CANCERCANCERQUESTIONSQUESTIONSANDANDCONTROVERSIESCONTROVERSIES

A Seminar by Robert Buist PhD

Copyright © 2012 International Academy of Nutrition

Current cost of cancer research in US:

US $110 billion/year

($1 trillion spent since 1971)

25% breast cancers diagnosed are slow-to-develop (ductal or lobar carcinomas2% become malignant

CISS 24(3)11 (2004)

80% of all DCIS’s (ductile 80% of all DCIS’s (ductile carcinoma-in-situ) never carcinoma-in-situ) never become invasive even if left become invasive even if left untreateduntreated

Townsend p124 June 2004

More than half of women More than half of women diagnosed with breast cancer at diagnosed with breast cancer at Roswell Park Memorial Centre Roswell Park Memorial Centre Hospital had Hospital had benign lesions that benign lesions that were unable to spreadwere unable to spread

80% of all DCIS’s (ductile 80% of all DCIS’s (ductile carcinoma-in-situ) never become carcinoma-in-situ) never become invasive even if left untreatedinvasive even if left untreated

Townsend p124 June 2004

Fibrocystic Breast DiseaseFibrocystic Breast Disease

PREVENTIONNo caffeine, coffee, chocNo dairy productsLow fat dietOmega-3 Fish Oil 3g/dayFresh fruit and veg 7serveNo alcohol

Only Only one in six biopsies one in six biopsies revealed cancerrevealed cancer after a positive after a positive mammogrammammogram

CISS 24(3)11 (2004)

Cochrane Review of Cochrane Review of Mammography Mammography

1. 1. No reliable evidenceNo reliable evidence that screening for that screening for breast cancer reduces mortality. breast cancer reduces mortality.

Olsen & Gotzsche Olsen & Gotzsche 20002000

2. Cochrane Review confirmed these 2. Cochrane Review confirmed these findings that findings that mammography did not mammography did not reduce all cause mortalityreduce all cause mortality

Olsen & Gotzsche Lancet 358, 1340-42 (2002)

SCREENING CAUSES SCREENING CAUSES INCREASED MASTECTOMY INCREASED MASTECTOMY

AND LUMPECTOMY AND LUMPECTOMY Screening identified slow-growing

tumours that would never develop into tumours

Even cancerous pathology tests may not mean development of life-threatening tumours Olsen & Gotzsche Lancet 358, 1340-42 (2001)

Mammogram End Points Mammogram End Points should be should be OVERALLOVERALL Mortality Mortality

Treatment of early cancers by Treatment of early cancers by tumourectomy and radiotherapy might tumourectomy and radiotherapy might increase the likelihood that deaths increase the likelihood that deaths among screen-detected breast cancer among screen-detected breast cancer cases will be misclassified as deaths cases will be misclassified as deaths from other causes, especially other from other causes, especially other cancerscancers

Lancet 358, 1340 (2001)

Seven Randomised Trials Seven Randomised Trials for Screening Mammographyfor Screening Mammography

There is There is NO survival benefit of mass NO survival benefit of mass

screening screening for breast cancer for breast cancer

Gotzsche et al, Lancet 355, 129-34 (2000)

NIH 1997 consensus conference NIH 1997 consensus conference recommend recommend againstagainst routine routine screening mammography for 40-screening mammography for 40-49year olds49year olds

N Engl J Nutr 336,1180-3 (1997)

Subjects between 40-50 years Subjects between 40-50 years who had a yearly mammogram who had a yearly mammogram showed a showed a 36 to 52% INCREASE in 36 to 52% INCREASE in breast cancer mortalitybreast cancer mortality

Lancet 1992

The number one enemy of The number one enemy of the cancer patient is:the cancer patient is:

metastasismetastasis

Townsend p125 June 2004

Needle BiopsiesNeedle Biopsies

There is a clear danger of There is a clear danger of seeding seeding needle tracks with malignant cellsneedle tracks with malignant cells which may enter vascular which may enter vascular channels or even be transported channels or even be transported to lymph nodes.to lymph nodes.

Danish Med Bulletin 25(2) 82-87 (1978)

Problems with SurgeryProblems with Surgery

Cell debris stimulates tumour growth Inflammation promotes tumour cells Post op bacterial infections (endotoxin) Cauterisation is tissue damage (inflammation) General anaesthesia potentiates tumour growth

Int Clin Nutr Rev 8(2) 62-68 (1988)

Cancer cells were found in Cancer cells were found in 59% of samples of blood59% of samples of blood lost lost by patients during surgery by patients during surgery for lung, ovarian, colon, for lung, ovarian, colon, oesophageal and other cancersoesophageal and other cancers

Dr Fedorine, Sydney Morning Herald, June 13, 2001

Pelvic Radiation Therapy forPelvic Radiation Therapy for

Rectal Cancer Rectal Cancer 8000 patients enrolled in 14 preoperative

and 8 postop randomised trials. 5 year survival was marginally better in

those who received radiotherapy (62.2% vs 63.3% dead (p=0.06)

Reduced local recurrence not overall survival.

