INTRODUCTION:

Malignancy is recognized as the second leading cause of death in developed countries.¹ Breast cancer is the most common cancer among women with many differences in the extent of its incidence in different countries and regions. Common treatments for malignancies include chemotherapy and radiotherapy.^2-6 Today, various treatments are being used to treat cancer patients.

The goal of all of these treatments is to destroy cancer cells without damaging the host cells. There are three main methods in this regard including surgery, chemotherapy and radiation therapy. Over the years, the use of chemotherapy has helped patients with cancer to be treated so that their lifespan has been significantly extended, but unfortunately, in addition to all benefits of chemotherapy, it has consequences as well.^7-11 Chemotherapy alone or in combination with head and neck radiotherapy can cause complications in the oral mucosa.^12-15 It has been reported that one out of every 22 women in India and one out of eight women in the United States develops breast cancer. Mucositis refers to a form of mucosal injury caused by a series of clinical manifestations such as erythema and pain, being the common complications of some chemotherapy and radiotherapy drugs.¹⁶ Mucositis is a painful inflammatory reaction of the oral mucosa, which is accompanied by infiltration of inflammatory cells, associated with the destruction of the epithelium and serious ulcers. It starts 4 to 7 days after high-dose courses of medication and disappears 2 to 4 weeks after the end of treatment. Various studies have indicated that the higher the dose and frequency of medications, the higher the risk of oral mucositis. Patients’ risk factors for oral mucositis include age, poor oral hygiene, trauma, and kidney diseases. Oral mucositis is seen in 40% of adult patients receiving standard chemotherapy doses and 60% of patients receiving preparatory therapy. ^17,18 Oral mucositis is more common in children and is seen in 65% of children with cancer undergoing chemotherapy.^19-21 Animal studies have also shown that vinblastine, vincristine, doxorubicin, and cyclophosphamide act as agents of dental problems, and cyclophosphamide acts as an alkylating agent.^22,23 According to what stated above, the present study attempts to investigate the oral and dental complications caused by cyclophosphamide in patients with breast cancer in the chemotherapy ward of Shahid Mostafa Hospital, Ilam province in 2019.

MATERIALS AND METHODS:

The present study is a cross-sectional analytical one conducted on patients with breast cancer in Shahid Mostafa Hospital in Ilam in 2020-2021, based on a researcher-made questionnaire. The participants were selected and investigated according to the inclusion and exclusion criteria from the patients who had referred to the chemotherapy ward of Shahid Mostafa Hospital in Ilam. At first, the patient’s information was evaluated and then they were examined in the same session. Before the examination, patients were given full explanations and written consent was obtained. The inclusion criteria were as follows: female patients with breast cancer who were receiving specific treatment with cyclophosphamide. Oral complications included: plaque, debris, looseness, dry mouth, mucositis and other oral lesions. The information obtained for each patient was scored separately and according to the score or grade specified for each complication, the effectiveness or ineffectiveness of the stated drug was judged (Table 1). The information was collected by a researcher-made questionnaire. Also, t-test and chi-square test were used to analyze the data. To describe the results, mean and standard deviation were sused for quantitative variables, and frequency and percentage were used for qualitative variables and all statistical tests were conducted at a significant level of 0.05.^{24, 27}

RESULTS:

The present study was conducted on 69 patients with breast cancer with a mean age of 50.89±8.81 and an age range of 36-69 years, and a mean body mass index of 24.18±2.56 ranging between 19 to 29. All patients were female. There was no significant relationship between age and mucosal severity in patients with breast cancer (P-value = 0.43). There was no significant relationship between the severity of mucositis and body mass index. 68.1% of patients had mobility, 20.3% had no dental plaque, and 11.6% had no debris (Table 2). The results have indicated that 89.9% of patients who used oral cyclophosphamide suffered from oral and dental complications; 44.9% of patients had mild mucositis and 55.1% had severe mucositis, only one patient had severe dry mouth and 46.6% had a mild degree of dry mouth. The results have also indicated that 29% of patients developed painful ulcers that covered more than half of the oral mucosa (Table 3). There was a significant difference between the status of plaque index and the severity of mucositis (P-value = 0.003); there were 8 mild cases of muscositis among the individuals with desirable plaque index. Two cases with poor plaque index had mild muscositis, and 6 cases had severe muscositis. A significant relationship was found between dry mouth and mucosal severity. 31.3% of patients with low-degree dry mouth suffered from severe muscositis, and 75% of patients with moderate-degree dry mouth suffered from severe mucositis.

