Jewish World Review Feb. 24, 2003 / 22 Adar I, 5763




Tamoxifen & Benign Breast Disease

By Robert A. Wascher, M.D., F.A.C.S.

http://www.NewsAndOpinion.com | Tamoxifen has been shown in large studies to effectively reduce the incidence of hormonally responsive breast cancers by nearly 50% in women who are at high risk of developing the disease.

The current issue of the Journal of the National Caner Institute contains a very interesting study that evaluated the impact of tamoxifen on benign breast disease, as well. The overwhelming majority of breast biopsies performed in the United States result in a diagnosis of benign breast lesions.

The authors of this study hypothesized that tamoxifen's ability to block the stimulatory effects of estrogen on the female breast might also reduce the risk of developing benign breast masses.

A total of 13,203 women who had previously participated in a large tamoxifen breast cancer prevention study were included in the current analysis. The researchers evaluated the incidence of biopsies for breast lesions that turned out to be benign in women who received tamoxifen, and in those who received a placebo pill only.

This retrospective study determined that the women who had received tamoxifen had a 28% reduction in the risk of developing non-cancerous breast tumors. The types of benign breast tumors that were favorably influenced by tamoxifen included cysts, fibrocystic disease, and fibroadenomas. Compared with the group receiving a placebo, the tamoxifen group also underwent 29% fewer breast biopsies. This reduction in the risk of benign breast tumors and biopsies occurred primarily in premenopausal women less than 50 years of age.

This study suggests a potential prevention role for tamoxifen in women with a predisposition towards not only malignant breast lesions, but also in at least some women with a high incidence of benign breast lesions that require biopsy to exclude cancer. Some of the benign lesions that appear to be favorably impacted upon by tamoxifen are, in themselves, associated with a slight increase in the risk of developing breast cancer.

These include ductal hyperplasia and metaplasia, as well as fibroadenomas. The potential risks of tamoxifen, however, must be carefully weighed against its benefits. Some of the risks associated with tamoxifen, although quite uncommon, can include such potentially life-threatening complications as stroke, blood clots in the veins, and uterine cancer.

Nonetheless, this study provides an intriguing look at the effects of tamoxifen on the premenopausal breast, and may lead to the development of other anti-estrogen drugs with better safety profiles than tamoxifen. Such drugs are already undergoing early clinical testing, and may have an important role to play in the prevention of both benign and malignant breast disease in high-risk women.

NEW RECOMMENDATION ON DIGITALIS DOSING

Digitalis is one of the oldest medications in continuous use by physicians. Digitalis is derived from the Foxglove plant, and has been prescribed for a variety of maladies since the 18th century. It is still used by contemporary physicians to improve cardiac function in patients with congestive heart failure (CHF), and to regulate abnormally fast heart rates in patients with cardiac arrhythmias.

Although this medication is still frequently prescribed, recent studies have called into question its effectiveness in preventing cardiac complications and death. Now, a new study in the current issue of the Journal of the American Medical Association takes a look at clinical outcomes in patients associated with various blood levels of this medication.

A total of 3,782 male patients with CHF were treated with varying doses of digitalis, and an additional 2,611 patients with CHF took placebo pills. The group taking digitalis was further divided into 3 subgroups, based upon the levels of digitalis in their blood (0.5-0.8 ng/ml, 0.9-1.1 ng/ml, 1.2 ng/ml or greater).

The authors then looked at the incidence of death among all of the study volunteers.

The study determined that patients with the lowest blood levels of digitalis (0.5-0.8 ng/ml) also had the lowest death rate among all of the patient groups in the study, including the placebo group. At the same time, patients with the highest levels of digitalis in their blood (1.2 ng/ml or greater) had the highest mortality rates.

This study suggests that achieving relatively low blood levels of digitalis appear to provide the greatest protection against premature death in patients with CHF, while increasing blood levels of digitalis are associated with a greater risk of dying.

The authors, therefore, suggest that patients (and men in particular) taking digitalis should have their doses optimized to obtain blood levels in the range of 0.5 to 0.8 ng/ml. If you are currently taking digitalis for CHF, you should consult with your physician prior to making any changes in your daily digitalis dose. Under no circumstances should you alter your digitalis intake without the assistance and advice of your physician.

