Post-COVID-19 cardiorespiratory profile in breast cancer patients: a comparative analysis

Abstract

Objective

To perform a comparative analysis of the post-COVID-19 cardiorespiratory profile in women with breast cancer.

Methods

A mixed case–control study was conducted from January 2020 to June 2024 at the Francisco Beltrão Cancer Hospital in Paraná. Four groups of 14 participants, matched by age, were analyzed based on their history of COVID-19 and breast cancer. All participants underwent tests to assess respiratory muscle strength, cardiorespiratory functional capacity, and dyspnea. For women with breast cancer, additional data on the clinical-pathological profile of the disease were also collected.

Results

COVID-19 exacerbated the reduction in respiratory muscle strength already present in women with breast cancer and contributed to the occurrence and persistence of dyspnea, even 24 months post-infection. However, it did not significantly affect functional exercise capacity.

Conclusion

These findings emphasize the need for a multidisciplinary approach to conduct more comprehensive assessments, particularly in patients with breast cancer during the post-COVID phase.

Introduction

Breast cancer is the leading cause of cancer-related deaths among women in Brazil [1]. This heterogeneous disease results from the uncontrolled proliferation of abnormal breast cells, which may form tumors with invasive potential [2]. Advancing age is the main risk factor, along with genetic, endocrine, behavioral, environmental factors, and reproductive history [3].

Chronic inflammation and impaired cellular immunity contribute to disease progression by fostering a pro-tumor environment [4]. Metabolic and systemic inflammatory dysregulation can cause musculoskeletal loss and weakness [5], while antineoplastic therapies increase susceptibility to secondary diseases and infections [6].

In March 2020, the World Health Organization (WHO) declared COVID-19, caused by SARS-CoV-2, a pandemic. This infection can severely affect the lungs, particularly in immunocompromised individuals, leading to respiratory failure, long-term pulmonary complications, and death [7,8]. Its clinical spectrum ranges from asymptomatic to critical cases, with severity influenced by genetic background, comorbidities (diabetes, hypertension, asthma, obesity), advanced age, lifestyle, and conditions such as cancer [9].

Persistent symptoms—including fatigue, dyspnea, and muscle weakness—have been reported months after infection [10]. impairing physical performance even in previously healthy individuals. Due to lung involvement and respiratory symptoms, COVID-19 can also disrupt the balance between ventilatory demands and respiratory muscle strength [11].

Although COVID-19 epidemiology and treatment are widely studied, little is known about its impact on breast cancer patients [6]. This study therefore aimed to analyze the post-COVID-19 cardiorespiratory profile of women with breast cancer treated in the SUS and its correlation with clinical-pathological parameters.

Methods

This is a mixed-method, observational, case–control study conducted at the Francisco Beltrão Cancer Hospital (CEONC) – Associação Beneficente Deus Menino in Paraná between January 2020 and June 2024. The proposal was approved by the Institutional Ethics Committee under CAAE number 35524814.4.0000.0107, with opinion number 6.129.064. All participants provided informed consent by signing the Free and Informed Consent Form.

Between January 2020 and December 2023, 498 women with a confirmed diagnosis of breast cancer were screened. Those willing to participate in the proposed physiotherapy evaluation were included in the study. Consequently, two groups of women with breast cancer were formed: one with a positive history of COVID-19 and the other without a history of the disease. Simultaneously, two control groups were created, matched by age to the cancer groups, consisting of women without breast cancer, both with and without a history of COVID-19.

Patients diagnosed with COVID-19 were in the post-infection period, and only women with proof of infection through a positive RT-PCR test or medical diagnosis were considered positive. Women who had cognitive or motor limitations that prevented them from performing the proposed tests, those who chose to withdraw from participation, and those with lung metastasis were excluded.

In addition to the proposed assessment, participants with breast cancer also had additional information collected regarding their clinical-pathological profile. This included the expression of hormone receptors (estrogen and progesterone), amplification of the HER2 oncogene, histological grade, presence of metastases in axillary lymph nodes, tumor size, molecular subtype of breast cancer, age at diagnosis, body mass index (BMI), menopausal status, occurrence of recurrence, sites of metastasis, and the 5-year survival profile. The activity level was determined through self-reports from participants, based on the type of physical exercise and its weekly frequency. Additionally, data on smoking status, mastectomy, and the need for hospitalization were collected during the interview.