Table 1: Oral mucositis scale according to EORTC / RTOG

Grade	Oral toxicity scale
Grade 1	Diffuse erythema, patients can eat solid food
Grade 2	Erythema and small foci of ulcers, patient can take soft diet
Grade 3	Painful ulcers extending to more than half of the oral mucosa, patient can take liquids only
Grade 4	Painful ulcers covering almost all mucosal surfaces, alimentation is not possible

Table 2: Demographic characteristics of breast cancer patients

Variable			Mean ± SD
		Age	50.89 ± 8.81
			Frequency (percent)
Mobility of tooth	Lack of Mobility		47 (68.1)
	Mobility in buccolingual <1mm		22 (31.9)
Dental plaque	No plaque is observed		14 (20.3)
	Coverage *<1/3*		24 (34.8)
	Coverage *<2/3* X 1/3		27 (39.1)
	Coverage < 2/3		4 (5.8)
Debris	No debris was observed		8 (11.6)
	Coverage *<1/3*		17 (24.6)
	Coverage *<2/3 X1/3*		36 (52.2)
	Coverage < 2/3		8 (11.6)

Table 3: The presence of mucositis in patients with breast cancer

The presence of mucositis	Frequency	Percentage
Diffuse erythema	12	17.4
Erythema and small ulcers	19	27.5
Painful ulcers that extend to more than half of the oral mucosa	20	29
Oral ulcers that cover almost the entire oral mucosa	18	26.1

DISCUSSION:

Oral mucositis is a serious complication of radiotherapy and chemotherapy. Specific chemotherapy regimens with similar cytotoxic potency have different destructive effects on patients’ oral mucosa.²⁸ However, the mechanism of chemotherapy-induced mucosal damage and how these drugs work has not been fully explained. Moreover, information about the toxicity of some drugs differs in different studies.¹ In the present study, as many as 46.4% of patients were young and 53.6% of them were middle-aged. The severity of mucositis in middle-aged patients was higher than that of young patients (59.5%). This is in line with the results of the study conducted by Ashghyar et al. indicating a high percentage of this complication in adults and elderly age groups.⁸ The results indicated that there was a significant difference between the status of plaque index and the severity of mucositis; there were 8 mild cases of muscositis among the individuals with desirable plaque index, and two cases with poor plaque index had mild muscositis, and 6 cases had severe muscositis. This is in line with the study conducted by Cheng et al., indicating the effective role of oral condition before chemotherapy and oral hygiene in the development of oral mucositis.²⁹ In the study conducted by Borowski et al., it has been indicated that oral hygiene can reduce oral mucositis by up to 70% and delay the onset of mucositis and reduce the duration of moderate to severe mucositis in patients undergoing bone marrow transplantation;³⁰ this is in line with the results of the present study. There was no significant relationship between age and mucosal severity in patients with breast cancer. There was no significant difference between two degrees of mucosal severity and the mean age. The study conducted by Rosen et al. has indicated an association between age and moderate and severe mucositis; this has been confirmed in another study conducted by Rick et al.^31,32 The results of the present study are in line with those of the study conducted by Cheng, ruling out any association between oral mucositis and age. ³³ In terms of gender, only women have been investigated in the present study. The relationship between patients’ gender and the incidence of oral mucositis has been ruled out in the studies conducted by McCarthy, Rick and Cheng.^{29, 32,34} However, Rosen et al. have reported that being female is an independent risk factor for oral mucositis.¹ In contrast, Chiara et al. have reported that mucositis develops more frequently in men, yet no difference was observed in mucositis incidence in terms of age or history of chemotherapy.³⁵ Given this contradictory information, how age and sex affect the incidence and severity of oral mucositis in patients is still unknown, and it seems essential to conduct further studies with an emphasis on the effect of sex and age on oral mucositis. There was a significant relationship between dry mouth and mucosal severity; this is in line with the results of the study conducted by Acharya et al. indicating that the incidence of xerostomia, taste changes and oral mucosal pigmentation in patients with breast cancer undergoing chemotherapy increased from 28% to 50%.⁹ In this study, the severity of oral mucositis was higher due to the use of cyclophosphamide; this is not in line with the results of the study conducted by El-Husseini et al., indicating that anti-metabolite chemotherapy drugs are the most effective factor associated with oral mucositis. ³⁶

CONCLUSION:

Regarding mucositis, the importance of oral hygiene in cancer patients is required to be taken into serious consideration. Although there is no scientific evidence to support the role of oral hygiene in the prevention and treatment of mucositis, most researchers believe that following oral hygiene can reduce the duration and severity of mucositis. It is recommended that studies with a larger sample size and a larger statistical population, including men and women with cancer, be investigated in later studies for acquiring more accurate results.

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Received on 20.03.2022 Modified on 23.06.2022

Research J. Pharm. and Tech 2022; 15(12):5517-5520.

DOI: 10.52711/0974-360X.2022.00931