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Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer...
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Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 6006

Special Issue Editors

Prof. Dr. Laura Ottini

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Guest Editor
Department of Molecular Medicine, University La Sapienza, 00161 Rome, Italy
Interests: hereditary cancer; breast cancer; prostate cancer; gastrointestinal cancer; melanoma; cancer genetics and genomics; cancer risk assessment; molecular epidemiology
Special Issues, Collections and Topics in MDPI journals
Dr. Valentina Silvestri

E-Mail Website
Guest Editor
Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Interests: breast cancer; hereditary cancers; cancer genetics and genomics; cancer risk assessment; molecular epidemiology
Special Issues, Collections and Topics in MDPI journals
Dr. Arianna Nicolussi

E-Mail Website
Guest Editor
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Interests: oncology; hereditary breast and ovarian cancer; breast cancer susceptibility; BRCA genes; variants of unknown significance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

This Special Issue is the second edition of the previous one, "Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment" (https://www.mdpi.com/journal/cancers/special_issues/GMCRT).

Breast cancer is the most common cancer among women, accounting for about 30% of all cancers. In contrast, breast cancer is a rare disease in men, accounting for less than 1% of all cancers. Approximately 10% of both male and female breast cancer cases are thought to be hereditary, being caused by inherited germ-line mutations in breast cancer susceptibility genes. The genetic architecture of breast cancer susceptibility is similar in men and women, with high-, moderate-, and low-penetrance risk variants, although some differences in the impact of the risk conferred by specific genetic factors have emerged.

The discovery of the first two breast cancer genes, BRCA1 and BRCA2, dates back to more than two decades ago. Since then, the expanding use of next-generation sequencing (NGS), both in research settings and in clinical screenings for breast cancer inheritance in both sexes, has allowed for the identification and validation of additional susceptibility genes, mainly those involved in homologous recombination (HR) repair of DNA double-strand breaks. Moreover, genetic variations in low-penetrance susceptibility loci have been shown to affect male and female breast cancer genetic predisposition and/or to be genetic risk modifiers, particularly through a polygenic inheritance model.

An expanded knowledge on the genetic factors contributing to male and female breast cancer genetics is the first step to improving risk assessment, and may also have important clinical and therapeutic impacts for all patients, regardless of gender. Personalized therapeutic strategies in BRCA-associated tumors, such as the use of PARP inhibitors, have proved very promising and are incorporated in the clinical setting. Additional genetic defects in HR and other DNA repair pathways may also account for constitutional or acquired resistance/sensitivity to PARP inhibitors.

This Special Issue will focus on the genetics of breast cancer in men and women, with the aim of providing more insight into the role of genetic factors in breast cancer risk assessment and as predictive biomarkers for personalized therapy. For this Special Issue of Cancers, we welcome research articles describing novel data, methods, collaborative initiatives, editorials, and reviews related to these topics.

We look forward to receiving your contributions.

Prof. Dr. Laura Ottini
Dr. Valentina Silvestri
Dr. Arianna Nicolussi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hereditary cancers
  • male breast cancer
  • genetic predisposition to breast cancer
  • breast cancer risk
  • NGS of gene panels

Related Special Issue

Published Papers (5 papers)

