CDH1 mutations recurrence and global clustering in genetically tested families with hereditary diffuse gastric cancer syndrome: results from a systematic study.

The global distribution of germline CDH1 mutations in hereditary diffuse gastric cancer families, is highly heterogenous. The aim of this study was to determine if there is any geographic clustering of CDH1 mutations in families with the hereditary diffuse gastric cancer syndrome. Data from 1998 to 2021 were collected systematically according to the PRISMA guidelines. 571 germline CDH1 mutations were recorded worldwide, with 387 (67.8%) of them reported in 108 families. The largest clusters of CDH1 mutations were identified in central Europe, north America, northern Europe, New Zealand (Maori), and south America. A high penetrance risk for GC development was observed for c.1008G > T in New Zealand (Maori), c.1565 + 2insT in northern Europe, c.1901C > T in Portugal, and c.1003C > T in the USA. Our observations are consistent with a specific local clustering of some recurrent CDH1 mutations within specific countries.

A New Level II Oncoplastic Technique for Inferior Pole Defects: The Three-Petal Glandular Reconstruction (3-PR).

INTRODUCTION: Oncoplastic surgery (OPS) allows wide excisions and accurate tumor resection and reduces breast deformities by immediate reconstruction of large defects. Superior pedicled mammaplasties allow excellent results in large breasts. Conversely, loco-regional flaps are the standard of care in small-to-medium breasts. However, both techniques show limitations in case of large resections of the lower pole, resulting in skin retraction and downward deviation of nipple and areola. We present a new technique for inferior pole reconstruction to overcome these limitations. It is called "the three-petal reconstruction" (3-PR). METHODS: Between September 2016 and May 2019, ten patients with invasive breast cancer of the lower pole underwent breast conservation and 3-PR. RESULTS: The 3-PR was uneventful in all patients. No major or minor complications were recorded. Patient and surgeon evaluations scored as good to excellent in all cases. Surveillance examinations in the follow-up did not reveal calcifications nor any findings of suspicion within the reconstructed area. CONCLUSIONS: In case of very large defect of lower pole, the 3-PR reveals to be an easy, fast, reproducible method for inferior pole reconstruction. It can represent a niche between therapeutic mammaplasty and perforator flaps, and it could be added to existing available options for tailored reconstruction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Local treatment in patients with hereditary breast cancer: decision-making process in low-, moderate-, high-penetrance pathogenic germline mutation carriers.

PURPOSE OF REVIEW: We summarize recent evidence regarding commonly tested breast cancer susceptibility genes and review indications derived from recently published guidelines regarding management of carriers affected by early breast cancer (BC). RECENT FINDINGS: Management of affected women with a known genetic predisposition to BC was matter of debate at the most relevant international conferences, such as St. Gallen International Consensus Conference and San Antonio Breast Cancer Symposium held both in 2021. At the same time, a joint Experts Panel from American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology (ASCO/ASTRO/SSO) convened to develop recommendations to support clinical decision-making in this specific setting and results about administration of new systemic therapies such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors became available. SUMMARY: Population of patients affected by BC and carriers of mutations in susceptibility genes is progressively increasing, but new mutations identified do not always have a clear clinical impact.To date, we have data to support consideration of different local management choices for affected patients carrying specific mutations, but some issues especially relating to breast-conserving surgery or administration of radiotherapy in these patients, still need to be better addressed. Opinions about the best way to treat these patients are still heterogeneous and information deriving from different sources seems to be conflicting at times. Our purpose is to offer a synopsis of the different evidence available that may be helpful in clinical decision making.

Surgical Management of Inherited Breast Cancer: Role of Breast-Conserving Surgery.