CREUTZFELDT-JAKOB DISEASE & THE NOSE

Creutzfeldt-Jakob Disease (CJD) is a member of the family of diseases caused by protein particles called prions. The spontaneous variety of CJD is extremely rare, occurring in less than one per million people. While 10-15% of cases of CJD are thought to be inherited, the remaining cases fall within the "sporadic" category. Sporadic CJD has been eclipsed in recent years by the development of bovine spongiform encephalopathy (BSE), more commonly called "mad cow disease."

These and other related diseases fall within the transmissible spongiform encephalopathy (TSE) category of prion-mediated brain disease, and are characterized by the very gradual onset, often over many years, of progressive dementia and wasting, followed by death.

The exact mechanism whereby spontaneous CJD is transmitted is not clear. While occasional cases are thought to have been passed along to patients receiving transplanted tissue from other patients already infected with CJD, the majority of cases arise by unknown mechanisms. An intriguing study in the current issue of the New England Journal of Medicine builds upon previous studies that have shown the presence of the CJD-causing prions in the olfactory lobes of patients who have died of this illness.

The authors performed autopsies on 9 patients with documented sporadic CJD, and evaluated the brain (including the olfactory lobes), the thin plate of bone (the cribriform plate) through which the olfactory nerves travel from the nasal cavity to the olfactory lobes, the lining of the nose (mucosa) containing the receptors for smell (olfaction), and the lining of the trachea and lungs.

All of these tissues were analyzed for the presence of the CJD prion, in an effort to identify possible sites of initial infection by the deadly protein particles.

In all 9 patients, the CJD prions were shown to be present in the olfactory receptor cells lining the upper nasal cavity, the olfactory nerves leading from the nasal cavity to the olfactory lobes of the brain, and in the olfactory lobes as well. However, the lining of the respiratory tract did not contain any of the prions. As a control, identical autopsy studies were performed on 11 deceased people without a history of CJD.

No CJD prions were identified in any of the tissues in these control patients. The implications of these findings are very significant, for they suggest that sporadic CJD may find entry into the brain via the nasal cavity, but not through the respiratory tract. This study also suggests that patients suspected of having sporadic CJD might be able to undergo biopsy of the nasal lining rather than the current standard of undergoing a biopsy of their brain through holes drilled into the skull.

While the precise mechanism whereby sporadic CJD is introduced into a new host is not answered by this study, it strongly suggests that the route of infection is likely to be via the nasal cavity, with subsequent spread of prions throughout the brain.

RADIOLOGIST EXPERIENCE & ACCURACY OF MAMMOGRAM INTERPRETATION

In the surgical world, there is ample evidence that patients undergoing complex surgical procedures tend to have a better outcome in the hands of surgeons with the most experience in performing such operations. Thus, it would seem logical that the interpretation of mammograms would be more accurate among older and more experienced radiologists. According to a new study in the Journal of the National Cancer Institute, this may not be so.

Previous studies have shown that radiologists who, in general, review high volumes of mammograms tend to identify subtle abnormalities more frequently than low-volume radiologists. However, these studies have been limited in their scope, and in the numbers of radiologists evaluated. In the current study, 110 radiologists around the United States were asked to review the mammograms of 148 randomly selected women.

After controlling for potentially confounding variables, the study determined that neither the current volume of mammograms reviewed nor the radiologists' number of years of experience in reading mammograms were statistically associated with accuracy.

Instead, the study found that radiologists who most recently completed their training produced the most accurate readings! Additional factors that correlated with accurate mammogram results included the designation of a radiographic center as a comprehensive breast imaging center (and, in particular, the frequent performance of mammograms and mammogram-guided needle biopsies at the facility), and centers where each mammogram was reviewed by at least two radiologists.

While the findings of this study have met with understandable disbelief among many experts, it is not surprising that busy comprehensive breast diagnostic centers tend to do a better job of accurately interpreting mammograms than smaller multi-specialty radiology centers. As for the finding that recently trained radiologists may have an edge over their older colleagues, much speculation abounds as to the possible reasons behind this finding.

In an accompanying editorial, women are advised to obtain their annual mammograms at a single facility so as to allow for comparisons between current and previous mammogram films. It is also suggested that women who are still menstruating undergo mammography during the first half of their menstrual cycle, when the breast tissue is least dense.

