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Health Report:

Breast Cancer Recurrence & Hormone Replacement Therapy (HRT)

Carotid Artery Disease:  Surgery vs. Stents?

Statin Drugs & Cancer Prevention



"A critical weekly review of important new research findings for health-conscious readers..."


By, Robert A. Wascher, MD, FACS


Photo of Dr. Wascher

Last Updated: 4/13/2008


The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author.  Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.

BREAST CANCER RECURRENCE & HORMONE REPLACEMENT THERAPY (HRT)

Regular readers of this column are already well informed about the known risks associated with taking hormone replacement therapy (HRT) to relieve the symptoms of menopause.  With the results of the landmark Women’s Health Initiative Study (WHIS), and similar studies, clearly implicating combination HRT with an increased risk of breast cancer, heart disease, stroke, dementia, and other serious illnesses, physicians and their patients are, increasingly, taking a more conservative approach to dealing with the unpleasant symptoms that often accompany the onset of menopause. 

Among women who have previously been diagnosed with breast cancer, the risk of developing a recurrence of their cancer, and new breast cancers as well, is known to be higher than for women of otherwise average breast cancer risk, and with no prior history of breast cancer. 

Up until now, there has not been a great deal of research data looking specifically at the added risk, if any, of taking HRT after a prior diagnosis of breast cancer, although most experts believe that HRT is almost certainly a risk factor for breast cancer recurrence (i.e., in addition to the development of new cancers in the breast).  Now, a new study, from multiple university medical centers in Europe, looks at the impact of HRT in breast cancer recurrence among women with a prior history of this form of cancer.  This new research study, just published in the Journal of the National Cancer Institute, is part of a prospective study, called the HABIT Study, which consisted of 442 Scandinavian breast cancer survivors.  A total of 221 women were randomized to receive HRT, while the remaining 221 women were randomized to no HRT at all.

The results of this study were quite striking.  Among the 221 women taking HRT, just over 22% of these women were estimated to develop recurrent breast cancer after an average of 5 years of follow-up.  Among the 221 women who did not take HRT, only 8% went on to develop a recurrence of their previous breast cancer at 5 years.  This represents a nearly two-and-a-half fold increase in the risk of breast cancer associated with the use of HRT and, with respect to the natural history of breast cancer recurrence, within a rather short period of time as well.  In fact, because the risk of recurrent breast cancer appeared to be so high in the group of women taking HRT, this research study was prematurely halted in 2004 (just as the WHIS was prematurely terminated in 2002) , and the women taking HRT were warned about the apparent increased risk of breast cancer recurrence associated with taking HRT. 

As multiple other previous studies have shown, and as I and other breast cancer experts have warned for years, the use of HRT (and combination HRT in particular) appears to have significantly contributed to the decades-old gradual rise in the annual number of breast cancer cases diagnosed in the United States since the mid-1960s, when HRT became especially popular in the U.S. and in other western countries around the world.  The striking and unprecedented recent decline in the annual incidence of breast cancer in the United States, and in other western countries, following the publication of the preliminary results of the WHIS in 2002, has paralleled the declining number of prescriptions written for HRT since this landmark study was published in the Journal of the American Medical Association.  Ironically, I wrote a book on this very topic (including the shameful history of misrepresentation, and the covert financial and marketing support provided to pro-HRT physicians, by the dominant pharmaceutical manufacturer of HRT drugs in the mid-1960s, and thereafter) in 2004.  However, the majority of senior publishing house editors who reviewed the manuscript (most of whom were women, it must be said) dismissively accused me of being “biased” against HRT; and several opined that, as a man, I simply could not understand the ravages of menopause and, hence, the quality-of-life improvement brought about by HRT medications (notwithstanding decades of clinical research showing that only 2-5% of women experience profoundly disabling symptoms associated with menopause, and in the majority of all women passing through menopause, these symptoms significantly and spontaneously abate within 3-5 years).

The results of this new study are completely consistent with what we now know about the molecular biology of estrogen and progesterone (the primary female sex hormones), and their stimulatory effects on the proliferation of breast cancer cells (the overwhelming majority of breast cancers, especially in women aged 50 and older, have chemical receptors for these sex hormones, which stimulate these cancer cells to grow and divide).  My advice to all women, and especially to women with a prior history of breast cancer, is to avoid HRT drugs, period.  This has been my consistent recommendation for the past 20 years, based upon clinical research and observations dating back to the 1930s.  With the enormous amount of confirmatory data that has been subsequently published since 2004, I don’t appear to be the one with significant biases in this area….


CAROTID ARTERY DISEASE:  SURGERY VS. STENTS?

