Adapted physical activity along with the introduction of Mediterranean diet and their early application in postoperative period may be a successful strategy to improve the physical and psychological health of BC patients underwent surgery ( Figure 1 ).

The primary objective of the study is to compare whether implementation of an APA and healthy lifestyle (Mediterranean diet) will result in an overall improvement of physical and mental status including reduction in the number and severity of clinically relevant adverse events (AEs), in the study group compared with the control group during a 24-month enrollment period.

The secondary aim is to compare whether APA improves perception of cancer-related fatigue (CRF) and sleep quality (both measured via specific questionnaires), BMI, bone health, aerobic capacity, heart rate and serum lipid profile in the study arm. In addition, levels of Work Ability as well as health care provider and patient attitudes toward APA as adjunctive therapy will be assessed. Finally, the effect of adapted physical activity and a healthy diet on reducing the recurrence of the disease is being investigated.

Considering the high technical component of foil and saber, two fencing specialties, an adapted form of fencing is proposed that allows participants to enjoy the training more. As it is a one-sided sport, participants are encouraged to change the grip of the weapon several times during training in order to use both limbs equally and not to neglect the operated side. To avoid possible complications, low weight foil and saber are used within the APA. The wide use of parries forces the fencer to make larger movements that allow greater involvement of the shoulder joint to improve the range of movement of the operated arm. The content was developed by the Università degli Studi di Roma Tor Vergata in collaboration with Daniele Garozzo, specialist in sports medicine and Olympic foil champion; Fabio Maria Galli and Lucio Landi, foil, and saber coaches of Olympic fencers, respectively. From an athletic performance perspective, it must be considered a moderate-intensity physical activity (i.e., participants feel increased heart rate, respiration, and body temperature, but are still able to carry on a conversation), with the added benefit of being safe, psychologically engaging, fun, and social to encourage broad participation and minimal dropout (44).

The FENICE study is a mono-center, randomized clinical trial targeting women with stages I-III BC within four weeks from surgery, conducted at the Breast Unit of Policlinico Tor Vergata Rome and Frascati Scherma ASD. The sequence of study and control group is randomized to minimize the influence of time-dependent variables. The participants, regardless of arm dominance, will be followed up by oncologists, radiotherapists, and surgeons according to the BC guidelines. All subjects participating in the study will undergo a sports medicine examination to objectify whether there are any alterations or diseases that pose a risk to the patient and to determine whether the patient needs to have additional tests and more specific examinations performed. For participants in the study arm only, APA consists of two fencing sessions (1 h/session) per week within 15 days of enrollment. The minimum number of sessions for the assessment of the primary endpoint is 48 sessions over six months up to a maximum of 96 sessions over 12 months ( Figure 2 ).

After a warm-up period dedicated to muscle awakening and progressive cardio-respiratory stress, participants begin specific fencing exercises, starting with basic footwork (advance, retreat, lunge) and ending with actions in which the injured side holds the saber. During the main activity (40 minutes of fencing), exercise intensity will be individually tailored based on a preliminary assessment. All participants will undergo an exercise stress test on a cycle ergometer during the recruitment phase of the study. This test will measure key physiological parameters, including heart rate, oxygen consumption (V’O2), and the MET (Metabolic Equivalent of Task) values achieved (45). The MET value, which represents the energy cost of physical activities, will be used to calibrate the intensity of physical exertion during training sessions. Specifically, the fencing exercises will be designed to reach an intensity that is approximately 60-70% of the participants’ maximal MET values determined during the stress test. This range corresponds to moderate-intensity exercise, which has been shown to be effective in improving cardiovascular fitness and overall health. Additionally, to ensure safety and maximize adherence, participants’ heart rates will be monitored during training to maintain the desired intensity. The target heart rate zone will be calculated using the Karvonen formula, which considers the participants’ resting heart rates and the intensity percentage derived from their stress test results. This individualized approach ensures that participants engage at a cardio-respiratory intensity that is challenging yet enjoyable. They will be encouraged to maintain a level of exertion where they can still respond verbally (the “talk test”), indicating they are working within a safe and effective moderate-intensity zone (46–48).

Adapted fencing includes offensive and defensive actions, which are performed considering the mobility of the shoulder. The primary (tierce = outside; quart = inside; fifth = head) and secondary blocks are therefore performed by patients with maximum mobility, without ever causing pain. Coordination, agility, and strength are encouraged during exercises between patients and during lessons with the fencing master. The adapted fencing lesson ends with a cool-down period. Since different subjects experience different physical outcomes for the cancer and the subsequent treatment, the program must address these individual needs while respecting safety principles. Therefore, rest and water breaks will be provided when necessary, and simplified or less strenuous movements will be suggested as alternatives for those who find parts of the workout too challenging or unsafe. In addition, participants are encouraged to use both saber and foil, also depending on which master is holding the training session. In any case, the weapons used will be adapted in material to avoid excessive strain or fatigue as stated above. Moreover, the courses and masters allow 12 participants per session with a maximum ratio of 1 master per 2.5 participants. During the study protocol, participants are also encouraged to follow healthy diet and adhere to the standards of the Mediterranean diet through the prescription of a personalized diet by a nutritional biologist involved in the project. Conventional bioelectrical impedance (BIA) testing to assess body composition is also planned during protocol follow-ups. To assess adherence to the Mediterranean diet, the Prevención con Dieta Mediterránea (PREDIMED) questionnaire will be completed both at the beginning and at the end of the study (49). The participants of the FENICE study will be followed up by several specialists before and during the APA period ( Figure 3 ). This study was approved by the ethic board of the Policlinico Tor Vergata of Univeristy of Rome and the enrollment will start in September 2024 and the recruitment will take an 18 months’ time window for the inclusion of the expected 150 participants.

