# A Case of Occult Breast Cancer Diagnosed during Immune Checkpoint Inhibitor Treatment for Recurrent Metastatic Lung Cancer

## TL;DR

A rare case of occult breast cancer was diagnosed in a lung cancer patient during immune therapy, highlighting the need to consider new cancers during long-term treatment.

## Contribution

Presents a novel clinical case linking immune checkpoint inhibitor therapy with detection of a second primary occult breast cancer.

## Key findings

- Axiillary lymphadenopathy during ICI treatment may indicate a second primary cancer like occult breast cancer.
- Complete remission of lung cancer allowed detection of previously undiagnosed occult breast cancer.
- Immunohistochemistry confirmed the axillary lesion as metastatic invasive ductal carcinoma consistent with OBC.

## Abstract

Occult breast cancer (OBC) is a rare subtype of breast cancer, typically presenting as axillary lymph node metastasis without an identifiable primary tumor in the breast. Axillary lymphadenopathy requires differential diagnosis, including OBC. However, in patients undergoing treatment for another malignancy, distinguishing OBC from axillary metastasis of the known primary cancer can be challenging. Immune checkpoint inhibitors (ICIs) have extended survival in advanced non-small cell lung cancer (NSCLC), potentially allowing time for 2nd primary cancers to develop and be detected.

A 71-year-old woman underwent right upper lobectomy for stage IIIA lung adenocarcinoma. Four months postoperatively, CT revealed a right chest wall mass and right axillary lymphadenopathy, which was interpreted as recurrence. Systemic therapy was administered, and third-line atezolizumab monotherapy led to complete remission of the chest wall mass; however, progressive enlargement of the axillary lymph nodes was subsequently observed. Imaging showed no detectable lesion in the breast, but core needle biopsy of the axillary node revealed metastatic invasive ductal carcinoma, negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) with a Ki-67 index of 80%. Immunohistochemistry was positive for GATA3 and negative for thyroid transcription factor-1 (TTF-1), consistent with OBC. The patient underwent axillary lymph node dissection, and postoperative observation without additional treatment was selected due to comorbidities. She has remained disease-free for 1 year.

This case illustrates that axillary lymphadenopathy during treatment for another malignancy may represent a 2nd primary cancer such as OBC. As ICI therapy prolongs survival, clinicians should pay attention for new malignancies, including breast cancer, even in the absence of breast lesions.