Cancers

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15 pages, 1009 KiB

Open AccessArticle

Spectrum of Germline Pathogenic Variants in BRCA1/2 Genes in the Apulian Southern Italy Population: Geographic Distribution and Evidence for Targeted Genetic Testing

by Margherita Patruno, Simona De Summa, Nicoletta Resta, Mariapia Caputo, Silvia Costanzo, Maria Digennaro, Brunella Pilato, Rosanna Bagnulo, Antonino Pantaleo, Cristiano Simone, Maria Iole Natalicchio, Elisabetta De Matteis, Paolo Tarantino, Stefania Tommasi and Angelo Paradiso

Cancers 2021, 13(18), 4714; https://doi.org/10.3390/cancers13184714 - 21 Sep 2021

Cited by 4 | Viewed by 2985

Abstract

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we [...] Read more.

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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15 pages, 4599 KiB

Open AccessArticle

The Combination of Single-Cell and Next-Generation Sequencing Can Reveal Mosaicism for BRCA2 Mutations and the Fine Molecular Details of Tumorigenesis

by Alexandra Gráf, Márton Zsolt Enyedi, Lajos Pintér, Éva Kriston-Pál, Gábor Jaksa, Árpád Bálind, Éva Ezer, Péter Horváth, Farkas Sükösd, Ernő Kiss and Lajos Haracska

Cancers 2021, 13(10), 2354; https://doi.org/10.3390/cancers13102354 - 13 May 2021

Cited by 4 | Viewed by 3326

Abstract

Germline mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome. Germline and somatic BRCA1/2 mutations may define therapeutic targets and refine cancer treatment options. However, routine BRCA diagnostic approaches cannot reveal the exact time and origin [...] Read more.

Germline mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome. Germline and somatic BRCA1/2 mutations may define therapeutic targets and refine cancer treatment options. However, routine BRCA diagnostic approaches cannot reveal the exact time and origin of BRCA1/2 mutation formation, and thus, the fine details of their contribution to tumor progression remain less clear. Here, we establish a diagnostic pipeline using high-resolution microscopy and laser microcapture microscopy to test for BRCA1/2 mutations in the tumor at the single-cell level, followed by deep next-generation sequencing of various tissues from the patient. To demonstrate the power of our approach, here, we describe a detailed single-cell-level analysis of an ovarian cancer patient we found to exhibit constitutional somatic mosaicism of a pathogenic BRCA2 mutation. Employing next-generation sequencing, BRCA2 c.7795G>T, p.(Glu2599Ter) was detected in 78% of reads in DNA extracted from ovarian cancer tissue and 25% of reads in DNA derived from peripheral blood, which differs significantly from the expected 50% of a hereditary mutation. The BRCA2 mutation was subsequently observed at 17–20% levels in the normal ovarian and buccal tissue of the patient. Together, our findings suggest that this mutation occurred early in embryonic development. Characterization of the mosaic mutation at the single-cell level contributes to a better understanding of BRCA mutation formation and supports the concept that the combination of single-cell and next-generation sequencing methods is advantageous over traditional mutational analysis methods. This study is the first to characterize constitutional mosaicism down to the single-cell level, and it demonstrates that BRCA2 mosaicism occurring early during embryogenesis can drive tumorigenesis in ovarian cancer. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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Graphical abstract

11 pages, 576 KiB

Open AccessArticle

The Screen Project: Guided Direct-To-Consumer Genetic Testing for Breast Cancer Susceptibility in Canada

by Steven A. Narod, Nicole Gojska, Ping Sun, Angelina Tryon, Joanne Kotsopoulos, Kelly Metcalfe and Mohammad R. Akbari

Cancers 2021, 13(8), 1894; https://doi.org/10.3390/cancers13081894 - 15 Apr 2021

Cited by 12 | Viewed by 2580

Abstract

There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation [...] Read more.

There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Patients enrolled in the study from 2017 to 2019 and were followed for one year after the receipt of a genetic test result. Study subjects registered online and were sent a saliva sample kit, which was shipped to the reference laboratory. Pre-test genetic counselling and counselling for mutation-negative subjects was optional and at the individual’s discretion. There were 1269 tested individuals between March 2017 and January 2019. A total of 1157 (93%) were women and 87 (7%) were men. Sixty-six percent had a first- or second-degree relative with breast or ovarian cancer. Of the 1269 tested individuals, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. Genetic counselling was available at no cost to all participants but was requested by only 5% of the non-carriers. The study subjects expressed a high degree of satisfaction with the process. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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10 pages, 294 KiB

