BACKGROUND: Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool.
METHODS: Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan-Meier curve to show the probability of locoregional relapse.
RESULTS: A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

BACKGROUND: Management of pathogenic variants in high penetrance genes related to breast cancer (BC), such as BRCA1 and BRCA2, are well established. However, moderate penetrance mutations are understudied. We aim to compare risk reduction decision-making patterns in patients with a moderate penetrance BC-related genetic mutations, without a prior BC diagnosis.
METHODS: Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center\'s database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared.
RESULTS: A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05).
CONCLUSIONS: Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.

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.
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.
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.
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.

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation.
METHODS: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted.
METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities.
RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±).
CONCLUSIONS: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

OBJECTIVE: To determine the value of performing a risk-reducting mastectomy (RRM) in the absence of a deleterious variant of a breast cancer susceptibility gene, in 4 clinical situations at risk of breast cancer.
METHODS: The CNGOF Commission of Senology, composed of 26 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The Commission of Senology adhered to the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted.
METHODS: The Commission of Senology considered 8 questions on 4 topics, focusing on histological, familial (no identified genetic abnormality), radiological (of unrecognized cancer), and radiation (history of Hodgkin\'s disease) risk. For each situation, it was determined whether performing RRM compared with surveillance would decrease the risk of developing breast cancer and/or increase survival.
RESULTS: The Commission of Senology synthesis and application of the GRADE method resulted in 11 recommendations, 6 with a high level of evidence (GRADE 1±) and 5 with a low level of evidence (GRADE 2±).
CONCLUSIONS: There was significant agreement among the Commission of Senology members on recommendations to improve practice for performing or not performing RRM in the clinical setting.

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.
CONCLUSIONS: 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.

BACKGROUND: Many women with increased lifetime risk of developing breast cancer, due to pathogenic gene variants or family history, choose to undergo bilateral risk reducing mastectomies (BRRM). Patient reported outcome measures (PROMS) are an increasingly important part of informed consent but are little studied in women undergoing BRRM.
METHODS: We used a validated PROMS tool for breast reconstruction (BREAST-Q) in 297 women who had BRRM and breast reconstruction, 81% of whom had no malignancy (Benign Group, BG) and 19% in whom a perioperative breast cancer was diagnosed (Cancer Group, CG). 128 women also completed a Hospital Anxiety & Depression Score (HADS) questionnaire to test if preoperative HADS score could predict PROMS outcomes.
RESULTS: Women in the CG had lower PROMS scores for satisfaction with their breasts, nipple reconstruction and sexual wellbeing. Both groups reported equal satisfaction with BRRM outcome and psychosocial well-being. Physical well-being PROMS of the abdomen and chest were high in women in both groups as were scores for satisfaction with the care they received. The CG group reported suboptimal quality of patient information. A higher presurgical HADS anxiety score predicted less favourable postoperative psychosocial well-being despite similar levels of satisfaction with aesthetic outcome.
CONCLUSIONS: We show a high degree of patient reported satisfaction by woman undergoing BRRM and reconstruction. There was a negative association with a cancer diagnosis on quality of life PROMS and higher preoperative anxiety levels negatively affected postoperative psychosocial well-being. These important findings should be part of the informed consent process during preoperative counselling.

Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in a population-based cohort of women in Western Sweden, under surveillance and after risk reducing surgery. Women who tested positive for a BRCA variant between 1995-2016 (n = 489) were prospectively registered and followed up for cancer incidence, risk reducing surgery and mortality. The Swedish Cancer Register was used to compare breast and ovarian cancer incidence and mortality with and without risk reducing surgery for women with BRCA variants in comparison to women in the general population. SIR for breast cancer under surveillance until risk-reducing mastectomy (RRM) was 14.0 (95% CI 9.42-20.7) and decreased to 1.93 (95% CI 0.48-7.7) after RRM. The SIR for ovarian cancer was 124.6 (95% CI 59.4-261.3) under surveillance until risk reducing salpingo-oophorectomy (RRSO) and decreased to 13.5 (95% CI 4.34-41.8) after RRSO. The SMR under surveillance before any risk reducing surgery was 5.56 (95% 2.09-14.8) and after both RRM and RRSO 4.32 (95% CI 1.62-11.5). Women with cancer diagnoses from the pathology report after risk reducing surgery were excluded from the analyses. Risk reducing surgery reduced the incidence of breast and ovarian cancer in women with BRCA variants. However, overall mortality was significantly increased in comparison to the women in the general population and remained elevated even after risk reducing surgery. These findings warrant further research regarding additional measures for these women.

