Diagnostic potentials of modern radiothermometry in oncomammological practice

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LIST OF ABBREVIATIONS

MG — mammary gland

BС ― breast cancer

RTM — radiothermometry

BACKGROUND

Despite significant achievements of recent years in personalized and target approaches in breast cancer (BC) diagnosis and management, the problem of its early identification remains the basis of a good patient prognosis [1]. “Rejuvenation” of breast oncopathology in some cases hinders the effectiveness of routine diagnostic methods making specialists use combinations of expensive and sometimes invasive methods of tumor process visualization and verification [2–4]. Besides direct breast neoplasm localization and confirmation, determining its biological properties, which define the management algorithm of a particular patient, is necessary.

One of the visualization methods of breast pathology is radiothermometry (RTM), which is firmly included in the routine algorithm of complex breast examination in many clinics [5–7]. Numerous studies revealed that this non-invasive method is a highly sensitive method, which is capable of differentiation between malignant and benign breast tissue alterations at the preclinical stage in different age groups [8–12], based on the measurement of the difference between electromagnetic radiation of healthy and neoplastic tissue cells in the microwave range at the depth up to 5 cm [13]. The study of thermoasymmetry of healthy and altered breast structures that was conducted by M. Gauthiere in 1965 on 85,000 patients revealed that a malignant tumor has a higher temperature than normal tissues due to enhanced metabolism [14, 15]. Concurrently, the breast that is affected by a malignant process, as a rule, possesses higher parameters relative to the healthy side, which, in turn, can be attributed to the active angiogenesis [16]. Additionally, in a group of females (n = 1245) with questionable thermograms without any clinical or radiological breast alterations, further observation within 8 years revealed BC in 40.2% of cases [17–19]. This method has also been proven effective in evaluating benign processes with high and low proliferative activity [20]. Therefore, RTM is an actual method of breast examination since it permits metabolism quality evaluation, besides direct pathological foci visualization [21–23]. This is important from the point of view of biological BC subtypes determination since the reliable differences of thermograms of different histological forms of cancer were proven as early as the 60s. Additionally, of importance is also a question about the possibility of evaluation of the extent of tumor aggressiveness before the immunohistochemical analysis [10].

Aim — to determine the potentials of the modern RTM in the differential diagnosis of benign and malignant breast pathology and different biological BC subtypes.

MATERIALS AND METHODS

The study was conducted based on Ryazan Regional Oncological Dispensary and included 118 females with different breast pathology. All procedures were performed as part of the dispensary/routine examination. No additional interventions were performed. The females signed Informed consent within the frames of standard procedures of Ryazan Regional Oncological Dispensary.

The studied parameters were assessed on RТМ 01 РЭС computerized diagnostic complex consisting of internal temperature meter, IR skin temperature meter, a means for visualization, processing, and analysis of the obtained information by the expert system [24].

Following the RTM recommendations, measu-rements were taken in nine points: directly on the breast to visualize the tumor, in two control points in the epigastrium and xiphoid process region of the sternum, and one axillary point on both sides for identification of probable metastases [5, 13]. The examination duration was 15–20 min for each participant.

Further on, participants were divided into two groups:

• The control group (n = 32) with benign breast alterations (mastopathy, fibroadenoma, intraductal papilloma, mastitis, and lipoma) (age 18–79 years);
• The main group (n = 86) with malignant breast neoplasms [25] (age 24–73 years).

The main group (n = 84) was predominated with BC of different stages (I and II: 28.7% in each, III: 42.8%) of different phenotypes, as well as one case of melanoma metastasis and one sarcoma breast metastasis. Here more aggressive phenotypes of BC were more common in young patients (Figure 1).

 

Fig. 1. Relationship of BC phenotype (n) with age (years).

 

Additionally, RTM data were compared with the results of histological verification, ultrasound, mammographic, and clinical picture.

