Etiology of Breast Cancer

Most common cancer among women. Truly genetic breast cancers have been estimated to account for only 5% of the incidence. Family history accounts for increased risk, however only a first degree association accounts for more than a trivial amount. Longer intervals between menarche to the first full-term pregnancy and from menarche to cessation of menses are associated with significantly higher risks.

Women whose menarche begins at age 12 or earlier have twice the risk of developing breast cancer. Women who have a natural menopause after 55 are at twice the risk as prior to 44.

The increased risk associated with ERT in postmenopausal women or oral contraceptives in premenopausal women is either very small or nonexixtent. Highest risk is prolonged use prior to first full-term pregnancy before age 45.

Regional differences: San Francisco is very high. Japan is very low. Risk equal after 2nd generation relocation. Fat intake has mixed results. Most consistently shown to increase risk is alcohol intake. Most breast cancers occur in patients not at high risk. Less than 1/3 of all patients with a diagnosis of breast cancer will die of the disease. (Patients die of distant mets.) Frying or broiling of fish and meat. Well done meats, bacon, gravy. (Carcinogen PhIP). Total low fat intake (less than 20% of total caloric intake). Diets rich in PUFA and omega-3 (fish oils)

Excerpts of Cancer Studies

Taken from ‘Clinical Pearls in Nutrition and Integrative Medicine.’