Lancet 358, 1285 (2001)

Randomised controlled trials Randomised controlled trials compare one chemotherapeutic compare one chemotherapeutic agent with anotheragent with another

We need to compare agents with We need to compare agents with doing nothing (or with a placebo) doing nothing (or with a placebo) or with approaches using or with approaches using alternative therapiesalternative therapies

Townsend Letter for Doctors Feb-Mar (2004) pp 99-108

Approx 20 chemotherapeutic Approx 20 chemotherapeutic agents have been shown toagents have been shown to cause cancer cause cancer

(50 more are suspect)(50 more are suspect)

Survivors of ovarian cancer treated Survivors of ovarian cancer treated with chemo have 100 times higher with chemo have 100 times higher incidence of leukaemia. This is incidence of leukaemia. This is worsened when combined with worsened when combined with radiationradiation

Chemotherapy may produce good Chemotherapy may produce good

initial results but frequently poorer initial results but frequently poorer long-term prognosislong-term prognosis

Tumour regression by itself is a bad Tumour regression by itself is a bad predictor predictor for progression of diseasefor progression of disease

Regression is not likely to improve Regression is not likely to improve survivalsurvival

Townsend p33 2004

Breast cancer tissue samples Breast cancer tissue samples were co-cultured with patients’ were co-cultured with patients’ lymphocytes:lymphocytes:

After 12 years-After 12 years-

A. Lymphocytes that had no reaction A. Lymphocytes that had no reaction - - 47% women had died47% women had died B. Lymphocytes that were stimulated andB. Lymphocytes that were stimulated and

proliferated - proliferated - 95% women still alive95% women still alive

Dr James McCoy Annals NY Acad Sci 1993

Cancer Prevention is notCancer Prevention is notCancer Diagnosis Cancer Diagnosis

Mammograpy, breast palpation, PSA, Mammograpy, breast palpation, PSA, scans,endoscopy, X-rays, PAP smear, scans,endoscopy, X-rays, PAP smear, biopsy, tumour markers - AFP, HCG, PSA, biopsy, tumour markers - AFP, HCG, PSA, [CEA for colorectal], paraprotein [myeloma][CEA for colorectal], paraprotein [myeloma]

These are not Preventive MedicineThese are not Preventive Medicine

Prostate Cancer Incidence Prostate Cancer Incidence and PSA and PSA

Since introduction of PSA screening in Since introduction of PSA screening in US, US, incidence has doubledincidence has doubled between 1983- between 1983-87 and 1993-95 (55 to 110 per 100,000)87 and 1993-95 (55 to 110 per 100,000)

In UK: In UK: less PSA screening - less incidenceless PSA screening - less incidence

Lancet 359, 1341-1342 (2002)

Prostate Cancer Survival Prostate Cancer Survival after 10 Years after 10 Years

Watchful waiting - 91.5% (223 men)

Radiation therapy - 77% (682 men)

Radical Prostatectomy - 90% (1143 men)

(but depends on tumour size and differentiation)

Seven times Seven times as many cancer as many cancer tumours are discovered during tumours are discovered during autopsyautopsy than are discovered than are discovered during a person’s lifetimeduring a person’s lifetime

Townsend p124 June 2004

Strength of recommendationStrength of recommendation::A.A. PAP Smear High costs, data unreliable PAP Smear High costs, data unreliable A.A. Mammography>50yrs Better evidence Mammography>50yrs Better evidence C. C. Mammography <49yrs No evidence screening Mammography <49yrs No evidence screening reduces mortality reduces mortality B.B. FOBT,Colonoscopy & Sigmoidoscopy FOBT,Colonoscopy & Sigmoidoscopy No reduction in overall mortality No reduction in overall mortalityD.D. PSA An unproven intervention PSA An unproven intervention not specificnot specificD. D. Lung CT scan No evidence of reduced mortalityLung CT scan No evidence of reduced mortality

Thomas G Gates (Am Fam Physician 2001;63:513-22)Thomas G Gates (Am Fam Physician 2001;63:513-22)

Cancer delay by decrease in Cancer delay by decrease in mutation ratemutation rate

TypeType of Age (year) Average age Age of death

Cancer of cancer of death if mutation rate

is halved

Hepatoma 10 50 90

Lung 35 55 75

Prostate 40 85 130

The Handbook of Preventive Medicine Florence & Setright Kingsclear 1994

Blueberries rich in AnthocyaninsBlueberries rich in Anthocyanins

Greater firepower against cancer-causing free radicals than 40 other fresh fruits and vegetables

Research by the Human Nutrition Research Centre on Aging

DO NOT USE SINGLE DO NOT USE SINGLE

PHYTONUTRIENT SUPPLEMENTSPHYTONUTRIENT SUPPLEMENTS Beta carotene 30mg (Scand. Study) Lycopene (tomato paste) Lutein (egg yolk) Quercetin (onions) Genistein (carcinogenic)

Carotenoids, flavonoids & polyphenolics are involved in competitive inhibition.