In statistical analysis, methods of descriptive (%) and comparative (T-Student test, Mann-Whitney test) statistics were used, sensitivity and specificity of the diagnostic method (RTM) were determined. Differences were considered statistically significant at р < 0.05.

A statistically significant result was obtained compared to the frequency and difference of thermoasymmetry in groups with aggressive phenotypes (р < 0.05). Here, the group of non-luminal HER2-positive phenotype had a greater difference of the average temperature between affected and healthy tissue was greater (by 1.8 °С) than in triple-negative variant (by 0.9 °С, Table 2). This fact does not confirm the hypothesis that more aggressive phenotypes, particularly, triple-negative subtype, should give a more resonant picture of thermometry.

 

Table 2. Distribution of Average Temperatures in Groups of Aggressive Breast Cancer Phenotype

Average Temperature, °С	Aggressive Phenotypes of Breast Cancer
	Non-luminal HER2+	Triple-negative
Pathological breast	34.7	35.4
Healthy breast	32.9	34.5

 

Of special interest is Ki67, tumor biological potential index (RTM is based on metabolism in tumor tissue). Our study revealed that the highest average value of Ki67 was observed in triple-negative cancer (63.3%), somewhat lower in groups with HER2-positivity (50.6%), in truly luminal subtypes this parameter was reliably lower, that is 42.2% in luminal B and 10.6% in luminal А. However, no correlation was found between tumor proliferative activity index and frequency of thermoasymmetry or the extent of its evidence (r < 0.3).

RESULTS

The result analysis revealed the following patterns:

RTM is effective in the differential diagnosis of benign and malignant breast processes (for the Student t-test, р = 0.00053), the sensitivity of RTM in breast pathology diagnosis compared with histological verification, ultrasound, mammographic, and clinical picture results were 96.9%, specificity for aggressive and non-aggressive BC subtypes differentiation was low (6.6%).

The temperature difference evaluation between pathological and normal tissue, a tendency to increase measured values above the tumor compared to the unaffected tissue was found; however, no statistically significant differences were obtained either between the average temperatures of healthy and affected breast or between different phenotypes (Table 1). The Mann-Whitney test showed no temperature differences between luminal A and B groups (U = 342), nor did it confirm more aggressive properties of luminal human epidermal growth factor receptor 2 (HER-2)-positive phenotype relative to luminal HER-2-negative type (U = 114.5), which does not speak in favor of the hypothesis about the effectiveness of RTM in aggressive and non-aggressive BC diagnosis. Ambiguous is the fact of a complete absence of thermoasymmetry in sarcoma and melanoma metastasis to the breast, since a high degree of aggressiveness of both tumors is evident a priori.

Evaluation of the extent of spread of the process by temperature measurement of axillary regions revealed no reliably significant deviations (U = 182). Additionally, hypothermia relative to even healthy tissues in cases with confirmed axillary lymph nodes metastases (Table 1).

 

Table 1. Distribution of Average Temperatures in Groups with Different Breast Cancer Phenotypes

Average Temperature, °С	Breast Cancer Phenotypes
	Luminal A	Luminal B (-)	Luminal B HER2+	Non-Luminal HER2+	Triple-Negative
Above tumor	34.4	34.1	34.1	34.5	35.4
Pathological breast	33.6	33.3	33.1	33.6	34.7
Healthy breast	33.2	32.5	32.4	32.8	34.8
Altered lymph nodes	33.9	33.4	33.9	33.1	34.3
Non-altered lymph nodes	33.9	33.3	33.0	32.9	34.0

 

DISCUSSION

Thus, diffused (locally spread) forms of BC are presented in the forms of thermograms with the most significant spread and large areas of maximal and minimal temperatures.

Below, several demonstrative results of RTM of benign process, localized, and diffused BC are presented (Figure 2).

 

Fig. 2. Examples of radiothermometry results: A — benign breast tumor; B — breast cancer, triple-negative, localized form; C — breast cancer, luminal B, diffused form.