Inspiratory (PiMax) and expiratory (PeMax) muscle strength were measured using a Digital Manovacuometer (model MVD300-U, Homed), with MVC300 System Software employed to calculate the reference values for each participant. To assess cardiorespiratory functional capacity, a six-minute walk test (6MWT) was conducted. After completing the test, participants' perception of dyspnea was evaluated based on their self-report.

Four groups were evaluated based on the presence or absence of breast cancer and a diagnosis of COVID-19. Both qualitative and quantitative variables were considered. For each variable, the Chi-square test for independence was performed to analyze the association between categories and groups. In cases where the assumption of a minimum expected frequency of 5 was violated, the Monte Carlo method was employed as the association test, with a significance level set at 5%. Data distribution was assessed using the Shapiro–Wilk test. Variables with a normal distribution were analyzed using parametric tests, while non-parametric tests were applied for variables that did not meet the normality assumption. To compare data between two groups, the Student's t-test or the Mann–Whitney test was utilized. The results were analyzed using GraphPad Prism 9.0 software (GraphPad Software, San Diego, CA, USA).

Results

The study population comprised 56 women with an average age of 56 years, divided into four groups of 14 participants each, matched by age. The clinical-pathological profile of the participants with breast cancer is detailed in Table 1. Regardless of the clinical-pathological parameters of breast cancer patients, no significant differences were observed between those with and without COVID-19 (p > 0.05).

Table 1.

Clinicopathological profile of patients with breast cancer.

		COVID-19 negative	COVID-19 positive	p-value
Age	<50 years >50 years	3 (21.4%)11 (78.5)	4 (28.5%)10 (71.4%)	0.662
Age at diagnosis	<50 years >50 years	5 (35.7%) 9 (64.2%)	4 (28.5%)10 (71.4%)	0.898
Menopause	NoYes	5 (35.7%) 9 (64.2%)	3 (21.4%) 11 (78.6%)	0.555
Mastectomy	NoYes	1 (7.1%)13 (92.9%)	1 (7.1%)13 (92.9%)	0.999
Molecular subtype	Luminal ALuminal BHER-amplifiedTriple negative	6 (42.8%)3 (21.4%)1 (7.1%)4 (28.4%)	6 (42.8%)2 (14.2%) 2 (14.2%)4 (28.4%)	0.940
Tumor Size	Up to 2 cmBetween 2–5 cm >5 cm	5 (35.7%)4 (28.5%)5 (35.6%)	10 (71.4%)3 (21.4%) 1 (7.1%)	0.292
Tumor Grade	Grade 1 and 2Grade 3	10 (71.4%) 4 (28.6%)	10 (71.4%)4 (28.6%)	0.590
Angiolymphatic Emboli	NoYes	12 (85.7%) 2 (14.2%)	11 (78.5%) 3 (21.4)	0.307
Lymph Node Invasion	NoYes	11 (78.6%) 3 (21.4%)	12 (85.8%) 2 (14.2%)	0.692
Distant Metastasis	NoYes	11 (78.6%)3 (21.4%)	12 (85.8%)2 (14.2%)	0.7007
Chemoresistance	NoYes	13 (92.9%) 1 (7.1%)	13 (92.9%)1 (7.1%)	0.8923
Recurrence	NoYes	13 (92.9%) 1 (7.1%)	12 (85.8%) 2 (14.2%)	0.590

HER: Human epidermal growth receptor.

Fig. 1 illustrates the results of the physiotherapeutic evaluation and compares the groups regarding inspiratory and expiratory muscle strength and cardiorespiratory functional capacity. A total of 30% of the sample was classified as obese, 14% of patients reported being smokers, and 71% engaged in some form of physical exercise weekly. Most participants with breast cancer underwent mastectomy. Notably, the hospitalization rate was higher in the group without breast cancer, which also had a greater prevalence of obesity compared to the post-COVID-19 participants.

Figure 1.

Data concerning the physiotherapeutic evaluation of patients. (A) inspiratory, (B) expiratory muscle strength, and (C) cardiorespiratory functional capacity.

Regarding respiratory muscle strength (Fig. 1A and B), both inspiratory and expiratory measures were markedly lower in women with breast cancer who had a history of COVID-19 (p < 0.05). Control groups, regardless of COVID-19 status, showed higher values, while women with breast cancer presented reduced strength, which was further diminished in those with previous COVID-19 infection.

