Table 2.
The overview of clinical trials on phytochemicals utilized in mitigating side effects of breast cancer conventional therapies (surgery, radiotherapy, chemotherapy, and targeted therapy by aromatase inhibitors)
| Phytochemical | Study design | Year | Study participants (number) | Results | Reference |
|---|---|---|---|---|---|
| Surgery | |||||
| Linfadren® (contains diosmin, Mellilotus officinalis extract rich in coumarins, and Uva ursi extract rich in arbutin) | Randomized controlled trial | 2019 | BCRL patients (n = 50) | Safe and effective when combined with CDT for reducing BCRL when compared with CDT alone | [66] |
| Radiotherapy | |||||
| Silymarin | Randomized, double-blind, placebo-controlled clinical trial | 2019 | BC patients undergoing radiotherapy (n = 40); silymarin or placebo group on chest wall skin following radical mastectomy and starting at the first day of radiotherapy | Reduced severity of radiodermatitis | [67] |
| Nigella sativa L. extract | Randomized, double-blind, placebo-controlled, clinical trial | 2019 | BC patients undergoing radiotherapy (n = 62); Nigella sativa gel group or placebo group | Decreased severity of ARD and delayed moist desquamation onset | [68] |
| EGCG | Single-institution phase II trial | 2016 | BC patients that underwent mastectomy followed by adjuvant radiotherapy (n = 49); topical EGCG applied daily (starting when grade I dermatitis appeared and ending 2 weeks after radiotherapy) | Reduced pain in 85.7% of patients, burning feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6% | [69] |
| Chemotherapy | |||||
| Nutritional intervention on healthy eating (emphasizing fruits, vegetables, grains, fat-free or low-fat milk products; low saturated fats, trans fats, cholesterol, salt, and added sugars) | Randomized controlled trial | 2021 | BC patients at the beginning of neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, and an intravenous antiemetic pattern); intervention group receiving an individualized diet plan (n = 19) and control group (n = 15) | Preserved the role function of QoL and handgrip strength reduced the occurrence of nausea/vomiting, loss of appetite, and the frequency of leukopenia and abdominal pain | [70] |
| PG (thew form not stated) | Randomized, double-blind, placebo-controlled trial | 2020 | Early BC patients (n = 125) receiving AT-based chemotherapy, randomized into PG group or placebo group | Lower incidence of subclinical heart failure and lower cardiac troponin T levels in PG group vs placebo group | [71] |
| Peppermint (Super mint oral drop™) | Randomized controlled trial | 2020 | BC patients undergoing chemotherapy, experimental group received 40 drops of peppermint extract (n = 42) and control group (n = 42) | Mean score of severity of nausea, vomiting, and anorexia lower in experimental group vs. control group | [72] |
| Mistletoe extracts (Helixor A™, Iscador M Spez™) | Randomized controlled trial | 2018 | 95 BC patients undergoing surgery and adjuvant chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil; mistletoe extracts group (n = 64) injected three times/week week during 18 weeks of chemotherapy and control group (n = 31) | Trend toward less neutropenia and improved pain and appetite loss scores in breast cancer patients | [73] |
| Ginger (powdered rhizoma) | Randomized, double-blind and clinical trial study | 2016 | BC patients undergoing chemotherapy (n = 65); ginger group – regimen for 5 days before and 5 days after chemotherapy (twice daily 500-mg capsules of powdered ginger root) | Effective to relieve chemotherapy-induced nausea and vomiting (reduced vomiting, frequency of nausea) | [74] |
| Aromatase inhibitors | |||||
| Hydroxytyrosol, omega-3 fatty acids, and curcumin | Prospective, multicentre, open-label, single-arm, clinical trial | 2019 | Post-menopausal BC patients (n = 45) with elevated CRP receiving predominantly AI | Reduce pain and inflammation (decreased CRP) in breast cancer patients with aromatase-induced musculoskeletal symptoms | [75] |
| Yi Shen Jian Gu | Randomized controlled trial | 2018 | Postmenopausal BC patients (n = 77) with hormone-receptor positive stage I – III receiving AI | Improved musculoskeletal conditions | [76] |
AI; aromatase inhibitors, ARD; acute radiation dermatitis, AT; anthracycline, BC; breast cancer, BCRL; breast cancer-related lymphedema, CDT; complex decongestive therapy, CRP; C-reactive protein, EGCG; epigallocatechin-3-gallate, PG; Platycodon grandiflorum, QoL; quality of life, TCM; traditional Chinese medicine