Evaluation of an Early Individualized Integrated Rehabilitation Program versus Standard Rehabilitation Program for Smoking Cessation in 115 Smokers Among 467 Female Breast Cancer Patients 2019–2021 in Slovenia

Background

Tobacco-related illnesses are an important public health issue on a global level [1,2]. Among other things, cigarette smoking affects cancer and cardiovascular risk and survival [1,2]. Earlier smoking cessation is associated with a reduced risk of all-cause mortality and confers substantial benefits on general health and, as such, is the most effective way to reduce smoking-induced health burdens [1].

Breast cancer incidence is globally increasing [3]. Breast cancer is diagnosed in a total of 2.3 million new cases annually, which represents 11.7% of all cancers [4]. The long survival of breast cancer patients sets a new challenge for healthcare systems: How to successfully improve the quality of life of breast cancer patients during and after treatment, and in the long term [5].

Rehabilitation can help survivors achieve and maintain the highest possible physical, social, psychological, and occupational functioning within the limitations imposed by cancer and its treatment [6]. The implementation of integrated rehabilitation is best accomplished by an interdisciplinary team that tailors interventions to the needs of the individual patient [7]. Patients are therefore referred to appropriate specialists for care according to the recommended interventions. The outcomes are most successful when rehabilitation starts early, ideally before the start of treatment [7].

Our hypothesis is that the early introduction of integrated and tailored rehabilitation from the beginning of cancer treatment is associated with a higher rate of smoking cessation in breast cancer patients compared to patients who undergo non-integrated rehabilitation. This study aimed to evaluate an early individualized integrated rehabilitation program and standard rehabilitation program for smoking cessation in 115 smokers among 467 female breast cancer patients between 2019 and 2021 in Ljubljana, Slovenia.

Material and Methods

ETHICS STATEMENT:

The study was reviewed and approved by the Protocol Review Board (Approval 0082/2020) and the Ethics Committee of the Institute of Oncology Ljubljana (Approval 0086/2019). The study was performed in accordance with the ethics standards laid down in the latest version of the 1964 Declaration of Helsinki and conducted with the understanding and consent of all the subjects involved.

PATIENTS:

The present prospective pilot study included 467 breast cancer patients (29–65 (mean 52) years of age) treated consecutively at the Institute of Oncology Ljubljana from 2019 to 2021. Lymph node metastases were present in 34% of patients and distant metastases in 5% of patients (Table 1). All patients were followed longer than 1 year. The control group and intervention group included 282 and 185 patients, respectively. We did not collect data on the length of smoking or the number of cigarettes smoked per day.

The inclusion criteria were invasive breast cancer first diagnosed in 2019–2021 and an age of less than 65 years at the time of diagnosis. The exclusion criterion was if the patient was unable to fill in the questionnaires due to misunderstanding the questions. Only patients who gave informed consent for participation in the study were included.

QUESTIONNAIRES FOR MONITORING OF PATIENTS’ NEEDS: The EORTC (European Organisation for Research and Treatment of Cancer) quality of life questionnaires (QLQ) and NCCN (National Comprehensive Cancer Network) questionnaire are an integrated and internationally used system for assessing the health-related quality of life of cancer patients [7–9]. All patients filled out 3 standardized questionnaires (EORTC QLQ - C30 (Core 30), EORTC QLQ - BR23 (Breast Cancer Module 23), and NCCN) before and half a year and 1 year after the beginning of treatment. The following problems of the patients were monitored: depression, anxiety, cognitive functions, fatigue, insomnia, lymphedema, problems with the shoulder joint, scarring, heart function, lack of female hormones, gynecological problems, sexual problems, muscle and joint pain, smoking, alcohol consumption, diet, pain issues, alopecia, and returning back to work. During a regular check-up with the oncologist, each patent filled in the 3 standardized questionnaires.

CONTROL GROUP OF PATIENTS:

Patients from the control group obtained the same rehabilitation as was offered to all breast cancer patients at the Institute of Oncology Ljubljana before the start of the prospective study. The patients from the control group were referred to rehabilitation only if the oncologist identified medical problems that needed to be treated.

INTERVENTION GROUP OF PATIENTS: The patients from the intervention group had an additional interview with a specially designated nurse (hereinafter referred to as coordinator) at the beginning of the treatment, after half a year, and after a year. The coordinator recorded the problems each patient was experiencing on the basis of the triage questionnaires and interviews with each patient, and educated the patient on how to manage their symptoms by themselves, and prevent adverse effects. The coordinator was always available to meet the patient or answer to their questions and coordinated the integrated rehabilitation for this study. The documentation of each patient from the intervention group was discussed at the multidisciplinary meeting for integrated rehabilitation before, half a year, and 1 year after the beginning of treatment. The multidisciplinary rehabilitation team recommended appropriate interventions according to the patient’s needs, and referred the patient accordingly to the Institute of Oncology’s clinical pathway of integrated rehabilitation [9]. All patients who had medical needs or were smokers were referred to general practitioner at the beginning of the treatment, after half a year, and after 1 year. If necessary, the coordinator referred the patient for additional consultation with an oncologist, psychologist, physiotherapist, and/or clinical nutritionist. For all patients in the intervention group, physical exercise guided by a kinesiologist was provided online twice a week. If the patient had more pronounced psychological problems, they were referred to a psycho-oncologist for treatment. Depending on the patient’s needs, the patient was referred to their oncologist, the appropriate departments of the Institute of Oncology or to other healthcare providers within the framework of the Slovenian health system. All the interventions were covered by health insurance.