The analysis of cardiorespiratory functional capacity, assessed by the six-minute walk test (6MWT), showed that just over half of the participants reached their predicted values, with no significant differences between groups (Fig. 1C). Control groups, regardless of COVID-19 history, achieved the longest walking distances. Among women with breast cancer, those who had not been infected by COVID-19 recorded the lowest performance, while greater variability was observed in participants with a history of the infection.

Regarding the occurrence of dyspnea, 25% of participants reported experiencing it, predominantly among those who tested positive for COVID-19. It is noteworthy that the COVID-19-positive control group had a significantly higher proportion of dyspnea compared to the COVID-19-negative control group, with a statistically significant difference (p = 0.029). Similarly, among women with breast cancer, dyspnea was reported in 50% of the COVID-19-positive sample, with a statistically significant difference (p = 0.002) compared to the COVID-19-negative breast cancer group.

The investigation of the correlation of time between the date of diagnosis of SARS-CoV2 infection and the date of the physiotherapy evaluation, as well as the date of diagnosis of breast cancer and the date of the physiotherapy evaluation, was carried out in order to verify whether these were influencing factors for the respiratory impairment observed in patients with breast cancer who were positive for COVID-19 (Table 2).

Table 2.

Interval between the diagnosis of COVID-19, the diagnosis of breast cancer, and the physiotherapy assessment.

Patient	Age (Years)	COVID-19 diagnosis	Breast Cancer diagnosis	Physiotherapy Assessment Date	Interval between COVID-19 diagnosis and physiotherapy evaluation	Interval between breast Cancer diagnosis and physiotherapy evaluation
Patient 1	32	Feb/21	23.05.22	19.12.23	34 months	19 months
Patient 2	32	Out/22	17.11.21	29.11.23	13 months	24 months
Patient 3	51	Feb/24	21.09.22	03.04.24	2 months	19 months
Patient 4	45	Mar/20	05.07.23	15.02.24	46 months	7 months
Patient 5	52	Nov/20	03.11.21	12.01.24	38 months	26 months
Patient 6	53	Feb/22	21.10.21	29.11.23	21 months	25 months
Patient 7	55	Ago/20	24.07.23	16.01.24	41 months	6 months
Patient 8	60	Nov/20	23.02.22	06.03.24	40 months	25 months
Patient 9	61	Nov/20	07.03.22	12.12.23	37 months	21 months
Patient 10	63	Mai/20	21.02.20	29.11.23	43 months	45 months
Patient 11	82	Feb/21	05.06.23	17.04.24	38 months	10 months
Patient 12	67	Jul/22	24.09.20	12.12.23	17 months	39 months
Patient 13	71	Set/22	14.04.22	06.03.24	18 months	23 months
Patient 14	75	Jan/22	05.06.23	18.01.24	24 months	7 months

Feb: February; Oct: October; Mar: March; Nov: November; Aug: August; May: May; Jul: July; Sep: September.

When correlating the evaluated parameters (PiMax, PeMax, cardiorespiratory function, and dyspnea) with the time interval between these events, no statistical correlation was found (p > 0.05). This suggests that the evaluation interval did not influence the results obtained by the breast cancer sample with a history of COVID-19. Additionally, a Spearman correlation test was conducted to investigate the impact of the presence of COVID-19 on the clinicopathological variables of the breast cancer group (Table 3).

Table 3.

Significant correlations between the presence of COVID-19 and the clinicopathological variables in patients with breast cancer.

COVID vs	BMI	Pimax	Dyspnea	Tumor Size
r	− 0.473	− 0.408	0.577	− 0.560
95% confidence interval	− 0.725 to − 0.110	− 0.684 to − 0.029	0.249 to 0.787	− 0.795 to − 0.180
p-value	0.011*	0.031*	0.001*	0.005*

BMI: body mass index. Pi: inspiratory pressure.

*

p < 0.05.

In women with breast cancer, the presence of COVID-19 showed a significant inverse correlation with body mass index (r = −0.473, p = 0.011), indicating that infected patients tended to have lower BMI values. COVID-19 was also moderately correlated with reduced inspiratory muscle strength (PiMax; r = −0.4082, p = 0.031), presence of dyspnea (r = 0.577, p = 0.001), and smaller tumor size (r = −0.560, p = 0.005). No significant associations were observed with the other variables.

When analyzing the six-minute walk test (6MWT) in the breast cancer groups, longer distances were correlated with younger age (r = − 0.503, p = 0.006) and lower PiMax values (r = −0.417, p = 0.027), as shown in Table 4.

