Publication: npj Precision Oncology | (2025) 9:63

Authors: Jailan Elayoubi , Yu Zong & Erich J. Schwartz

Title: Successful unconventional precision treatment of inflammatory hormone receptor-positive breast cancer guided by molecular profiling

Abstract: We present a unique case of locally advanced, inflammatory hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in a young woman. A MammaPrint gene signature performed on the core biopsy indicated a very high risk of recurrence (MammaPrint high risk 2, MPH2). BluePrint 80-gene signature was used for the molecular subtyping and identified the tumor as a basal subtype, resembling triple-negative breast cancer (TNBC) despite the strong estrogen receptor (ER) expression on immunohistochemical (IHC) staining. We treated the patient with a TNBC protocol, incorporating carboplatin and immunotherapy into the anthracycline-based chemotherapy backbone in the neoadjuvant setting. The patient achieved a complete response and remains to be disease-free after 2 years, with ongoing follow-up.

Results:

Clinical case

A 30-year-old woman presented to our department with a very painful, rapidly growing right breast mass and skin discoloration (Fig. 1) over a period of 3 months. Diagnostic ultrasound showed a 6 cm hypoechoic mass and several enlarged right axillary lymph nodes with cortical thickening. A core biopsy of the primary tumor showed grade 3 infiltrative ductal carcinoma. ER expression by Allred score was 5/8 (35%, 1+), PR was 0/8; HER2 was 1+. Ki-67 was 90%, while programmed death-ligand 1 (PD-L1) by combined positive score (CPS) score was 70. Tumor-infiltrating lymphocytes (TILs) were 40% (Fig. 2). The lymph node biopsy was negative for cancer metastasis, but it was discordant. Staging computed tomography (CT) scan of the chest, abdomen, and pelvis showed a partially necrotic mass in the right breast compatible with malignancy; enlarged right axillary and subpectoral lymph nodes suggestive of metastases; otherwise, no evidence of distant metastasis. Magnetic resonance imaging (MRI) of the breast showed a 6.4 × 6 × 4.9 cm tumor at 6 o’clock position with a necrotic center. Irregular non-mass enhancement extended anteriorly towards the nipple and posteriorly towards the chest wall abutting the pectoralis muscle with no evidence of chest invasion. Diffuse skin thickening along the antero-inferior right breast with maximum thickness of up to 0.5 cm was also noted. Axillary and subpectoral lymph nodes were again demonstrated, the largest measuring 1.6 × 1.6 cm.

MammaPrint signature score on the tumor core biopsy was (−1.00), which was the highest possible score, indicating an extremely high risk of recurrence without chemotherapy (MammaPrint high risk 2, MPH2). BluePrint test confirmed a basal subtype (+0.52) (Fig. 3). Given the aggressive presentation of her tumor and the basal subtype confirmation by BluePrint, we opted for a TNBC treatment regimen. She received neoadjuvant Adriamycin-Cyclophosphamide for 4 cycles, followed by triweekly carboplatin area under the curve (AUC) 5 for 4 cycles and weekly paclitaxel for 9 weeks, though the last 3 doses were omitted due to progressive neuropathy. We successfully obtained compassionate use of pembrolizumab from our institution per the KEYNOTE-522 trial. It was given every 3 weeks only in the neoadjuvant setting. Following bilateral mastectomy and sentinel lymph node biopsy without reconstruction, pathology revealed a complete response (pCR) in the right breast and lymph nodes. The patient completed adjuvant radiation to her chest wall and chose to take tamoxifen without ovarian suppression, understanding that her tumor might not be truly hormone-dependent. She remains disease-free 2 years after her surgery, with semi-annual surveillance.

Article by npj Precision Oncology under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.