Only 32.3% of Breast Cancer Families with Pathogenic Variants in Cancer Genes Utilized Cascade Genetic Testing.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. METHODS: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. RESULTS: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. CONCLUSIONS: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

Influence of the Alcohols on the ZnO Synthesis and Its Properties: The Photocatalytic and Antimicrobial Activities.

Zinc oxide (ZnO) nanomaterials are used in various health-related applications, from antimicrobial textiles to wound dressing composites and from sunscreens to antimicrobial packaging. Purity, surface defects, size, and morphology of the nanoparticles are the main factors that influence the antimicrobial properties. In this study, we are comparing the properties of the ZnO nanoparticles obtained by solvolysis using a series of alcohols: primary from methanol to 1-hexanol, secondary (2-propanol and 2-butanol), and tertiary (tert-butanol). While the synthesis of ZnO nanoparticles is successfully accomplished in all primary alcohols, the use of secondary or tertiary alcohols does not lead to ZnO as final product, underlining the importance of the used solvent. The shape of the obtained nanoparticles depends on the alcohol used, from quasi-spherical to rods, and consequently, different properties are reported, including photocatalytic and antimicrobial activities. In the photocatalytic study, the ZnO obtained in 1-butanol exhibited the best performance against methylene blue (MB) dye solution, attaining a degradation efficiency of 98.24%. The comparative study among a series of usual model dyes revealed that triarylmethane dyes are less susceptible to photo-degradation. The obtained ZnO nanoparticles present a strong antimicrobial activity on a broad range of microorganisms (bacterial and fungal strains), the size and shape being the important factors. This permits further tailoring for use in medical applications.

Successful Dabrafenib Desensitization Protocols in a Patient with Metastatic Melanoma.

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.

Pathological Response and Survival after Neoadjuvant Therapy for Her-2 Positive Breast Cancer.

Background: Pathological complete response (pCR) after neoadjuvant systemic treatment represents a good surrogate marker for the prognosis of Her-2 positive Breast Cancer (BCs). The results improved after adding anti-Her-2 therapy to chemotherapy in neoadjuvant setting. Methods: Our retrospective study enrolled a cohort of 56 invasive Her-2 positive non-metastatic BCs treated with neoadjuvant systemic therapy between 2001 and 2018. The patients received neoadjuvant chemotherapy with or without anti-Her-2 therapies before surgery and adjuvant endocrine and anti-Her-2 treatment together with adjuvant radiotherapy, based on clinical, pathological and hormonal receptor expression characteristics. The primary end point was pCR rate and disease-free-survival (DFS), defined as the interval between surgery and documented disease recurrence, progression, or death from any cause. Results: The rate of pCR for our patients was 41% independent of type of chemotherapy regimen and the anti-Her-2 therapy used. The results were improved by adding Trastuzumab in the neoadjuvant setting with statistical significance (p = 0.038). Median DFS was 68 months for the entire cohort. The risk of recurrence was higher in the group without pCR after neoadjuvant treatment (52% vs 17%; p = 0.003). 10 patients died (18%), all of them from group without pCR. The prognosis at 36-months was good, with 84% survival chance at 3 years follow-up. Conclusion: Our retrospective study underlines the positive impact of neoadjuvant systemic treatment on pCR rate and on disease-free survival in real-life Her-2 positive breast cancer patients.

Breast Cancer Immunotherapy.

Although unlikely to replace current standard of care therapies, immunotherapy is emerging as a critical component of breast cancer treatment. Despite initial setbacks, clinical benefit is now evident through immunomodulation and cancer vaccines. Over the past decade, passive immunotherapeutic strategies such as anti-HER2 monoclonal antibody (mAb) therapy have significantly improved the prognosis in HER2 overexpressing breast cancers. Novel active immunotherapeutic strategies include checkpoint blockade modifiers, also a mAb therapy. Although non-specific, checkpoint blockade modifiers show great promise in clinical trials. A form of active and specific immunotherapy, cancer vaccines may be used alone or in conjunction with these aforementioned mAb therapies. While there is significant initial promise, the complexities of the host immune system-tumor interaction and the vast array of potential immune targets require the field of cancer immunotherapy to be further developed. Here, we briefly discuss the field of breast immunotherapy to date and its implications for the future of breast cancer care.