Prophylactic Mastectomy Research Articles

Disparity Reduction in United States Breast Reconstruction: An Analysis From 2005-2017 Using 3 Nationwide Data Sets.

Following passage of the Women's Health and Cancer Rights Act (WHCRA), a steady rise in breast reconstruction rates was reported; however, a recent update is lacking. This study aimed to evaluate longitudinal trends in breast reconstruction (BR) rates in the U.S. and relevant sociodemographic factors. Mastectomy cases with/without BR from 2005 through 2017 were abstracted from the National Surgical Quality Improvement Program (NSQIP), Surveillance, Epidemiology, and End Results (SEER) Program, and National Cancer Database (NCDB). BR rates were examined using Poisson regression. Multivariable logistic regression analysis of NCDB data was used to identify predictors of reconstruction. Race and insurance distributions were evaluated over time. Of 1,554,381 mastectomy patients, 507,631 (32.7%) received BR. Annual reconstruction rates per 1000 mastectomies increased from 2005 to 2012 (NSQIP: Incidence Rate Ratio (IRR) 1.077; SEER: 1.090; NCDB: 1.092) and stabilized from 2013 to 2017. NCDB data showed that patients who were younger (≤59 years), privately insured, had fewer comorbidities, and underwent contralateral prophylactic mastectomy were more likely to undergo BR (all p<0.001). Over time, the increase in BR rates was higher among Black (252.3%) and Asian (366.4%) patients than White patients (137.3%). BR rates increased more among Medicaid (418.6%) and Medicare (302.8%) patients than privately insured (125.3%) patients. This analysis demonstrates stabilization in immediate BR rates over the last decade; reasons behind this stabilization are likely multifactorial. Disparities based on race and insurance type have decreased, with a more equitable distribution of BR rates.

The comparison of effectivity in breast cancer prevention between skin sparing and subcutaneous mastectomy - 20 years of experience.

Breast cancer is the leading cause of neoplasm mortality among women. Several prevention strategies have been implemented to early detect and prevent the cancer occurrence. The most effective protocol includes prevention mastectomy for the high-risk patients. In our study, we have compared the efficacy of subcutaneous mastectomy (SCM) and skin sparing mastectomy (SSM) in long-term follow up. We have included 201 female patients who have been treated at our department over the course of 20 years between 2000 and 2019. All the patients were at high risk of developing breast cancer and therefore were indicated for the prophylactic mastectomy. The main indication was the presence of the mutation in the BRCA1 or BRCA2 cluster, however, even in the lack of such mutation, the family history was sufficient for the mastectomy indication. Patients underwent either SCM, SSM or areola sparing mastectomy (ASM), and were allocated to aforementioned groups, respectively. We have collected the data regarding the reconstruction method along with age, weight, height, body mass index (BMI) and presence of predisposing genetic mutations such as BRCA positivity. The patients who underwent SSM compared to those who underwent SCM were of higher age, with higher BMI and body mass. The patients in SSM group had statistically significantly higher BMI than in ASM. There was no difference in efficacy between patients who underwent SSM and SCM. The majority of patients (91.5%) were positive for BRCA1 or BRCA2 mutation. In our study, only four patients were tested negative for known breast cancer inducing mutation (three in SCM and one in SSM). The most common reconstruction method was an abdominal flap and breast implant. Prophylactic mastectomy is a reliable strategy for significantly reducing the number of breast cancer incidence in high-risk patients regardless of the selected method of mastectomy. These operations allow for the subsequent reconstruction with the whole spectrum of reconstructive options.

Abstract 3389: Intraductal ablative procedure for local preventive intervention in rat models of breast cancer