REGULAR REST BREAKS & THE RISK OF INDUSTRIAL ACCIDENTS

A new study in the journal Lancet confirms what common sense should already dictate: accidents within industrial work environments can be reduced by scheduling all workers for brief regular rest breaks. The authors of this study reviewed accident records from a large engineering company over a period of 3 years.

By studying 2-hour blocks of work periods, the study identified a two-fold increase in the risk of industrial accidents in the last half hour of the 2-hour shift when compared to the first half hour. At the same time, there was no apparent difference in the incidence of accidents among the three 2-hour work shifts present in each workday.

The implications of these findings are that periods of continuous work for as little as 2 hours are associated with a significant increase in the risk of industrial accidents. When brief regular breaks are scheduled at 2-hour intervals, no further increase in accidents rates are seen during the course of the workday in industrial work environments.

MORE DATA ON THE INCIDENCE OF GI SIDE EFFECTS WITH SELECTIVE COX-2 NSAIDs

A recently published study called into question the belief that the COX-2-specific nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., Vioxx and Celebrex) are safer for the GI tract than the non-specific anti-inflammatory drugs (e.g., ibuprofen, Motrin, Naprosyn, Indocin, aspirin, etc.). In the journal Gastroenterology, this question is evaluated in a large-scale prospective study.

A total of 8,076 patients with rheumatoid arthritis were randomly assigned to take either Vioxx (50 mg per day) or Naprosyn (500 mg twice a day) for at least 1 year. The rate of serious GI events was then assessed, including GI bleeding, perforation of the stomach or intestine, obstruction of the stomach, or diverticulitis (inflammation of the colon).

The study found that the rate of serious GI events was 54% lower among patients taking the selective COX-2 inhibitor than was seen in the group taking Naprosyn. This rather large and prospective study appears to rather convincingly substantiate the premise that COX-2-selective NSAIDs are associated with a reduced incidence of upper and lower GI tract complications when compared to their non-selective cousins.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.

Up

02/18/03: Update on Alzheimer's Disease; Very Low Birth-weight Babies & Cognitive Development; The Great Blood Pressure Medication Debate

02/03/03: Update on C-reactive Protein; COX-2 Inhibitors & Arterial Function; COX-2 Inhibitors and Gastrointestinal Complications; Telomere Shortening & Risk of Death

01/24/03: Bo-tox that BO Away!; The Super-sizing of America; Marijuana: A Gateway Drug?

01/21/03: Dietary Soy & Prostate Cancer Risks; Retention of Surgical Foreign Bodies after Surgery; Diet & hormone levels in adolescent girls

01/10/03: Can Aspirin Prevent Esophageal Cancer?; A Drink to Your Health!; Hormones & Breast Cancer; The Impact of Obesity on Lifespan

01/06/03:"The Pill" for Males?; Obesity & Diabetes Trends in the United States; Binge Drinking in the United States; One Less Reason to be Depressed; Liver Failure: Trends

12/20/02: Citrus Pectin & Cancer; Echinacea & the Common Cold; Update on High Blood Pressure Treatment

12/06/02: Calcium Intake & Prostate Cancer Risk; Alcohol Consumption & Risk of Breast Cancer; Reducing Blood Transfusions in Critically Ill Patients

12/06/02: Alcohol, Tamoxifen & Carotid Artery Wall Thickness; Coffee & Gallstones?; Irritable Bowel Syndrome Update; Statins: More Good News

11/22/02:Alcohol, HRT & the risk of breast cancer; hormone replacement therapy: more bad news; new vaccines may eliminate cervical cancer; more

11/15/02: The Effects of Diet & Exercise on Blood Pressure & Health; Growth Hormone & Sex Steroid Supplements & the Elderly; C-Reactive Protein & Cardiovascular Disease Risk

11/08/02: More Good News About Statin Drugs; Hormone replacement Therapy (HRT) & Alzheimer's Disease; A Role for Antibiotics in the Treatment of Vascular Disease?; more

11/01/02: Digoxin & gender; driving & degenerative disc disease; Coenzyme Q10 & Parkinson's Disease; Ginseng & erections; Viagra & stroke

10/25/02: Aspirin & coronary artery bypass surgery; glucosamine sulfate & progression of knee arthritis; hospital nurse staffing & patient mortality

10/18/02: Motor Vehicle Exhaust Pollution & Mortality; CT Scans, C-Reactive Protein & Heart Disease; Antiperspirant Use & the Risk of Breast Cancer; Atomic Bomb Radiation Exposure Update; more

10/04/02: Antioxidants & the Risk of Stomach Cancer; Best Way to Diagnose Appendicitis?; Coronary Artery Disease: Stent or Surgery?