  • 3.75g of calcium carbonate daily had a reduction in the colon cancer labeling index by 58%. This study showed that long-term calcium supplementation significantly suppressed the rectal epithelial proliferation in adenoma patients.
  • 2g of elemental calcium and 3.5g of ispaghula husk were administered to colorectal cancer patients. The odds ratio for recurrence was 0.66 for the calcium treatment and 1.67 for the fiber treatment.
  • It was found that in males, the risk of adenoma was significantly associated with an intake of animal protein and vitamin A. There was an inverse association seen with carbohydrate intake.
  • Low levels of circulating 1,25-dihydroxyvitamin D in women may indicate a higher risk of distal colorectal adenomas.
  • The risk of lymphomas increased by 25% and 51% when there was a doubling of concentrations of benzene and nitrogen dioxide, respectively, during pregnancy.
  • The consumption of animal products which is high in the diet in the US, may have contributed to the rise in prostate cancer. Lycopene from New World tomatoes reduces the risk of prostate cancer.
  • 68.7% of cancer patients used complementary and alternative therapies. Alternative therapies appear to be part of oncology, irrespective of geographic location.
  • Use of Complimentary and Alternative Medicine by cancer patients is not associated with perceived distress or poor compliance with standard treatment, but with active coping behavior.
  • In 18 subjects who applied vitamin E oil at 400IU/ml at 1ml, to oral lesions that developed during chemotherapy, 6 of 9 subjects had a complete resolution of their lesions within 4 days of initiation of therapy whereas 8 of 9 patients receiving placebo did not have complete resolution.
  • Supplementation of Vitamin C at 1g significantly reduced chromosomal damage, suggesting it reduces the risk of chemotherapy-induced carcinogenesis.
  • IV infusion of glutathione shortly before administration of cisplatin protects against its neurotoxic (ie. myelosupression and peripheral neuropathy)and nephrotoxic effects. Hair loss was also diminished.
  • N-acetylcystine was partially protective against ifosfamide-induced cystitis.
  • Oral, not IV glutamine inhibited the increased GI permeability that resulted from chemotherapy (cisplatin and 5-FU plus mediastinal radiation therapy).
  • Selenium administration resulted in significant protection from cisplatin-induced nephrotoxicity. Selenium administration was also associated with less leukopenia, less use of granulocyte colony-stimulating factor, and less need for blood transfusions.
  • Genistein is an isoflavone derived from soy. Genistein has antiestrogenic properties. This may make it beneficial in tumors that possess estrogen receptor positiveness such as in certain breast cancers. Some have found a synergism between tamoxifen and genistein in down-regulating signal transduction and inhibiting the growth of human breast cancer cells in culture. Genistein has been shown to enhance the accumulation of cisplain and doxorubicin in accumulation-defective resistant cancer cells and to increase the accumulation of cisplatin in nonresistant cancer cells. Soybean products have been shown to reduce methotrexate-induced damage of the gastrointestinal mucosa.
  • Quercetin has been shown to inhibit the growth of several human and animal cancer cell lines in vitro. It has been shown to enhance the cytotoxicity of several neoplastic agents. Quercetin has enhanced the growth-inhibitory effects of doxorubicin. It has also been shown to enhance the antiproliferative activity of cisplatin, nitrogen mustard, busulfan and cytosine arabinoside.
  • Extra virgin olive oil: potent inhibitor of reactive oxygen species (ROS). ROS may be a cause of fat-related neoplasms, such as cancer of the breast and colorectum.
  • Monounsaturated fatty acids had an inverse association with bladder cancer.
  • Total vitamin E intake was inversely associated with bladder cancer.
  • High levels of cadmium, lead and mercury were associated with brain tumors.  Smoking and dental amalgams have been associated with accumulation of cadmium and mercury in brain tissue.
  • The risk of postmenopausal breast cancer may be increased in those women with low intakes of folate if they consume alcohol-containing beverages.
  • Approximately 66.7% of breast cancer sufferers reported using complementary or alternative medicine.
  • Vitamins A,E, beta-carotene and C have been shown to be associated with a lower risk of breast cancer when supplemented. CoQ has antioxidative and antiproliferative effects and anecdotally may have benefit in breast cancer. Green tea may increase the effectiveness of doxorubicin. Soy may lower the risk of breast cancer in premenopausal women.
  • Those who breastfed for more than 2 years had a 54% reduced risk of developing breast cancer.
  • Low rates of breast cancer in southern European countries may be due to their high use of olive oil.
  • Hyperbaric oxygen treatments resulted in significant reductions in pain, edema, and erythema for persistent symptoms following breast-conserving therapy.
  • Consumption of a soy diet reduced levels of 17 beta-estradiol by 25% and progesterone by 45%.
  • Premenopausal breast cancer risk is inversely related to the consumption of onions, lettuce, and spinach.  Onions are one of the richest sources of the flavonoid quercetin. It is the highest food antioxidant source in the Western diet.  Quercetin inhibits proliferation of human breast cancer cells in vitro and delays mammary tumorigenesis in vivo.
  • Vitamin E inhibited the growth of breast cancer cells in vitro and in vivo. Vitamin E succinate’s in vivo inhibitory effect may be due to the inhibition of tumor angiogenesis.
