Treatment of a Patient With AML and mTNBC
Initial Presentation, Workup, and Treatment
A 66-year-old female presented to the emergency department in February 2022 with acute onset of bilateral upper extremity pain. Her white blood count was 85, hemoglobin was 6.7, platelets were 28, and she was experiencing hepatosplenomegaly. She was diagnosed with acute myeloid leukemia (AML).
During staging, a right breast mass of 4.3 x 4 cm was revealed. It was thought to be highly suspicious for primary breast cancer, as well as suspicious for right axillary lymphadenopathy.
A core biopsy of the breast and fine needle aspiration in the axillary node found poorly differentiated carcinoma, estrogen-negative, progesterone-negative, and HER-negative by FISH (i.e., triple-negative breast cancer with a Ki-67 of 98%). Tests also showed she was androgen receptor-positive (AR+). Staging scans showed that she was negative for metastatic disease.
During admission on the leukemia service, she was initiated on cytarabine + daunorubicin + gemtuzumab, and midostaurin was added given her FLT3 positivity. Midostaurin is an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation. Her case was presented at the multidisciplinary tumor board, and a recommendation was made for surgical intervention.
She had a right mastectomy and axillary lymph node dissection in April 2022. Pathology showed a 9-cm breast mass with 5 of 23 positive lymph nodes, T3, N2a (4 to 6 regional lymph nodes are positive), and thus a pathologic stage III.
She then received 3 cycles of consolidation chemotherapy for her AML. A repeat of the bone marrow biopsy revealed minimal residual AML. However, there were now worsening changes on her right chest wall. Because of concern over the disease extension into the chest wall, treatment of her breast cancer was resumed and her AML treatment was paused.
The patient completed 4 weeks of palliative radiation therapy to the chest in October 2022, and was started on capecitabine. Another repeat of the bone marrow biopsy in November 2022 was negative for AML. The patient declined genetic counseling or testing.
Guardant testing in January 2023 showed no actionable targets and one alteration in the TP53 gene at only 0.06%.
In March 2023 she had progression of disease with recurrent skin nodules on the mastectomy chest wall. She was started on sacituzumab govitecan. In late June 2023, restaging scans showed increasing lung nodules and pleural effusions, liver and bone metastases, and worsening nodular skin thickening on chest wall. She became increasingly short of breath. Sacituzumab was discontinued. She next received pembrolizumab with a plan to add albumin-bound paclitaxel (Abraxane), but 11 days later she was admitted for hypoxic respiratory failure and biopsy-proven lymphangitic spread.
She was started on methylprednisolone at 60 mg every 6 hours for likely immune checkpoint inhibitor-induced pneumonitis.
Given that the tumor was androgen receptor positive (AR+,) she was prescribed bicalutamide because it blocks the use of androgens by the tumor cells, and her oxygen requirements improved on steroids.
Discussion Points
This very complex case presented multiple treatment challenges. The patient’s AML required immediate induction chemotherapy. Her triple-negative breast cancer was found incidentally on workup of the AML. A key to managing this case was ongoing communication with the multidisciplinary team, including hematologic oncology, surgical oncology, and medical oncology.
Giving capecitabine as initial chemotherapy post-mastectomy and radiation was recommended given the significant myelosuppressive therapy for her AML.1 Per recent guidelines, sacituzumab govitecan was given next but in only a few months the disease again progressed.
The risk of pneumonitis with immune checkpoint inhibitors2 (i.e., pembrolizumab) was reviewed in detail with this patient who already had extensive pulmonary disease. She agreed to proceed, but unfortunately she developed acute respiratory hypoxia requiring discontinuation. Standard treatment with high dose steroids was initiated.
The fact that her disease was AR+ meant the only other targeted treatment thought to be safe for the patient at this juncture was bicalutamide. However, it should be noted that this is not in the NCCN guidelines.3 Clinical trials looking at potential use of the AR receptor as a target are ongoing.
Simultaneously treating two very aggressive cancers, acute myeloid leukemia and triple-negative breast cancer, presented unique challenges. The role of the APP was critical in clinical assessment, symptom management, and care coordination. The APP on the breast team worked closely with the leukemia team to maximize communication and deliver optimal care safely.
References
- Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147-2159. doi:10.1056/NEJMoa1612645
- Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809
- National Comprehensive Cancer Network. NCCN Guidelines 2023. https://www.nccn.org/guidelines/category_1