The inclusion and exclusion criteria for the FENICE trial are listed in Table 3 .

Patients of any ethnicity who are at least 18 years old with diagnosis of non-metastatic BC and already treated with surgery for primary tumor are eligible. The recruiting physicians will check the in- and exclusion criteria and determine whether the patient is eligible for participation (see Table 3 ). Participation in the FENICE study is on a voluntary basis. Participants will be informed about the aims of the study both verbally and in writing and will have the opportunity to ask questions and refuse participation.

The study will determine which group between subjects practicing APA and following Mediterranean diet (study arm) and those following the normal BC guidelines (standard of care) will benefit the most. Written informed consent, approved by an Italian Ethics Committee (R.S 100.23 5^th May 2023), will be obtained from each participant. Health complications for the participants will be addressed by the multidisciplinary team involved in the research and, if necessary, by contacting the patients’ MMG. If any complications that endanger the patient’s health, should arise the participant will be asked to withdraw from the study. Finally, subjects can leave the study at any time for any reason without any consequences, and, likewise, the research physicians can decide to withdraw a subject from the study for urgent medical reasons.

Participants will be included in the FENICE study for a total of 24 months and will be followed up differently based on the inclusion arm. In the study arm (APA and Mediterranean diet arm) patients will be monthly followed up for comorbidities, co-medication and herbal remedies, adverse events, and body mass index (BMI). Moreover, every three months also clinical evaluation, blood parameters, instrumental exams and QoL questionnaires will be carried out for the study arm patients. In the control arm, instead, all the mentioned parameters will be followed up every three months (see Figure 2 ).

Participants will be included in the study and will undergo several follow-up visits. During the follow-up period trained research nurses/data managers will contact patients at baseline (T=0) (± one week), and subsequently every four weeks (± two weeks), to go through a standardized questionnaire and to collect data on the outcomes of sequelae and clinical symptoms/AEs. In addition, all patients will be contacted by the research nurse/data manager at the end of the APA period (± two weeks from the end) to complete a last questionnaire. Research nurses/data managers additionally will collect required laboratory and or test results from participants’ (electronic) medical records. If a subject discontinues the APA and lifestyle interventions during the 12-week follow-up period, follow-up will continue.

The questions within the surveys will be performed to assess the occurrence and severity of any new symptoms experienced by the participants, and the global physical and psychological health after the beginning of APA. The questionnaires that will be administered to participants during the study period are listed in Table 4 .

The hypothesis guiding the formal determination of the sample size proposes an expected improvement of at least 15 points in the mean DASH score. The DASH score is a valuable, pragmatic, and frequently utilized metric in individuals with various musculoskeletal disorders of the upper limb. Ranging from 0 to 100, it encompasses responses to 30 questions (https://orthotoolkit.com/dash/) An improvement of at least 15 points is considered clinically significant in enhancing functional ability. The statistical parameters are configured in a highly conservative manner, considering the non-pharmacological nature of the intervention (adapted physical activity) and the inherent inter-individual variability in response, particularly within the treated group (Group 1). Therefore, with alpha and beta errors set at 0.01, a standard deviation in Group 1 that is twice that of Group 2 (SD: 20 compared to 10), even exceeding the hypothesized difference (15 points), 56 patients per group are deemed necessary. Considering the enrollment capabilities of our group and potential physiological withdrawal of patients, the sample size has been increased to 150 total patients. The target population will be at least 18 years of age (of any ethnicity) with a diagnosis of non-metastatic breast cancer and already treated with surgery for the primary tumor. This total will be divided into two sub-groups by randomization in blocks of 75 patients each (intervention group, Group 1, and control group, Group 2). The first group will be distinguished by subjects treated with adapted physical activity rehabilitation and with correct lifestyle suggestions. The second group, on the other hand, will be characterized by standard care without physical activity rehabilitation or lifestyle suggestions.

The descriptive statistical analyses, the central tendency, variability, symmetry and kurtosis will be calculated, all accompanied by appropriate graphical representations. Regarding the inferential analyses, we will continue with the verification of the parametric and non-parametric hypotheses, respectively for the quantitative variables with parametric tests such as: Student’s t-test, Fisher’s F-test, etc. and for categorical variables using non-parametric tests such as: chi-square, Mann Wittney’s U, Fisher’s exact test, etc. Only results with p-values ≤ 0.05 will be considered statistically significant. Principal component analysis (PCA) will be adopted to explore the relationships among secondary variables and identify patterns of improvement related to the APA intervention (50).