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Research

8 pages, 425 KiB  
Communication
HER2-Low Expression in Male Breast Cancer: Results from a Multicenter Series in Italy
by Valentina Silvestri, Virginia Valentini, Agostino Bucalo, Giulia Conti, Livia Manzella, Daniela Turchetti, Antonio Russo, Carlo Capalbo and Laura Ottini
Cancers 2024, 16(3), 548; https://doi.org/10.3390/cancers16030548 - 27 Jan 2024
Viewed by 1570
Abstract
In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody–drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. [...] Read more.
In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody–drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials. Full article
(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition))
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11 pages, 1030 KiB  
Article
Talking about Familial Breast and Ovarian Cancer Risk—Evaluation of a Psychosocial Training Module for Gynecologists in Germany
by Friederike Kendel, Dorothee Speiser, Karen Fechner, Christine Olbrich, Stephanie Stegen, Alina Rörig, Markus A. Feufel and Stephanie Haering
Cancers 2024, 16(2), 310; https://doi.org/10.3390/cancers16020310 - 11 Jan 2024
Viewed by 793
Abstract
Primary care gynecologists are increasingly integrated into the care of patients with hereditary breast and ovarian cancer (HBOC) risks. These physicians should not only have basic genetic knowledge; they should also feel able to sensitively address an increased HBOC risk and deal with [...] Read more.
Primary care gynecologists are increasingly integrated into the care of patients with hereditary breast and ovarian cancer (HBOC) risks. These physicians should not only have basic genetic knowledge; they should also feel able to sensitively address an increased HBOC risk and deal with emotional, stressful situations in this context. Our project aimed at developing a training module, ‘iKNOWgynetics’, addressing psychosocial challenges in the context of HBOC care for primary care gynecologists. We developed the psychosocial training module in three phases: first, we conducted an online survey with n = 35 women with a family history of breast or ovarian cancer to assess patients’ experiences and needs. Second, based on the results of the needs assessment, we developed the training module. Third, we evaluated the training by assessing physicians’ (n = 109) self-efficacy with regard to communication skills in the context of HBOC before and after the training. In the needs assessment, seven psychosocial themes emerged. These themes, complementing a review of the literature, informed the training curriculum. The training was divided into two parts: (1) communicating with women before genetic testing and (2) care co-management for women with HBOC after genetic testing. After the training, participants reported a significant increase in self-efficacy in three domains: communicating empathetically, educating patients in a comprehensible way and dealing with emotionally challenging situations. Our results highlight the relevance of psychosocial issues for patients with HBOC. A genetic literacy training module that integrates aspects of psychosocial care increases physicians’ confidence in dealing with emotionally challenging situations before and after their patients’ genetic testing. Thus, such trainings may improve the care of women with hereditary cancer risks. Full article
(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition))
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14 pages, 3062 KiB  
Article
Expression and Localization of Ferritin-Heavy Chain Predicts Recurrence for Breast Cancer Patients with a BRCA1/2 Mutation
by Shuoying Qu, A. Mieke Timmermans, Bernadette A. M. Heemskerk-Gerritsen, Anita M. A. C. Trapman-Jansen, Renée Broeren-Foekens, Wendy J. C. Prager-van der Smissen, Hoesna El Hassnaoui, Tim van Tienhoven, Claudia K. Bes-Stobbe, Pieter J. Westenend, Carolien H. M. van Deurzen, John W. M. Martens, Maartje J. Hooning and Antoinette Hollestelle
Cancers 2024, 16(1), 28; https://doi.org/10.3390/cancers16010028 - 20 Dec 2023
Viewed by 733
Abstract
The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector [...] Read more.
The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector T cells. However, whether the expression and localization of FTH1 are also associated with clinical outcome in other BC subtypes is unknown. Here, we investigated the association of FTH1 with time to survival in BCs from 222 BRCA1/2 mutation carriers by immunohistochemistry on tissue microarrays. In addition, for 51 of these patients, the association between FTH1 and specific subsets of T cells was evaluated on whole slides using automatic scoring algorithms. We revealed that nuclear FTH1 (nFTH1) expression, in multivariable analyses, was associated with a shorter disease-free (HR = 2.71, 95% CI = 1.49–4.92, p = 0.001) and metastasis-free survival (HR = 3.54, 95% CI = 1.45–8.66, p = 0.006) in patients carrying a BRCA1/2 mutation. However, we found no relation between cytoplasmic FTH1 expression and survival of BRCA1/2 mutation carriers. Moreover, we did not detect an association between FTH1 expression and the amount of CD45+ (p = 0.13), CD8+ (p = 0.18), CD4+ (p = 0.20) or FOXP3+ cells (p = 0.17). Consequently, the mechanism underlying the worse recurrence-free survival of nFTH1 expression in BRCA1/2 mutation carriers needs further investigation. Full article