Open AccessArticle

Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer

by Alicja Łukomska, Janusz Menkiszak, Jacek Gronwald, Joanna Tomiczek-Szwiec, Marek Szwiec, Marek Jasiówka, Paweł Blecharz, Tomasz Kluz, Małgorzata Stawicka-Niełacna, Radosław Mądry, Katarzyna Białkowska, Karolina Prajzendanc, Wojciech Kluźniak, Cezary Cybulski, Tadeusz Dębniak, Tomasz Huzarski, Aleksandra Tołoczko-Grabarek, Tomasz Byrski, Piotr Baszuk, Steven A. Narod, Jan Lubiński and Anna Jakubowska Show full author list Hide full author list

Cancers 2021, 13(4), 849; https://doi.org/10.3390/cancers13040849 - 18 Feb 2021

Cited by 15 | Viewed by 3210

Abstract

The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped [...] Read more.

The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in BRCA1 (9 mutations), BRCA2 (4 mutations), RAD51C (3 mutations), PALB2 (2 mutations), and CHEK2 (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in BRCA1 (OR = 40.79, 95% CI: 18.67–114.78; p = 0.29 × 10⁻¹⁵), in BRCA2 (OR = 25.98; 95% CI: 1.55–434.8; p = 0.001), in RAD51C (OR = 6.28; 95% CI 1.77–39.9; p = 0.02), and in PALB2 (OR 3.34; 95% CI: 1.06–14.68; p = 0.06). There was no association found for CHEK2. We found that pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

11 pages, 366 KiB

Open AccessArticle

Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy

by Gisella Figlioli, Arcangela De Nicolo, Irene Catucci, Siranoush Manoukian, Bernard Peissel, Jacopo Azzollini, Benedetta Beltrami, Bernardo Bonanni, Mariarosaria Calvello, Davide Bondavalli, Barbara Pasini, Francesca Vignolo Lutati, Paola Ogliara, Monica Zuradelli, Valeria Pensotti, Giovanna De Vecchi, Sara Volorio, Paolo Verderio, Sara Pizzamiglio, Giuseppe Matullo, Serena Aneli, Giovanni Birolo, Federica Zanardi, Carlo Tondini, Alberto Zambelli, Luca Livraghi, Michela Franchi, Paolo Radice and Paolo Peterlongo Show full author list Hide full author list

Cancers 2021, 13(3), 532; https://doi.org/10.3390/cancers13030532 - 30 Jan 2021

Cited by 8 | Viewed by 2728

Abstract

Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV [...] Read more.

Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 BRCA1/2 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo BRCA1/2 PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo BRCA1/2 PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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12 pages, 535 KiB

Open AccessArticle

Breast Cancer Mortality among Women with a BRCA1 or BRCA2 Mutation in a Magnetic Resonance Imaging Plus Mammography Screening Program

by Ellen Warner, Siqi Zhu, Donald B. Plewes, Kimberley Hill, Elizabeth A. Ramsay, Petrina A. Causer, Jean Seely, Roberta A. Jong, Pamela Lenkov, Christine Elser, Pavel Crystal, Martin J. Yaffe, Vasily Giannakeas, Ping Sun and Steven A. Narod

Cancers 2020, 12(11), 3479; https://doi.org/10.3390/cancers12113479 - 23 Nov 2020

Cited by 15 | Viewed by 3871

Abstract

Annual breast magnetic resonance imaging (MRI) plus mammography is the standard of care for screening women with inherited BRCA1/2 mutations. However, long-term breast cancer-related mortality with screening is unknown. Between 1997 and June 2011, 489 previously unaffected BRCA1/2 mutation carriers aged 25 to [...] Read more.

Annual breast magnetic resonance imaging (MRI) plus mammography is the standard of care for screening women with inherited BRCA1/2 mutations. However, long-term breast cancer-related mortality with screening is unknown. Between 1997 and June 2011, 489 previously unaffected BRCA1/2 mutation carriers aged 25 to 65 years were screened with annual MRI plus mammography on our study. Thereafter, participants were eligible to continue MRI screening through the high-risk Ontario Breast Screening Program. In 2019, our data were linked to the Ontario Cancer Registry of Cancer Care Ontario to identify all incident cancers, vital status and causes of death. Observed breast cancer mortality was compared to expected mortality for age-matched women in the general population. There were 91 women diagnosed with breast cancer (72 invasive and 19 ductal carcinoma in situ (DCIS)) with median follow-up 7.4 (range: 0.1 to 19.2) years. Four deaths from breast cancer were observed, compared to 2.0 deaths expected (standardized mortality ratio (SMR) 2.0, p = 0.14). For the 489 women in the study, the probability of not dying of breast cancer at 20 years from the date of the first MRI was 98.2%. Annual screening with MRI plus mammography is a reasonable option for women who decline or defer risk-reducing mastectomy. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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16 pages, 1274 KiB