Abstract There are limited options for primary prevention of breast carcinoma (BC). Prophylactic mastectomy and systemic hormonal therapy are only recommended for high-risk individuals. Prophylactic mastectomy is a drastic surgery that removes the entire breast, including the epithelial cell-lined ductal trees where BC arises but also uninvolved stroma. Even with a 90% risk reduction, many women are deterred from prophylactic mastectomy due to its associated risk of infection, lymphedema, painful recovery time, and mental health toll. Hormonal therapies, tamoxifen and raloxifene, reduce BC risk by upwards of 50% but also increase the risk of uterine cancer and stroke. Thus, new interventions to reduce the risk of BC and minimize deterrents are necessary. Intraductal (ID) injection is a minimally invasive procedure that avoids systemic toxicity by cannulating a needle directly into the ductal tree opening to directly administer a solution to the epithelial cells. We previously reported that ID infusion of 70% ethanol (EtOH) as a cell-killing solution prevents tumor formation in an aggressive genetically engineered mouse model of BC with minimum collateral tissue damage. Here, we investigated the therapeutic efficacy of EtOH-based ablative solutions in a Methyl-N-Nitrosourea (MNU) chemically induced rat model of BC to assess scalability of this procedure towards clinical trials. Two weeks after tumor induction, rats received ID infusions of a solution containing 70% EtOH to ablate epithelial cells, ethyl cellulose (EC) to minimize collateral tissue damage, and/or Tantalum Oxide (TaOx) to visualize infused ductal trees via micro-CT imaging. EtOH-infused glands had the longest tumor latency (273 days vs 97 days in control group, p &amp;lt; 0.0001). No statistically significant differences were noted in epithelial ablation or collateral tissue damage between treatment groups receiving ID injections of 70% EtOH with varying concentrations of EC, but there was a trend to lower collateral damage with EC-containing solutions. Local clearance of TaOx in infused mammary glands enabled post-procedure MR imaging surveillance after 15 d of ID procedure. This preclinical study demonstrates that ID injection of a refined solution containing 70% EtOH and TaOx is an efficacious and scalable procedure for primary prevention of BC. Citation Format: Erin Zaluzec, Mohamed Ashry, Elizabeth G. Phelps, Katarzyna Kempinska, Elizabeth Kenyon, Legend Kenny, Max Volk, Katherine Powell, Jeremy ML Hix, Christiane Mallett, Matti Kiupel, Erik M. Shapiro, Lorenzo F. Sempere. Intraductal ablative procedure for local preventive intervention in rat models of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3389.

Non-sclerosing (T-cell) and sclerosing (B-cell) lymphocytic lobulitis in diagnostic breast biopsies: Clinical, imaging, and pathologic features

Lymphocytic lobulitis (LL) is characterized by prominent lymphocytic infiltrates centered on lobules. Sclerosing lymphocytic lobulitis (SCLL) associated with diabetes mellitus (DM) or autoimmune disease (AI) was the first type to be described. Subsequently, non-sclerosing LL (NSCLL) was reported as an incidental finding in prophylactic mastectomies due to high risk germline mutations or a family history of breast cancer. The two types of LL were distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter. In this study, 8 cases of NSCLL detected clinically or by screening were compared to 44 cases of SCLL. One case of NSCLL presented as a palpable mass, 2 as masses on screening, and 5 as MRI enhancement. In contrast, 80% of SCLL cases presented as palpable masses. Half the cases of NSCLL were associated with a BRCA1 or 2 mutation compared to 1 case of SCLL (2%). Three additional cases of NSCLL were associated with a strong family and/or personal history of breast cancer. Almost half (52%) of SCLL cases were associated with DM or AI, but only 25% of NSCLL. Immunoperoxidase studies confirmed a predominance of T-cells in NSCLL and B-cells in SCLL associated with DM or AI. It is important for pathologists to be aware of this new observation that NSCLL can be detected as a palpable mass or an imaging finding in diagnostic biopsies, as its presence can be indicative of a significant risk for breast cancer.

Breast Implant Illness May Be Rooted in Mast Cell Activation: A Case-Controlled Retrospective Analysis.

To investigate the possible association between breast implant illness (BII) and mast cell activation syndrome (MCAS), which often manifests increased mast cells (MCs) in assorted tissues and may explain BII symptoms. Mechanisms by which implants cause BII symptoms remain unclear, but BII and MCAS symptom profiles heavily overlap, warranting investigation of potential linkage. We retrospectively analyzed 20 implant patients who underwent explantation and total capsulectomy; 15 self-reported preoperatively they had BII (subject group); 5 felt they did not [control group 1 (CG1)]. Five prophylactic mastectomy patients constituted control group 2 (CG2). Subjects and CG1 patients completed BII symptom questionnaires preoperatively and multiple points postoperatively. With CD117 staining, average and maximum mast cell counts (MCCs) in resected tissues were determined. Mean BII symptom score 2 weeks postexplantation was reduced by 77% (P < 0.0001), and 85% by 9 months. Analysis suggested BII in CG1 patients, too, who improved similarly. Among CG2 patients, healthy breast tissue showed mean and maximum MCCs of 5.0/hpf and 6.9/hpf. Mean and maximum MCCs in capsules in BII patients were 11.7/hpf and 16.3/hpf, and 7.6/hpf and 13.3/hpf in CG1 patients. All intergroup comparisons were significantly different (P < 0.0001). MCCs in peri-implant capsules in BII patients are increased; some implanted patients appear to have unrecognized BII. Given that neoantigenic/xenobiotic exposures commonly trigger dysfunctional MCs in MCAS to heighten aberrant mediator expression driving inflammatory and other issues, further investigation of whether BII represents an implant-driven escalation of preexisting MCAS and whether an MCAS diagnosis flags risk for BII seems warranted.

