Case Report

Oxygen-Ozone Therapy in Rheumatic Symptoms in 3 Patients with Breast Cancer Undergoing Aromatase-Inhibitors: A Successful Approach

Umberto Tirelli^1,2,*, Cinzia Cirrito¹, Martina Pavanello¹ and Arben Lleshi²

Tumor Center, CFS, Fibromyalgia and Oxygen Ozone Therapy Unit, Tirelli Medical Clinic, Pordenone, Italy

National Cancer Institute, Aviano, Italy.

^*Corresponding author: Umberto Tirelli, Tumor Center, CFS, Fibromyalgia and Oxygen Ozone Therapy Unit, Tirelli Medical Clinic, Pordenone, Italy, Tel. +390434086508; E-mail: utirelli@cro.it

Citation: Tirelli U, Cirrito C, Pavanello M, Lleshi A (2019) Oxygen-Ozone Therapy in Rheumatic Symptoms in 3 Patients with Breast Cancer Undergoing Aromatase-Inhibitors: A Successful Approach. J Clinical Case Rep Case Stud 2019: 59-62

Received: 15 October, 2019; Accepted: 29 October, 2019; Published: 02 November, 2019

Abstract

Background: In patients with positive hormone receptors, aromatase inhibitors are effective in reducing the risk of breast cancer recurrences. On the other hand, painful side effects like dysfunction and musculo-skeletal pain can reduce the treatment compliance.

With not many treatment options controlling these symptoms, non-pharmaceutical interventions such as oxygen-ozone therapy may play a key role for managing the rheumatologic symptomatology. We have reported on the effectiveness of oxygen-ozone in the treatment of fatigue in oncological patients, Chronic Fatigue Syndrome and fibromyalgia patients.

Methods: in this study we are reporting the effectiveness of oxygen ozone therapy in three patients with breast cancer accusing rheumatic symptoms such as muscular-skeletal pain and fatigue, while undergoing aromatase-inhibitors therapy.

We are describing our successful experience with oxygen-ozone therapy in treating severe rheumatologic symptoms, mainly muscular-skeletal pain and fatigue, in three women with breast cancer undegoing Anastrazole.

Conclusions: Oxygen-ozone therapy, in the management of rheumatic symptoms in patients with breast cancer undergoing aromatase inhibitors, showed to be efficient with no side effected associated with its use.

Keywords: Breast cancer; Aromatase inhibitors; Muscular-skeletal pain; Fatigue; Ozone therapy

Introduction

Aromatase inhibitors have demonstrated efficiency in reducing the threat of breast cancer recurrences in patients with positive hormone receptors. However, the drug compliance can be limited because its painful side effects such as musculo-skeletal pain and dysfunction. Five to 61% of patients undergoing aromatase inhibitors complain of muscolo-skeletal symptoms [1], and one study has shown that 20% of patients have stopped the medication due to these side effects [2].

Multi-joint arthralgias are the most frequent symptoms, although specific joints such as small joints of the hands and feet, shoulders, hips and lower back are also involved. In addition, focal inflammation with edema may be the cause of carpal tunnel syndrome, trigger finger or De Quervain’s tenosynovitis of the wrist.

The etiology of these symptoms is still unknown, even if there are many conjectures. Maybe estrogen deficiency leads to degradation of joint cartilage and joint inflammation [3], as demonstrated by radiographic studies showing an increase in joint and tenosynovial fluid in patients on these medications [4]. Or estrogen may have antinoceptive properties and the estrogen deficiency caused by aromatase inhibitors are causing patients to be hypersensitized to pain.

Patients with breast cancer have often many symptoms quite difficult to be managed by the physicians. They often complain of rheumatic symptoms when undergoing chemotherapy or Anastrazole. These painful symptoms may hold back patients from daily activities, negatively impacting on their quality of life. There are not many pharmacologic options for controlling these symptoms, therefore non-pharmaceutical interventions such as oxygen-ozone therapy are playing an important role in the management of rheumatologic symptoms [5]. Oxygen-ozone therapy has been previously reported by our group to be effective in fatigue of patients with tumors, Chronic Fatigue Syndrome and in patients with fibromyalgia [6,7].