Table 4.

Correlation between the distance covered, age, and inspiratory muscle strength (PiMax).

6MWT vs	Age	Pimax
R	− 0.503	− 0.417
95% confidence interval	− 0.743 to − 0.149	− 0.689 to − 0.0405
p-value	0.006*	0.027*

6MWT: six-minute walk test. PiMax: Maximum inspiratory pressure.

*

p < 0.05.

Discussion

This study demonstrates the impact of COVID-19 on the cardiorespiratory profile of patients with breast cancer. It identifies parameters distinctly associated with both the infection and the presence of cancer.

Initially, an examination of the clinical-pathological profile of breast cancer patients revealed that a history of COVID-19 did not influence the general characteristics or behavior of the disease. However, when analyzing the COVID-positive cancer group specifically, it was observed that these patients had smaller tumors and lower body mass index (BMI). To our knowledge, these findings have not been reported in the existing literature.

When examining the clinical profiles of the evaluated groups, it was observed that the obesity rate was lower among patients with breast cancer, particularly in those who had COVID-19. This finding may be attributed to the compromised nutritional status that is commonly seen in cancer patients. These individuals often experience a high frequency of malnutrition due to various metabolic changes, including an increase in inflammatory molecules that reduce appetite, the presence of lipolytic mediators that induce lipolysis, and an elevated energy demand for tumor progression. Additionally, the side effects of antineoplastic therapies—such as surgery, chemotherapy, and radiotherapy—can contribute to this issue, leading to symptoms like nausea, vomiting, loss of taste, fatigue, and pain [12,13].

Normotrophism is associated with a poorer prognosis in certain types of cancer, particularly breast and colon cancer [14], and BMI is a risk factor for progression to severe forms of COVID-19. In the present study, although the number of hospitalizations—indicative of severity—did not show a statistically significant difference among the COVID-19-positive groups, the frequency of hospitalization was higher in the group of women without cancer, who also had higher obesity rates. This can be attributed to hyperadiposity, which is associated with a chronic pro-inflammatory state linked to the overexpression of inflammatory adipokines. These factors reduce the immune system's ability to respond to infections, particularly those affecting the lungs, a situation further exacerbated by decreased ventilatory capacity due to thoracic and abdominal fat deposits [15].

Regarding respiratory muscle strength, the overall reduction in strength was primarily influenced by the presence of breast cancer rather than by SARS-CoV-2 infection. However, when analyzing the sample of women with cancer separately, it was observed that the presence of COVID-19 was associated with lower inspiratory muscle strength in this population. These findings support the notion that respiratory muscle strength, already diminished due to neoplasia, can be further exacerbated by a history of COVID-19. Studies indicate that metabolic changes and an increased systemic inflammatory state in cancer contribute to cachexia, a complex disorder characterized by significant and progressive loss of skeletal muscle mass, with or without concurrent loss of adipose tissue [5]. In addition to the loss of muscle mass in cancer patients, there is an increased production of inflammatory cytokines that triggers the release of various myofibrillar proteins associated with sarcopenia [12,13].

Sarcopenia is characterized by low musculoskeletal mass, diminished grip strength, and reduced walking speed, and it is associated with a decline in quality of life and decreased tolerance to therapies, ultimately leading to a poor prognosis. A study [1] indicates that thoracic radiotherapy for breast cancer can lead to a decrease in inspiratory capacity and vital capacity, adversely affecting lung volume and respiratory muscle strength. Therefore, the findings of the present study align with the existing literature.

The exacerbation of respiratory muscle strength loss caused by COVID-19 in the present study aligns with findings from a study [16] conducted on volleyball players, which compared the respiratory muscle strength of athletes with and without a history of COVID-19 three months post-infection. Although the players with a history of the disease did not exhibit severe symptoms and were not hospitalized, their respiratory muscle strength was significantly lower than that of players without a history of infection. Indeed, respiratory muscle impairment may contribute to the persistence of post-infection symptoms, such as dyspnea [11].

The presence of dyspnea in participants with a history of COVID-19 was reported regardless of the presence or absence of cancer. This finding aligns with the potential occurrence of a clinical condition known as long COVID, characterized by persistent systemic symptoms that can last for months or even years after the acute phase of the disease. These symptoms may include dyspnea, fatigue, muscle weakness, difficulty sleeping, anxiety, and depression [7,8,10,17–20]. Although post-COVID-19 sequelae are more common in patients who experienced the severe form of the disease, individuals with moderate cases who did not require hospitalization may also exhibit some degree of functional impairment [20]. This reinforces the findings of the present study, where the number of participants who had COVID-19 and required hospitalization was very low, indicating that the infection was of low severity during the acute phase.