Recent studies have demonstrated that hereditary breast cancer (BC) has a prevalence of 5-10% among all BC diagnoses. Nowadays, significant technological advances in the identification of an increasingly broad spectrum of genetic mutations allow for the discovery of an ever-growing number of inherited pathogenic (P) or likely pathogenic (LP) variants of breast cancer susceptibility genes. As the management of BC patients carrying mutations in the BRCA1/2 genes or other high-penetrance genes is currently a challenge, extensive research is being carried out and a lively scientific debate has been taking place on what the most appropriate local therapy, especially surgical treatment, of patients with inherited BC should be. In many studies, BC outcomes in BRCA carriers and non-carriers have been compared. A number of them showed that, when compared with mastectomy, breast-conserving surgery in BRCA patients is oncologically safe in terms of overall survival, although an increased risk of ipsilateral recurrence was reported. In these patients, devising a specific therapeutic strategy is an inevitably complex process, as it must take into consideration a series of factors, require a multimodal approach, guarantee personalization, strictly adhere to scientific international guidelines, and consider all available evidence. The present narrative review purposes to identify and illustrate evidence from significant selected studies that discussed those issues, as well as to suggest useful tools to clinicians managing this specific clinical condition in daily clinical practice.

Multistage Latissimus Dorsi Flap with Implant for Complex Post-Mastectomy Reconstruction: An Old but Still Current Technique.

INTRODUCTION: The latissimus dorsi (LD) flap has been used for reconstructing mastectomy defects since the early 1900s. Although its popularity has declined over the last decades, it still retains an important role in breast reconstruction. We present our recent experience with the multistage LD flap and implant for extremely complex post-mastectomy defects. PATIENTS AND METHODS: Between 2011 and 2020, 42 consecutive patients underwent post-mastectomy LD reconstruction with an expander (STAGE 1). Some of them received prior fat-grafting of the mammary region (STAGE 0). All patients were scheduled for an expander-definitive implant change (STAGE 2). Some of them completed the program with fat-grafting, nipple and areola reconstruction, and other refinements (STAGE 3 or 4). RESULTS: Two patients underwent fat-grafting at STAGE 0. Mean age at STAGE 1 was 46.7 years, mean BMI was 23.6, 14.4% of the patients were smokers, and 21.4% had comorbidities. Immediate reconstructions were performed in 35.7% and delayed in 64.3%. Mean surgical time at STAGE 1 was 194.7 min for delayed reconstructions and 242.3 min for immediate ones. Mean hospital stay for STAGE 1 procedures was 3.8 days; all other STAGES were performed as ambulatory surgery. No flap necrosis was observed and only 1 patient required a surgical revision for bleeding. Dorsal seroma occurred in 45.2% of cases. CONCLUSIONS: The multistage LD flap with implant is a useful and safe tool within the reconstructive armamentarium for post-mastectomy defects. It combines multiple simple procedures and does not require specific skills and surgical training (level of evidence 4).

A Novel Method of Implant Coverage for Post-Mastectomy Reconstruction after Previous Augmentation: A Case Report.

BACKGROUND: Breast augmentation is the most common -cosmetic surgical procedure in the USA, with nearly 300,000 women undergoing surgery annually. National incidence rates predict that among women undergoing breast augmentation each year, approximately 35,000 will eventually be diagnosed with breast cancer, in particular individual BRCA1/2 germline mutant carriers. CASE REPORT: Our case introduces a novel method of implant coverage after immediate post-mastectomy reconstruction in augmented patients. A novel "capsular flap" (flap of the pre-existing old capsule) is isolated and refolded to cover the outer lower portion of the implant. CONCLUSION: Tailored surgical approaches can be offered to those patients previously augmented and requiring mastectomy after breast cancer diagnosis.

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

BACKGROUND: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. METHODS: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. RESULTS: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5-43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0-108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4-10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9-30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. CONCLUSION: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

Surgical treatment of breast lesions at a Day Centre: Experience of the European Institute of Oncology.

Breast cancer is the commonest malignancy in women worldwide. The reduced aggressiveness of breast cancer surgery has made it possible treat patients in the day surgery setting. The European Institute of Oncology, Milan, opened its new Day Center in May 2010. From May 2010 to December 2014, 17,087 patients with breast conditions were treated by the Institute's Division of Senology, 4132 (24.2%) of these in the day surgery setting, including malignant and benign conditions; 204 (4.9%) were not discharged on the day of surgery, being converted to inpatients; five (0.1%) patients returned to hospital for persistent hematoma. Our experience of performing breast cancer surgery in the day surgery setting is in line that of the literature. It is safe, but requires a well-organized unit and multidisciplinary medical team to function smoothly, with much attention paid to patient comfort and education, so as to ensure maximum patient acceptance and satisfaction.