRCA1/2 Pathogenic Variant Carriers after Risk-Reducing Mastectomy and Reconstruction Using the BREAST-Q Questionnaire.

Risk-reducing mastectomy (RRM) is the most efficient form of breast cancer (BC) risk reduction in BRCA1/2 pathogenic variant (pV) carriers. However, this intervention in physical integrity is associated with significant morbidity. We assessed long-term perception of satisfaction and health-related quality of life (QoL) after bilateral RRM and reconstruction using the validated BREAST-Q. We searched the prospective database of the Center for Hereditary Breast and Ovarian Cancer Cologne for previvors and survivors who underwent bilateral RRM from 1994 to 2015 and evaluated the results of their BREAST-Q scores. The study enrolled 43 previvors and 90 survivors after a mean follow-up of 46.3 ± 45.3 months after RRM. Satisfaction and QoL were independent of the technique of RRM or type of reconstruction but depended on the time of RRM. Compared to survivors, previvors had significantly higher mean satisfaction scores in their psychosocial, sexual, and physical well-being (chest) in both modules. Among previvors and survivors, higher psychological well-being correlated with a higher satisfaction with information and higher satisfaction with outcome. As psychological well-being correlated with satisfaction with information and outcome, we developed decision aids to improve shared decision making and long-term satisfaction with the decision and the postoperative outcome.

Risk-reducing mastectomy for women with hereditary breast and ovarian cancer (HBOC): analytical results of data from the Japanese Organization of HBOC.

BACKGROUND: Risk-reducing mastectomy is one option for women with hereditary breast and ovarian cancer to reduce the risk of breast cancer. PATIENTS AND METHODS: We analyzed data of the Japanese Organization of Hereditary Breast and Ovarian Cancer on women who were diagnosed as hereditary breast and ovarian cancer by BRCA germline genetic testing between 2010 and 2019 to reveal the rate and likelihood of risk-reducing mastectomy. RESULTS: There were 412 women with BRCA1, 271 with BRCA2 and 4 with both female pathogenic variants. Ninety (13.1%) received risk-reducing mastectomy. The rates of risk-reducing mastectomy were statistically significantly higher in women with BRCA1 pathogenic variants than BRCA2, in women who had breast cancer than those who did not, in women with a breast cancer family history than in those without, in mothers than in those without children, in women who were receiving surveillance with MRI than those who were not and in women who received risk-reducing salpingo-oophorectomy than in those who did not on univariate analyses. The ages when they received the genetic testing were statistically significantly younger in the women receiving risk-reducing mastectomy than those who did not receive it. The women with BRCA1 pathogenic variants, personal history of breast cancer, mothers, those receiving MRI surveillance and younger women were independently significantly more likely to receive risk-reducing mastectomy based on multivariate analysis. CONCLUSIONS: The rate of risk-reducing mastectomy was not high in Japan; however, risk-reducing surgery was approved by the Japanese National Medical Insurance for hereditary breast and ovarian cancer patients with breast and/or ovarian cancer in 2020, so this rate will increase.

Satisfaction with Long-Term Aesthetic and 10 Years Oncologic Outcome following Risk-Reducing Mastectomy and Implant-Based Breast Reconstruction with or without Nipple Preservation.

Incidence of bilateral risk-reducing mastectomies (RRMs) is increasing. The aim of this study was to compare satisfaction, aesthetic and oncological outcomes in women undergoing RRM with implant-based reconstruction comparing nipple-sparing mastectomy (NSM) with skin-sparing mastectomy (SSM) (sacrificing the nipple +/− nipple reconstruction). Women who had undergone bilateral RRM between 1997 and 2016 were invited. Aesthetic outcome and nipple symmetry were evaluated using standardized anthropometric measurements. The oncological outcome was assessed at last documented follow up. Ninety-three women (186 breasts) participated, 60 (64.5%) had NSM, 33 (35.5%) SSM. Median time between surgery and participation was 98.4 months (IQR: 61.7−133.9). Of the women, 23/33 (69.7%) who had SSM underwent nipple reconstruction. Nipple projection was shorter in the reconstructed SSM group than the maintained NSM group (p < 0.001). There was no significant difference in overall symmetry (p = 0.670), satisfaction regarding nipple preservation (p = 0.257) or overall nipple satisfaction (p = 0.074). There were no diagnoses of breast cancer at a median follow up of 129 months (IQR: 65−160.6). Women who undergo nipple-sparing RRM maintain long-term nipple symmetry. Nipple projection was less maintained after nipple reconstruction. Although satisfaction with the nipples was higher in the NSM group, this did not reach statistical significance. No breast cancers developed after RRM with long-term follow up.

