Long overdue presentation for a mammary malignancy: real-life medicine experience

1. Introduction

Breast cancer is the most frequent type of cancer that women suffer from, and the prime cause of death among females globally, with a median age at diagnosis of 62 years old and with a higher risk later in life^(1-3). It can be classified, according to the expression of human epithelial growth factor receptor 2 (HER2), estrogen receptors (ERs) and progesterone receptors (PRs), into HER2-enriched (negative ERs and PRs, positive HER2), hormone receptor-positive (negative HER2, positive ERs and PRs), and triple-negative (negative ERs, PRs and HER2)^(4,5). Of these, triple-negative breast cancers occur in 15% to 20% of the cases, and have a markedly more aggressive evolution than the other subtypes, with onset at younger ages and with a worse outcome^(6,7).

Prompt diagnosis and immediate treatment are the cornerstone of decreasing mortality caused by breast malignancy; however, an increase in resistance to endocrine therapies is an ongoing challenge in the management of such patients^(8,9). Furthermore, adjuvant and neoadjuvant treatments have their own pitfalls, as they target not only breast cancerous cells, but also other health tissues, including cardiovascular, metabolic and osseous^(10,11).

On one hand, the malignancy may be completely asymptomatic, thus the diagnosis may be delayed, and on the other hand, one patient’s decision to delay the presentation despite clinical evidence is strictly correlated to personal choice and opinion. Moreover, a delayed presentation and fear of medical checkup were registered during the COVID-19 pandemic, as seen in other medical and surgical areas regardless of oncologic profile^(12,13).

2. Materials and method

We aim to introduce a case of advanced-stage breast cancer that the patient had neglected and presented not for the fulminant evolution of the local tumor, but for neurological symptoms which she considered to impair her quality of life. The endocrine and imaging data are provided.

3. Results: case presentation

A 68-year-old female smoker presented with severe, debilitating vertigo and balance disorder that developed during the past few weeks. She entered menopause at the age of 40 years old, without hormone replacement therapy. The family medical history was irrelevant. The clinical examination showed a severe breast asymmetry, with a large, solid and immobile mass in the lower outer quadrant of the left breast of 5 cm, accompanied by changes of the overlying skin such as thickening (“orange peel” aspect), large erythematous patches, and crusted lesions. Voluminous lymphadenopathies were detected at palpation in the left axilla, left supraclavicular region and left laterocervical region. The biochemical assays revealed hepatocellular injury by elevated liver enzymes, dyslipidemia, an inflammatory syndrome, and hyperglycemia (notably, the rapid COVID-19 test was negative) – Table 1.
 

The hemogram was abnormal in terms of leukocytosis and neutrophilia, with an increased number of monocytes and high hemoglobin and hematocrit. Notably, the erythrocyte sedimentation rate was high, too (Table 2).
 

The hormonal evaluation detected a normal level of TSH (thyroid-stimulating hormone) of 3.57 µIU/mL (normal range: 0.35-4.94) and free levothyroxine of 12.45 pmol/L (normal range: 9-19), and negative thyroid antibodies such as anti-thyroperoxidase antibodies, anti-thyroglobulin antibodies and anti-TSH receptor antibodies. Moreover, the adrenal panel showed normal values of ACTH (adrenocorticotropic hormone) and morning plasma cortisol (Table 3).
 

Blood mineral metabolism assays showed a decreased level of bone formation marker osteocalcin and increased P1NP, with the rest of the parameters within normal range (Table 4).
 

Neck ultrasound revealed a right thyroid lobe of 1.42 by 1.25 by 3.97 cm and left thyroid lobe of 1.45 by 1.27 by 4.4 cm, with hypoechoic inhomogeneous pattern, suggestive for autoimmune thyroid disease. Inflammatory lymphadenopathies were present bilaterally, in the left laterocervical region, of 1.01 by 0.7 cm, 0.64 by 0.51 cm and 1.1 by 0.75 cm, respectively (Figure 1).
 

Computed tomography of the thorax revealed voluminous infiltrative masses, spiculated, confluent, of 5 by 8 cm, in the left breast, surrounded by intense areas of edema and fibrosis that extended to cervical, nuchal and anterior, lateral and posterior thorax level (suggestive for infected cellulitis); microadenopathy and conglomerated lymph nodes were detected in the left axilla, together with microadenopathy in the right axilla (Figure 2).
 

The lungs displayed consolidation and air bronchograms in the anterior segment of the right upper lobe, right middle lobe and superior and posterior segment of the right inferior lobe; ground-glass opacities were detected in the superior, lateral and posterior segments of the right lower lobe and in the superior and lateral segments of the left lower lobe; right fissure thickening and left hilar lymphadenopathy (Figure 3).
 

Cerebral computed tomography revealed a space-occupying, dense and heterogeneous mass in the left lateral part of the posterior fossa, adjacent to the bone, of 2.17 by 2.29 by 2.9 cm, and another intensely hypo­dense lesion in left parietal region, of 1.79 by 3.8 by 1.8 cm (suggestive for possible edema surrounding a metastasis). The patient declined any further intervention and released herself home. Symptomatic medication for her vertigo was recommended, as well as antibiotics. Any further attempt of additional evaluations or starting any therapy was unsuccessful, and the patient was lost for evidence.

4. Discussion

Encouraging women to follow mammographic screening programs and advanced diagnostic techniques could improve the survival of such patients by early detection and adequate therapy^(14,15). The first choice of treatment for breast malignancy is surgery, although it is not always effective in eliminating all cancer cells, and the risk of metastasis, recurrence and resistance to chemotherapy or radiotherapy persists^(16,17).

This patient displayed clinical evidence of an inflammatory breast cancer, based on the local skin modifications and the rapid evolution within six months, which would require a cross-disciplinary approach involving surgery, endocrine therapy, chemotherapy and radiotherapy^(18,19). However, this type of cancer is characterized by uncertainty in the differential diagnosis with a long-standing breast tumor that develops inflammatory changes, which was also a question to be answered in the case of this patient^(14,20). Additionally, brain metastases are particularly present in cases with HER2-positive and triple-negative breast cancers, thus immunohistochemistry would be a helpful tool in determining the type and aggressiveness of the patient’s tumor and in deciding the course of treatment^(21,22).

In this instance, the patient had impressive skin involvement at the area of primary mammary lesion, a source of local discomfort, and a reduced quality of life, as seen in other conditions⁽²³⁾. However, the lady displayed a massive resistance to further investigations and therapy, as she delayed the hospital admission⁽²⁴⁾. A local biopsy should have been helpful to navigate the next logical step of the case strategy and to differentiate not only from other types of malignancies, but from other autoimmune/immune, tumor-like or infectious conditions^(25-27). A good collaborative team with her family physician should have been helpful to an early admission⁽²⁸⁾. 

5. Conclusions

The delayed presentation in case of a fulminant malignancy such as mammary cancer complicated with local and distance metastases and local cellulitis represents a dramatic point in real-life medicine that, despite medical progress, cannot surpass one individual’s options and choice.  

Acknowledgment: We thank Dr. Anda Dumitraşcu, MD, PhD, for her support with computed tomography captures, interpretation and selection of images.

Corresponding author: Claudiu Nistor, e-mail: ncd58@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.