A relatively common manifestation of peripheral arterial atherosclerotic disease (“hardening of the arteries”) is carotid artery stenosis.  The carotid arteries supply most of the blood to the brain, and when they become clogged with atherosclerotic plaque and blood clots, bits of these materials can break off (or embolize) and lodge in the smaller arteries that feed the brain, causing temporary or permanent damage to the brain.  These embolic complications of carotid artery disease are referred to as, respectively, transient ischemic attacks and strokes (the same vascular disease process occurs in the coronary arteries, and leads to heart attacks, or myocardial infarctions). 

Nearly 150,000 operations for carotid artery stenosis are currently performed each year in the United States, as there is abundant research evidence supporting surgical over medical treatment in patients with significant narrowing of their carotid arteries (the primary risk of untreated carotid artery stenosis is stroke).  In this operation, the clogged-up, narrowed artery is surgically opened, and the surgeon then carefully peels the thickened, diseased lining away from the wall of the artery, leaving a clean surface behind.  The artery is then sewn shut (often, a synthetic patch is also used to reconstruct the artery, to prevent narrowing of the artery).  This operation, referred to as carotid endarterectomy, is not without risk (as with any operation), however, and is associated with a 0.5-2% risk of postoperative stroke, as well as a small risk of bleeding, infection and death. 

A relatively recent innovation in the management of arterial atherosclerotic disease has involved the use of shunts, most of which can be placed through small, superficial incisions in the groin or arm, much as cardiologists and interventional radiologists have been doing for decades in order to perform x-rays studies of the arterial system (“angiography”), and more recently, to treat diseased coronary arteries with balloon catheters and stents.  This minimally-invasive approach to atherosclerotic vascular disease has revolutionized the management of not only coronary artery disease, but also for aneurysms (abnormal dilation of atherosclerotic arteries) of the aorta (the largest artery in the body), and the large branch arteries that arise from the aorta to supply the lower extremities (the iliac and femoral arteries).  However, given the potentially catastrophic complications (including death) associated with strokes, the use of balloon catheters and stents to treat narrowed areas of the carotid arteries has not advanced as rapidly as it has for other diseased arteries in the body. 

A new study from Harvard University, and several other collaborating U.S. medical centers, and just published in this week’s New England Journal of Medicine, provides important clinical data to suggest that minimally invasive carotid artery stenting may finally have become at least the equal of carotid endarterectomy, at least in highly selected patients.  In this prospective randomized clinical study, a total of 334 patients with narrowed carotid arteries were randomized to either standard surgical treatment (i.e., carotid endarterectomy) vs. carotid artery stenting.  The average follow-up of these patients was 3 years.

Altogether, almost 80% of the patients participating in this clinical trial were available for follow-up evaluation after 3 years.  The bottom line: patients in both treatment groups experienced a statistically equivalent incidence of stroke, myocardial infarction and death (the average incidence of any of these three complications in both groups of patients, at 3 years, was 27%). 

This study will likely be considered a landmark research trial regarding the optimal management of severe carotid artery stenosis, especially in patients who are considered to be at very high risk of complications following traditional surgical intervention.  The use, in this study, of a special device designed to catch errant bits of clot and plaque that might be dislodged during placement of the stent very likely helped to achieve the excellent results reported in this high-quality research trial, and sets this study apart from some earlier studies that did not use such “anti-embolization” devices (and which often reported prohibitive stroke rates associated with carotid artery ballooning and stenting).

As a reminder to my readers, the risk factors most commonly associated with carotid artery atherosclerosis (and, indeed, with atherosclerosis throughout the body) include smoking, elevated cholesterol and fat levels in the blood, obesity, a sedentary lifestyle and high blood pressure.  Given that an ounce of prevention is worth far more than a pound of cure when it comes to your health, if you currently have any of these risk factors, then please see your physician soon, and modify your lifestyle to eliminate (or control) these risk factors.


STATIN DRUGS & CANCER PREVENTION

There continues to be a great deal of debate regarding the class of cholesterol-lowering drugs referred to as statins, and their effects (if any) on lowering the risk of developing certain cancers.  In addition to their potent ability to reduce the levels of so-called “bad cholesterol” (LDL) in the blood, and to increase the levels of “good cholesterol” (HDL), most statins appear to have at least mild anti-inflammatory effects as well.  (Chronic inflammation in the body has been linked both to the development of atherosclerotic narrowing of the arteries in our bodies as well as to the development of many cancers.)  Multiple prior laboratory and clinical research trials have generated conflicting data regarding the effects of statin drugs on cancer risk, with some studies showing a reduction in the risk of at least certain types of cancer with prolonged statin use, and other studies showing no apparent cancer-prevention benefit at all.

A newly published study, in The American Journal of Medicine, provides results that suggest, as other recent studies have, that there may actually be a small, but significant, cancer-prevention effect associated with at least some of the statin drugs.  This study, from Quebec, Canada, was based upon a large public health clinical data registry, and looked at patients aged 45 years and greater, between 1998 and 2004, who had survived a heart attack, and had been prescribed a statin drug as a results of their heart attack. Four statin drugs within the so-called “lipophilic class” (atorvastatin, simvastatin, lovastatin and fluvastatin) were specifically included in this retrospective research study.  More than 30,000 patient histories were evaluated in this large public health study, including more than 18,000 patients who were never prescribed a statin drug, 6,015 patients who received high-dose statin medications, and 5,323 patients who were prescribed low-dose statin medications.