La mastectomía como medida de reducción de riesgo de cáncer de mama / Risk-reducing mastectomy in breast cancer

Objetivos: Evaluar las mastectomías reductoras de riesgo realizadas y analizar las indicaciones y resultados según las características individuales, oncológicas y quirúrgicas de nuestras pacientes.MétodosEstudio observacional retrospectivo de todas las mastectomías con reconstrucción inmediata en mamas sanas realizadas desde 2013 a 2019. Se dividieron las pacientes en tres grupos: I) riesgo genético de cáncer de mama, II) cáncer de mama diagnosticado y III) antecedente de cáncer de mama.ResultadosSe realizaron 56 mastectomías reductoras de riesgo a 46 pacientes, 15% grupo I, 50% grupo II y 35% grupo III, pero tras estudios diferidos, 20 pacientes (43%) presentaban mutación genética. La media de edad en este subgrupo fue de 40 años y con predominio de tumores HER2+ (40% frente al 12%, p=0,164). En el grupo III observamos más complicaciones inmediatas (31%, p=0,014) y tardías (69%, p=0,027) relacionadas con la reconstrucción protésica, y más evidente en mamas que tuvieron enfermedad (73% frente al 39% sanas, p=0,002). Se encontró relación entre contractura capsular y la radioterapia postoperatoria (p=0,008) y entre necrosis y radioterapia preoperatoria (p=0,001). Se reintervino al 7% por complicaciones en mastectomías profilácticas. No hemos tenido recidivas locales.ConclusionesConsideramos justificada la mastectomía reductora de riesgo realizada a mujeres jóvenes con mutación genética y a pacientes con cáncer precoz, HER2+ y riesgo familiar. En pacientes ya tratadas por cáncer, el riesgo de complicaciones supera el valor profiláctico de la técnica. La reconstrucción mamaria es la principal responsable de complicaciones postoperatorias y las pacientes deben ser plenamente conscientes de ello. (AU)

Objectives: To evaluate the risk-reducing mastectomies performed and to analyse the indications and results according to the individual, oncological and surgical characteristics of our patients.MethodsRetrospective observational study of all mastectomies with immediate reconstruction in healthy breasts performed from 2013 to 2019. The patients were divided into three groups: I) genetic risk of breast cancer, II) diagnosed breast cancer and III) history of cancer breast.ResultsA total of 56 risk-reducing mastectomies were performed in 46 patients, 15% in group I, 50% in group II and 35% in group III. After deferred studies, 20 (43%) patients had a genetic mutation. This subgroup had an average age of 40 years and a predominance of HER2+ tumours (40% versus 12%, p=0.164). In group III, we observed more immediate (31%, p=0.014) and late (69%, p=0.027) complications related to prosthetic reconstruction, which were more evident in breasts with disease (73% versus 39% healthy, p=0.002). A relationship was found between capsular contracture and postoperative radiotherapy (p=0.008) and between necrosis and preoperative radiotherapy (p=0.001). Reoperation was required in 7% for complications of prophylactic mastectomies. There were no local relapses.ConclusionsWe consider risk-reducing mastectomy to be justified in young women with a genetic mutation and in patients with early cancer, HER2+ and family risk. In patients already treated for cancer, the risk of complications exceeds the prophylactic value of the technique. Breast reconstruction is primarily responsible for postoperative complications and patients should be fully aware of this. (AU)