Introduction: Approximately 30% of breast cancer cases involve a significantly increased familial risk, often associated with pathogenic germline mutations. This study evaluates the spectrum of pathogenic variants identified, systemic therapy patterns, tumor biology, and treatment response among breast cancer patients treated at the Regensburg Center of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) between 2012 and 2020. Methods: A retrospective analysis was performed on 385 breast cancer patients who met the GC-HBOC criteria for elevated familial risk. Patients were categorized based on genetic status (pathogenic BRCA1/2-variants, pathogenic variants in other breast and ovarian cancer-related genes such as CHEK2, ATM, PALB2, RAD51C, RAD51D, or BARD1 [BRCA-related], or negative) and tumor subtype (triple-negative breast cancer [TNBC], hormone receptor-positive/HER2-negative [HR+/HER2−], or HER2-positive [HER2+]). The use of chemotherapy, including platinum-based regimens, and rates of pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) were analyzed. Results: In this study, pathogenic variants in established breast and ovarian cancer-predisposing genes were identified in 49%, primarily in BRCA1 and BRCA2 (36%). TNBC was predominant in BRCA1-positive patients (61%), whereas BRCA2-positive and variant-negative patients more commonly presented with HR+/HER2− tumors. Chemotherapy was administered in 76% of patients, with the highest rate in BRCA1 carriers (89%). The use of platinum-based chemotherapy increased significantly among TNBC patients after 2014, reaching 100% by 2020. Among 144 patients who received NACT, 22% achieved a pCR. BRCA1-positive patients had the highest pCR rate (35%), with TNBC/BRCA1-positive patients achieving a pCR in 67% of cases. Conclusion: The study demonstrates the effective implementation of genetic testing and guideline-based therapy in a real-world, high-risk breast cancer cohort. BRCA1-associated TNBC exhibited the highest chemotherapy sensitivity, as evidenced by elevated pCR rates. However, incomplete documentation of treatment outcomes somewhat limits the strength of the latter. Overall, these findings reinforce the value of personalized treatment strategies in hereditary breast cancer and underscore the need for more comprehensive real-world data collection to optimize patient management.