SMOKING CESSATION TREATMENT:

All smokers were advised to stop smoking by an oncologist, a coordinator, and a general practitioner. Furthermore, they were referred to a general practitioner for counseling on leading a healthy lifestyle. General practitioners had the possibility to refer patients to a number of workshops held at the Center for Health Promotion, which operates as part of community health centers. Among the workshops there are also smoking cessation workshops to which all smokers were referred.

STATISTICAL ANALYSIS:

Data on the patients’ demographics, extent of disease, and oncological treatment were collected. Self-reported prevalence of tobacco smoking before treatment and 1 year after the beginning of cancer treatment were collected. Data were managed in REDCap (Research Electronic Data Capture) Version 12.4.22. Additional data processing was performed in Excel (Microsoft Office Professional Plus 2016). The distribution of categorical variables was analyzed using the chi-square test and analysis of variance was used for numeric variables in Version 27 of SPSS statistical software.

Results

CHARACTERISTICS OF SMOKERS AND NON-SMOKERS:

The demographic and clinical characteristics of the patients, pathological characteristics of tumors, and treatment of the smokers and non-smokers are presented in Table 1. Lymph node metastases were present in 34% of patients and distant metastases in 5% of patients (Table 1). There were no differences between the smokers and non-smokers in terms of age, living environment, extent of disease, or treatment. In comparison to non-smokers, smokers were found to have a lower level of education (P=0.001) and lower socioeconomic status (P=0.01).

CHARACTERISTICS OF THE CONTROL AND INTERVENTION GROUP OF PATIENTS:

The demographic and clinical characteristics of the patients, pathological characteristics of tumors, and treatment of the patients from the intervention and the control group are presented in Table 2. The control group of patients did not differ statistically significantly from the intervention group of patients in terms of age, education, or systemic cancer treatment. A higher proportion of patients from the intervention group came from an urban environment than those from the control group. Lymph node metastases were more often present in the intervention group than in the control group (P=0.05). Lymph node metastases were present in the intervention group and in the control group of patients in 40% and 32% of cases, respectively. Breast-conserving surgery was performed in the intervention group and control group in 58% and 52% of cases, respectively. Therefore, a higher share of patients in the intervention group received external beam radiotherapy of the breast and/or axillary region in comparison to the control group (P=0.04). Radiotherapy was performed in the intervention group and the control group of patients in 80% and 72% of cases, respectively.

SMOKING BEFORE AND ONE YEAR AFTER THE BEGINNING OF CANCER TREATMENT:

In total, 115 patients were tobacco smokers before the beginning of cancer treatment. There were no differences between the intervention and control group of patients in the prevalence of smoking before the treatment. Before cancer treatment, smoking was present in the intervention and control group in 22% and 27% (P=0.27) of cases, respectively. One year after the beginning of cancer treatment, 45 patients had stopped smoking and 4 patients from the control group of patients began to smoke. One year after the beginning of cancer treatment, smoking was present in the intervention group in 10% of cases and in control group in 20% of cases. Therefore, smoking was less common in the intervention group than in the control group (P=0.004). The frequency of smoking in the intervention and control group of patients before and 1 year after the beginning of cancer treatment is presented in Figure 1.

CHARACTERISTICS OF PATIENTS WHO CONTINUED SMOKING AND THOSE WHO STOPPED SMOKING:

The demographic and clinical characteristics of patients, pathological characteristics of tumors, and treatment of patients who continued smoking and stopped smoking are presented in Table 3. None of the characteristics correlated with smoking cessation. However, 2 treatment options showed a trend toward statistical significance: breast reconstruction and chemotherapy. Patients with breast reconstruction and those without reconstruction stopped smoking in 51% and 34% (P=0.08) of cases, respectively. This may be due to surgeons strongly advising patients against smoking before any reconstruction and advising patients to quit smoking. On the other hand, patients treated with chemotherapy have greater difficulty with smoking cessation. This is indicated in the trend of a smaller proportion of those patients treated with chemotherapy stopping smoking in comparison with those not treated with chemotherapy (P=0.06). Among the patients treated with chemotherapy and those not treated with chemotherapy, cessation of smoking was present in 30% and 48% of cases, respectively.

Discussion

The aim of this study was to compare the outcome of simple, non-integrated rehabilitation compared to integrated rehabilitation on cessation of smoking. We found that integrated rehabilitation from the beginning of cancer treatment was associated with a higher rate of smoking cessation in breast cancer patients in comparison to non-integrated rehabilitation. Before rehabilitation, there was no difference in the rate of smoking between the intervention and control groups of patients, while 1 year after the beginning of cancer treatment there was statistically significant difference in number of smokers in favor of the intervention group of patients (P=0.004).