After an average of 7 years of follow-up, this study determined that the high-dose statin users, when compared to patients not taking any statin drugs, experienced a 25% reduction in the likelihood of admission to a hospital with a new diagnosis of cancer.  The low-dose statin users also appeared to experience a reduction in hospital admissions related to the diagnosis of cancer, with a more modest 11% reduction in the incidence of admissions for cancer.  Unlike similar recent clinical studies that have shown that only prolonged statin use may be associated with a reduction in the risk of developing cancer, this particular study found that even relatively short durations of statin usage appeared to be associated with a reduced risk of being admitted to a hospital with a new diagnosis of cancer, especially among patients receiving higher doses of these medications.

This study offers some further encouragement to those who believe that at least some statin drugs may be associated with the incidental benefit of reducing the risk of cancer.  However, I think that the jury is still out on this one, for now anyway.  As with most retrospective studies based upon public health databases, there are many potential sources of bias in retrospective epidemiological studies such as this one.  Unlike randomized, prospective controlled studies, which seek to control as many potentially confounding variables as possible up front, retrospective studies are far more prone to bias, which can lead to erroneous conclusions. 

At this time, I would not recommend that anyone take a statin drug primarily to reduce their risk of cancer.  However, if you are already taking a lipophilic statin for elevated cholesterol levels, then there is at least the possibility that you may be receiving an additional health benefit from your statin drug.  Obviously, a prospective, randomized, placebo-controlled study of statins would have to be done to definitively answer the question regarding statins and cancer risk.  Until such a study is performed, we cannot be completely certain that statins really do reduce the risk of cancer.


 
Disclaimer:  As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.


Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html


Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
 


Links to Other Health & Wellness Sites


Copyright 2008.  Robert A. Wascher, MD, FACS.  All rights reserved.


Dr. Wascher's Archives:

4-6-2008:  Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)


3-30-2008:  Abdominal Obesity & the Risk of Death in Women; Folic Acid Pretreatment & Heart Attacks; Pancreatic Cancer Regression after Injections of Bacteria


3-23-2008:  Age of Transfused Blood & Risk of Complications after Surgery; Obesity, Blood Pressure & Heart Size in Children


3-16-2008:  Benefits of a Full Drug Coverage Plan for Medicare Patients?; Parent-Teen Conversations about Sex; Soy (Genistein) & Prostate Cancer


3-9-2008:  Flat Colorectal Adenomas & Cancer; Health Risks after Stopping Hormone Replacement Therapy (HRT); Television, Children & Obesity 


3-2-2008:  Medication & Risk of Death After Heart Attack; Hormone Replacement Therapy (HRT) & Mammogram Results; Selenium: Cancer, Heart Disease & Death


2-23-2008:  Universal Healthcare Insurance Study; Glucosamine & Arthritis


2-17-2008:  Exceptional Longevity in Men; Testosterone & Risk of Prostate Cancer; Smoking & Pre-malignant Colorectal Polyps


2-10-08:  Thrombus Aspiration from Coronary Arteries; Intensive Management of Diabetes & Death; Possible Cure for  Down's Syndrome?


2-3-2008:  Vitamin D & Cardiovascular Health; Vitamin D & Breast Cancer; Green Tea & Colorectal Cancer


1-27-2008:  Colorectal Cancer, Esophageal Cancer & Pancreatic Cancer: Update from the 2008 American Society of Clinical Oncology's Gastrointestinal Cancers Symposium


1-20-2008:  Testosterone Levels & Risk of Fractures in Elderly Men; Air Pollution & DNA Damage in Sperm; Statins & Trauma Survival in the Elderly


1-12-2008:  Statins, Diabetes & Stroke and Obesity; GERD & Esophageal Cancer


1-7-2008:  Testosterone Supplements in Elderly Men; Colorectal Cancer-- Reasons for Poor Compliance with Screening Recommendations


12-31-2007:  Minority Women, Hormone Replacement Therapy & Breast Cancer; Does Health Insurance Improve Health?


12-23-2007:  Is Coffee Safe After a Heart Attack?; Impact of Divorce on the Environment; Hypertension & the Risk of Dementia; Emotional Vitality & the Risk of Heart Disease


12-16-2007:   Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality 


12-11-2007:  Bias in Medical Research; Carbon Nanotubes & Radiofrequency: A New Weapon Against Cancer?; Childhood Obesity & Risk of Adult Heart Disease


12-2-2007:  Obesity & Risk of Cancer; Testosterone Level & Risk of Death; Drug Company Funding of Research & Results; Smoking & the Risk of Colon & Rectal Cancer 


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