  • Sugars and refined cereals have a higher rate of digestion and may cause a glycemic overload, which increases plasma insulin concentrations and insulin-like growth factor 1, which is an important mitogenic stimulant of tumor cell growth in vitro.
  • Mean high levels of serum retinol suggested a reduced risk of cervical dysplasia.
  • Low levels of serum vitamin A and E in the blood leads to a subsequent risk for cervical cancer.
  • Vitamin C appeared to increase the chemotherapeutic response of cisplatin and etoposide in cervical cancer.
  • Electroacupuncture reduced the frequency of vomiting in chemotherapy patients.
  • Vitamin C reduced platelet lipid peroxidation and ROS generation produced by cisplatin.  Vitamin C can lower the toxicity of cisplatin.
  • Plasma concentrations of CoQ increased in patients receiving doxorubicin.
  • Physical activity and cereals may be protective against colon cancer.
  • Dietary folate was significantly inversely associated with colon cancer in men.
  • Rectal epithelial proliferation (REP) labeling index decreased 58% in calcium-supplemented individuals.
  • Males exposed to chlorinated water for 35 to 40 years had an increased risk of colon cancer.
  • Total fruit and vegetable consumption was inversely related to colorectal cancer risk. The association was mainly due to the fruit consumption.
  • Meat and fish were positively associated, and olive oil was negatively associated with colorectal cancer.
  • High intakes of raw and cooked garlic may be associated with a protective effect against stomach and colorectal cancers.
  • In a recent study, 83% of patients from across a wide spectrum of cancers at different disease stages used complementary health practices.
  • Exercise has been shown to reduce psychological stress and fatigue in patients receiving radiotherapy and after high-dose chemotherapy with peripheral blood stem cell transplantation. A reduction of treatment-related complications has been seen in cancer patients participating in exercise programs during cancer treatments.
  • Vitamin C was found to be inversely associated with gastric cancer. Reductions were between 40%-60%.
  • Survival of gastric cancer was associated with high intake of vitamin E.
  • Whey protein shows an antitumor effect on prostate, uterine, kidney and bladder cancers. (10-30g/day).
  • Sodium-selenium used to treat the side effects of radiochemotherapy with patients with squamous cell carcinoma. A positive reduction in edema was noted.
  • Mistletoe extract (iscador) increased the survival time up to 40% for all types of cancer examined, including rectal, colon, stomach, small cell, non-small cell, and breast cancer with or without axillary metastasis or remote metastasis. It is the most commonly used oncological drug in Germany.
  • Natrium-selenit had a positive effect on acute and chronic lymphedemas in radiation oncology.
  • Cisplatinum therapy can result in magnesium loss. Severe hypomagnesemia is associated with vertigo, ataxia, cramps, cardiovascular symptoms, and arrhythimias.
  • In 700 patients with malignant hematological and lymphatic diseases, the median survival time was 11.4 years for those treated with mistletoe extract compared with 8.6 years for those who didn’t.
  • It was found that use of aspirin at least 3 times per week for a period of 6 months was associated with a 40% reduction in the risk of ovarian cancer. Chronic inflammation that is seen in endometriosis and pelvic inflammatory disease may be related to ovarian cancer.
  • Women using estrogen replacement therapy at baseline had higher death rates from ovarian cancer than those who never used the therapy.
  • Leisure time physical activity was significantly associated with reduced occurrence of ovarian cancer.
  • There was a significant trend of increasing risk with increasing exposure level to pesticides in pancreatic cancer patients.
  • The risk of colon cancer is reduced between 40%-50% among the most active individuals. There was a reduction of 25%-30% in breast cancer risk with physical activity.
  • Nutrients including phytoestrogens, found in cereals, grains, legumes, soybeans, fruits and vegetables, vitamin E, lycopene, and selenium may have a protective effect against prostate cancer. Vitamin E is found in spinach, nuts, green leafy vegetables and vegetable oils. Selenium is found in seafood, meat, grain cereals, milk, and garlic.
  • Vitamin C intake is inversely related to prostate cancer risk.
  • The intake of yellow-orange and cruciferous vegetables was inversely related to prostate cancer risk, especially for advanced cases of cancer.
  • The risk of prostate cancer declined with increasing concentrations of alpha-tocopherol. For gamma-tocopherol, there was a 5-fold reduction. Soybeans contain an 8:1 ratio of gamma to alpha tocopherol.
  • Green tea polyphenols have an anti-inflammatory and anticarcinogenic potential for skin cancers. Green tea polyphenols may be a new chemoprotective agent against UV-induced skin cancer.
  • Constituents of soy, which include protease inhibitors, saponins, and phytic acid, may have anticarcinogenic effects. Isoflavones are found in soybeans and forage plants. The anticancer effects of isoflavone phytoestrogens may be due to their ability to bind to estrogen receptor sites. Genistein (soybeans) has been shown to inhibit cell proliferation in estrogen receptor-positive and estrogen receptor-negative human cancer cell lines. Isoflavones may inhibit tumor growth through a reduction in invasion and angiogenesis.
  • Vitamin B1 promotes tumor cell proliferation. Clinical and experimental data have shown that increased thiamine utilization occurs in human tumors and can interfere with experimental chemotherapy.
  • The World Cancer Research Fund suggests eating 400-800 g/day or 5 or more portions per day of a variety of vegetables and fruits year round, and this may lead to a 30%-40% reduction in world cancer incidence.