It was also observed that participants with a history of COVID-19 in this study were evaluated between 2 and 46 months post-infection. The interval between the date of SARS-CoV-2 infection and the date of the physical therapy evaluation did not influence the impairment observed in the sample, including the reduction in respiratory muscle strength and the presence of dyspnea. This finding aligns with existing literature, which suggests that the chronicity of these symptoms is independent of the time elapsed since infection [17]. Literature [21] categorizes it as symptoms likely related to infection (4–5 weeks), acute post-COVID symptoms (5–12 weeks), prolonged post-COVID symptoms (12–24 weeks), and chronic post-COVID symptoms (lasting more than 24 weeks).

The correlation of the 6MWT results with the variables analyzed in the groups of women with breast cancer, regardless of COVID-19, revealed that greater distances covered in the walking test were associated with lower age and lower inspiratory muscle strength. While respiratory fitness is closely related to the physical performance of these women, it is noteworthy that despite impaired respiratory muscle strength, most participants still achieved the predicted values. Although age does impact performance on the proposed tests, the finding that women with lower inspiratory muscle strength covered the greatest distances supports previous studies [10]. This finding aligns with reports suggesting that health status is not determined solely by exercise capacity. Additionally, during the assessment of these tests, the determination and willpower exhibited by these women were evident, even in the face of the limitations imposed by their condition.

While the study provides valuable insights into the impact of COVID-19 on respiratory muscle strength, dyspnea, and functional capacity in this population, limitations such as the single-center design and potential variability in participants' performance on assessments should be considered. Recruiting women with both a confirmed breast cancer diagnosis and documented COVID-19 positivity proved highly challenging. Of the 498 screened patients, only a small subset met the strict eligibility criteria, which included proof of infection and exclusion of confounding conditions. Despite this, we formed four balanced, age-matched groups, ensuring methodological consistency. While the reduced sample limits statistical power, we consider these exploratory findings valuable, as they provide rare insights into this specific and hard-to-recruit population and may guide future multicenter studies. Additionally, assessments conducted through manovacuometry and the six-minute walk test (6MWT) may be influenced by the participants' emotional states on the day of evaluation. Despite these limitations, our findings provide new insights into the impact of COVID-19 on patients with breast cancer, particularly regarding its correlation with clinical-pathological parameters that influence prognosis.

In conclusion, our findings suggest that COVID-19 exacerbated the reduction in respiratory muscle strength already present in women with breast cancer and contributed to the occurrence and persistence of dyspnea even after 24 months post-infection, without significantly affecting functional exercise capacity. These findings highlight the necessity for a multidisciplinary approach to conduct more comprehensive assessments, particularly in patients with breast cancer in the post-COVID phase. These findings have clear clinical implications for the follow-up and rehabilitation of post-COVID-19 breast cancer patients, since the exacerbation of respiratory muscle weakness and persistence of dyspnea, even months after infection, highlight the need for targeted interventions, including respiratory muscle training, individualized physiotherapy programs, and long-term monitoring of cardiorespiratory function. These strategies may help mitigate functional impairments, improve exercise tolerance, and enhance quality of life in this vulnerable population, while also informing personalized rehabilitation plans based on each patient's clinical-pathological profile and history of COVID-19.

Ethics approval and consent to participate

All ethical issues were considered in the study and are reported accordingly in the methods section.

Funding

Brazilian National Council for Scientific and Technological Development (CNPq; Grants 402364/2021–0, 441017/2023–1, and 305335/2021–9), Secretariat of Science, Technology, and Higher Education of the State of Paraná (SETI, grant 220/2024), Araucária Foundation (Grants 147/2025 and 08/2025), Unioeste PRPPG/PROEX/EXPOS (Grant 001/2024), and Itaipu Binacional (grant 4500007500/2024).

Author's contribution

All authors contributed to the study conception and design, material preparation, data collection and analysis. The first draft of the manuscript was written by Ani Paula Brasil and Carolina Panis, and all authors read and approved the final manuscript.

Acknowledgments

The authors thank the Brazilian National Council for Scientific and Technological Development (CNPq; Grants 402364/2021-0, 441017/2023-1, and 305335/2021-9) for supporting this study.