Abstract A002: Collaboration between the physician/researcher and patient/survivor is key

Abstract In May 2009, I went to see my primary care physician for a routine annual physical exam. I told her that I thought I was starting menopause. She did a typical physical including a pelvic exam and did not notice anything abnormal; but she decided to send me for a vaginal ultrasound. The ultrasound revealed that both my ovaries were massive. My physician sent me to my gynecologist for further follow up. My gynecologist advised me to have a complete hysterectomy and she had a CA-125 blood test done. It came back elevated. She told me I had ovarian cysts. A family friend, an OB-GYN, reviewed my test results and urged me to get a second opinion with a gynecological oncologist. Fortunately, I was able to see a Gyn-Onc who scheduled surgery. This doctor confirmed that I had complex ovarian cysts but could not determine if there was any malignancy until my surgery. Urging patients to see gynecological oncologists is one of the most important things that can be done to save women’s lives. During my debulking surgery it was discovered that I had High Grade Epithelial Ovarian Cancer. I started a six-month chemotherapy regime of Taxol and Carboplatin. It was hard on my body—I became anemic, required blood transfusions, had digestive problems, and experienced a level of fatigue that I never knew existed. Halfway through chemo I had genetic counseling and decided to take the BRCA1 gene mutation test. I tested positive—most likely because of my Eastern European Ashkenazi Jewish heritage. There is a history of breast cancer, pancreatic cancer, colon cancer and brain cancer in my family. Due to my BRCA1+ status I had a prophylactic mastectomy and breast reconstruction which took place in December 2010. Here is a video that I created to help bring awareness to the importance of genetic testing: https://youtu.be/Fm72svK2zKw I am a Research Advocate for OVCA patients and survivors. I participate in clinical trials. I teach yoga and mindfulness practices at retreats for cancer survivors. I participate in OCRA’s Survivors Teaching Students program at the University of Washington Medical School. I am a peer mentor for Imerman’s Angels, OCRA and Sharsheret. I serve as a Survivor Ambassador for: Clearity Foundation, Amy K. Rosenthal Foundation, Rivkin Foundation and Powell Drescher OVCA Research Foundation. I am a peer reviewer for the DOD’s Ovarian OCRP. In April 2023 I attended the Annual Meeting of American Association for Cancer Research as part of the AACR Scientist↔Survivor Program. During the poster sessions I met almost 100 researchers whose focus is Ovarian Cancer and only six of them had ever met an actual Ovarian Cancer patient/survivor. I want my survivorship to impact the discovery of effective tests for early diagnosis and treatment of OVCA. I believe that the collaboration between the physician/researcher and the patient/survivor will bring new solutions to dealing with an OVCA diagnosis and treatments. Citation Format: Deborah J. Binder. Collaboration between the physician/researcher and patient/survivor is key [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A002.

Screening chest wall ultrasound in the mastectomy patient

BackgroundWhile there are clear guidelines regarding chest wall ultrasound in the symptomatic patient, there is conflicting evidence regarding the use of ultrasound in the screening of women post-mastectomy. ObjectiveTo assess the utility of screening chest wall ultrasound after mastectomy and to assess features of detected malignancies. MethodsThis IRB approved, retrospective study evaluates screening US examinations of the chest wall after mastectomy. Asymptomatic women presenting for screening chest wall ultrasound from January 2016 through May 2017 were included. Cases of known active malignancy were excluded. All patients had at least one year of clinical or imaging follow-up. 43 exams (8.5 %) were performed with a history of contralateral malignancy, 465 exams (91.3 %) were performed with a history of ipsilateral malignancy, and one exam (0.2 %) was performed in a patient with bilateral prophylactic mastectomy. ResultsDuring the 17-month period, there were 509 screening US in 389 mastectomy patients. 504 (99.0 %) exams were negative/benign. Five exams (1.0 %) were considered suspicious, with recommendation for biopsy, which was performed. Out of 509 exams, 3 (0.6 %) yielded benign results, while 2 (0.39 %) revealed recurrent malignancy, with a 95 % confidence interval (exact binomial) of 0.05 % to 1.41 % for screening ultrasound. Both patients who recurred had previously recurred, and both had initial cancer of lobular histology. ConclusionOf 509 chest wall screening US exams performed in mastectomy, 2 malignancies were detected, and each patient had history of invasive lobular carcinoma and at least one prior recurrence prior to this study, suggesting benefit of screening ultrasound in these populations.

