Rescue Mastectomy in a Patient With Locally Advanced Triple-Negative Breast Cancer and Severe Biochemical Hypothyroidism: A Multidisciplinary Ethical and Surgical Dilemma.

1. Introduction
Triple‐negative breast cancer (TNBC) is an aggressive subtype characterized by rapid growth, early recurrence, and limited therapeutic targets [1]. Optimal outcomes depend on strict adherence to multimodal treatment strategies, including timely systemic therapy and surgery [2]. Disruptions in treatment continuity may result in rapid disease progression and loss of curative opportunities.
Rescue mastectomy represents a controversial but sometimes indispensable option in patients with locally advanced breast cancer who fail systemic therapy [3]. In such cases, surgical delay may result in permanent loss of operability and increased risk of locoregional and systemic progression. The decision to proceed with surgery is further complicated when severe comorbidities are present.
Severe hypothyroidism is classically considered a contraindication to major elective surgery due to its association with cardiovascular instability, respiratory depression, altered drug metabolism, and the risk of myxedema coma [4–6]. Current perioperative guidelines, however, are largely derived from nononcologic scenarios and provide limited guidance for time‐sensitive cancer cases [7, 8]. We report a case illustrating this dilemma and highlight the role of individualized, multidisciplinary surgical decision‐making.

2. Case Presentation
A middle‐aged woman was diagnosed in September 2024 with right‐sided breast cancer, initially staged as IIA (cT2N0M0), with a triple‐negative molecular profile. She received four cycles of neoadjuvant anthracycline–cyclophosphamide chemotherapy, completed in November 2024 at an outside institution. After this, the patient discontinued oncologic follow‐up at the initial treating institution and pursued alternative therapies, including apitherapy, leading to rapid locoregional progression with skin ulceration.
Upon presentation to our comprehensive cancer center in 2025, the tumor was restaged as IIIB (cT4bN0M0). Neoadjuvant chemotherapy with carboplatin and taxanes combined with immunotherapy (pembrolizumab) was initiated. After three cycles, the patient showed clear local progression (Figure 1), and further systemic therapy was considered unlikely to achieve meaningful tumor regression. Rescue mastectomy was therefore indicated as the only remaining oncologic option to achieve local control and prevent further progression to unresectability.
Preoperative anesthetic evaluation on August 15, 2025, unexpectedly revealed severe biochemical hypothyroidism, with a thyroid‐stimulating hormone (TSH) level of 103.1 μIU/mL (reference range: 0.35–4.94 μIU/mL) and a free thyroxine (FT4) level of 0.4 ng/dL. The patient had minimal clinical manifestations despite the severity of the biochemical hypothyroidism. The patient had no known prior history of thyroid disease, no previous use of thyroid medication, and no history of neck irradiation or endocrine comorbidities. Before the diagnosis of breast cancer, she had been considered previously healthy. Given the narrow oncologic window, she was admitted for inpatient endocrine optimization and close monitoring. Intravenous levothyroxine was not available in our institution at the time of hospitalization. Given the patient′s clinical stability and absence of features suggestive of myxedema coma, oral levothyroxine therapy was initiated with close inpatient monitoring in consultation with internal medicine and endocrinology. Oral levothyroxine was initiated at 150 μg daily. Serial laboratory measurements demonstrated a gradual increase in FT4 over the following days, while TSH remained markedly elevated. On August 26, 2025, the levothyroxine dose was increased to 175 μg daily, with recognition that complete biochemical euthyroidism would require several weeks to months. Serial thyroid function tests demonstrated progressive improvement in free thyroxine levels following initiation of levothyroxine therapy (Table 1), although TSH levels remained markedly elevated.
After multidisciplinary tumor board discussion involving surgical oncology, anesthesiology, internal medicine, and endocrinology, and following extensive informed consent addressing the elevated risk of perioperative metabolic decompensation and potential myxedema coma, the decision was made to proceed with surgery during the same hospitalization. An intensive care unit bed was reserved preoperatively.
On August 28, 2025, the patient underwent rescue mastectomy (Figure 2). A wide elliptical skin incision was designed to accommodate the predominantly vertical cephalocaudal distribution of the tumor and the extensive area of skin involvement (Figure 3). The procedure consisted of a total mastectomy with axillary lymph node dissection. The pectoralis major and minor muscles were preserved, as there was no evidence of direct muscular invasion. The incision design resembled the classic vertical elliptical approach historically described in early mastectomy techniques. Given the severity of the biochemical hypothyroidism, particular attention was paid to perioperative anesthetic management. General anesthesia was administered with careful monitoring due to the potential risks of hypoventilation, hypothermia, and hemodynamic instability associated with severe hypothyroidism. Temperature control and hemodynamic stability were maintained throughout the procedure. The patient remained intraoperatively stable and did not require vasopressor support. The patient had an uneventful postoperative course and was discharged on August 30, 2025.
Final pathology revealed an invasive carcinoma of no special type (NST), Grade 3, measuring 16 × 8 × 7 cm, with associated high‐grade ductal carcinoma in situ showing cribriform, solid, and comedo patterns. Necrosis involved approximately 30% of the specimen. The overlying skin was ulcerated, consistent with the clinical T4b classification. All peripheral and deep surgical margins were free of tumor. Seventeen axillary lymph nodes were dissected, all negative for metastasis (0/17). Lymphovascular and perineural invasion were absent.
During follow‐up, germline genetic testing identified a pathogenic heterozygous BRCA1 mutation, consistent with the patient′s strong family history of breast cancer. She subsequently completed adjuvant radiotherapy to the chest wall using intensity‐modulated radiotherapy (IMRT), delivering a total dose of 40 Gy in 15 fractions, with partial use of bolus according to the radiation treatment plan. She remains under multidisciplinary oncologic follow‐up (Figure 4).