(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition))
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15 pages, 2322 KiB  
Article
PALB2 Variants Extend the Mutational Profile of Hungarian Patients with Breast and Ovarian Cancer
by Henriett Butz, Petra Nagy, János Papp, Anikó Bozsik, Vince Kornél Grolmusz, Tímea Pócza, Edit Oláh and Attila Patócs
Cancers 2023, 15(17), 4350; https://doi.org/10.3390/cancers15174350 - 31 Aug 2023
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Abstract
Background: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile of PALB2, the third most important breast cancer gene, may vary between different populations. Methods: PALB2 was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March [...] Read more.
Background: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile of PALB2, the third most important breast cancer gene, may vary between different populations. Methods: PALB2 was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years, yBC) patients. These data were compared with data of 134,187 non-cancer individuals retrieved from the Genome Aggregation Database. Results: Altogether, 235 cases (235/1280; 18.3%) carried at least one P/LP variant in one of the HBOC susceptibility genes. P/LP PALB2 variants were identified in 18 patients (1.4%; 18/1280) in the HBOC and 3 cases (1.5%; 3/191) in the yBC group. In the control group, only one patient had a disease-causing PALB2 variant (0.17%; 1/568) as a secondary finding not related to the disease, which was similar (0.15%; 205/134,187) in the non-cancer control group. The NM_024675.4:c.509_510delGA variant was the most common among our patients (33%; 6/18). We did not find a significant difference in the incidence of PALB2 disease-causing variants according to age; however, the median age of tumor onset was lower in PALB2 P/LP carriers versus wild-type patients (44 vs. 48 years). In our cohort, the odds ratio for breast cancer risk in women with PALB2 P/LP variants was between 8.1 and 9.3 compared to non-HBOC cancer patients and the non-cancer population, respectively. Conclusions: PALB2 P/LP variants are not uncommon among breast and/or ovarian cancer patients. Their incidence was the same in the two breast cancer cohorts studied but may occur rarely in patients with non-breast/ovarian cancer. The c.509_510delGA variant is particularly common in the studied Hungarian patient population. Full article
(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition))
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13 pages, 1889 KiB  
Article
Clinical Impact of Polygenic Risk Score for Breast Cancer Risk Prediction in 382 Individuals with Hereditary Breast and Ovarian Cancer Syndrome
by Sarah Stiller, Stephan Drukewitz, Kathleen Lehmann, Julia Hentschel and Vincent Strehlow
Cancers 2023, 15(15), 3938; https://doi.org/10.3390/cancers15153938 - 2 Aug 2023
Cited by 1 | Viewed by 1173
Abstract
Single nucleotide polymorphisms are currently not considered in breast cancer (BC) risk predictions used in daily practice of genetic counselling and clinical management of familial BC in Germany. This study aimed to assess the clinical value of incorporating a 313-variant-based polygenic risk score [...] Read more.
Single nucleotide polymorphisms are currently not considered in breast cancer (BC) risk predictions used in daily practice of genetic counselling and clinical management of familial BC in Germany. This study aimed to assess the clinical value of incorporating a 313-variant-based polygenic risk score (PRS) into BC risk calculations in a cohort of German women with suspected hereditary breast and ovarian cancer syndrome (HBOC). Data from 382 individuals seeking counselling for HBOC were analysed. Risk calculations were performed using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm with and without the inclusion of the PRS. Changes in risk predictions and their impact on clinical management were evaluated. The PRS led to changes in risk stratification based on 10-year risk calculations in 13.6% of individuals. Furthermore, the inclusion of the PRS in BC risk predictions resulted in clinically significant changes in 12.0% of cases, impacting the prevention recommendations established by the German Consortium for Hereditary Breast and Ovarian Cancer. These findings support the implementation of the PRS in genetic counselling for personalized BC risk assessment. Full article
(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment (2nd Edition))
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