HerbalGram 62, 54-55 (2004)

Effects of single flavonoidsEffects of single flavonoidsSingle flavonoids (quercitin, fisetin, flavone, luteolin and genistein) cross the placenta and induce DNA cleavage and infant leukemia.

These same chromosomal translocations involving the MLL gene are present in 80% of infants (<1yr) with Acute myelogenous and acute lymphoblastic leukemia.

NOTE: Glycosylated/methylated bioflavonoids and flavanones/flavanols do not cause these problems

Proc Natl Acad Sci (USA) 97 (9) 4790 - 4795 (2000)

Antioxidants in Cancer Therapy; Their Actions Antioxidants in Cancer Therapy; Their Actions and Interactions With Oncologic Therapiesand Interactions With Oncologic Therapies Davis W. Lamson, MS, ND and Matthew S. Brignall, ND

….exogenous antioxidants alone produce beneficial effects in various cancers... animal and human studies demonstrate no reduction of efficacy of chemotherapy or radiation when given with antioxidants. In fact, considerable data exists showing increased effectiveness of many cancer therapeutic agents, as well as a decrease in adverse effects, when givenconcurrently with antioxidants. Altern Med Rev 1999;4(5):304-

329

Food oils which promote Food oils which promote CANCERS CANCERS

High linoleic acid-containing oils and trans fatty acids (TFA) (corn, soya, safflower, sunflower, margarine)

Oils which prevent cancer: High lauric acid containing oils (coconut and palm),

omega-3 oils (fish, flax seeds, nuts)

Townsend 102-194, June 2002

Monounsaturated fats Monounsaturated fats cut breast cancer riskcut breast cancer risk Every 5 gram increase in dietary

polyunsaturated fat INCREASED by 69% the the relative risk for invasive breast cancer.

Conversely, for each 10g increment of monounsaturated fat, the relative risk for invasive cancer DECREASED by 45%

Archives of Internal Medicine 158,41-45 (1998)

ANTICANCER EFFECTS ANTICANCER EFFECTS

OF OMEGA-3 OILS OF OMEGA-3 OILS Low breast and prostate cancer in Japan Reduction in colonic adenomas Inhibition of promotion and progression Reduction in inflammatory eicosanoids

(PGE2, leukotriene B4, 12 OH eicosaetraenoic acid)

Decreases oestrogen production (PGE2 stimulates aromatase P450 which converts 19-carbon steroids to oestrogens)

Alpha-linolenic acid Alpha-linolenic acid RISK FACTOR for breast cancer when:RISK FACTOR for breast cancer when:

low dietary linoleic acid (GLAor EPA)

oxidised diet high in alcohol, saturated fats stress levels high

Better to add ground whole linseeds to diet - less oxidation and high lignan content (enterolactone and enterodiol) blocks oestrogen and oestrogen dependent tumours.

Results of 47,866 Men StudyResults of 47,866 Men Study

…”High alpha-linolenic acid (ALA) intake is associated with an increased risk of advanced prostate cancer.”

In contrast EPA and DHA intakes may be associated with a decreased risk of total and advanced prostate cancer.

Am J Clin Nutr 80, 204-16 (2004)

ALA Function Different to EPA ALA Function Different to EPA

ALA less effective in displacing AA from cell membrane phospholipids and inhibiting prostaglandin synthesis.

ALA has little conversion to EPA and almost zero conversion to DHA (may decrease DHA levels)

ALA has little influence on immune function and inflammatory cytokine production.

Genistein and Daidzein block TAMOXIFEN (at low not high concentrations)

1. Better to tell women on Tamoxifen to avoid low levels of soy

2. High soy eaters (70g/day) not on Tamoxifen have lower levels of

breast cancer

and genistein acts as an agonist in oestrogen-dependent target cells promoting breast cancer cell proliferation at low concentrations

Black Cohosh (40mg extr/day)Black Cohosh (40mg extr/day)safely and effectively treats hot safely and effectively treats hot flashes in women with a history flashes in women with a history of of ER-positive breast cancerER-positive breast cancer taking tamoxifentaking tamoxifen

HerbalGram 62,20-21 (2004)HerbalGram 62,20-21 (2004)

Psychoneuroimmunology Psychoneuroimmunology & Cancer & Cancer

Factors affecting outcome:

Practitioner attitude Social Isolation/Group support Fighting spirit/helplessness Optimistic/pessimistic attitude Will to live/faith

Lancet 1(8431) 750 (1985)Clin Oncol 21(3) 543-8

(2003)

COLORECTAL CANCER & STRESSCOLORECTAL CANCER & STRESS

Of 569 colorectal cancer patients those who experience on-the-job aggravation were 5.5 times as likely to develop cancer (compared with 510 matched health controls).

