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Highlights • Breast cancer arising in association with a fibroadenoma (FA) is rare and usually early-stage. • We report a rare case of an advanced triple negative breast cancer, with lymph node metastases, within a long-standing FA. • Pathological complete response was achieved after neoadjuvant chemotherapy, as proven on mastectomy with axillary clearance., Introduction Breast cancer arising from benign fibroadenoma (FA) is rare. The histological type of the former was either carcinoma in situ or early-stage invasive breast carcinoma with hormone receptor positive/HER2 (human epidermal growth factor receptor-2)-negative phenotype. Meanwhile, advanced breast cancer of triple negative (TN) phenotype such as our case is extremely uncommon and clinically challenging. Presentation of case We experienced a case of a 53-year-old woman that had invasive ductal carcinoma of TN phenotype in FA with multiple lymph node metastases. After receiving neoadjuvant chemotherapy (NAC), she underwent breast mastectomy and axillary dissection. The pathological examination on postoperative specimens revealed the dense fibrous stroma in the FA without any residual viable tumor cells and was considered as pathological complete response (pCR). Discussion This is the first report presenting a case of NAC treatment for invasive ductal carcinoma (IDC) in FA. Furthermore, the patient achieved pCR even if IDC was located within FA. Diagnosing breast cancer in FA may be challenging as the carcinoma component may be hidden by the FA component. If imaging of FA became larger or abnormal changes during follow-up examinations, needle biopsy should be recommended for assessment of the lesion positively. Conclusion This is the first report presenting a case of advanced breast cancer in FA of TN phenotype with multiple lymph node metastases who achieved pCR even if IDC was located within FA.

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties., Graphical abstract This review summarized the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors, as well as the application of SHP2 inhibitors for tumor therapies. The discovery and development of each type inhibitors were discussed based on their chemotypes, activity, selectivity and cocrystal structures.Image 1