 

CONCLUSIONS

1. Radiothermometry demonstrated effectiveness in the differential diagnosis of benign and malignant breast tissue alterations.
2. Radiothermometry is not a method of choice in diagnosing the extent of spread and evaluating the biological subtype of breast cancer , since no correlation was found between the frequency and extent of thermoasymmetry and phenotype, nor the connection between temperature difference with Ki67, as well as with metastatic regional lymph node lesions.

ADDITIONAL INFORMATION

Gratitude. The team of authors expresses gratitude for the provided equipment and advice on the correctness of the conduct and interpretation of the results to Irina Vladimirovna Zorova, Irina Petrovna Kriulkina and Sergey Georgievich Vesnin.

Funding. This study was not supported by any external sources of funding.

Conflict of interests. The authors declare no conflicts of interests.

Contribution of the authors: A. A. Volkov ― concept and design of research, collection and processing of material, statistical processing, writing text, A. N. Demko ― concept and design of research, writing and editing text, E. P. Kulikov ― concept and design of research, text editing, A. N. Budanov ― performing ultrasound research, N. S. Orlova ― performing radio telemetry. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

Благодарность. Коллектив авторов выражает благодарность за предоставленное оборудование и консультации по правильности проведения и трактовки результатов Зоровой Ирине Владимировне, Криулькиной Ирине Петровне и Веснину Сергею Георгиевичу.

Финансирование. Авторы заявляют об отсутствии внешнего финансирования при проведении исследования.

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов: Волков А. А. ― концепция и дизайн исследования, сбор и обработка материала, статистическая обработка, написание текста, Демко А. Н. ― концепция и дизайн исследования, написание и редактирование текста, Куликов Е. П. ― концепция и дизайн исследования, редактирование текста, Буданов А. Н. — выполнение ультразвукового исследования, Орлова Н. С. ― выполнение радиотелеметрии. . Все авторы подтверждают соответствие своего авторства международным критериям ICMJE (все авторы внесли существенный вклад в разработку концепции, проведение исследования и подготовку статьи, прочли и одобрили финальную версию перед публикацией).

About the authors

E P. Kulikov

Ryazan State Medical University

Email: rzgmu@rzgmu.ru
ORCID iD: 0000-0003-4926-6646
ResearcherId: S-1851-2016

MD, PhD, Professor, Head of the Department of Oncology

Russian Federation, Ryazan

Anna N. Demko

Ryazan State Medical University; Ryazan Oncological Dispensary

Email: naetochka@yandex.ru
ORCID iD: 0000-0002-7941-5158
SPIN-code: 2512-4630

Candidate of Medical Sciences, Assistant of the Department of Oncology, Oncologist of the Dispensary

Russian Federation, 9, str. Vysokovoltnaya Ryazan, 3900262; 11, Dzerzhinskiy str, Ryazan, 390011

Alexander A. Volkov

Moscow Regional Oncology Center

Email: aavolkov58rus@yandex.ru
ORCID iD: 0000-0003-0244-4951
SPIN-code: 3668-6377

oncologist

Russian Federation, 6 str. Karbysheva, Balashikha, 143900

Andrey N. Budanov

Ryazan State Medical University; Ryazan Oncological Dispensary

Email: andrewbudanof@yandex.ru
ORCID iD: 0000-0002-8706-2655

Assistant of the Department of Oncology, Head. department of ultrasound diagnostics, oncologist

Russian Federation, 9, str. Vysokovoltnaya Ryazan, 3900262; 11, Dzerzhinskiy str, Ryazan, 390011

Nina S. Orlova

Ryazan Oncological Dispensary

Author for correspondence.
Email: nina.orlova.6161@mail.ru
ORCID iD: 0000-0001-9934-9242

radiologist of the highest category

Russian Federation, 11, Dzerzhinskiy str, Ryazan, 390011

References

Supplementary files