Ozone is a gas discovered in the mid-nineteenth century, it is a molecule of three atoms of oxygen in a dynamically unstable structure because the mesomeric states present. Ozone has no color and a strong odor; it is explosive in solid or liquid form. Its half-life is 40 min at 20°C and is about 140 min at 0°C. In the atmosphere, its purpose is to protect us from the damaging effects of UV radiation. Ozone occurs at less than 20 µg/m3 from the Earth's surface at concentrations that are absolutely compatible with life. Researchers believe ozone has many therapeutic properties, regardless of its dangerous effects [8]. The establishment of accurate medical ozone generators has only recently made permissible the evaluation of the mechanisms, action and possible toxicity of ozone in clinical trials [9]. Ozone can tarnish organic compounds [10], and, when present in smog, has well-known toxic effects on the respiratory tract [11,12]. The ozone employed in medicine derives from medical grade oxygen and is administered in accurate therapeutic doses, but it is never inhaled [13,14]. Ozone has health benefits in dental caries, decreases blood cholesterol and stimulates anti-oxidative responses, it modifies oxygenation in inactive muscles and is used in complementary treatment of hypoxic and ischemic syndromes [15,16].

All treatments for cancer can cause fatigue, perhaps because of the tissue damage, or the accumulation of products derived from dead cells. Cancer treatments are also the cause of pro-inflammatory cytokines development, important in patients complaining fatigue after the treatment [17]. Fatigue increases during radiation therapy, reaching its peak at about half cycle and improving about two months after the end of therapies. Biotherapies expose patients to endogenous and exogenous cytokines causing a flu-like syndrome with symptoms such as fever, chills, general malaise, fatigue, myalgias, and headaches, as well as cognitive deficits and mental fatigue. Chemotherapy also relates to fatigue and when pain, anxiety and depression are also present, it worsens it. The patient’s characteristics associated with aggravation or decrease of fatigue are unknown. Overall, fatigue and pain are often related with cancer treatments [18].

The objective of the present study is to report the efficacy of oxygen ozone therapy in three patients with breast cancer experiencing rheumatic symptoms such as muscular-skeletal pain and fatigue, while on aromatase inhibitors therapy.

Case Report - 1

A 54-year-old female in post-menopausal state has been diagnosed with a high-grade, estrogen-receptor positive invasive mammary carcinoma, for which she has been treated with a modified radical mastectomy. She has gone on to receive adjuvant chemotherapy consisting of four cycles of Adriamycin/Cyclophosphamide followed by four cycles of Paclitaxel. This chemotherapy has been well tolerated in general apart from for episodic myalgia and weakness, which resolved after a dose-reduction for Paclitaxel. After completing chemotherapy, patient has been started on adjuvant Anastrazole, 20 mg/day as a single daily oral dose. Shortly after starting Anastrazole therapy, the patient has started to experience excruciating muscle spasms, weakness, insomnia and fatigue. She has rated her musculo-skeletal discomfort as 10 on 10-point scale (0: none to 10: severe discomfort). These symptoms have been quite severe, and the patient’s daily activities have been adversely affected to a great extent. This appeared to be clearly related to the use of Anastrazole as the temporary withdrawal of Anastrazole has resulted in improvement of all of her symptoms. Analgesics and physical therapy have not been successful in providing even modest relief of symptoms with continued use of Anastrazole. In light of both progression-free and overall survival advantage of continuing adjuvant hormonal therapy, the patient has been referred to our Tumor Center and Oxygen Ozone Therapy Unit, Tirelli Medical Clinic, Pordenone, Italy for oxygen-ozone therapy for symptom management.

Patient informed consent was provided. Ozone has been given according to the SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, twice a week for one month at a concentration of 50 mg in 200 cc of blood in 3-4 50 ml syringes (each 50 cc of blood equals to one 50 ml syringe with 50 µg of Oxygen-Ozone) and then twice a month as maintenance therapy. Shortly after the start of the therapy the patient has obtained a significant reduction of her musculo-skeletal discomfort and it has been reduced to 2-3 on a 10-point scale. In addition, energy and sleep have been improved. Her symptomatic improvement has continued at this level for over 6 months after the introduction of ozone therapy and it’s lasting while receiving Anastrazole therapy without any significant side effect.

