HER2-positive invasive lobular breast cancer in a transgender man: disease-free after multimodality care

What happened, in summary

This 70-year-old transgender man had been receiving weekly testosterone injections for gender-affirming hormone therapy since age 64. In September 2023, he developed pain and swelling in the left underarm. Imaging showed a 2.7 cm central left breast mass and abnormal lymph nodes in the left axilla. Biopsy of the breast and an axillary node confirmed grade 2 invasive lobular carcinoma with apocrine features. The tumor was ER-negative, PR-negative, HER2-positive by IHC 2+ with positive in situ hybridization, and strongly androgen receptor-positive. PET imaging showed disease in the left breast and multiple ipsilateral axillary lymph-node levels, but no distant metastasis. His disease was staged cT2N3aM0, with anatomic and clinical prognostic stage reported as IIIC/IIIB. Germline testing did not find pathogenic or likely pathogenic variants. He received 6 cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab. PET imaging after this treatment showed a complete metabolic response. He then underwent bilateral total mastectomies with targeted axillary dissection on the left. Pathology found only a 2.5 mm residual focus of invasive lobular carcinoma in the breast, clear margins, and complete response in 3 recovered axillary lymph nodes. He completed proton beam radiation to the left chest wall and regional lymph nodes and received adjuvant trastuzumab emtansine. Because the cancer was androgen receptor-positive, he and his care team discussed whether testosterone might affect recurrence risk. He chose to stop testosterone, despite fatigue, joint pain, insomnia, and worsened gender dysphoria. Nearly 2 years after diagnosis, he remained disease-free and continued survivorship care with exercise, meditation, diet changes, and counseling.