194 (PB-101) Poster - Preshaping surgery of ptotic breasts prior prophylactic nipple-sparing mastectomy and immediate reconstruction: A single-center five-year retrospective study

194 (PB-101) Poster - Preshaping surgery of ptotic breasts prior prophylactic nipple-sparing mastectomy and immediate reconstruction: A single-center five-year retrospective study

Contralateral prophylactic mastectomy in a rural population: A single-institution experience

BackgroundThe incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer (UBC) has continued to increase, despite an absent survival benefit except in populations at highest risk for developing contralateral breast cancer (CBC). CPM rates may be higher in rural populations but causes remain unclear. A study performed at our institution previously found that 21.8 % of patients with UBC underwent CPM from 2000 to 2009. This study aimed to evaluate the CPM trend at a single institution serving a rural population and identify the CPM rate in average-risk patients. MethodsRetrospective review of patients who underwent mastectomies for UBC at our institution from 2017 to 2021 was performed. Analysis utilized frequencies and percentages, descriptive statistics, chi-square, and independent sample t-tests. ResultsA total of 438 patients were included, of whom 64.4 % underwent bilateral mastectomy for UBC (CPM). Patients who underwent CPM were significantly younger, underwent genetic testing, had germline pathogenic variants, had a family history of breast cancer, had smaller tumors, underwent reconstruction, and had more wound infections. Of CPM patients, 50.4 % had no identifiable factors for increased risk of developing CBC. ConclusionsThe rate of CPM in a rural population at a single institution increased from 21.8 % to 64.4 % over two decades, with an average-risk CPM rate of 50.4 %. Those that undergo CPM are more likely to undergo reconstruction and have more wound infections. Identifying characteristics of patients undergoing CPM in a rural population and the increased associated risks allows for a better understanding of this trend to guide conversations with patients. Key messageThis study demonstrates that the rate of contralateral prophylactic mastectomy for unilateral breast cancers performed at a single institution serving a largely rural population has nearly tripled over the last two decades, with half of these patients having no factors that increase the risk for developing contralateral breast cancers. Contralateral prophylactic mastectomy was significantly associated with smaller tumors, younger age, genetic testing, germline pathogenic variants, family history of breast cancer, breast reconstruction, and increased wound infections.

Quantitative measurement of mammographic density in breast-tissue explants using portable NMR: Precision and accuracy.

Single-sided portable NMR (pNMR) has previously been demonstrated to be suitable for quantification of mammographic density (MD) in excised breast tissue samples. Here we investigate the precision and accuracy of pNMR measurements of MD ex vivo as compared with the gold standards. Forty-five breast-tissue explants from 9 prophylactic mastectomy patients were measured. The relative tissue water content was taken as the MD-equivalent quantity. In each sample, the water content was measured using some combination of three pNMR techniques (apparent T2, diffusion, and T1 measurements) and two gold-standard techniques (computed microtomography [μCT] and hematoxylin and eosin [H&E] histology). Pairwise correlation plots and Bland-Altman analysis were used to quantify the degree of agreement between pNMR techniques and the gold standards. Relative water content measured from both apparent T2 relaxation spectra, and diffusion decays exhibited strong correlation with the H&E and μCT results. Bland-Altman analysis yielded average bias values of -0.4, -2.6, 2.6, and 2.8 water percentage points (pp) and 95% confidence intervals of 13.1, 7.5, 11.2, and 11.8 pp for the H&E - T2, μCT - T2, H&E - diffusion, and μCT - diffusion comparison pairs, respectively. T1-based measurements were found to be less reliable, with the Bland-Altman confidence intervals of 27.7 and 33.0 pp when compared with H&E and μCT, respectively. Apparent T2-based and diffusion-based pNMR measurements enable quantification of MD in breast-tissue explants with the precision of approximately 10 pp and accuracy of approximately 3 pp or better, making pNMR a promising measurement modality for radiation-free quantification of MD.

