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In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.

Epidemiological studies suggest that around 10% of breast cancers are due to hereditary predisposition. The risk of cancer is exponentially increased in patients harboring or mutations. Cumulative breast cancer risk by age 80 is estimated to 72% for mutation carriers and 69% for . The cumulative risk estimates for developing ovarian cancer by age 80 are 44% for mutation carriers and 17% for . We present here the case of a 59-year-old woman who developed a left breast cancer in 2014 treated by conservative surgery, radiotherapy, and endocrine therapy with letrozole. The diagnosis of mutation was performed in 2015. In 2018, the patient was referred to our institution for treatment of an aggressive angiosarcoma developed in the same breast. She had undergone radical hysterectomy by the age of 49 years for a benign uterine pathology. In 2020, she developed a tumor in the gastric wall; histological analysis confirmed a serous papillary carcinoma of ovarian origin. She was treated - after gastrectomy and lymphadenectomy - with 6 courses of carboplatin and paclitaxel followed by olaparib therapy. In 2021, she suffered from a chest recurrence of high grade angiosarcoma. New resection with free margins was performed. We discuss the link between angiosarcomas and BRCA mutations, the therapeutic options for angiosarcoma and ovarian cancer of extra ovarian origin and the follow-up modalities.

The ETV6::NTRK3 fusion is the most common gene alteration in infantile fibrosarcoma, a soft tissue tumor affecting patients under two years of age. Less frequently, these tumors harbor fusions of genes encoding other kinases, such as BRAF, which activates MEK in the mitogen-activated protein kinase pathway. The identification and characterization of these oncogenes is crucial to facilitate diagnosis, validate new treatments and better understand the pathophysiology of these neoplasms. Herein, we analyzed an ETV6::NTRK3-negative infantile fibrosarcoma from a 5-day-old patient by RNA-sequencing to identify new fusion transcripts. Functional exploration of the fusion of interest was performed by in vitro assays to study its activity, oncogenicity and sensitivity to the MEK inhibitor trametinib. We identified a novel fusion involving the PHIP and BRAF genes. The corresponding fusion protein constitutively activated the mitogen-activated protein kinase pathway, resulting in fibroblast transformation. Treatment of transfected cells with trametinib effectively inhibited signaling by PHIP::BRAF. PHIP::BRAF is a novel fusion oncogene that can be targeted by trametinib in infantile fibrosarcoma. This article is protected by copyright. All rights reserved.

The occurrence of a pathological fracture in children requires a rigorous diagnostic approach in order to establish the etiology and to develop a precise therapeutic strategy. Several causes are associated with these fractures, the most frequent being benign tumors in children in developed countries and chronic osteomyelitis in developing countries. More rarely, malignant tumors must however always be considered. The differential diagnosis on imaging may be difficult to establish between bone tumors and chronic infection. Surgical biopsy is therefore often performed to establish the precise origin of the fracture. We report the case of an adamantinoma (osteofibrous dysplasia-like) of the fibula in a 7-year-old child, discovered during the management of a pathologic fracture. The presumed diagnosis before biopsy was chronic osteomyelitis. A 14-cm-resection of the affected fibula was performed with good functional result. Differential diagnosis between adamantinoma, osteofibrous dysplasia and osteofibrous dysplasia-like adamantinoma remains very challenging.

Acrometastasis is an uncommon metastatic location appearing in the small bones of hands and feet (1). Its low incidence, around 0,1% of all bone metastases, may be due to the subclinical presentation and the lack of attention to the extremities in routine examination (1- 5). However, it sometimes represents the first expression of an occult malignancy (1-4). The symptoms are aspecific and may mimic a local infection, an inflammatory disease (arthritis, tenosynovitis) or a dermatologic lesion (1-5). The correct diagnosis of this atypical entity is important to draw the attention of the clinicians to the metastatic dissemination of the disease, to initiate adequate treatment and reduce patient morbidity.

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

Epidemiological studies suggest that around 10% of breast cancers are due to hereditary predisposition. The risk of cancer is exponentially increased in patients harboring or mutations. Cumulative breast cancer risk by age 80 is estimated to 72% for mutation carriers and 69% for . The cumulative risk estimates for developing ovarian cancer by age 80 are 44% for mutation carriers and 17% for . We present here the case of a 59-year-old woman who developed a left breast cancer in 2014 treated by conservative surgery, radiotherapy, and endocrine therapy with letrozole. The diagnosis of mutation was performed in 2015. In 2018, the patient was referred to our institution for treatment of an aggressive angiosarcoma developed in the same breast. She had undergone radical hysterectomy by the age of 49 years for a benign uterine pathology. In 2020, she developed a tumor in the gastric wall; histological analysis confirmed a serous papillary carcinoma of ovarian origin. She was treated - after gastrectomy and lymphadenectomy - with 6 courses of carboplatin and paclitaxel followed by olaparib therapy. In 2021, she suffered from a chest recurrence of high grade angiosarcoma. New resection with free margins was performed. We discuss the link between angiosarcomas and BRCA mutations, the therapeutic options for angiosarcoma and ovarian cancer of extra ovarian origin and the follow-up modalities.