Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

4.2. Antioxidant Vitamins and Minerals

There is scientific documentation that relates the high intake of antioxidant with both a lower risk of developing breast cancer [104, 110] and a positive impact in the mortality rates of cancer. In accordance with the American Cancer Society and Cancer Research UK, although the studies of nutritional supplements to reduce cancer risk have not all been disappointing, until now there is no consistent evidence that any type of nutritional supplement can help to prevent cancer, in contrast with the nutrients (including antioxidant) obtained in a healthy and balanced diet with abundance of fruits and vegetables [108, 384, 385]. Therefore, according to the American Cancer Society, the best advice is to get antioxidants through food sources rather than supplements.

The use of antioxidant agents in patients with cancer seems to be an intelligent idea based on their biologic mechanism, first because of their potential anticancer properties—that is, diminished oxidative damage; reduced proliferation and angiogenesis; increased apoptosis [386]—and second because they may reduce the oxidative damage from conventional cancer treatments involving chemo- and radiotherapy and therefore limited the toxicity of these therapies [383].

Despite the potential improvement outcomes, the supplementation with antioxidant agents (e.g., vitamin A, vitamin E, vitamin C, and selenium) during cancer treatment is discussed controversially mainly due to the probable interaction with or modification in the effects of conventional cancer treatments [386, 387]. Since radiotherapy and several chemotherapy agents (e.g., alkylating agents, anthracyclines, podophyllin derivatives, platinum complexes, and camptothecins) exert their anticancer properties through production of reactive oxygen species (ROS) and promoting apoptosis, the antioxidant agents may reduce the efficacy of radio- and chemotherapy-related cytotoxicity and consequently act as potential cancer-promoting. Antioxidant supplements appear to successfully block otherwise effective prooxidant therapies and protect both normal and tumour cells from the oxidative damage [106]. In this context, some studies highlight the adverse effects of antioxidant supplementation on overall mortality for patients with cancer [388, 389]. However, other studies proved the benefits of antioxidant supplementation in a specific treatment (e.g., chemotherapy [112]; radiotherapy [390]; and both [381]). Based on these restricted outcomes of the observational studies and clinical trials, there does not appear to be obvious evidence concerning the effect of antioxidant supplementation and its use during chemo and radiation treatments. Therefore, high-quality placebo-controlled trials are needed.

4.2.1. Vitamin A and Carotenoids

Vitamin A refers to a group of compounds named retinoids which cooperate in a large variety of physiological processes such as in vision, bone growth, reproduction, cell division, and differentiation [391, 392]. Two forms of vitamin A can be ingested via diet: preformed vitamin A, found in foods derived from animal sources (e.g., liver, whole milk) and absorbed as retinol, and provitamin A carotenoids, derived from fruits and green leafy vegetables and converted into retinol once ingested. Most of the supplements contain the preformed vitamin A [391]. It is stored in the liver. Synthetic retinoids are also available such as bexarotene and fenretinide.

Various longitudinal cohort studies, performed in different ethnical groups and geographic locations worldwide, evaluated the intake of carotenoid and endogenous retinol levels with the risk for developing breast cancer [115–118]. The type of beneficial carotenoids is controversial [115–121]. For example, in the postmenopausal women population, some studies did not correlate the retinol levels with breast cancer risk [115, 117]. Other studies demonstrated different effects between the lycopene levels (i.e., a carotenoid substance that does not convert into vitamin A) and the risk of breast cancer, that is, an increased risk [116, 119] or a protective effect among ER-positive and progesterone receptor-positive breast cancer [120].

The European Prospective Investigation into Cancer and Nutrition cohort studied 1502 female incident breast cancer cases (premenopausal () and oestrogen receptor-negative cases ()). Carotenoids, tocopherols, vitamin C, and retinol plasma levels were determined to find an association with risk of breast cancer. The results showed that a higher concentration of plasma β-carotene and α-carotene is associated with lower breast cancer risk of oestrogen receptor-negative tumours and higher risk of breast cancer was found for retinol in relation to oestrogen receptor-negative/progesterone receptor-negative tumours. There was no statistical difference for the other studied compounds [121].

A positive relationship between a high plasma carotenoids and breast cancer survivals was reported by Rock et al. in the Women’s Healthy Eating and Living study [122].

Higher biological exposure to carotenoids, when assessed over the period of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.