BACKGROUND: Increasingly, women elect breast reconstruction after mastectomy. However, their expectations of surgery are often not met, and dissatisfaction with outcome and ongoing psychosocial concerns and distress are common. We developed a patient-centered intervention, PEGASUS:(Patients\' Expectations and Goals: Assisting Shared Understanding of Surgery) which supports shared decision making by helping women clarify their own, individual goals about reconstruction so that they can discuss these with their surgeon. Our acceptability/feasibility work has shown it is well received by patients and health professionals alike. We now need to establish whether PEGASUS improves patients\' experiences of breast reconstruction decision making and outcomes. The purpose of this study is, therefore, to examine the effectiveness of PEGASUS, an intervention designed to support shared decision making about breast reconstruction.
METHODS: A multi-centered sequential study will compare the impact of PEGASUS with usual care, in terms of patient reported outcomes (self-reported satisfaction with the outcome of surgery, involvement in decision making and in the consultation) and health economics. Initially we will collect data from our comparison (usual care) group (90 women) who will complete standardized measures (Breast-Q, EQ5D -5 L and ICECAP- A) at the time of decision making, 3, 6 and 12 months after surgery. Health professionals will then be trained to use PEGASUS, which will be delivered to the intervention group (another 90 women completing the same measures at the time of decision making, and 3, 6 and 12 months after surgery). Health professionals and a purposefully selected sample of participants will be interviewed about whether their expectations of reconstruction were met, and their experiences of PEGASUS (if appropriate).
CONCLUSIONS: PEGASUS may have the potential to provide health professionals with an easily accessible tool aiming to support shared decision making and improve patients\' satisfaction with breast reconstruction. Results of this study will be available at the end of 2019.
BACKGROUND: ISRCTN 18000391 (DOI 10.1186/ISRCTN18000391) 27/01/2016.

Comprehensive studies of somatosensory change following breast reconstruction are limited. We investigated altered sensation quantitatively and qualitatively in patients undergoing mastectomies for cancer treatment and unaffected individuals who had risk-reducing mastectomies (RRM) for cancer predisposing genes.
Women attending breast clinic review at Royal Marsden Hospital, London were invited to participate. Sensory testing was performed a minimum of 1 year after surgery. Quantitative assessment of light touch and temperature sensation was performed at six points on the breast mound using Semmes-Weinstein monofilaments and temperature regulated droplets. Subjective sensibility of pain, tingling and pleasurable sensation was assessed using a four-point Likert scale questionnaire.
181 breast envelopes were examined, 77 following mastectomy for cancer, 68 after RRM and 36 controls. Partial sensation was maintained with normal light touch in at least 1 quadrant in 57% following surgery. Preserved sensation was highest in the medial breast mound (p = 0.001). On qualitative assessment 74% reported significant loss of pleasurable sensation and 9% reported chronic pain. No difference in light touch and temperature sensation was noted in cancer versus RRM groups but loss of pleasurable sensation was more frequent in the former. Radiotherapy did not affect sensory change post-mastectomy. Following nipple sparing mastectomies, 47% retained normal touch sensation in the preserved areola and nipple.
Breast sensibility is significantly impaired following mastectomy and reconstruction but sensory loss is partial in the majority of women. Patients should be informed of these adverse post-operative effects to facilitate an informed decision if there is a surgical choice other than mastectomy as a surgical option.