Open AccessArticle

Tumor BRCA Testing in High Grade Serous Carcinoma: Mutation Rates and Optimal Tissue Requirements

by Gulisa Turashvili, Conxi Lazaro, Shengjie Ying, George Charames, Andrew Wong, Krista Hamilton, Denise Yee, Evangeline Agro, Martin Chang, Aaron Pollett and Jordan Lerner-Ellis

Cancers 2020, 12(11), 3468; https://doi.org/10.3390/cancers12113468 - 21 Nov 2020

Cited by 14 | Viewed by 3099

Abstract

Background: Approximately 25% of women diagnosed with tubo-ovarian high-grade serous carcinoma have germline deleterious mutations in BRCA1 or BRCA2, characteristic of hereditary breast and ovarian cancer syndrome, while somatic mutations have been detected in 3–7%. We set out to determine the BRCA [...] Read more.

Background: Approximately 25% of women diagnosed with tubo-ovarian high-grade serous carcinoma have germline deleterious mutations in BRCA1 or BRCA2, characteristic of hereditary breast and ovarian cancer syndrome, while somatic mutations have been detected in 3–7%. We set out to determine the BRCA mutation rates and optimal tissue requirements for tumor BRCA testing in patients diagnosed with tubo-ovarian high-grade serous carcinoma. Methods: Sequencing was performed using a multiplexed polymerase chain reaction-based approach on 291 tissue samples, with a minimum sequencing depth of 500X and an allele frequency of >5%. Results: There were 253 surgical samples (87%), 35 biopsies (12%) and 3 cytology cell blocks (1%). The initial failure rate was 9% (25/291), including 9 cases (3%) with insufficient tumor, and 16 (6%) with non-amplifiable DNA. Sequencing was successful in 78% (228/291) and deemed indeterminate due to failed exons or variants below the limit of detection in 13% (38/291). Repeat testing was successful in 67% (28/42) of retested samples, with an overall success rate of 86% (251/291). Clinically significant (pathogenic, likely pathogenic) variants were identified in 17% (48/276) of complete and indeterminate cases. Successful sequencing was dependent on sample type, tumor cellularity and size (p ≤ 0.001) but not on neoadjuvant chemotherapy or age of blocks (p > 0.05). Conclusions: Our study shows a 17% tumor BRCA mutation rate, with an overall success rate of 86%. Biopsy and cytology samples and post-chemotherapy specimens can be used for tumor BRCA testing, and optimal tumors measure ≥5 mm in size with at least 20% cellularity. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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Review

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11 pages, 737 KiB

Open AccessReview

BRCA Genetic Test and Risk-Reducing Salpingo-Oophorectomy for Hereditary Breast and Ovarian Cancer: State-of-the-Art

by Masayuki Sekine, Koji Nishino and Takayuki Enomoto

Cancers 2021, 13(11), 2562; https://doi.org/10.3390/cancers13112562 - 23 May 2021

Cited by 14 | Viewed by 4104

Abstract

In the field of gynecology, the approval of the PARP inhibitors (PARPi) has been changing the treatment of ovarian cancer patients. The BRCA genetic test and the HRD test are being used as a companion diagnosis before starting PARPi treatment. BRACAnalysis CDx^® [...] Read more.

In the field of gynecology, the approval of the PARP inhibitors (PARPi) has been changing the treatment of ovarian cancer patients. The BRCA genetic test and the HRD test are being used as a companion diagnosis before starting PARPi treatment. BRACAnalysis CDx^® and Myriad myChoice^® HRD test are widely used as a BRCA genetic test and HRD test, respectively. In addition, FoundationOne^®CDx is sometimes used as a tumor BRCA test and HRD test. In clinical practice, gynecologists treating ovarian cancer are faced with making decisions such as whether to recommend the gBRCA test to all ovarian cancer patients, whether to perform the gBRCA test first or HRD test first, and so on. Regarding the judgment result of the HRD test, the cutoff value differs depending on the clinical trial, and the prevalence of gBRCA pathogenic variant rate is different in each histological type and country. A prospective cohort study showed that RRSO reduced all-cause mortality in both pre- and postmenopausal women; however, RRSO significantly reduced the risk of breast cancer for BRCA2 pathogenic variant carriers, but not for BRCA1 pathogenic variant carriers. Moreover, salpingectomy alone is said to not decrease the risk of developing ovarian or breast cancer, so further discussion is evidently required. We discuss the current situation and problems in doing BRCA genetic test and RRSO in this review article. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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14 pages, 352 KiB

Open AccessReview

Psychosocial Interventions for Women with a BRCA1 or BRCA2 Mutation: A Scoping Review

by Talin Boghosian, Jeanna M. McCuaig, Lindsay Carlsson and Kelly A. Metcalfe

Cancers 2021, 13(7), 1486; https://doi.org/10.3390/cancers13071486 - 24 Mar 2021

Cited by 12 | Viewed by 2877

Abstract

This scoping review aimed to explore the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Four electronic bibliographic databases were searched. After review, 23 articles that described or assessed forms of an additional psychosocial intervention for individuals with a BRCA mutation [...] Read more.

