It is no longer the time to disregard thyroid metastases from breast cancer: A case report and review of the literature

Background: Metastases to the thyroid gland are more frequent than previously thought, although most of them are occult or not clinically relevant. Overall, only 42 cases of metastases to thyroid from breast cancer have been reported thus far. Here we report the case of a patient with breast cancer metastatic to the thyroid. We also review the 42 previously reported cases (published between 1962 and 2012). This is the first review about metastases to thyroid gland from breast cancer. Case presentation: A 64-year-old woman of Caucasian origin was diagnosed with a lobular invasive carcinoma of the breast (luminal A, stage II). She received adjuvant chemotherapy, followed by endocrine therapy. During follow- up, fine-needle cytology of a thyroid nodule revealed malignant cells that were estrogen-positive, which suggested a diagnosis of metastases to the thyroid. Imaging did not reveal any other metastatic site and showed only enlargement of the left thyroid lobe and an inhomogeneous pattern of colloid and cystic degeneration and calcifications. The patient underwent left hemithyroidectomy. Histology of thyroid tissue showed a colloid goitre containing dispersed small atypical neoplastic cells with eccentric nuclei. Immunohistochemistry showed cytokeratin-19 and oestrogen receptor, but not tireoglobulin, e-cadherin or cytokeratin-7, thereby confirming metastases from a lobular breast carcinoma. Hormonal treatment is ongoing. Conclusion: This case report and first review of the literature on metastases to thyroid from breast cancer highlight the importance of a correct early diagnostic work-up in such cases. Indeed, a primary lesion should be distinguished from metastases given the different treatment protocol related to primary cancer and the clinical impact on prognosis

Combined effect of obesity and diabetes on early breast cancer outcome: A prospective observational study

Background: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. Materials and Methods: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. Results: At diagnosis, obese and diabetic patients were more likely to be older (p < 0.0001) and post-menopausal (p < 0.0001) and to have a tumor larger than 2 cm (p < 0.0001) than patients in groups 1–3. At univariate analyses, obese and diabetic patients had a worse disease-free survival (p = 0.01) and overall survival (p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for diseasefree survival (hazard ratio=2.62, 95% CI 1.23–5.60) but not for overall survival. Conclusions: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cance

Male Breast Cancer: From Molecular Genetics to Clinical Management

MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes

Male Breast Cancer: From Molecular Genetics to Clinical Management

MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes

Informativa sui Tumori Ereditari e Familiari

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Two novel sequence variants in MSH2 gene in a patient who underwent cancer genetic counseling for a very early-onset epithelial ovarian cancer

Early-onset or hereditary ovarian cancer is mostly associated with BRCA1 or BRCA2 mutations. Mismatch repair genes sequence alteration frequently cause colorectal cancer, and, in less extent, other tumors, such as ovarian cancer. Subjects with personal and/or family history suggestive for hereditary cancer should be addressed to cancer genetic counseling. The multistep Cancer Genetic Counseling model, adopted at our unit, is aimed to identification, definition and management of hereditary cancer syndrome, by a multidisciplinary approach. A woman with a very early onset epithelial ovarian cancer underwent to cancer genetic counseling and genetic testing. Two germ-line mutations have been identified in exon 11 of MSH2 gene: c.1706A>T (p.Glu569Val) and c.1711G>T (p.Glu571*). Both DNA alterations were novel mutations not yet described in literature. The first is a missense mutation that is to be considered an unclassified variant; the second is nonsense mutation that created a premature stop codon resulting in a truncated not functioning protein. In conclusion, the present report finds out two unpublished sequence alterations in exon 11 of the MSH2 gene, one on which can be considered causative of Lynch phenotype, and stresses the importance of the onco-genetic counselling in order to offer the most appropriate management of the cancer risk for the patients and her family members

Malignant melanoma Clustering with some familial/hereditary tumors

Germline mutations of the CDKN2 and CDK4 genes that are involved in the cell cycle regulation, have been associated with malignant melanoma (MM). However, these mutations have been detected only in some cases of familial MM, particularly in Sweden and in Italy, which suggests that other genes are involved in the pathogenesis of hereditary MM. Few data are available about the clustering between MM and familial or hereditary tumours (e.g. breast cancer, ovarian cancer, colon cancer, pancreatic cancer). In this respect, the Breast Cancer Linkage Consortium reported that carriers of germline mutations in the BRCA2 predisposing gene have a significantly increased risk for MM (RR = 2.58; 95% CI = 1.28-5.17). The aim of the present study was to determine the family history of 342 consecutive cases of MM observed from 1994 to date. Specifically, we looked for: MM associated with other malignant neoplasias; familial clustering of MM; and a family history of cancer. Malignant melanoma was associated with other tumours in 20/342 patients (5.84%); a history of MM was associated to a positive family history of cancer in 31/342 cases (9.06%); and familial clustering of MM was detected in 22/342 (6.4%) of the consecutive series of patients analysed. The pedigree of patient who have a family history of MM or other cancers is being constructed