Epidemiol 495) 407-14 (1993)

Factors Predisposing toFactors Predisposing to Gastric Cancer Gastric Cancer

242 Japanese gastric cancer patients (484 controls)

*Eating quickly *Irregular sleeping *Overeating *Grey hair in males *Stress *Having dentures *Long working hours *Lack of teeth

Oncol Rep 5(5) 1191-4 (1998)

#Psychological factors #Psychological factors positively associated with positively associated with

lung cancer (preclinical)lung cancer (preclinical) Uncontrollable bursts of emotion (OR 1.8) Poor working circumstances - including

bad relationships with colleagues and superiors (OR 1.4)

Long term depression (OR 4.1)

#Study involved 750,000 including 309 lung cancer cases.

Chung Hua Liu Ksing Ping Hsueh Tsa Chih 18(5) 289-92 (1997)

Breast Cancer and Breast Cancer and Social Isolation Social Isolation

A population based sample of 525 black and 486 white women with newly diagnosed breast cancer

Fewer close friends and relatives (RR 2.1) Fewer sources of emotional support (RR1.8)

Cancer Epidemiol Biomarkers Prev 3(3), 253-9 (1994)

Chronically elevated levels of cortisone accompany the perception of loneliness which in turn reduces the immune defences of the body against malignant progression.

CANCER CELLS CAN REMAIN CANCER CELLS CAN REMAIN DORMANT - DORMANT - WHYWHY??

WHAT FACTORS RETARD WHAT FACTORS RETARD CANCER GROWTH?CANCER GROWTH?

SOYA MILK &SOYA MILK & PROSTATE CANCER PROSTATE CANCER

Men who consumed soya milk

more than once daily had a 70% REDUCTION in risk of prostate cancer

Cancer Causes and Control 9, 553-557 (1998)

LOW BLOOD LEVELS OF CoQ10 LOW BLOOD LEVELS OF CoQ10 in in

Cancer of breast, lung, prostate, pancreas, colon, kidney, head

and neck

Also in myeloma and lymphoma

Folkers K. Biochem Biophys Res Comm 224(2) 358-61 (1996)

CoQ10 improves survivalCoQ10 improves survival32 Breast cancer patients,18 months on CoQ10

90mg daily (plus other antioxidants, vitamins

and minerals plus surgery, radiation and chemotherapy)

Survival rate - 100% over 24 months (Expected - 6 deaths)

Remission - 6 patients. Decreased use of pain killers, improved quality of life, no weight loss.

Molecular Aspects of Medicine 15S, S231-S240 (1994)

Incomplete Removal of Incomplete Removal of Breast Tumour in 2 PatientsBreast Tumour in 2 Patients

3-4 months of high dose CoQ10 (390 and 300mg/day) resulted in complete regression of both residual breast tumours.

Biochem Biophy Res Comm 199(3) 1504-1508 (1994)

High Dose CoQ10 and High Dose CoQ10 and Tumour Remission Tumour Remission

3 Breast cancer patients on 390mg CoQ10/day for 3-5 years.

Patient 1 - complete remission of liver metastases

Patient 2 - remission of tumour spread to chest wall

Patient 3 - no microscopic evidence of remaining

tumour after mastectomy

Biochem Biophy Res Comm 212(1) 172-177 (1995)

VITAMIN D VITAMIN D NONCALCAEMIC FUNCTIONS NONCALCAEMIC FUNCTIONS

Most cells in the body have nuclear receptors for 1,25(OH)2D e.g. heart, stomach, panceas, brain, gonads

and activated T and B lymphocytes.

Vitamin D (1,25) can down regulate hyperproliferative cell growth.

ANTI CANCER EFFECT OF 1,25OHANTI CANCER EFFECT OF 1,25OH22DD Sunlight or dietary vitamin D leads to

increased 25-OH2 Vitamin D which acts as a substrate for 25OH2D-1-hydroxylase in colon, breast, lung, prostate, etc. to produce 1,25OH2D which acts to regulate cell growth and decrease proliferative activity.

Am J Clin Nutr 79, 362-71 (2004)

Normal cells can convert 25(OH)D to 1,25(OH)2 D Am J Clin Nutr 79, 368 (2004)

Colon Cancer DietColon Cancer Diet Worst - high fat, low fibre, high

refined carbs (increase beta-glucuronidase)

Best - high protein, higher in unrefined carbs, lower in fat and rich in fibre (lowers beta-glucuronidase)

Nutr Cancer 27(3),250-255(1997)