Case Report – 2

A 62 years old female in post-menopausal state has been diagnosed with high-grade, estrogen-receptor positive invasive mammary carcinoma for which she has been treated with a quadrantectomy and local radiotherapy. Sentinel lymph node biopsy has been performed resulting negative. She has been started on adjuvant Anastrazole 20 mg/die at a single day oral dose, but after three month of therapy, due to muscolo-skeletal symptoms, she has been referred to our Tumor Center and Oxygen Ozone Therapy Unit, Tirelli Medical Clinic, Pordenone, Italy for oxygen-ozone therapy for possible oxygen-ozone therapy for symptoms management. Patient informed consent was provided. She has been started on intravenous ozone to the SIOOT protocols, twice a week for one month at a concentration of 50 mg in 200 cc of blood in 3-4 50 ml syringes (each 50 cc of blood equals to one 50 ml syringe with 50 µg of Oxygen-Ozone) and then twice a month as maintenance therapy. Her muscolo-skeletal symptoms have been significantly reduced to 1 on a 10-point scale and she is still on therapy after nine months from starting the therapy without any significant side effects. She is on Anastrazole for a 5-year long therapy.

Case Report – 3

A 56-year-old female in post-menopausal state has been diagnosed with a high grade estrogen-receptor positive invasive mammary carcinoma for which she has been treated with surgery and put on adjuvant anastrazole therapy due to the estrogen-receptor positivity. The drug has been given at 20 mg/die at a single day oral dose, but after two month of therapy she has stopped the treatment with benefit on her muscolo-skeletal symptoms. She has been referred to our Tumor Center and Oxygen Ozone Therapy Unit, Tirelli Medical Clinic, Pordenone, Italy for oxygen-ozone therapy for possible oxygen-ozone therapy for symptoms management. Patient informed consent was provide. She has been started on intravenous ozone to the SIOOT protocols, twice a week for one month at a concentration of 50 mg in 200 cc of blood in 3-4 50 ml syringes (each 50 cc of blood equals to one 50 ml syringe with 50 µg of Oxygen-Ozone) and Anastrazole has been reintroduced as adjuvant therapy. At this time, she has not experience any of the previous muscolo-skeletal symptoms and she is on ozone therapy for one year without side effects. She is scheduled to receive Anastrazole for a 5-years therapy.

Discussion and Conclusions

To-date there aren’t many important studies on the therapeutic interventions for these symptoms. A physiatric approach will take into account all of the patient’s physical symptoms and how they impact on their lives, using a biopsychosocial model. In addition, talking to patients about their attitude toward the aromatase inhibitor could be noteworthy; in fact, there are patients that would consider discontinuing the therapy with aromatase inhibitors because the side effects, while others would never consider stopping the medication, in spite of its side effects.

Other therapies could also be considered for these symptoms, even if research is lacking on what is most appropriate. The most frequently used pain medications like acetaminophen, topical or oral non-steroidal anti-inflammatory drugs, tramadol, or opioids, should be employed even if there are very few evidence-based literatures available on these treatments.

A single-arm trial of duloxetine-up to 120 mg/d, in patients undergoing aromatase inhibitors therapy, has demonstrated a clinically significant improvement in pain scores [19]. Glucosamine (1,500 mg/d) and chondroitin sulfate (1,200 mg/d) administered for 24 weeks, have shown a moderate improvement in the musculoskeletal symptomatology [20].

Vitamin D level studies have shown contradictory results on ameliorating the musculoskeletal symptoms induced by aromatase inhibitor [21,22]. Acupuncture has also been studied with mixed results [23,24].

Our case reports describe a successful experience of using oxygen-ozone therapy to treat severe rheumatologic symptoms, mainly muscular-skeletal pain and fatigue, in three women with breast cancer on Anastrazole. Many patients with breast cancer develop somatic complaints such as those experienced by our patients. These symptoms are common amongst breast cancer survivors on Aromatase inhibitors and are difficult to manage, especially in a busy oncology practice.

Oxygen-ozone therapy should be taken in consideration for the management of rheumatic symptoms in patients with breast cancer undergoing aromatase inhibitors, as integrative medicine [24], both for the efficacy of this approach and for the lack of side effected associated with ozone therapy.

Institutional Review Board Statement: Accepted

Conflict of Interest Statement: None of the Authors declare any conflict of interest

References

NORCAL Publications