This scoping review aimed to explore the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Four electronic bibliographic databases were searched. After review, 23 articles that described or assessed forms of an additional psychosocial intervention for individuals with a BRCA mutation were identified and included. Intervention types discussed in the articles were telephone-based peer-to-peer counselling (5), online communities (4), in-person group counselling (8), and one-day sessions (6). Outcomes investigated within the articles included psychosocial outcomes (18), satisfaction (8), health behaviours (7), and knowledge (5). The included studies suggested that telephone-based peer-to-peer counselling and online communities improve patient knowledge and psychosocial functioning and can overcome challenges such as scheduling and travel associated with in-person support groups, but may have challenges with recruitment and retainment of participants. Group in-person education sessions satisfied the need amongst BRCA1/2 carriers in terms of accessing necessary information regarding cancer risk assessment and management; however, the impact of group education sessions on psychological outcomes was variable across the included studies. Overall, all the forms of intervention described in this scoping review were well-received by participants; some have been shown to reduce distress, depression, and anxiety. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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Other

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15 pages, 1959 KiB

Open AccessStudy Protocol

A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study

by Julie Lapointe, Michel Dorval, Jocelyne Chiquette, Yann Joly, Jason Robert Guertin, Maude Laberge, Jean Gekas, Johanne Hébert, Marie-Pascale Pomey, Tania Cruz-Marino, Omar Touhami, Arnaud Blanchet Saint-Pierre, Sylvain Gagnon, Karine Bouchard, Josée Rhéaume, Karine Boisvert, Claire Brousseau, Lysanne Castonguay, Sylvain Fortier, Isabelle Gosselin, Philippe Lachapelle, Sabrina Lavoie, Brigitte Poirier, Marie-Claude Renaud, Maria-Gabriela Ruizmangas, Alexandra Sebastianelli, Stéphane Roy, Madeleine Côté, Marie-Michelle Racine, Marie-Claude Roy, Nathalie Côté, Carmen Brisson, Nelson Charette, Valérie Faucher, Josianne Leblanc, Marie-Ève Dubeau, Marie Plante, Christine Desbiens, Martin Beaumont, Jacques Simard and Hermann Nabi Show full author list Hide full author list

Cancers 2021, 13(11), 2729; https://doi.org/10.3390/cancers13112729 - 31 May 2021

Cited by 8 | Viewed by 3601

Abstract

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de [...] Read more.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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9 pages, 8996 KiB

Open AccessBrief Report

Risk-Reducing Mastectomy and Reconstruction Following Prophylactic Breast Irradiation: Hope Sustained

by Merav A. Ben David, Ella Evron, Adi F. Rasco, Ayelet Shai and Benjamin W. Corn

Cancers 2021, 13(11), 2694; https://doi.org/10.3390/cancers13112694 - 30 May 2021

Cited by 2 | Viewed by 2371

Abstract

Risk-reducing mastectomy (RRM) is often advocated for BRCA1/2 mutation carriers who face a heightened lifetime risk of breast cancer. However, many carrier patients seek alternative risk-reducing measures. In a phase II nonrandomized trial, we previously reported that prophylactic irradiation to the contralateral breast [...] Read more.

Risk-reducing mastectomy (RRM) is often advocated for BRCA1/2 mutation carriers who face a heightened lifetime risk of breast cancer. However, many carrier patients seek alternative risk-reducing measures. In a phase II nonrandomized trial, we previously reported that prophylactic irradiation to the contralateral breast among BRCA carriers undergoing breast-conserving treatment significantly reduced subsequent contralateral breast cancer. Herein, we report the outcome of salvage mastectomy and reconstruction in 11 patients that suffered reoccurrences of breast cancer in either the ipsilateral or contralateral breast or elected to have the procedure for risk reduction during the eight-year follow-up period. Patients’ satisfaction with the procedure and physicians’ assessment of the cosmetic outcome were not inferior for previously irradiated compared to non-irradiated breasts. Although the numbers are small, the results are encouraging and sustain hope in a challenging population. Our findings support continuing research as well as a discussion of risk-reduction alternatives besides mastectomy, including prophylactic breast irradiation, in BRCA1/2 mutation carriers. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer)

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