3. Discussion
Locally advanced TNBC is characterized by aggressive biological behavior and rapid locoregional progression [1]. In cases with extensive skin involvement or ulceration, continued tumor growth may lead to chest wall invasion, worsening ulceration, infection, or systemic deterioration, which can ultimately compromise surgical resectability. Therefore, prolonged surgical delay while awaiting full biochemical normalization of thyroid function posed a significant oncologic risk in this patient. In this context, the multidisciplinary team considered that the potential oncologic harm associated with prolonged surgical delay outweighed the metabolic risks associated with operating under partially corrected hypothyroidism.
Rescue mastectomy remains a controversial but sometimes necessary intervention in such scenarios [3]. Although not always curative, surgery may represent the only opportunity to achieve local disease control and prevent irreversible loss of operability [3, 9]. Therefore, prolonged surgical delay while awaiting complete biochemical normalization of thyroid function posed a significant oncologic risk in this patient. Delaying surgery in patients with progressive, skin‐infiltrating tumors may result not only in technical inoperability but also in ongoing tumor burden with increased risk of locoregional complications and potential systemic progression [10].
Current endocrine guidelines generally recommend postponing elective surgery in patients with severe hypothyroidism because of increased perioperative risks, including hypotension, hypothermia, respiratory depression, and in extreme cases myxedema coma [4–6]. However, these recommendations are largely derived from nononcologic settings and provide limited guidance in situations in which delaying surgery may result in significant oncologic harm [7, 8, 11, 12]. In this case, severe biochemical hypothyroidism was incidentally detected during preoperative evaluation, despite minimal clinical manifestations, highlighting the potential dissociation between laboratory severity and clinical presentation.
Although the primary focus of this report is surgical decision‐making, it is noteworthy that immune checkpoint inhibitors are associated with endocrine adverse events, including hypothyroidism [13]. Although a definitive causal relationship could not be established, treatment‐related thyroid dysfunction cannot be excluded. Importantly, acknowledging this possibility does not imply causation or fault, but rather underscores the importance of multidisciplinary vigilance.
This case posed a genuine ethical dilemma: Proceeding with surgery entailed a substantial metabolic risk, whereas delaying surgery to achieve biochemical euthyroidism would likely have resulted in definitive loss of resectability. The decision to operate was therefore based on individualized risk–benefit assessment, multidisciplinary consensus, and shared decision‐making with the patient.
From a technical standpoint, a wide vertical‐elliptical skin incision was selected over more conventional incision patterns, such as Stewart or Orr designs, which would not have permitted adequate oncologic skin sacrifice. This highlights the importance for breast surgeons to remain familiar with less commonly employed surgical designs to manage atypical tumor topographies in rescue scenarios.

4. Limitations
As a single case report, definitive causal relationships cannot be established, and long‐term oncologic outcomes remain unknown. Additionally, full biochemical correction of hypothyroidism prior to surgery was not achievable within the available oncologic timeframe. Nevertheless, this case provides valuable insight into real‐world decision‐making when standard perioperative recommendations conflict with oncologic urgency.

5. Conclusion
Severe biochemical hypothyroidism may be clinically silent yet pose significant perioperative risks. In selected patients with time‐sensitive oncologic indications, rescue surgery may be justified despite incomplete metabolic optimization when guided by multidisciplinary evaluation, thorough preoperative planning, and shared decision‐making. This case supports an individualized approach to surgical decision‐making in complex oncologic emergencies.

Funding
No funding was received for this manuscript.

Ethics Statement
Written informed consent for publication of clinical details and images was obtained from the patient.

Conflicts of Interest
The author declares no conflicts of interest.