Complex breast reconstruction using bilateral profunda artery perforator-free-flaps in a resource-limited setting: a case report

Interestingly, the current shift in mastectomy patterns and advances in reconstruction techniques have contributed to an increasing number of patients requesting breast reconstruction postmastectomy every year. Depending on available expertise, patients can access breast reconstruction options (immediate or delayed), autologous, or implant-based. We present a case of a 36-year-old female patient 5 years into remission, having undergone mastectomy for invasive ductal carcinoma of the right breast and now preferred risk reduction surgery (prophylactic mastectomy) of her left unaffected breast with immediate reconstruction. The microsurgical technique utilized bilateral profunda artery perforator flaps from both thighs for (immediate and delayed) breast reconstruction. In our scenario, the authors had an unfavorable outcome on the side of delayed breast reconstruction (right) with a venous insufficiency diagnosis leading to unilateral complete flap loss, which was subsequently debrided and reconstructed with an obliquely-oriented pedicled Latissimus dorsi flap. In contrast, following risk reduction surgery and immediate reconstruction on the left side, the buried flap was a complete success, with the free nipple graft doing well postoperatively.

Abstract A065: Single cell transcriptomics reveals putative tumor promoting subpopulation in Brca1 mutant breast cancer mouse model

Abstract Women with BRCA1 (B1) mutations have an exceptionally high risk of developing breast cancer. The only effective preventive strategy currently offered to these women is the life altering prophylactic mastectomy. Considering the limited treatment options available, it is critical that new preventive strategies be identified. Design of such strategies requires an understanding of early events in the breast cells that drive tumorigenesis. B1 heterozygous mouse models can help us identify these early changes however, despite the well-established association between B1 heterozygosity and cancer predisposition in humans, there are currently no such B1 mouse models that faithfully recapitulate this high risk of tumor formation. We have now established a mouse model that induces mammary tumors in B1 heterozygous (Brca1wt/flx,Trp53flx/flx,K14cre) mice upon replication stress (RS). Our approach is based on our published work that reveals haploinsufficiency for RS suppression in B1 heterozygous cells. We find that increasing RS in B1 heterozygous mice results in accelerated mammary tumorigenesis. RS in this mouse model was delivered by injecting DNA-adduct forming 4-nitroquinoline-1-oxide (4NQO) via mammary intraductal injections over a course of 4 weeks. RS served as an efficient and abnormally rapid driver of tumor formation (30 days post completion of injection regimen) in B1 heterozygous mice. B1 heterozygous mice formed mammary adenocarcinoma. These tumors exhibit a triple negative breast cancer phenotype similar to that found in human BRCA1 mutant breast cancer. Our scRNAseq-based analysis of 42,000 cells from mouse mammary tissue collected at different time points during tumorigenesis has identified early transcriptomic changes that occur in different mammary cell types (e.g., luminal and basal) as they respond to RS. We find that in response to RS, a population of trans-differentiated cells accumulates in the mammary tissue. This population is bi-potent (expresses both luminal progenitor and basal epithelial markers), is specifically enriched in Brca1 heterozygous mammary tissue and expresses certain prognostic markers with a strong correlation to poor outcome in human breast cancer. This population is also enriched for proliferation markers. We suspect that this transdifferentiated population, which is primarily enriched in B1 heterozygous mammary tissue undergoing RS, marks the earliest cancer promoting cell population. Finally, pseudotime reconstruction-based lineage analysis reveals that alveolar luminal progenitor cells are the most likely cell of origin for this putative tumor promoting cell population in the breast. Altogether, our integrative approach reveals that B1 heterozygosity in combination with RS leads to accumulation and proliferation of a specific mammary cell population with a unique transcriptomic profile, that contributes to breast tumorigenesis. Identification of such early drivers is critical for the design of effective preventive and therapeutic strategies for women with BRCA1 mutation. Citation Format: Shailja Pathania, Joshua Rivera, Stevension Tran, Carman Man Chung Li, Joan Brugge, Kourosh Zarringhalam. Single cell transcriptomics reveals putative tumor promoting subpopulation in Brca1 mutant breast cancer mouse model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A065.

