Synchronous HER2-Positive Breast and Gastric Cancers: A Dual Diagnostic Challenge With a Single Treatment Possibility

Synchronous primary malignancies are rare and represent a significant diagnostic and therapeutic challenge, particularly when both tumors share a targetable molecular alteration. We present a case of synchronous human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers treated using a common HER2-directed strategy. A 77-year-old female was admitted with a right breast lesion classified as Breast Imaging Reporting and Data System (BI-RADS) 5. A core needle biopsy was performed, which confirmed a grade 2 invasive ductal carcinoma. The results showed positivity for estrogen receptor and progesterone receptor, a HER2 immunohistochemical score of 2+, and a Ki-67 index of 15%. Chromogenic in situ hybridization (CISH) confirmed HER2 amplification, establishing a luminal B/HER2-positive subtype (cT4b cN0 cM0). The patient was started on a course of tamoxifen treatment. During the course of treatment, there was a progression of dysphagia and rapid weight loss, which prompted further investigation. A CT scan revealed thickening of the gastric cardia. Following the failure of gastroscopies due to esophageal stenosis, exploratory laparoscopy was performed. The histopathological examination revealed that the gastric cardia tumor was grade 1 tubular adenocarcinoma, with HER2 overexpression (immunohistochemistry (IHC) 3+), proficient mismatch repair (pMMR)/microsatellite stability (MSS) status, and no hormone receptor expression. Due to the unresectable nature of the disease, the patient received a combination of palliative mFOLFOX6 (leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin) and trastuzumab, in addition to ongoing endocrine therapy. Following four cycles, imaging showed disease stabilization, with decreased cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) levels, and evidence of local tumor regression. Despite an initial positive response, the patient subsequently experienced disease progression and clinical deterioration after three months. The overall survival rate was 11.25 months. This case demonstrates the importance of comprehensive molecular diagnostics and the potential of HER2-targeted therapy as a unified treatment approach for synchronous HER2-positive malignancies.