09/27/02: Breast Feeding & the Risk of Asthma; HMOs & Quality of Care Scores; Red Wine & Vascular Disease

09/20/02: Dietary Folate & the Risk of Colorectal Cancer; Risks Associated with Smoking after Heart Attacks; BRCA1 Gene Mutation & the Risk of Breast & Non-breast Cancers; Breast Tissue Density & Inheritance

09/13/02: Dairy Products, Calcium, Vitamin D & the Risk of Breast Cancer; Efficacy of Nonprescription Smoking Cessation Aids; A Nutty Approach to Heart Disease Prevention; Update on Prostate Cancer

09/06/02: C-Reactive Protein & Estrogen Replacement Therapy; Walking Women & Cardiovascular Disease; Physical Activity Among Teenaged Girls

08/30/02: Babbling babies & brain function; homocysteine levels, vitamins & coronary artery disease; St. John's Wort & chemotherapy

08/16/02: A New Weapon Against Anthrax?; cataracts & motor vehicle accidents; gingko biloba takes a hit; air pollution & heart function during exercise; breast cancer genes & the estimated risk of breast cancer

08/09/02: Botulinum Toxin & Post-Stroke Spasticity; Intestinal Hormone Kills Appetite; Bone Marrow Cells Improve Blood Flow in Vascular Disease; Effectiveness of Restraining Orders on Domestic Violence

08/02/02: Mammography Saves Lives!; Obesity & the Risk of Heart Failure; High Sugar Diets & the Risk of Colon Cancer; Abuse During Childhood & Possible Effects of Genes on Antisocial Behaviors

07/26/02: Cancer: Nature vs. Nurture; Cardiorespiratory Fitness & Inflammation; Kidney Transplants from Cadaver Donors; Aircraft Cabin Air Recirculation & the Common Cold

07/19/02: PCBs & the Gender of Babies; Breastfeeding & the Risk of Breast Cancer; More Bad News About Hormone replacement Therapy

07/12/02: A cancer surgeon's perspective on hormone replacement therapy

07/08/02: Hormone replacement therapy & the risk of disease; more good news about statins; antioxidant vitamins & disease prevention; more

06/28/02: Antioxidants & the Risk of Alzheimer's Disease; Effects of Exercise on the Hearts of Patients with Mild Hypertension; Statins reduce cardiac events following angioplasty; more

06/21/02: Sex & violence and Advertising: Do Advertisers Get What they Pay For?; Don't Drink the Water (or the Salsa Either!); Vasectomy & Prostate Cancer Risk; Update on Smoking & Disease

06/14/02: Young Men, Obesity & Heart Disease; Breastfeeding & Obesity; Irritable Bowel Syndrome & rectal pain threshold; more data on cox-2 inhibitors & cancer; more

06/07/02: New coronary artery stent reduces risk of restenosis; possible cause of Parkinson's Disease identified; more

05/31/02: New biological insights into obesity & weight loss; broccoli kills cancer-causing stomach bug; anti-inflammatory drugs and the risk of heart attack

05/24/02: Molecular detection of tumor cells in the blood & prognosis; Cox-2 & breast/lung cancers; BRCA2 gene mutations & the risk of breast cancer; breast density & the risk of breast cancer

05/19/02: Moderate alcohol intake and blood sugar levels; more good news for tea drinkers; blood potassium levels & the risk of cardiovascular disease; ethnic differences in diabetic complications

05/10/02: Tea drinkers and the risk of death following heart attack; duration of breastfeeding & adult intelligence; abdominal aortic aneurysms: surgery or observation?