It is well known that income, occupation, and education are related to smoking behavior [10–12]. Our study has also shown that smoking is associated with a lower level of education and lower socioeconomic status, which is in concordance with the frequency of smoking in the general Slovenian female population [13].

In a national population study of 21 970 smokers from the Netherlands, Willemsen et al [14] found that relatively large numbers of people who stopped smoking were in the ≥45 age group, but in our patients, age was not correlated with cessation of smoking. Physicians encourage patients to stop smoking completely, at least during treatment, as this is important in reducing the complications of treatment, especially after surgical treatment and/or radiotherapy [15]. Smoking is one of the predictive factors for surgical site infections in patients undergoing surgery for breast carcinoma, besides other factors such as mastectomy, diabetes, chronic obstructive lung disease, and a BMI of >35 kg/m2 [16]. Before any reconstruction was performed on the patients included in the present study, surgeons strongly advised them against smoking, and 51% of smokers in this study took their advice seriously and were still not smoking 1 year after surgery. On the other hand, of the patients who had chemotherapy and were smokers, only 30% managed to quit smoking, which was less than among those who were not treated with chemotherapy (48%). Obviously, chemotherapy presents such a significant psychological burden that patients should probably be offered additional help to relieve them of the associated psychological stress.

A Cohrane systematic review showed that behavioral support may help people to stop smoking for 6 months or longer [17]. We believe that our intervention group of patients had such support. The mainstay of our integrative rehabilitation was patient education about what they themselves can do to manage their symptoms, and to mitigate or even prevent the adverse effects of treatment. In contrast to the control group, the patients from the intervention group had 3 interviews with the integrated rehabilitation coordinator, who during each interview educated smokers about the risks of smoking and how to stop smoking. All smokers were referred to a general practitioner for counseling on leading a healthy lifestyle. General practitioners referred smokers to a smoking cessation workshop organized by the Center for Health Promotion at community health centers. Additionally, the intervention group of patients were advised to be physically active and were provided with physical exercise guided by a kinesiologist twice per week, which was carried out online.

When patients learn that they have cancer and are faced with the possible consequences, they are also faced with the fact that cancer can be fatal. At that point, many patients feel ready to radically change their lives. We believe that this presents a window of opportunity to quit smoking. Therefore, our opinion is that every oncologist and general practitioner should advise breast cancer patients who smoke to quit smoking. We completely agree with Wong et al [15], who recommends all physicians include a thorough conversation about smoking during their initial diagnoses, treatment, and follow-up appointments, while also providing useful information, evidence, and support. It is well known that smoking is a risk factor for the development of breast cancer [18,19], and a recent meta-analysis has shown that there is an increased risk of cancer recurrence in smokers [20]. An excellent argument to use in convincing patients to stop smoking was provided in a large systematic review and meta-analysis by Sollie and Bille [20], who reported a 28% increase in breast cancer-associated mortality in current smokers, but the mortality in former smokers was equal to never smokers. It seems that ceasing to smoke can lower a patient’s risk of dying from breast cancer [20]. Moreover, smoking cessation is one of the most effective ways to improve one’s health, as it reduces the risk of cardiovascular and lung diseases, and reduces the risk of developing new cancers [1,2].

Our rehabilitation approach of integrated medicine is based on a decentralized model, as there are no special medical institutions for oncological integrated rehabilitation in our country. As in many other countries, there is a shortage of staff at our tertiary medical center. In addition, the centralized model causes high travel costs and longer transport times for many patients. Clearly, a decentralized model is more patient-friendly, as highlighted in a systematic review of the delivery of smoking cessation interventions for tobacco users in oncology settings by Young et al [21]. This is why a decentralized model is used in the treatment of smoking cessation in our country as well.

In our intervention group of patients, a combination of brief advice based on risk communication [22] and referal of smokers to smoking cessation workshops was used. Our results are better than results of Li et al [22], who reported that only brief advice based on risk communication was not effective for quitting but only improved the rate of smoking reduction [22]. We believe that also other interventions used as part of integrative medicine probably helped our intervention group of patients to smoking cessation. One year after the beginning of cancer treatment, smoking was present in the intervention group in 10% of patients and in 20% in the control group.

Our study has many limitations. First of all, it was not randomized and the number of included patients was relatively small. Furthermore, we did not assess the duration (years) or intensity (number of cigarettes smoked per day) of smoking. Our prospective study on integrative rehabilitation was planned to improve many aspects of rehabilitation and not only smoking cessation, so different interventions were used simultaneously to achieve the maximum benefit for patients. Therefore, it was not possible to determine the contribution of each intervention to smoking cessation. However, our study provides a realistic presentation of smoking cessation in breast cancer smokers who received either standard rehabilitation or integrative rehabilitation in our country.

Conclusions

Smoking cessation was more common after early integrated rehabilitation than after standard rehabilitation in breast cancer patients.