Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.

Germline CDH1 variants in hereditary diffuse gastric cancer syndrome with focus on younger women.

PURPOSE: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. METHODS: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. RESULTS: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). CONCLUSIONS: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.

Breast Cancer Surgery: New Issues.

Since ancient times, breast cancer treatment has crucially relied on surgeons and clinicians making great efforts to find increasingly conservative approaches to cure the tumor. In the Halstedian era (mid-late 19th century), the predominant practice consisted of the radical and disfiguring removal of the breast, much to the detriment of women's psycho-physical well-being. Thanks to enlightened scientists such as Professor Umberto Veronesi, breast cancer surgery has since impressively progressed and adopted a much more conservative approach. Over the last three decades, a better understanding of tumor biology and of its significant biomarkers has made the assessment of genetic and molecular profiles increasingly important. At the same time, neo-adjuvant treatments have been introduced, and great improvements in genetics, imaging technologies and in both oncological and reconstructive surgical techniques have been made. The future of breast cancer management must now rest on an ever more precise and targeted type of surgery that, through an increasingly multidisciplinary and personalized approach, can ensure oncological radicality while offering the best possible quality of life.

Long-term outcome and axillary recurrence in elderly women (≥70 years) with breast cancer: 10-years follow-up from a matched cohort study.

BACKGROUND AND OBJECTIVES: The oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. METHODS: Patients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan-Meier method and univariate Cox-proportional hazard ratio analysis. RESULTS: A total of 1.748 patients were identified and stratified by age (70-74, 75-79, 80-84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2-46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6-33.3) and luminal B tumors (16.8%, 95% CI 5.9-35.5). CONCLUSIONS: Axillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.