A very controversial therapy. In essence, some are afraid that antioxidants also protect cancer cells. This does not appear to be the case.Most chemotherapeutic agents do not involve the production of free radicals (the cytotoxicity of most agents does not depend upon the induction of oxidative stress). However, many types of anticancer drugs induce oxidative stress ( anthracyclines, alkylating agents, platinum coordination complexes and epipodophyllotoxins), and oxidative stress slows the growth rate of cancer cells. Since rapidly growing cancer cells are more sensitive to the cytotoxic effects of anticancer drugs than are slow growing cancer cells, oxidative stress induced by the drugs can reduce the effectiveness of cancer chemotherapy. Antioxidants, however, can counteract the oxidative stress induced by the chemotherapeutic agents, thus enhancing the growth rate of cancer cells and improving the response to chemotherapy.

Many side effects of cancer chemotherapy are caused by the oxidative stress induced by anticancer agents. Examples include doxorubicin-induced cardiotoxicity, bleomycin-induced pulmonary fibrosis, cisplatin-induced nephrotoxicity and the induction of secondary malignancies due to the mutagenic effect of free radicals and other radical oxygen species (ROS) that are generated upon exposure to cancer chemotherapeutic agents. Vitamin E, C, CoQ, beta-carotene, glutathione, acetylcysteine, and selenium have been shown to reduce the side effects and/or enhance the efficacy of cancer chemotherapy.

Certain nutrients including sulfhydryl antioxidants, selenium and some plant polyphenolic compounds (bioflavonoids) may interfere with the anticancer activity of some chemotherapeutic agents. The strongly electrophilic anticancer agents, which include the platinum-coordination compounds (cisplatin and carboplatin) and the alkylating agents can form covalent complexes with the nucleophylic sulfhydryl antioxidants N-acetyl cysteine, alpha lipoic acid and glutathione. A similar concern exists with selenium and the platinum-coordination compounds. St. John’s Wort should also be avoided during chemotherapy. Administration of antioxidants should preferable begin at least 2 weeks prior to administration of chemotherapy.

Excerpts of Review of Dietary Antioxidants During Cancer Chemotherapy: Impact on Chemotherapeutic Effectiveness and Development of Side Effects, by Kenneth A Conklin, MD, PhD


  • Effective for HRT.
  • Blocks estrogens bad effects.
  • Hinders neovascularization.
  • Prevents buildup of arterial plaque, reducing risk of CV disease and stroke.
  • May prevent prostate cancer by hindering cell growth.
  • Fights osteoporosis by stimulating bone formation and inhibiting bone resorption.
  • Lowers levels of estrogen in the blood by 30 to 40%.
  • The higher the levels of soy isoflavones in the body, the lower the chance you will be diagnosed with breast cancer.
  • The FDA did not find evidence to warn any group of patients when it approved a heart health claim for soy protein. Neither did the American Heart Association.
  • Soy decreases breast inflammation, which may be a precursor to breast cancer.
  • Genistein and diadzein are plant phytoestrogens which resemble human estrogen, yet are weaker.  Mimics estrogen and binds to receptor sites.
  • Soy may involve modulation of estrogen synthesis and metabolism away from genotoxic metabolites to an inactive metabolite.
  • No human studies have ever shown that soy increases risk of cancer. The FDA hasn’t issued a single warning for eating soy protein.
  • High soy intake during adolescence may reduce the risk of breast cancer later in life.
  • A study in Asia of soy with Tamoxifen showed tamoxifen equally as effective with consumption of soy.
  • In vitro studies showed additive positive results between soy and tamoxifen at slowing breast cancer cell growth. Soy may also help counteract uterine stimulation associated with ERT or tamoxifen.
  • Mice studies showed synergistic benefits when combining soy and tamoxifen.
  • Univ of Illinois at Chicago study: rats exposed to carcinogens. Rats fed a diet of soy combined with tamoxifen, tumors were reduced by 62%. Soy used alone reduced tumors by 37%. Tamoxifen used alone reduced tumors by 29%.
  • Univ of Illinois at Urbana study: Genistein stimulates the growth of estrogen-dependent human breast cancer cells implanted into mice.