Construction and Validation of a Nomogram Predicting the Overall Survival Benefit of Unilateral Breast Cancer Patients Undergoing Contralateral Prophylactic Mastectomy

BackgroundCurrently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). MethodsIn this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. ResultsThe prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. ConclusionThis study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.

Breast Reconstruction following Mastectomy for Breast Cancer or Prophylactic Mastectomy: Therapeutic Options and Results.

(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in age-standardized breast cancer mortality and have also witnessed a reduction in the medium age at diagnosis, which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we have seen a marked trend toward mastectomies in breast-conserving surgery-eligible patients. Prophylactic mastectomies have also registered an upward trend. This trend together with new uses for breast reconstruction like chest feminization in transgender patients has increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results, and their safety profiles when used during the integrated treatment plan of the oncologic patient. (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures; summarized the findings; and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers, and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the "gold standard", but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients.

Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy.

Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient's age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.

Fear of cancer recurrence in breast cancer survivors carrying a BRCA1/2 mutation: A qualitative study.

There is preliminary evidence suggesting that FCR is a major problem for breast cancer survivors carrying a BRCA1/2 mutation. The goal of this qualitative study, conducted among women who were treated for breast cancer, was to provide a deeper understanding of how FCR is experienced in the context of a genetic predisposition to breast cancer. Three focus groups (90-110 min) were conducted with 19 breast cancer survivors carrying a BRCA1/2 mutation. The semistructured interview probed FCR level and impact, the role FCR played in the decision to have a prophylactic bilateral mastectomy and/or salpingo-oophorectomy, the effect that surgery had on FCR, and the relevance of offering a psychological intervention targeting FCR to this population. Findings indicated that FCR was a significant issue in these women, even though a majority had undergone a prophylactic surgery. Patients strongly affirmed the need to develop and provide access to FCR interventions that are specifically adapted to the needs of this group. These results suggest that, although being the most effective medical option to reduce the actual risk of local recurrence (or second breast cancer), prophylactic surgery only partially reduces FCR. A psychological intervention targeting specifically FCR would be an appropriate complement to preventive surgery.

Choosing contralateral prophylactic mastectomy for unilateral breast cancer in an urban South African breast cancer clinic

Abstract Background: International trends have shown that female patients with unilateral breast cancer are electing bilateral mastectomies as a prophylactic measure. The study aimed to determine the prevalence of unilateral mastectomies (UM) with and without contralateral prophylactic mastectomy (CPM) and to identify whether demographic and pathological characteristics predict the choice of CPM. Methods: A record review of demographic details and pathological results of all female patients undergoing mastectomy for unilateral breast cancer from 2013-2015 was conducted at the Helen Joseph Breast Care Clinic in Johannesburg, South Africa. Results: A total of 299 women who had mastectomies for unilateral breast cancer were included in the study. Of these, 59 had CPM (19.7%). Significantly more White women opted for a CPM than Black women (43.5% vs 10.6%, p♯αμπ;λτ;0.0001). Women who underwent CPM were significantly younger, and there was a trend for higher median breast weight than patients who only underwent UM (p = 0.03 and p = 0.09, respectively). There was no difference between the two groups with regard to patient income status, tumour histology, TNM stage or neoadjuvant chemotherapy. Conclusion: The demographic and histopathological characteristics of breast cancer which influence the choice of CPM in the South African context have some similarities to those in the international literature in that White and younger women more often choose CPM compared to other racial groups. The more advanced stages of breast cancer presentation in our study suggest that public health awareness and screening measures need to be significantly strengthened in South Africa.

Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers.

Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo prophylactic mastectomy. Using preneoplastic specimens from age-matched, premenopausal females, here we show broad dysregulation across the luminal compartment in BRCA2mut/+ tissue, including expansion of aberrant ERBB3lo luminal progenitor and mature cells, and the presence of atypical oestrogen receptor (ER)-positive lesions. Transcriptional profiling and functional assays revealed perturbed proteostasis and translation in ERBB3lo progenitors in BRCA2mut/+ breast tissue, independent of ageing. Similar molecular perturbations marked tumours bearing BRCA2-truncating mutations. ERBB3lo progenitors could generate both ER+ and ER- cells, potentially serving as cells-of-origin for ER-positive or triple-negative cancers. Short-term treatment with an mTORC1 inhibitor substantially curtailed tumorigenesis in a preclinical model of BRCA2-deficient breast cancer, thus uncovering a potential prevention strategy for BRCA2 mutation carriers.

Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers.

Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle-Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.