05/03/02: Risk of adverse drug reactions from newly released medications; preoperative beta-blockers may reduce heart bypass deaths; shape-shifting plastics may alter surgical practice; weight loss supplement may cause liver damage
04/26/02: Angry young men & risk of premature cardiovascular disease; stay-at-home dads & risk of cardiovascular disease; more on the effects of statins; dairy consumption and the risk of pre-diabetes; smallpox vaccine: good to the last drop?
04/19/02: Change your sex by drinking water?; Anti-inflammatory RXs may reduce growth of breast cancer cells; radiation treatment reduces repeat narrowing of bypass grafts
04/05/02: Fish & Omega-3 fatty acid consumption and cardiac health; news briefs
04/05/02: Can coffee reduce your risk of tooth decay?; exercise & blood pressure; a single high-fat meal reduces coronary artery function
04/01/02: Pre-diabetes: a newly defined category of health risk; teen television viewing and subsequent aggressive behavior; the benefits of strength training in the elderly; more ...
03/22/02: Bacteria, antibiotics & heart disease; mammograms: the debate continues; calcium & the risk of colon cancer ... and more
03/15/02: Mammography debate continues; statins & fracture risk; physical fitness & the risk of death; other intriguing findings
03/08/02: Blows to the chest & sudden cardiac death; air quality & the risk of lung cancer; tomatoes and your prostate
03/01/02: Diet & the risk of ovarian cancer; lifetime risk of developing high blood pressure; Osteoporosis prevention with a once-a-year injection?
02/26/02: The continuing controversy regarding screening mammography
02/22/02: Lowering body temperature after heart attack improves outcome; A silver lining for the chronically sleep-deprived?
02/15/02: Hormone replacement therapy & the risk of breast cancer; use it or lose it: Alzheimer's disease & cognitive stimulation; stress, divorce & death; child daycare, infections & parental guilt
02/08/02: Possible breakthrough in early cancer diagnosis; mammography: the controversy continues; CPR techniques revisited
02/01/02: Antibiotics in livestock feed & human disease; genetic detection of early colon cancer in the stool; genetic analysis of breast cancers may help decide treatment
01/25/02: Drug increases lifespan (if you're a fly...); workplace attitudes and smoking cessation; effects of inadequate sleep on surgeons
01/18/02: Lifelong effects of premature birth; smokers under the knife; aspirin and cardiovascular health
01/11/02: Estrogen levels in the blood & breast cancer risk; Heart attack: sex and survival; dangerous lettuce invaders
01/09/02: Cancer & aging: Two sides of the same coin?
01/04/02: Vitamin a & the risk of hip fracture in postmenopausal women; ovarian cancer risk and oral contraceptives
12/28/01: Magnetic Resonance Imaging (MRI) detects coronary artery disease; new development in obesity research; adverse childhood experiences & the risk of suicide attempts
12/21/01: Vaccination of children controls hepatitis a in the community; a possible cure for sickle cell disease; leptin and the risk of heart attacks
12/14/01: Chernobyl and the Risk of Thyroid Cancer in hildren; children & obesity; gastroesophageal reflux disease update
12/07/01: Update on school shootings; new implantable heart-assist device approved for further evaluation; prevention of fungal infections in pre-term babies
11/30/01: Flu vaccination in asthmatics; low-tar cigarettes are not less harmful; beans and your heart
11/21/01: Modified smallpox vaccine may reduce risk of cervical cancer; New approach to breast cancer diagnosis; New non-invasive prenatal diagnostic test for down's syndrome
11/16/01: Cholesterol-lowering drugs reduce risk of heart attack; supplemental radiation therapy reduces risk of breast cancer recurrence; brains of women may answer age-old questions
11/09/01: Bio-warfare (redux); my gray matter is bigger than yours; mad elk disease?
11/02/01: Making sense of bio-warfare
10/26/01: The impact of mammography on deaths due to breast cancer; diet & exercise may slow cancer cell growth; antidepressants and the risk of heart disease
10/19/01: New insights into autism; the wiley appendix
10/12/01: More bad news about obesity links to other diseases…Hey dad, can I borrow the car keys?
10/05/01: California leads nation in reduction of tobacco-related disease; exercise as an antidepressant?
09/25/01: Advances in the detection of breast cancer; primary care physician awareness of peripheral arterial disease; arsenic in the water
09/17/01: In perspective
09/12/01: Genes may hold secret to long life; men and women: cognitive function in the elderly; physical activity, obesity and the risk of pancreatic cancer
09/05/01: English milk cows prefer Beethoven and Simon & Garfunkel over Bananarama; new prostate cancer prevention study: looking for a few good men; exercise & diet can help prevent diabetes
08/28/01: Arthritis drugs may be linked with increased risk of heart disease; errors in blood clotting tests can be fatal; infant soy formula not associated with reproductive side effects

© 2002, Dr. Robert A. Wascher